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This study aimed to address a unique case of external nasal valve insufficiency characterized by subjective symptoms of excessive air entry into the nose and throat discomfort despite the absence of apparent anatomical abnormalities or underlying diseases. We focused on devising a novel surgical approach to alleviate patient symptoms and highlighted the importance of considering the structural and functional aspects of nasal airflow in diagnosis and treatment. Paranasal sinus computed tomography and acoustic rhinometry were used to evaluate the anatomical and functional abnormalities. The nose scale was used to assess the subjective symptoms. The patient experienced significant improvement in breathing comfort following surgical intervention. Imaging revealed a widened columella, and the subjective symptoms were alleviated. Acoustic rhinometry measurements within the nasal cavity showed no substantial changes, likely due to the surgical focus on the external nasal valve. This case highlights the complexity of diagnosing and treating external nasal valve insufficiency without traditional anatomical abnormalities. Successful symptomatic management using this novel surgical technique highlights the need to consider structural and functional factors in nasal airway assessments. Further research is encouraged to refine the diagnostic tools and validate the effectiveness of innovative interventions for external nasal valve insufficiency in larger cohorts.

The incidence of colitis‐associated colorectal cancer (CAC) has increased due to a high‐nutrient diet, increased environmental stimuli and inherited gene mutations. To adequately treat CAC, drugs should be developed by identifying novel therapeutic targets. E3 ubiquitin‐protein ligase pellino homolog 3 (pellino 3; Peli3) is a RING‐type E3 ubiquitin ligase involved in inflammatory signalling; however, its role in the development and progression of CAC has not been elucidated. In this study, we studied Peli3‐deficient mice in an azoxymethane/dextran sulphate sodium‐induced CAC model. We observed that Peli3 promotes colorectal carcinogenesis with increased tumour burden and oncogenic signalling pathways. Ablation of Peli3 reduced inflammatory signalling activation at the early stage of carcinogenesis. Mechanistic studies indicate that Peli3 enhances toll‐like receptor 4 (TLR4)‐mediated inflammation through ubiquitination‐dependent degradation of interferon regulatory factor 4, a negative regulator of TLR4 in macrophages. Our study suggests an important molecular link between Peli3 and colonic inflammation‐mediated carcinogenesis. Furthermore, Peli3 can be a therapeutic target in the prevention and treatment of CAC.

Abstract This study examines the PM2.5 characteristics in Seoul in relation to those of PM1.0 and PM10. Samples were typically collected daily on filters and a few hours sampling were conducted during a few haze events (March 2007 to June 2008). Mean mass concentrations of PM1.0, PM2.5, and PM10 were 19.7 μg/m3, 26.0 μg/m3, and 48.2 μg/m3, respectively, and PM2.5 was reasonably correlated with PM1.0 (γ=0.79) and PM10 (γ=0.52). Three mass group types were mainly distinguished. Group 1 (31%): linear increase of PM1.0 with PM10 and high OC and NO3−; Group 2 (17%): PM10 considerably higher than PM1.0 and high Ca2+ and SO42−; Group 3 (52%): PM1.0 relatively more enhanced than PM10 and highest carbonaceous fraction against mass. The fine mode fraction was lowest (highest) in Group 2 (Group 3). Haze and dust episodes relating to Chinese outflows were mostly evident in Groups 1 and 2, respectively; average PM2.5 concentrations were visibly higher than in Group 3. Non-Negative Matrix Factorization analysis demonstrated that traffic-related urban primary (28%) and coal-fired industry (27%) emissions equally contributed to the PM2.5 mass, followed by aged urban secondary (19%), soil mineral (16%), and biomass combustion (10%) sources. Seasonal variations were apparent in air mass trajectories. Urban primary and coal-fired industry factors were predominant in Group 3 under stagnant conditions in the warm season and under a strong northerly wind in the cold season, respectively. However, contributions of the other three factors were higher in Groups 1 and 2. This study shows that the PM2.5 mass in Seoul is largely dependent on high concentration episodes occurring mostly in cold seasons. It also shows that local emissions contribute considerably during warm months, while the influence of Chinese outflow predominates during cold months.

Climate change, a pressing global concern, poses significant challenges to agricultural systems worldwide. Among the myriad impacts of climate change, the cultivation of kiwifruit trees (Actinidia spp.) faces multifaceted challenges. In this review, we delve into the intricate effects of climate change on kiwifruit production, which span phenological shifts, distributional changes, physiological responses, and ecological interactions. Understanding these complexities is crucial for devising effective adaptation and mitigation strategies to safeguard kiwifruit production amidst climate variability. This review scrutinizes the influence of rising global temperatures, altered precipitation patterns, and a heightened frequency of extreme weather events on the regions where kiwifruits are cultivated. Additionally, it delves into the ramifications of changing climatic conditions on kiwifruit tree physiology, phenology, and susceptibility to pests and diseases. The economic and social repercussions of climate change on kiwifruit production, including yield losses, livelihood impacts, and market dynamics, are thoroughly examined. In response to these challenges, this review proposes tailored adaptation and mitigation strategies for kiwifruit cultivation. This includes breeding climate-resilient kiwifruit cultivars of the Actinidia species that could withstand drought and high temperatures. Additional measures would involve implementing sustainable farming practices like irrigation, mulching, rain shelters, and shade management, as well as conserving soil and water resources. Through an examination of the literature, this review showcases the existing innovative approaches for climate change adaptation in kiwifruit farming. It concludes with recommendations for future research directions aimed at promoting the sustainability and resilience of fruit production, particularly in the context of kiwifruit cultivation, amid a changing climate.

Background: Data on the durability of booster dose immunity of COVID-19 vaccines are relatively limited. Methods: Immunogenicity was evaluated for up to 9–12 months after the third dose of vaccination in 94 healthy adults. Results: Following the third dose, the anti-spike immunoglobulin G (IgG) antibody response against the wild-type was boosted markedly, which decreased gradually over time. However, even 9–12 months after the booster dose, both the median and geometric mean of anti-spike IgG antibody levels were higher than those measured 4 weeks after the second dose. Breakthrough infection during the Omicron-dominant period boosted neutralizing antibody titers against Omicron sublineages (BA.1 and BA.5) and the ancestral strain. T-cell immune response was efficiently induced and maintained during the study period. Conclusions: mRNA vaccine booster dose elicited durable humoral immunity for up to 1 year after the third dose and T-cell immunity was sustained during the study period, supporting an annual COVID-19 vaccination strategy.

The nasal tip is the central component of facial aesthetics and is important in the overall appearance of the nose. Footplates, located at the posterior end of the medial crura, significantly impact the aesthetic outcome of the nasal columella. In our case, a 60-year-old woman with an abnormal nasal shape due to footplate deformity underwent successful correction through rhinoplasty. Successful correction using rhinoplasty highlights its potential benefits in addressing nasal columellar irregularities and their functional aspects.

ABSTRACTPhotoelectrochemical (PEC) water splitting is one of the most sustainable approaches for converting solar energy into hydrogen fuel. Affordable and robust photoelectrodes are crucial for the commercialization of PEC technologies. Recently, transition metal-based co-catalysts, especially Ni- and Fe-based catalysts, have attracted much interest owing to their exceptional OER characteristics. Given this, we here proposed the decoration of a Fe-Ni-based cocatalyst on the surface of the TiO2 photoanode for PEC water splitting. The TiO2 photoanode was hydrothermally synthesized and then decorated by Fe-Ni hydroxide catalyst using photo-assisted electrodeposition. The optimized TiO2/FeNiOOH photoanode exhibited the maximum photocurrent density value of 1.36 mA cm−2, which is almost twice the value obtained for bare TiO2, at 1.23 V vs RHE under the AM 1.5 G illumination. Due to the enhanced light absorption in the UV region, the optimized photoanode exhibited remarkable IPCE and photoconversion efficiency of 87.8% and 0.93%, respectively. Furthermore, excellent faradaic efficiencies of ∼90% for H2 and ∼70% for O2 generations were obtained. Predominantly, the enhancement in the photocurrent potentials was explained in detail. Our study shows the roles and benefits of using bimetallic catalysts with TiO2 photoanodes for sustainable water-splitting applications.

Abstract The signaling pathways governing acetaminophen (APAP)-induced liver injury have been extensively studied. However, little is known about the ubiquitin-modifying enzymes needed for the regulation of APAP-induced liver injury. Here, we examined whether the Pellino3 protein, which has E3 ligase activity, is needed for APAP-induced liver injury and subsequently explored its molecular mechanism. Whole-body Peli3 −/− knockout (KO) and adenovirus-mediated Peli3 knockdown (KD) mice showed reduced levels of centrilobular cell death, infiltration of immune cells, and biomarkers of liver injury, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), upon APAP treatment compared to wild-type (WT) mice. Peli3 deficiency in primary hepatocytes decreased mitochondrial and lysosomal damage and reduced the mitochondrial reactive oxygen species (ROS) levels. In addition, the levels of phosphorylation at serine 9 in the cytoplasm and mitochondrial translocation of GSK3β were decreased in primary hepatocytes obtained from Peli3 −/− KO mice, and these reductions were accompanied by decreases in JNK phosphorylation and mitochondrial translocation. Pellino3 bound more strongly to GSK3β compared with JNK1 and JNK2 and induced the lysine 63 (K63)-mediated polyubiquitination of GSK3β. In rescue experiments, the ectopic expression of wild-type Pellino3 in Peli3 −/− KO hepatocytes restored the mitochondrial translocation of GSK3β, but this restoration was not obtained with expression of a catalytically inactive mutant of Pellino3. These findings are the first to suggest a mechanistic link between Pellino3 and APAP-induced liver injury through the modulation of GSK3β polyubiquitination.

Silent nociceptors remained enigmatic ever since they were first described decades ago. Here, Nees. et al. show that inflammation-induced upregulation of TMEM100 unsilences silent nociceptors, which triggers secondary mechanical pain hypersensitivity.

ABSTRACT The coronavirus disease 2019 pandemic persisted for 3 years and is now transitioning to endemicity. We illustrated the change in group immunity induced by vaccination (monovalent vaccines) and breakthrough infections (BIs) in a healthcare worker (HCW) cohort. Five sampling points were analyzed: before the third dose and 1, 3, 5, and 8 months after the vaccination. The last two points corresponded roughly to 1 and 4 months after omicron BA.1/BA.2 BI. A semi-quantitative anti-spike binding antibody (Sab) assay and plaque reduction neutralization test (PRNT) against circulating variants were conducted. A linear regression model was utilized to deduce correlation equations. Baseline characteristics and antibody titers after the third dose were not different between 106 HCWs with or without BI (54/52). One month after the third dose, BA.1 PRNT increased with wild-type (WT), but 3 months after the third dose, it decreased more rapidly than WT PRNT. After BI, BA.1 PRNT increased robustly and waned slower than WT. A linear equation of waning kinetics was deduced between log10Sab and months, and the slope became gradual after BI. The estimated BA.5 PRNT titers at the beginning of the BA.5 outbreak were significantly higher than the BA.1 PRNT titers of the initial BA.1/BA.2 wave, which might be associated with the smaller size of the BA.5 wave. BA.1/BA.2 BI after the third dose elicited robust and broad neutralizing activity, preferentially maintaining cross-neutralizing longevity against BA.1 and BA.5. The estimated kinetics provide an overview of group immunity through the third vaccination and BA.1/BA.2 BI, correlating with the actual outbreaks. IMPORTANCE This study analyzed changes in group immunity induced by coronavirus disease 2019 (COVID-19) vaccination and BA.1/BA.2 breakthrough infections (BIs) in a healthcare worker cohort. We investigated the longitudinal kinetics of neutralizing antibodies against circulating variants and confirmed that BA.1/BA.2 BIs enhance the magnitude and durability of cross-neutralization against BA.1 and BA.5. Correlation equations between semi-quantitative anti-spike antibody and plaque reduction neutralization test titers were deduced from the measured values using a linear regression model. Based on the equations, group immunity was estimated to last up to 11 months following the third dose of the COVID-19 vaccine. The estimated group immunity suggests that the augmented immunity and flattened waning slope through BI could correlate with the overall outbreak size. Our findings could provide a better understanding to establish public health strategies against future endemicity.

Introduction: Sterol regulatory element binding protein (SREBP) cleavage-associating protein (SCAP) is a sterol-regulated escort protein that translocates SREBPs from the endoplasmic reticulum to the Golgi apparatus, thereby activating lipid metabolism and cholesterol synthesis. Although SCAP regulates lipid metabolism in metabolic tissues, such as the liver and muscle, the effect of macrophage-specific SCAP deficiency in adipose tissue macrophages (ATMs) of patients with metabolic diseases is not completely understood. Objectives: Here, we examined the function of SCAP in high-fat/high-sucrose diet (HFHS)-fed mice and investigated its role in the polarization of classical activated macrophages in adipose tissue. Methods: Macrophage-specific SCAP knockout (mKO) mice were generated through crossbreeding lysozyme 2-cre mice with SCAP floxed mice which were then fed HFHS for 12 weeks. Primary macrophages were derived from bone marrow cells and analyzed further. Results: We found that fat accumulation and the appearance of proinflammatory M1 macrophages were both higher in HFHS-fed SCAP mKO mice relative to floxed control mice. We traced the effect to a defect in the lipopolysaccharide-mediated increase in SREBP-1a that occurs in control but not SCAP mKO mice. Mechanistically, SREBP-1a increased expression of cholesterol 25-hydroxylase transcription, resulting in an increase in the production of 25-hydroxycholesterol (25-HC), an endogenous agonist of liver X receptor alpha (LXRα) which increased expression of cholesterol efflux to limit cholesterol accumulation and M1 polarization. In the absence of SCAP mediated activation of SREBP-1a, increased M1 macrophage polarization resulted in reduced cholesterol efflux downstream from 25-HC-dependent LXRα activation. Conclusion: Overall, the activation of the SCAP-SREBP-1a pathway in macrophages may provide a novel therapeutic strategy that ameliorates obesity by controlling cholesterol homeostasis in ATMs.

In real-time strategy (RTS) games, to defeat their opponents, players need to choose and implement the correct sequential actions. Because RTS games like StarCraft II are real-time, players have a very limited time to choose how to develop their strategy. In addition, players can only partially observe the parts of the map that they have explored. Therefore, unlike Chess or Go, players do not know what their opponents are doing. For these reasons, applying generally used artificial intelligence models to forecast sequential actions in RTS games is a challenge. To address this, we propose depthwise separable convolution-based multimodal deep learning (DESEM) for forecasting sequential actions in the game StarCraft II. DESEM performs multimodal learning using high-dimensional frames and action labels simultaneously as inputs. We use a depthwise separable convolution as the backbone network for extracting features from high-dimensional frames. In addition, we propose a weighted loss function to resolve class imbalances. We use 1,978 StarCraft II replays where the Terrans win in a Terran vs. Protoss game. The experimental results show that the proposed depthwise separable convolution is superior to the conventional convolution. Furthermore, we demonstrate that multimodal learning and the weighted loss function contribute significantly to improving forecasting performance.

Background/Aims Endoscopic submucosal dissection (ESD) is an effective method for resecting gastric adenomas and adenocarcinomas. A significant discrepancy was observed between endoscopic and pathological sizes in samples obtained from patients undergoing ESD. This study elucidates the factors affecting size discrepancy after formalin fixation. Methods The records of 64 patients with 69 lesions were analyzed, including 50 adenomas and 19 adenocarcinomas. Data on location, gross shape, histology, and size after fixation in formalin were collected. Results The mean size of the resected specimen appeared to decrease after formalin fixation (37.5 mm prefixation vs. 35.8 mm postfixation, p

Deep reinforcement learning (DRL) is a powerful approach that combines reinforcement learning (RL) and deep learning to address complex decision-making problems in high-dimensional environments. Although DRL has been remarkably successful, its low sample efficiency necessitates extensive training times and large amounts of data to learn optimal policies. These limitations are more pronounced in the context of multi-agent reinforcement learning (MARL). To address these limitations, various studies have been conducted to improve DRL. In this study, we propose an approach that combines a masked reconstruction task with QMIX (M-QMIX). By introducing a masked reconstruction task as an auxiliary task, we aim to achieve enhanced sample efficiency-a fundamental limitation of RL in multi-agent systems. Experiments were conducted using the StarCraft II micromanagement benchmark to validate the effectiveness of the proposed method. We used 11 scenarios comprising five easy, three hard, and three very hard scenarios. We particularly focused on using a limited number of time steps for each scenario to demonstrate the improved sample efficiency. Compared to QMIX, the proposed method is superior in eight of the 11 scenarios. These results provide strong evidence that the proposed method is more sample-efficient than QMIX, demonstrating that it effectively addresses the limitations of DRL in multi-agent systems.

BackgroundThe emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants and the persistence of the pandemic, even with mass coronavirus disease 2019 (COVID-19) vaccination, have raised questions about the durability of immunity and extent of cross-reactive immunity after vaccination. This study aimed to characterize the humoral and cellular immune response to the mRNA-1273 vaccine using a prospective longitudinal cohort.MethodsWe recruited 177 young SARS-CoV-2 infection-naive adults. Two doses of mRNA-1273 vaccine were administered at 28-day intervals, and blood samples were collected at five time points: pre-vaccination (T0), 4 weeks after the first (T1) and second dose (T2), and 3 months (T3) and 6 months (T4) after the first dose. Anti-SARS-CoV-2 spike protein (anti-S) IgG antibody, neutralizing antibody, and T-cell immune responses were evaluated.ResultsThe two-dose mRNA-1273 vaccination induced robust anti-SARS-CoV-2 antibody responses, which remained higher than the titers at T1 until T4. A higher peak anti-S antibody titer at T2 was associated with better cross-reactive immunity against Delta and Omicron variants and long-lasting (anti-S IgG and neutralizing antibody) humoral immunity up to T4. The overall T-cell immune response was not correlated with peak antibody titers (T-lymphocyte subpopulation analysis was not performed).ConclusionThis study showed that an early strong antibody response is predictive of longer humoral immunity and better cross-reactive neutralizing immunity against Delta and Omicron variants.

To date, the development of anticancer drugs has been conducted using two-dimensional (2D) cell culture systems. However, since cancer cells in the body are generated and developed in three-dimensional (3D) microenvironments, the use of 2D anticancer drug screening can make it difficult to accurately evaluate the anticancer effects of drug candidates. Therefore, as a step towards developing a cancer cell-friendly 3D microenvironment based on a combination of vinylsulfone-functionalized polyethylene glycol (PEG-VS) with dicysteine-containing crosslinker peptides with an intervening matrix metalloproteinase (MMP)-specific cleavage site, the types of MMPs secreted from human hepatocarcinoma HepG2 cells, a representative cancer cell, were analyzed transcriptionally and translationally. MMP3 was confirmed to be the most highly expressed protease secreted by HepG2 cells. This knowledge will be important in the design of a crosslinker necessary for the construction of PEG-based hydrogels customized for the 3D culture of HepG2 cells.

Common methods for characterising cell viability involve cell staining with chemical reagents. Here the authors report a method for cell viability assessment that does not require labelling; this uses quantitative phase imaging combined with deep learning.

Objectives Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular disorder characterized by recurrent epistaxis, telangiectasia, and visceral arteriovenous malformations (AVMs). Activin A receptor-like type 1 (ACVRL1/ALK1) and endoglin (ENG) are the principal genes whose mutations cause HHT. No multicenter study has yet investigated correlations between genetic variations and clinical outcomes in Korean HHT patients. Methods Seventy-two members from 40 families suspected to have HHT based on symptoms were genetically screened for pathogenic variants of ACVRL1 and ENG. Patients with genetically diagnosed HHT were also evaluated. Results In the HHT genetic screening, 42 patients from 24 of the 40 families had genetic variants that met the pathogenic criteria (pathogenic very strong, pathogenic strong, pathogenic moderate, or pathogenic supporting) based on the American College of Medical Genetics and Genomics Standards and Guidelines for either ENG or ACVRL1: 26 from 12 families (50%) for ENG, and 16 from 12 families (50%) for ACVRL1. Diagnostic screening of 42 genetically positive HHT patients based on the Curaçao criteria revealed that 24 patients (57%) were classified as having definite HHT, 17 (41%) as having probable HHT, and 1 (2%) as unlikely to have HHT. Epistaxis was the most common clinical presentation (38/42, 90%), followed by visceral AVMs (24/42, 57%) and telangiectasia (21/42, 50%). Five patients (12%) did not have a family history of HHT clinical symptoms. Conclusion Only approximately half of patients with ACVRL1 or ENG genetic variants could be clinically diagnosed as having definite HHT, suggesting that genetic screening is important to confirm the diagnosis.

Abstract Cell death-inducing DNA fragmentation factor-like effector A (CIDEA) is a lipid droplet-associated protein and is a known marker of the thermogenic capacity of brown/beige adipocytes. To monitor the expression of CIDEA in live mice in a non-invasive manner, we generated CIDEA reporter mice expressing multicistronic mRNAs encoding CIDEA, luciferase 2, and tdTomato proteins under the control of the Cidea promoter. The expression level of endogenous CIDEA protein in adipose tissue was not affected by the expression of polycistronic reporters. The two CIDEA reporters, luciferase 2 and tdTomato, correctly reflected CIDEA protein levels. Importantly, luciferase activity was induced by cold exposure and the treatment with β3-adrenergic receptor agonist CL316,243 in interscapular and inguinal adipose tissue, which was detectable by in vivo bioluminescence imaging. We further evaluated the effects of candidate brown adipogenic agents using this CIDEA reporter system and demonstrated a positive correlation between drug-induced luciferase activity and thermogenic gene expression levels both in vitro and in vivo. Collectively, we established a dual CIDEA reporter mouse model in which fluorescence and luminescence signals correctly reflect CIDEA expression, and therefore, suggested that this reporter system can be used to evaluate the thermogenic efficacy of candidate molecules.

Evaluation of the safety and immunogenicity of new vaccine platforms is needed to increase public acceptance of coronavirus disease 2019 (COVID-19) vaccines. Here, we evaluated the association between reactogenicity and immunogenicity in healthy adults following vaccination by analyzing blood samples before and after sequential two-dose vaccinations of BNT162b2 and ChAdOx1 nCoV-19. Outcomes included anti-S IgG antibody and neutralizing antibody responses, adverse events, and proinflammatory cytokine responses. A total of 59 and 57 participants vaccinated with BNT162b2 and ChAdOx1 nCoV-19, respectively, were enrolled. Systemic adverse events were more common after the first ChAdOx1 nCoV-19 dose than after the second. An opposite trend was observed in BNT162b2 recipients. Although the first ChAdOx1 nCoV-19 dose significantly elevated the median proinflammatory cytokine levels, the second dose did not, and neither did either dose of BNT162b2. Grades of systemic adverse events in ChAdOx1 nCoV-19 recipients were significantly associated with IL-6 and IL-1β levels. Anti-S IgG and neutralizing antibody titers resulting from the second BNT162b2 dose were significantly associated with fever. In conclusion, systemic adverse events resulting from the first ChAdOx1 nCoV-19 dose may be associated with proinflammatory cytokine responses rather than humoral immune responses. Febrile reactions after second BNT162b2 dose were positively correlated with vaccine-induced immune responses rather than with inflammatory responses.

With the emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants, escaping vaccine-induced immunity is a concern. Three vaccination schedules, homologous or heterologous, have been initially applied due to an insufficient supply of vaccines in Korea. We investigated neutralizing activities against Omicron and Delta variants in each schedule. Three schedules using three doses of the BNT162b2 (BNT) or the ChAdOx1 (ChAd) vaccines include ChAd-ChAd-BNT, ChAd-BNT-BNT, and BNT-BNT-BNT. Neutralizing activities were evaluated using plaque-reduction neutralization test (PRNT) against wild type (WT) SARS-CoV-2, Delta variant, and Omicron variant. A total of 170 sera from 75 participants were tested, and the baseline characteristics of participants were not significantly different between groups. After the 2nd vaccine dose, geometric mean titers of PRNT ND50 against WT, Delta, and Omicron were highest after ChAd-BNT vaccination (2,463, 1,097, and 107) followed by BNT-BNT (2,364, 674, and 38) and ChAd-ChAd (449, 163, and 25). After the 3rd dose of BNT, the increase of PRNT ND50 against WT, Delta, and Omicron was most robust in ChAd-ChAd-BNT (4,632, 988, and 260), while the BNT-BNT-BNT group showed the most augmented neutralizing activity against Delta and Omicron variants (2,315 and 628). ChAd-BNT-BNT showed a slight increase of PRNT ND50 against WT, Delta, and Omicron (2,757, 1,279, and 230) compared to the 2nd dose. The results suggest that a 3rd BNT booster dose induced strengthened neutralizing activity against Delta and Omicron variants. The waning of cross-reactive neutralizing antibodies after the 3rd dose and the need for additional boosting should be further investigated.

Cannulation of the portal vein is a rare complication of ERCP. This paper reports a case of portal vein catheterization during ERCP in a patient with choledocholithiasis. A 62-year-old man was admitted to the Presbyterian Medical Center with right upper quadrant pain and jaundice. ERCP was performed under the suspicion of obstructive jaundice caused by a radiolucent stone. Bile duct cannulation using a pull-type papillotome was attempted, but it failed. After needle-knife fistulotomy, wire-guided cannulation was performed successfully, and 10 mL contrast was injected. On the other hand, the fluoroscopy image showed that the contrast medium disappeared very quickly. Pure blood was collected when the catheter was aspirated to identify the bile reflux, indicating possible cannulation of the portal vein. The procedure was terminated immediately and abdominal computed tomography showed air in the portal vein. One day after, a follow-up CT scan showed no air in the portal vein. The patient underwent repeated ERCP, and the common bile duct was cannulated. In most cases, isolated portal vein cannulation does not result in severe morbidity. However, it is important to aware of this rare complication so that no further invasive procedure is performed on the patient.

Abstract Central airway obstruction (CAO) can be attributed to several benign or malignant conditions. Although surgery is the preferred therapeutic option for the management of CAO, bronchoscopic treatment can be performed in scenarios where the surgical procedure is not possible. Recent years have witnessed several improvements in the field of bronchoscopic treatment, especially with regard to airway stents. Current research involves new attempts to overcome the existing shortcomings pertaining to the stents (migration, mucostasis, and granulation tissue formation). The authors have recently developed a new silicone airway stent (GINA stent) with an anti-migration design, dynamic structure that enables the reduction of stent cross-sectional area, and radio-opacity. The present study aimed to evaluate the mechanical characteristics and performance of the novel GINA stent using a porcine tracheal stenosis model. In the current study, all the tests involved the comparison of the GINA stent [outer diameter (OD, mm): 14; length (L, mm): 55] with the Dumon stent (OD: 14; L: 50). The mechanical tests were performed using a digital force gauge, in order to determine the anti-migration force, expansion force, and flexibility. The present study evaluated the short-term (3 weeks) performance of the two stents after implantation [GINA (n = 4) vs. Dumon (n = 3)] in the porcine tracheal stenosis model. The results pertaining to the comparison of the mechanical properties of the GINA and Dumon stents are stated as follows: anti-migration force (18.4 vs. 12.8 N, P = 0.008); expansion force (11.9 vs. 14.5 N, P = 0.008); and flexibility (3.1 vs. 4.5 N, P = 0.008). The results pertaining to the comparison of the short-term performance of the GINA and Dumon stents are stated as follows: mucus retention (0/4 vs. 0/3); granulation tissue formation (0/4 vs. 0/3); and migration (1/4 vs. 2/3). The GINA stent displayed better mechanical properties and comparable short-term performance, compared to the Dumon stent.

Messenger RNA (mRNA) vaccination was developed to mitigate the coronavirus disease 2019 pandemic. However, data on antibody kinetics and factors influencing these vaccines’ immunogenicity are limited. We conducted a prospective study on healthy young adults who received two doses of the mRNA-1273 vaccine at 28-day intervals. After each dose, adverse events were prospectively evaluated, and blood samples were collected. The correlation between humoral immune response and reactogenicity after vaccination was determined. In 177 participants (19–55 years), the geometric mean titers of anti-S IgG antibody were 178.07 and 4409.61 U/mL, while those of 50% neutralizing titers were 479.95 and 2851.67 U/mL four weeks after the first and second vaccine doses, respectively. Anti-S IgG antibody titers were not associated with local reactogenicity but were higher in participants who experienced systemic adverse events (headache and muscle pain). Antipyretic use was an independent predictive factor of a robust anti-SARS-CoV-2 antibody response after receiving both vaccine doses. Systemic reactogenicity after the first dose influenced antibody response after the second dose. In conclusion, mRNA-1273 induced a robust antibody response in healthy young adults. Antipyretic use did not decrease the anti-SARS-CoV-2 antibody response after mRNA-1273 vaccination.

Quantitative phase imaging suffers from a lack of specificity in label-free imaging. Here, the authors introduce Phase Imaging with Computational Specificity (PICS), a method that combines phase imaging with machine learning techniques to provide specificity in unlabeled live cells with automatic training.

In multi-agent reinforcement learning, it is essential for agents to learn communication protocol to optimize collaboration policies and to solve unstable learning problems. Existing methods based on actor-critic networks solve the communication problem among agents. However, these methods have difficulty in improving sample efficiency and learning robust policies because it is not easy to understand the dynamics and nonstationary of the environment as the policies of other agents change. We propose a method for learning cooperative policies in multi-agent environments by considering the communications among agents. The proposed method consists of recurrent neural network-based actor-critic networks and deterministic policy gradients to centrally train decentralized policies. The actor networks cause the agents to communicate using forward and backward paths and to determine subsequent actions. The critic network helps to train the actor networks by sending gradient signals to the actors according to their contribution to the global reward. To address issues with partial observability and unstable learning, we propose using auxiliary prediction networks to approximate state transitions and the reward function. We used multi-agent environments to demonstrate the usefulness and superiority of the proposed method by comparing it with existing multi-agent reinforcement learning methods, in terms of both learning efficiency and goal achievements in the test phase. The results demonstrate that the proposed method outperformed other alternatives.

Recently, magnetic measurement-based pose estimation technology increasingly attracts the researcher's attention as a complementary navigation technology. The main purpose of introducing magnetic fields is to secure a reliable pose estimation in non-line-of-sight (NLOS) environments where satellite navigation is unavailable or vision, lidar, and other auxiliary sensors that make use of signals of opportunity cannot provide robust performance. Unlike the previous researches, this paper proposes a new method for implementing the integrated magneto-inertial navigation system based on three-dimensional AC magnetic field vectors from concurrent measurements. Instead of taking an independent pose estimation result from the magnetic positioning system, the proposed algorithm investigates a direct integration scheme that employs the raw magnetic field vectors from concurrent measurement sources. A theoretic formulation is developed, which enables to establish the integrating framework with the INS mechanization. The presented algorithm is validated through trajectory experiments in a small-scale test platform. As a result, it is demonstrated that the computational efficiency is substantially enhanced to enable real-time implementation of the proposed magneto-inertial navigation system, while the estimation performance has sub-centimeter accuracy in a 3D dynamic experiment.

Antioxidant and anti-inflammatory properties of papaya (Carica papaya) fruits were evaluated to provide comprehensive information associated with the bioactive compounds. ‘Tainung No. 2’ papaya fruits, cultivated in a greenhouse, Korea, were harvested at unripe and ripe stages and then divided into seed and peel-pulp. Total phenolic and flavonoid contents were determined using spectrophotometry, and individual phenolic compounds were relatively quantified by HPLC-DAD and fifteen standards. Antioxidant activities were measured using four assays: DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)) scavenging activities, inhibition of lipid peroxidation, and FRAP (ferric reducing antioxidant power). Anti-inflammatory activities were measured by the regulation of NF-κB signaling pathways with the measurements of ROS and NO productions as the degree of oxidative stress. Total phenol contents increased in seed and peel–pulp extracts during ripening; flavonoid contents increased only in seed extracts. Total phenolic contents were associated with ABTS radical scavenging activity and FRAP. Of fifteen phenolic compounds, chlorogenic acid, cynarin, eupatorine, neochlorogenic acid, and vicenin II were identified among papaya extracts. ROS and NO productions were inhibited in papaya extracts. Especially, NO productions were inhibited higher in ripe seed extracts than in other extracts, which would be associated with the suppression of NF-κB activation and iNOS expression. These results suggest that papaya fruit extracts, including seeds, peels, and pulps, could be potential raw materials for functional foods.

BackgroundAlthough the guidelines recommend gynecological assessment and close monitoring for symptoms of endometrial cancer in postmenopausal breast cancer survivors taking tamoxifen (TAM), the risk of endometrial cancer in young breast cancer survivors has not yet been fully assessed. This study aimed to investigate the risk of developing endometrial cancer and the frequencies of gynecological examinations in young breast cancer survivors taking TAM in South Korea.MethodsA nationwide retrospective cohort study was conducted using the Health Insurance Review and Assessment Service claims data. Kaplan–Meier analyses and log-rank tests were used to assess the probability of endometrial cancer, benign endometrial conditions, and the probability of invasive endometrial procedure. To analyze the risk of endometrial cancer and benign endometrial conditions, we used a multivariable Cox proportional hazards regression model.ResultsBetween 2010 and 2015, 60,545 newly diagnosed female breast cancer survivors were included. The total person–years were 256,099 and 140 (0.23%) patients developed endometrial cancer during the study period. In breast cancer survivors aged ≥60 years [hazard ratio (HR), 5.037; 95% confidence interval (CI), 2.185–11.613], 50–59 years (HR, 4.343; 95% CI, 2.122–8.891), and 40–49 years (HR, 2.121; 95% CI, 1.068–4.213), TAM was associated with an increased risk of endometrial cancer. In subjects aged below 40 years, TAM did not significantly increase the risk of endometrial cancer. However, among the TAM subgroups, breast cancer survivors aged below 40 years [1.61 per 1,000 person–years (PY); HR, 12.460; 95% CI, 2.698–57.522] and aged 40–49 years (2.22 per 1,000 PY; HR, 9.667; 95% CI, 4.966–18.819) with TAM-related endometrial diseases showed significantly increased risks of endometrial cancer. Among the TAM subgroup with benign endometrial conditions, the ratios of the frequency of invasive diagnostic procedures to the incidence of endometrial cancer were higher in subjects under 40 than subjects aged 60 or more.ConclusionYoung breast cancer survivors with TAM-related benign endometrial diseases are at a higher risk of developing endometrial cancer. Gynecological surveillance should be tailored to the risk of endometrial cancer in young breast cancer survivors to improve the early detection of endometrial cancer and avoid unnecessary invasive procedures.

The Chicago classification (CC) defines an esophagogastric junction outflow obstruction (EGJOO) as the presence of several instances of intact or weak peristalsis, elevated median integrated relaxation pressure above 15 mmHg, and a discrepancy from the criteria of achalasia. The revised CC addresses the potential etiology of EGJOO, including the early forms of achalasia, mechanical obstruction, esophageal wall stiffness, or manifestation of hiatal hernia. A 58-year-old woman visited the Presbyterian Medical Center with swallowing difficulty. The patient underwent a high resolution manometry (HRM) examination and was diagnosed with EGJOO. Chest CT was performed to exclude a mechanical obstruction as a cause, and CT revealed a subepithelial tumor (SET) at the upper part of the esophagogastric junction. Therefore, laparoscopic surgery was performed and eccentric muscular hypertrophy of the distal esophagus was observed. Longitudinal myotomy and Dor fundoplication were also performed. The histology findings of the surgical specimens were consistent with achalasia. This paper reports a case of early achalasia that was finally diagnosed by the histology findings, but was initially diagnosed as EGJOO using HRM and misdiagnosed as SET in the image study.

A new artificially generated magnetic-field-based alternative navigation technique is investigated for achieving seamless navigation in non-line-of-sight (NLOS) environments where satellite navigation is unavailable, and where vision, lidar, and other sensors that make use of signals of opportunity cannot provide reliable estimation. Unlike the previously reported multilateration methods, which make use of the magnetic receiver coil's voltage model, the proposed method first extracts three-dimensional field vectors from concurrent ac magnetometer measurements, then establishes the spatial representation model of magnetic vectors for localization purpose. It does so by separating each frequency component and developing a geometric matching procedure using the interpolated data from the grid map in order to achieve a pose estimation. This study further presents an integrated navigation algorithm that associates an inertial measurement with the estimated pose information to secure a continuous navigation solution at a high output rate, where the extended Kalman filter (KF) formulation is typically employed. Finally, in order to validate the estimation performance of the proposed method, a small-scale trajectory experiment in 70cm × 70cm × 50 cm test platform was performed, by which the integrated navigation was verified as possessing an average position accuracy in the sub-cm range as well as a heading angle error in the sub-degree range.

Increasing the number of satellites in a global navigation satellite system (GNSS) improves the positioning accuracy and increases availability. However, it reduces the positioning accuracy improvement rate and increases the calculation loads, which can cause battery usage problems in mobile devices using a GNSS. An appropriate satellite selection method is required. One current method entails the use of ideal satellite placement with respect to the minimum geometric dilution of precision (GDOP). In this study, the described ideal satellite placement with the minimum GDOP were divided in terms of the horizontal dilution of precision (HDOP) and vertical dilution of precision (VDOP). HDOP and VDOP were mathematically derived and analyzed. The derived formula was verified using simulations. The analysis was performed with actual dual GNSS satellite data. The satellites adjacent to the ideal placement were selected and the DOP was calculated. Simply selecting satellites closest to the ideal placement afforded large values for HDOP and VDOP. This issue was addressed using a satellite changing algorithm considering the dual GNSS, resulting in reduced values of the HDOP and VDOP.

Phosphate overload contributes to mineral bone disorders that are associated with crystal nephropathies. Phytate, the major form of phosphorus in plant seeds, is known as an indigestible and of negligible nutritional value in humans. However, the mechanism and adverse effects of high-phytate intake on Ca2+ and phosphate absorption and homeostasis are unknown. Here, we show that excessive intake of phytate along with a low-Ca2+ diet fed to rats contributed to the development of crystal nephropathies, renal phosphate wasting, and bone loss through tubular dysfunction secondary to dysregulation of intestinal calcium and phosphate absorption. Moreover, Ca2+ supplementation alleviated the detrimental effects of excess dietary phytate on bone and kidney through excretion of undigested Ca2+-phytate, which prevented a vicious cycle of intestinal phosphate overload and renal phosphate wasting while improving intestinal Ca2+ bioavailability. Thus, we demonstrate that phytate is digestible without a high-Ca2+ diet and is a risk factor for phosphate overloading and for the development of crystal nephropathies and bone disease.

Elucidating the genetic basis of influenza A viruses (IAVs) is important to understand which mutations will determine the virulence and the host range of mammals. Here, seasonal H3N2 influenza was adapted in mice by serial passage and four mutants, each carrying amino acid substitutions related to mouse adaptation in either the PB2, HA, NP, or NA protein, were generated. To confirm the contribution of each gene to enhanced pathogenicity and mouse adaptation, mice were inoculated with the respective variants, and virulence, replication, histopathology, and infectivity were examined. The virus harboring HA mutations displayed increased infection efficiency and replication competence, resulting in higher mortality in mice relative to those infected with wild-type virus. By contrast, the NP D34N mutation caused rapid and widespread infection in multiple organs without presenting virulent symptoms. Additionally, the PB2 F323L mutation presented delayed but elevated replication competence in the respiratory tract, whereas the S331R mutation in NA showed no considerable effects on mouse adaptation. These results suggested that mouse-adapted changes in HA are major factors in increased pathogenicity and that mutations in NP and PB2 also contribute to cross-species adaptability. Our findings offer a better understanding of the molecular basis for IAV pathogenicity and adaptation in a new host.

BackgroundPulmonary arterial hypertension (PAH) is a progressive chronic disease with poor outcomes. One reason for poor prognosis is the lack of understanding regarding individual variability in response to treatment. Idiopathic PAH (IPAH) patients with bone morphogenetic protein receptor type 2 (BMPR2) mutations have distinct phenotypes that are crucial for individualized therapy but evidence regarding their prevalence and clinical features in the Korean population is lacking. Therefore, the present study aimed to screen Korean IPAH patients for BMPR2 mutations and analyze their clinical phenotypes.MethodsWe enrolled 73 unrelated IPAH patients for BMPR2 mutation screening between March 2010 to November 2015 from 11 hospitals in Korea. Thirty-three lineal family members from 6 families of BMPR2 mutation carriers were also screened.ResultsAmong 73 patients, 16 (22%) had BMPR2 mutations. Mutation carriers were younger (27 vs. 47 years; p = 0.02) and had a higher mean pulmonary arterial pressure (mPAP) than non-carriers (64 vs. 51 mmHg; pConclusionThe prevalence of BMPR2 mutations in Korean IPAH patients was 22%. Mutation carriers were younger and had a poorer hemodynamic profile compared with the non-carriers.Clinical trial registrationClinicaltrials.gov NCT01054105.

Deficient myelination of the brain is associated with neurodevelopmental delays, particularly in high-risk infants, such as those born small in relation to their gestational age (SGA). New methods are needed to further study this condition. Here, we employ Color Spatial Light Interference Microscopy (cSLIM), which uses a brightfield objective and RGB camera to generate pathlength-maps with nanoscale sensitivity in conjunction with a regular brightfield image. Using tissue sections stained with Luxol Fast Blue, the myelin structures were segmented from a brightfield image. Using a binary mask, those portions were quantitatively analyzed in the corresponding phase maps. We first used the CLARITY method to remove tissue lipids and validate the sensitivity of cSLIM to lipid content. We then applied cSLIM to brain histology slices. These specimens are from a previous MRI study, which demonstrated that appropriate for gestational age (AGA) piglets have increased internal capsule myelination (ICM) compared to small for gestational age (SGA) piglets and that a hydrolyzed fat diet improved ICM in both. The identity of samples was blinded until after statistical analyses.

A non-pumping reactive well (NPRW) is a subsurface structure that prevents contaminant spread using many non-pumping wells containing reactive media. For the construction of an effective NPRW, a sufficiently small spacing between wells is an important design factor to prevent contaminant leakage. However, close well construction is not recommended because of concerns about the decreased stability of adjacent wells under field conditions. In this research, we proposed a sawtooth array of NPRW as a practical configuration to minimize well spacing while meeting stability requirements in the field. To evaluate the performance of the novel NPRW configurations, a numerical modeling was conducted considering different well diameters and well spacings and their performance was compared taking into account the number of wells and the mass of the reactive material. The comparison results showed that the sawtooth configuration was more practical than a line of wells. The performance curve of NPRWs with the saw-toothed configuration was constructed from the relationship between the contaminant removal and configuration components (diameter and spacing of the well). This can be used to predict the contaminant removal performance of NPRWs with a sawtooth array.

Reactive oxygen species (ROS)-responsive nanocarriers have received considerable research attention as putative cancer treatments because their tumor cell targets have high ROS levels. Here, we synthesized a miktoarm amphiphile of dithioketal-linked ditocopheryl polyethylene glycol (DTTP) by introducing ROS-cleavable thioketal groups as linkers between the hydrophilic and hydrophobic moieties. We used the product as a carrier for the controlled release of doxorubicin (DOX). DTTP has a critical micelle concentration (CMC) as low as 1.55 μg/mL (4.18 × 10−4 mM), encapsulation efficiency as high as 43.6 ± 0.23% and 14.6 nm particle size. The DTTP micelles were very responsive to ROS and released their DOX loads in a controlled manner. The tocopheryl derivates linked to DTTP generated ROS and added to the intracellular ROS in MCF-7 cancer cells but not in HEK-293 normal cells. In vitro cytotoxicity assays demonstrated that DOX-encapsulated DTTP micelles displayed strong antitumor activity but only slightly increased apoptosis in normal cells. This ROS-triggered, self-accelerating drug release device has high therapeutic efficacy and could be a practical new strategy for the clinical application of ROS-responsive drug delivery systems.

Adenine nucleotide translocase (ANT) 2 promotes ADP/ATP exchange across the mitochondrial inner membrane. Choet al. show that liver specific Ant2 deletion increases uncoupled respiration and protects mice against fatty liver and obesity-induced insulin resistance.

Bougie or balloon dilation is a good short-term treatment for caustic esophageal strictures, although recurrence after dilation occurs in approximately 30% of these cases. Therefore, long-term treatment options are required in some cases, and endoscopic incisional therapy has been used for patients with an anastomotic stricture in the gastrointestinal tract. A 58-year-old woman presented with severe swallowing difficulty because of a caustic esophageal stricture, which was caused by accidental exposure to anhydrous acetic acid at infancy. She had undergone several previous bougie and balloon dilations but the stricture did not improve. We performed sequential treatment comprising incision with an insulated-tip knife, balloon dilation, and an oral steroid, which resulted in the patient’s symptoms markedly improving. Thus, we report this case of an intractable caustic esophageal stricture, which was successfully treated using combined endoscopic sequential treatment.

The preferential incorporation of carboxylic acids into aragonite and its effects on the crystal growth and physicochemical properties of aragonite were systematically investigated using a seeded co-precipitation system with different carboxylic acids (citric, malic, acetic, glutamic, and phthalic). Aragonite synthesized in the presence of citric and malic acids showed a remarkable decrease in the crystallinity and size of crystallite, and the retardation of crystal growth distinctively changed the crystal morphology. The contents of citric acid and malic acid in the aragonite samples were 0.65 wt % and 0.19 wt %, respectively, revealing that the changes in the physicochemical properties of aragonite were due to the preferential incorporation of such carboxylic acids. Speciation modeling further confirmed that citric acid with three carboxyl groups dominantly existed as a metal–ligand, (Ca–citrate)−, which could have a strong affinity toward the partially positively charged surface of aragonite. This indicates why citric acid was most favorably incorporated among other carboxylic acids. Our results demonstrate that the number of carboxyl functional groups strongly affects the preferential incorporation of carboxylic acids into aragonite; however, it could be suppressed by the presence of other functional groups or the structural complexity of organic molecules.

Objective This study aimed to compare intubation performance between blind intubation through supraglottic airway devices and direct laryngoscopy by novices under manikin simulation. We hypothesized that the intubation time by novices using supraglottic airway devices was superior to that with the Macintosh laryngoscope (MCL). Methods A prospective, randomized crossover study was conducted with 95 participants, to evaluate i-gel, air-Q, LMA Fastrach, and MCL devices. Primary outcomes were the intubation time and the success rate for intubation. Results The i-gel showed the shortest insertion and tube passing time among the four devices; the i-gel and air-Q also showed the shortest total intubation time (all P

Novel citrate/FeCO3 nanocomposites (CF-NCs) were synthesized for effective arsenic (III and V) sorption with constant addition of Fe2+ into HCO3− solution in the presence of citrate. This paper is the first report on the formation of CF-NCs, and in this study we investigate the mechanisms of arsenic uptake by the sorbent under anoxic conditions through various solid- and liquid-phase spectroscopic methods, including X-ray absorption spectroscopy. In CF-NCs, citrate was found to be incorporated into the structure of siderite (up to 17.94%) through (Fe2+citrate)− complexes. The crystal morphology of rhombohedral siderite was changed into hierarchically nanostructured spherical aggregates composed of several sheet-like crystals, which improved the surface reactivity in the presence of sufficient citrate. Compared to pure siderite (15.2%), enhanced removal of As(III) in the range of 19.3% to 88.2% was observed, depending on the amount of incorporated citrate. The maximum sorption capacities of CF-NCs for As(III) and As(V) were 188.97 and 290.22 mg/g, respectively, which are much higher than those of previously reported siderite-based adsorbents. It was found that arsenic (III and V) sorption on CF-NCs occurred via bidentate corner-sharing surface complexation, predominantly without changes in the arsenic oxidation states. These results suggest that arsenic (III and V) can be attenuated by siderite in anoxic environments, and this attenuation can be even more effective when siderite is modified by incorporation of organic compounds such as citrate.

The lymphatic vasculature, along with the blood vasculature, is a vascular system in our body that plays important functions in fluid homeostasis, dietary fat uptake, and immune responses. Defects in the lymphatic system are associated with various diseases such as lymphedema, atherosclerosis, fibrosis, obesity, and inflammation. The first step in lymphangiogenesis is determining the cell fate of lymphatic endothelial cells. Several genes involved in this commitment step have been identified using animal models, including genetically modified mice. This review provides an overview of these genes in the mammalian system and related human diseases.

Peroxiredoxins (PRDXs) are members of a highly conserved peroxidase family and maintain intracellular reactive oxygen species (ROS) homeostasis. The family members are expressed in most organisms and involved in various biological processes, such as cellular protection against ROS, inflammation, carcinogenesis, atherosclerosis, heart diseases, and metabolism. In mammals, six PRDX members have been identified and are subdivided into three subfamilies: typical 2-Cys (PRDX1, PRDX2, PRDX3, and PRDX4), atypical 2-Cys (PRDX5), and 1-Cys (PRDX6) subfamilies. Knockout mouse models of PRDXs have been developed to investigate their in vivo roles. This review presents an overview of the knockout mouse models of PRDXs with emphases on the biological and physiological changes of these model mice.

This paper proposes a novel and accurate method for estimating the flight coefficient of a flying disc typically operating at a high rotation rate. In particular, the proposed method introduces a new algorithm that takes advantage of magnetic data measured by a miniaturized sensor module onboard a conventional disc. Since the geomagnetic field measured by the magnetic sensor mounted on the rotating body yields a general sinusoidal waveform, a frequency domain analysis is employed in computing the rotational rate. Furthermore, on the basis of the estimated rate during a whole flight period, a yaw damping derivative coefficient is derived, which enables an accurate prediction of the disc’s flight trajectory. For performance verification, both a reference rotation table test and a real flight test are performed, for which a miniaturized embedded sensor module is designed and manufactured for an onboard flight test. A reference rotation test validates the performance of the proposed method. Subsequently, a flight test, in which a simulator-based trajectory is compared with the true reference trajectory, verifies that the proposed method better predicts the flight trajectory by incorporating the estimated coefficient.

One of main features in sensor networks is the function that processes real time state information after gathering needed data from many domains. The component technologies consisting of each node called a sensor node that are including physical sensors, processors, actuators and power have advanced significantly over the last decade. Thanks to the advanced technology, over time sensor networks have been adopted in an all-round industry sensing physical phenomenon. However, sensor nodes in sensor networks are considerably constrained because with their energy and memory resources they have a very limited ability to process any information compared to conventional computer systems. Thus query processing over the nodes should be constrained because of their limitations. Due to the problems, the join operations in sensor networks are typically processed in a distributed manner over a set of nodes and have been studied. By way of example while simple queries, such as select and aggregate queries, in sensor networks have been addressed in the literature, the processing of join queries in sensor networks remains to be investigated. Therefore, in this paper, we propose and describe an Incremental Join Algorithm (IJA) in Sensor Networks to reduce the overhead caused by moving a join pair to the final join node or to minimize the communication cost that is the main consumer of the battery when processing the distributed queries in sensor networks environments. At the same time, the simulation result shows that the proposed IJA algorithm significantly reduces the number of bytes to be moved to join nodes compared to the popular synopsis join algorithm.

In the present study, we investigated the effects of Uncariae Ramulus et Uncus (UR) on learning and memory in the Morris water maze task and the central cholinergic system of rats with excitotoxic medial septum (MS) lesion. In the water maze test, the animals were trained to find a platform in a fixed position during 6 days and then received a 60-s probe trial in which the platform was removed from the pool on the 7th day. Ibotenic lesion of the MS showed impaired performance of the maze test and severe cell losses in the septohippocampal cholinergic system (SHC), as indicated by decreased choline acetyltransferase-immunoreactivity and acetylcholinesterase-reactivity in the hippocampus. Daily administrations of UR (100 mg/kg, i.p.) for 21 consecutive days produced significant reversals of ibotenic acid-induced deficit in learning and memory. These treatments also reduced the loss of cholinergic immunoreactivity in the hippocampus induced by ibotenic acid. These results demonstrated that impairments of spatial learning and memory may be attributable to degeneration of SHC neurons and that UR ameliorated learning and memory deficits partly through neuroprotective effects on the central acetylcholine system. Our studies suggest that UR may be useful in the treatment of Alzheimer’s disease. Keywords:: Alzheimer’s disease, Uncariae Ramulus et Uncus, learning and memory, central cholinergic system, neuroprotection

Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic vascular disease in which arteriovenous malformations (AVMs) manifest in skin and multiple visceral organs. HHT is caused by heterozygous mutations in endoglin (ENG), activin receptor-like kinase 1 (ALK1), or SMAD4. ALK1 regulates angiogenesis, but the precise function of ALK1 in endothelial cells (ECs) remains elusive. Since most blood vessels of HHT patients do not produce pathological vascular lesions, ALK1 heterozygous ECs may be normal unless additional genetic or environmental stresses are imposed. To investigate the cellular and biochemical phenotypes of Alk1-null versus Alk1-heterozygous ECs, we have generated pulmonary EC lines in which a genotype switch from the Alk1-conditional allele (Alk1 (2f)) to the Alk1-null allele (Alk1 (1f)) can be induced by tamoxifen treatment. Alk1-null (1 f/1 f) ECs displayed increased migratory properties in vitro in response to bFGF compared with Alk1-het (2 f/1 f) ECs. The 1 f/1 f-ECs formed a denser and more persistent tubular network as compared with their parental 2 f/1 f-ECs. Interestingly, the response to BMP-9 on SMAD1/5 phosphorylation was impaired in both 2 f/1 f- and 1 f/1 f-ECs at a comparable manner, suggesting that other factors in addition to SMADs may play a crucial role for enhanced angiogenic activity in 1 f/1 f-ECs. We also demonstrated in vivo that Alk1-deficient ECs exhibited high migratory and invasive properties. Taken together, these data suggest that enhanced responses to angiogenic cues in ALK1-deficient ECs underlie the pathogenesis of HHT2.