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We report copper(II) arsenite-encapsulated ferritin nanoparticles (CuAS-FNs) as oxidative stress-amplifying anticancer agents. The CuAS-FNs were fabricated through CuAS mineralization in the cavity of the FNs. The formation of crystalline CuAS complex minerals in the FNs was systematically identified using various analytical tools, including X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM)-associated energy-dispersive X-ray spectroscopy (TEM-EDS). The CuAS-FNs showed pH-dependent release behavior, in which the CuAS mineral was effectively retained at physiological pH, in contrast, at lysosomal pH, the CuAS complex was dissociated to release arsenite and Cu2+ ions. At lysosomal pH, the release rate of arsenite (HAsO 3 2−) and Cu2+ ions from the CuAS-FNs more accelerated than at physiological pH. Upon transferrin receptor-1-mediated endocytosis, the CuAS-FNs simultaneously released arsenite and Cu2+ ions in cells. The released arsenite ions can increase the intracellular concentration of hydrogen peroxide (H 2 O 2), with which the Cu2+ ions can elevate the level of hydroxyl radicals (·OH) via Fenton-like reaction. Thus, the CuAS-FNs could target cancer cell through the recognizing ability of FNs and kill cancer cells by amplifying the ·OH level through the synergistic activity of Cu2+ and arsenic ions. Importantly, MCF-7 tumors were effectively suppressed by CuAS-FNs without systemic in vivo toxicity. Therefore, the CuAS-FNs is a promising class of Fenton-like catalytic nanosystem for cancer treatment. Copper(II) arsenite-encapsulated ferritin nanoparticles (CuAS-FNs) were developed as targeted and oxidative stress-amplifying anticancer agents. The CuAS-FNs were rationally designed by combining the TfR-1-mediated endocytosis of the FNs and the oxidative stress amplification of the CuAS. This study paves a way for a wide range of novel cancer-specific therapeutics by systematically modulating the oxidative stress in cancer cells. [Display omitted] [ABSTRACT FROM AUTHOR]

Background. The sepsis screening tool is essential because it enables the rapid identification of high-risk patients and facilitates prompt treatment. Quick Sequential Organ Failure Assessment (qSOFA) is a widely used screening tool for sepsis. However, it has limitations in predicting patient prognosis. We developed the S-S.M.A.R.T (sepsis evaluation with shock index, mental status, age, and ROX index on triage) and aimed at evaluating it as a screening tool for patients with suspected sepsis in the emergency department. Methods. We conducted a single-center retrospective chart review of patients with suspected sepsis in the emergency department. We compared the prognosis prediction abilities of the S-S.M.A.R.T and qSOFA scores in patients with suspected sepsis. The primary outcome was 7-day mortality, and the secondary outcomes included 30-day mortality and ICU admission. The receiver operating characteristic (ROC) curve analysis and the chi-square test were used. Results. In total, 401 patients were enrolled. The mean age of the patients was 72.2 ± 15.6 years, and 213 (53.1%) of them were female. The S-S.M.A.R.T had superior predictive ability for prognosis of patients with suspected sepsis compared to qSOFA (area under the ROC curve (AUC) of 0.789 vs. 0.699; p = 0.02 for 7-day mortality, AUC of 0.786 vs. 0.681; p < 0.001 for 30-day mortality, AUC 0.758 vs 0.717; p = 0.05 for ICU admission). Conclusion. The S-S.M.A.R.T can be useful in predicting the prognosis of patients with suspected sepsis in the emergency department. [ABSTRACT FROM AUTHOR]

The most promising approach for improving the electrical performance of connectors used in semiconductor test sockets involves increasing their electrical conductivity by incorporating one-dimensional (1D) conductive materials between zero-dimensional (0D) conductive materials. In this study, FeCo nanowires were synthesized by electroplating to prepare a material in which 1D materials could be magnetically aligned. Moreover, the nanowires were coated with highly conductive Au. The magnetization per unit mass of the synthesized FeCo and FeCo@Au nanowires was 167.2 and 13.9 emu/g, respectively. The electrical performance of rubber-based semiconductor connectors before and after the introduction of synthetic nanowires was compared, and it was found that the resistance decreased by 14%. The findings reported herein can be exploited to improve the conductivity of rubber-type semiconductor connectors, thereby facilitating the development of connectors using 0D and 1D materials. [ABSTRACT FROM AUTHOR]

This scientific report aims to investigate the genotype-phenotype correlations of retinal hemangioblastoma (RH) in von Hippel-Lindau (VHL) disease. The study included 77 patients with genetically confirmed VHL disease who visited an ophthalmology clinic for the evaluation of RH. The presence, location, and size of RH were evaluated, Patients were categorized into three groups based on variants: HIF-1α binding site missense (HM), non-HIF-1α binding site missense (nHM), and truncating (TR) mutations. Fifty-six patients (72.7%) had RH in either eye, and 24 had bilateral RH. Sixteen patients (20.8%) had juxtapapillary RH in either eye. Nine patients had RH ≥ 2.0 disc diameters in size. VHL c.208G>A variant was the most frequent single mutation. Compared with patients having nHM mutations (15 patients) in VHL gene, patients with HM mutations (33 patients) or TR mutations (26 patients) presented a greater number of eyes affected (p = 0.007 and 0.004, respectively), a greater number of RH (p = 0.012 and 0.003, respectively), and more frequent presentation of large RH ≥ 2.0 disc diameters (p = 0.012, and 0.013, respectively). In conclusion, this study provides a deeper understanding of the genetic spectrum of VHL disease in Korean VHL disease and highlights the importance of the location of missense mutations regarding the risk of RH. [ABSTRACT FROM AUTHOR]

Hepatic stellate cells (HSCs) play central roles in liver disease pathogenesis, spanning steatosis to cirrhosis and hepatocellular carcinoma. These cells, located in the liver's sinusoidal space of Disse, transition from a quiescent, vitamin A-rich state to an activated, myofibroblast-like phenotype in response to liver injury. This activation results from a complex interplay of cytokines, growth factors, and oxidative stress, leading to excessive collagen deposition and liver fibrosis, a hallmark of chronic liver diseases. Recently, HSCs have gained recognition for their dynamic, multifaceted roles in liver health and disease. Attention has shifted toward their involvement in various liver conditions, including acute liver injury, alcoholic and non-alcoholic fatty liver disease, and liver regeneration. This review aims to explore diverse functions of HSCs in these acute or chronic liver pathologies, with a focus on their roles beyond fibrogenesis. HSCs exhibit a wide range of actions, including lipid storage, immunomodulation, and interactions with other hepatic and extrahepatic cells, making them pivotal in the hepatic microenvironment. Understanding HSC involvement in the progression of liver diseases can offer novel insights into pathogenic mechanisms and guide targeted therapeutic strategies for various liver conditions. [Display omitted] [ABSTRACT FROM AUTHOR]

Gitelman syndrome is a salt-losing tubular disorder that is transmitted as an autosomal recessive trait. Variants in the SLC12A3 gene are found in the majority of Gitelman syndrome patients. A 26-year-old woman visited the genetic counseling clinic. Her fiancé was a known Gitelman syndrome patient who was previously diagnosed with 2 pathogenic variants in SLC12A3. In advance of marriage and future family planning, she wanted to perform genetic testing of SLC12A3. A silent exonic variant c.1050G>A was found, and multiple splice site in silico algorithms predicted this variant to have potential alteration of splicing. This variant was classified as "variant of uncertain significance," and RNA splicing analysis was additionally performed. RNA splicing analysis showed aberrant splicing of exon 7–8 skipping. The result points out the potential pathogenicity of this variant, which should be considered a candidate of variant reclassification in the future. We highly recommend the performance of additional RNA splicing analysis, especially for silent variants predicted to have potential alteration of splicing. [ABSTRACT FROM AUTHOR]

Purpose: Colder seasons can aggravate lower urinary tract symptoms, especially an overactive bladder (OAB). This aspect has been extensively studied in men and rarely in women. We investigated whether colder seasons influence OAB-drug prescription rates (OAB-DPRs) in women. Methods: Women aged > 18 years were selected from the Korean Health Insurance Review and Assessment Service-National Patient Sample data between 2012 and 2016. OAB-DPR was calculated according to age and seasonal groups. The prescription rates in summer (June, July, and August) and winter (January, February, and December) months were compared. Sub-analysis was performed according to age group. Results: In total, 3,061,343 adult women were included. The overall OAB-DPR was 3.75% (114,940/3,061,343). Overall OAB-DPRs in summer and winter were 1.41% (43,090/3,061,343) and 1.54% (47,038/3,061,343), respectively (p < 0.001). Seasonal variations in OAB-DPRs differed by age group (p < 0.001): OAB-DPRs were significantly lower in winter than in summer months in women aged < 50 years (odds ratio 0.942; 95% confidence interval 0.918–0.967; p < 0.001), but significantly higher in winter than in summer months in women aged ≥ 50 years (odds ratio 1.153; 95% confidence interval 1.135–1.171; p < 0.001). Conclusion: In this study, a correlation was noted between OAB-DPR and seasons. OAB-DPRs were higher in the summer in women aged < 50 years and higher in the winter in women aged ≥ 50 years. Our findings suggest that female hormonal status may be involved in the contradictory effect of seasons on OAB symptoms. [ABSTRACT FROM AUTHOR]

The principle of least effort has been widely used to explain phenomena related to human behavior ranging from topics in language to those in social systems. It has precedence in the principle of least action from the Lagrangian formulation of classical mechanics. In this study, we present a model for interceptive human walking based on the least action principle. Taking inspiration from Lagrangian mechanics, a Lagrangian is defined as effort minus security, with two different specific mathematical forms. The resulting Euler–Lagrange equations are then solved to obtain the equations of motion. The model is validated using experimental data from a virtual reality crossing simulation with human participants. We thus conclude that the least action principle provides a useful tool in the study of interceptive walking. [ABSTRACT FROM AUTHOR]

Objective. The aim of this study was to test whether Amflow® (a newly designed portable ventilation feedback device) can assist rescuers in delivering target tidal volume ( V T ) and respiration rate (RR) during self-inflating bag (SB) ventilations in various clinical scenarios. Method. This was a simulation study with a prospective cross-over design. A total of 40 trained participants who underwent training for SB ventilation were recruited. Using a SB with or without Amflow® alternately, participants delivered ventilations to test lungs connected to a gas flow analyser in each of three different scenarios: acute respiratory distress syndrome (ARDS; 315–385 ml ranges for 350 ml target V T , with 20 breaths/min); cardiopulmonary resuscitation (CPR; 450–550 ml ranges for 500 ml target V T with 10 breaths/min); and adult head trauma (630–770 ml ranges for 700 ml target V T with 15 breaths/min). Results. The feedback group (SB with Amflow®) demonstrated a significantly higher percentage of delivering the appropriate V T ranges than the no-feedback group for both ARDS (58.6% versus 23.5%, respectively) and CPR (85.4% versus 41.0%, respectively) (all p < 0.05). However, there was no significant difference between the two groups in the percentage of delivering the appropriate V T ranges in head trauma patients (65.9% versus 68.3%, respectively; p = 0.092). In all three scenarios, a higher percentage of target RR delivered was achieved in the feedback group (88.3%, 99.2%, and 96.3%, respectively) compared with the no-feedback group (5.8%, 12.5%, and 10.0%, respectively) (all p < 0.05). Conclusion. The Amflow® device could be useful for rescuers in delivering SB ventilation with appropriate V T and RR simultaneously in various critical situations, except for clinical cases that demand greater delivered V T . [ABSTRACT FROM AUTHOR]

Background: Cribriform–morular variant of papillary thyroid carcinoma (CMV–PTC) is a rare subtype of PTC, which occurrs predominantly in young women. This disease much more frequently presents in patients with familial adenomatous polyposis (FAP). FAP is an autosomal dominant inherited disease, which arises from germline mutations in the adenomatous polyposis coli (APC) gene. To clarify the distinctive clinical features of CMV–PTC, a comparison study was performed between familial types and sporadic types. Methods: Between 2007 and 2018, 15 CMV–PTC patients underwent thyroidectomy in Samsung Medical Center. The clinical features of these patients were retrospectively reviewed. Results: All patients were women with a median age of 26 years (range 17–46 years). The median maximum diameter was 1.0 cm (range 0.4–3.5 cm). All tumors underwent immunostaining and showed nuclear and/or cytoplasmic staining for β-catenin. On ultrasonography, most nodules had benign-looking features (well-defined, hypoechoic, and oval to round shapes without calcification), but a few nodules had capsular invasion and taller than wide shape. On preoperative fine-needle aspiration cytology, five patients (33%) were diagnosed as CMV–PTC, nine (60%) as PTC, but one (7%) as follicular neoplasm or PTC–follicular variant. Six patients (40%) had FAP, and four of them had total colectomy due to FAP. Five of them had a family history of FAP or colon cancer, or thyroid cancer. Germline mutations in the APC gene were found in all six patients with CMV–PTC associated with FAP, and five of them had de novo mutations. All patients with FAP-associated CMV–PTC had multiple tumors. All CMV–PTC patients had excellent response to initial therapy. Conclusions: Because of the association between FAP or colon cancer with multifocal CMV–PTC, we confirm that mutational analysis of the APC gene and colonoscopy should be carried out in these patients when multiple thyroid tumors are found. [ABSTRACT FROM AUTHOR]

Orostachys japonicus A. Berger and Momordica charantia Linn have been widely used as an alternative medicine. Recently, patients with type 2 diabetes (T2D) have paid increasing attention to medical nutrition therapy due to its safety and cost-effectiveness. Therefore, we have developed a new health functional food that consists of a mixed extract of O. japonicus and M. charantia. The aim of this study is designed to assess the antidiabetic efficacy of O. japonicus and M. charantia extracts (OME, in an 8:2 ratio), especially focusing on the effects of O. japonicus via in vivo and in vitro experiments. Seven-week-old C57BL/Ksj-db/db (db/db; a genetic animal model of T2D) mice were used for inducing diabetes. Mice were administered with various concentrations of OME (OME 0, 100, 200, or 400 mg/kg/day) for 6 weeks. Metabolic parameters, fasting blood glucose and glycosylated hemoglobin levels were measured. Histopathologic analysis and the levels of serum or hepatic biochemicals were assessed to evaluate diabetic liver injury and steatosis. The expression levels of lipogenic and gluconeogenic genes were determined by quantitative real-time polymerase chain reaction. Activation of Akt was assessed by western blot analysis. Administration of OME significantly improved metabolic parameters in db/db mice, and also reduced diabetic liver injury and steatosis were observed by OME administration in db/db mice as confirmed by histopathologic and serum or hepatic biochemical analysis. Consistently, treatment of OME significantly increased Akt activation resulting in decreased expression levels of lipid-accumulation or gluconeogenesis-related genes. Similar results were observed in in vitro experiments using single extract of O. japonicus and using OME. OME has antidiabetic effects with increased insulin sensitivity, and may be a safe alternative therapy for the management of T2D. [ABSTRACT FROM AUTHOR]

Plasma neutrophil gelatinase-associated lipocalin (NGAL) is a useful biomarker for predicting acute kidney injury (AKI). The purpose of this study was to evaluate the diagnostic performance of urinary NGAL in predicting AKI in sepsis patients in the emergency department. A total of 140 patients were enrolled. We compared serum procalcitonin and urinary NGAL concentrations between patients with local infection, sepsis, and septic shock, and between patients who did and did not develop AKI with sepsis. Receiver-operating characteristic curve analysis was used to evaluate the ability to predict AKI in sepsis patients. Both serum procalcitonin and urinary NGAL concentrations were significantly higher in the sepsis and septic shock groups than in the local infection group (both p < 0.001). In sepsis patients, serum procalcitonin and urinary NGAL concentrations were higher in AKI patients than in those without AKI (p = 0.006, p < 0.001, respectively). The area under the curve for predicting of AKI was higher for a urinary NGAL of 0.820 (95% confidence interval (CI) 0.721–0.895) than for a serum procalcitonin concentration of 0.76 (95% CI 0.597–0.800). Urinary NGAL concentration may predict AKI in patients with sepsis in the emergency department. • Urine NGAL is a useful biomarker for acute kidney injury. • Urine NGAL concentration was significantly higher in the AKI group than in the non-AKI group of the septic patients. • NGAL concentration is also useful for prediction AKI of septic patients. [ABSTRACT FROM AUTHOR]

• The experimental results of the NO X and SO X removal rates of blocks exposed to the external environmental are valuable. • This study provides the NO X and SO X removal rates of blocks under external environmental conditions. • This study provides the limitations of TiO 2 particles in an atmospheric environment without sunlight. • This study provides a promising additive technique using porous materials for reduction of NO X and SO X in blocks. This study examined actual nitrogen oxide (NO X) and sulfur oxide (SO X) removal rates of concrete permeable blocks in the atmospheric environment. To give the concrete permeable block a NO X and SO X removal function, TiO 2 submicron particle or coconut shell powder was embedded in the surface layer, and zeolite bead was embedded in the base layer. Using an actual factory production line, concrete permeable block specimens were prepared by adding TiO 2 submicron particles and coconut shell powder to the surface layer of the concrete permeable block. The prepared concrete permeable block specimens were placed in a parking lot, and then NO X and SO X removal rates were directly measured for 6 months on the concrete permeable block specimens placed in the parking lot. Test results showed that the clear day removal rates of NO X and SO X for the concrete permeable block specimens embedded with TiO 2 submicron particles during the day was 84% and 70%, respectively. Compared to the concrete permeable blocks embedded with coconut shell powder, the NOx removal rate of the specimens embedded with TiO 2 submicron particles was 1.45 times higher, while the SO x removal rate was similar. However, during cloudy days and nights, the NO X removal rate of the concrete permeable block specimens embedded with TiO 2 submicron particles was zero. On the other hand, NO X and SO X removal rates of the concrete permeable block specimens embedded with coconut shell powder and zeolite bead were maintained at approximately 51% and 77% for 6 months, respectively, in the atmospheric environment regardless of weather and day light conditions. Consequently, the coconut shell powder added to the surface layer of the concrete permeable block is a practically promising material in reducing the NO X in the atmospheric environment regardless of weather and day light conditions. [ABSTRACT FROM AUTHOR]

Korean red ginseng (KRG) is a traditional herbal medicine used to prevent several geriatric diseases due to its therapeutic effects on metabolic disorder, including type 2 diabetes and fatty liver disease. In this study, we investigated the effects of KRG on the progression of nonalcoholic steatohepatitis (NASH) in mice. NASH was induced by feeding a methionine- and choline-deficient high-fat or high-fat/high-sucrose diet for 6 or 13 weeks, respectively. Each diet group was also orally administered saline (group G0) or KRG extract (100, 200, or 400 mg/kg/day; groups G1, G2, and G4, respectively). KRG showed anti-inflammatory and antifibrogenic effects in the diet-induced NASH models. Furthermore, the expression levels of lipid metabolism-related genes were markedly decreased with KRG treatment in both diet-induced NASH groups. We next confirmed the expression levels of FABP4 in the liver and its ability to regulate inflammation and/or oxidative stress. We observed decreased levels of FABP4 mRNA and protein in the KRG-treated groups indicating that KRG affects the pathogenesis of NASH-related inflammatory responses by modulating FABP4 expression. Results of in vitro experiments showed similar patterns in cells treated with KRG, indicating that KRG treatment regulates the expression of FABP4 and subsequently reduces NASH related inflammation. Our findings suggest a novel role of KRG in NASH-related inflammatory responses via modulation of FABP4 expression in the liver. KRG may be a safe alternative therapy to prevent NASH progression. [ABSTRACT FROM AUTHOR]

Abstract Accumulative evidence showed that cigarette smoke (CS) detrimentally affects the pathogenesis of nonalcoholic steatohepatitis (NASH). The purpose of this study was to evaluate the effects of CS extract (CSE) or total particulate matter (TPM) on the in vitro steatohepatitis model using mouse primary hepatocytes treated with palmitic acid (PA) or PA plus LPS. Increased hepatocellular damage was observed in PA-treated hepatocytes with TPM or CSE treatment, but increased triglyceride level was only observed in PA plus LPS-treated hepatocytes with a high concentration of TPM. Also, expression levels of steatohepatitis-related genes such as TNF-α, NOS 2, and SREBP-1c were significantly increased after treatment of TPM. To further demonstrate the role of Kupffer cells (KCs) after CS extracts treatment, trans-well co-culture system of hepatocytes and KCs was utilized. The levels of inflammatory cytokines and the ratios of Bax/Bcl-2 (apoptosis-related genes) were markedly increased in co-cultured hepatocytes after TPM or CSE treatment. Interestingly, KCs activation was augmented in KCs upon treatment with CSE or TPM. Overall, our findings indicate that in vitro treatment with CSE or TPM differentially contributes to the severity of steatohepatitis by modulating steatohepatitis-related lipotoxicity and inflammation, which might be caused by KCs activation with subsequent induction of hepatocytes apoptosis. Highlights • 0.4 mM PA treatment could induce steatohepatitis on primary hepatocytes. • Increased hepatotoxicity was observed in PA-treated hepatocyte after CS treatment. • CS treatment enhanced PA-induced inflammation and oxidative stress levels. • TPM treatment increased PA plus LPS-induced lipotoxicity. • CS enhanced PA-induced apoptosis of hepatocytes when co-cultured with KCs. [ABSTRACT FROM AUTHOR]

Blood dendritic cell antigen 2 (BDCA-2) is a C-type lectin found on the surface of plasmacytoid dendritic cells. It functions as a glycan-binding receptor that downregulates the production of type I interferons and thus plays a role in oligosaccharide-mediated immunomodulation. The carbohydrate recognition domain in BDCA-2 binds selectively to galactose-terminated bi-antennary glycans. Because the plasmacytoid dendritic cells function in a plasma environment rich in glycoproteins, experiments have been undertaken to identify endogenous ligands for blood dendritic cell antigen 2. A combination of blotting, affinity chromatography and proteomic analysis reveals that serum glycoprotein ligands for BDCA-2 include IgG, IgA and IgM. Compared to binding of IgG, which was previously described, IgA and IgM bind with higher affinity. The association constants for the different subclasses of immunoglobulins are below and roughly proportional to the serum concentrations of these glycoprotein ligands. Binding to the other main serum glycoprotein ligand, α2-macroglobulin, is independent of whether this protease inhibitor is activated. Binding to all of these glycoprotein ligands is mediated predominantly by bi-antennary glycans in which each branch bears a terminal galactose residue. The different affinities of the glycoprotein ligands reflect the different numbers of these galactose-terminated glycans and their degree of exposure on the native glycoproteins. The results suggest that normal serum levels of immunoglobulins could downmodulate interferon stimulation of further antibody production. [ABSTRACT FROM AUTHOR]

Although a variety of non-viral gene delivery systems have been developed, they still suffer from low efficiency and specificity. Herein, we present the assembly of a dendrimer complex comprising a DNA cargo and a targeting moiety as a new format for targeted gene delivery. A PAMAM dendrimer modified with histidine and arginine (HR-dendrimer) was used to enhance the endosomal escape and transfection efficiency. An EGFR-specific repebody, composed of leucine-rich repeat (LRR) modules, was employed as a targeting moiety. A polyanionic peptide was genetically fused to the repebody, followed by incubation with an HR-dendrimer and a DNA cargo to assemble the dendrimer complex through an electrostatic interaction. The resulting dendrimer complex was shown to deliver a DNA cargo with high efficiency in a receptor-specific manner. An analysis using a confocal microscope confirmed the internalization of the dendrimer complex and subsequent dissociation of a DNA cargo from the complex. The present approach can be broadly used in a targeted gene delivery in many areas. [ABSTRACT FROM AUTHOR]

Zearalenone (ZEA) is a non-steroidal estrogenic mycotoxin produced byFusariumspecies. The toxicity of ZEA has been evaluated for reproductive and developmental effects; however, there is little evidence about its acute toxicity or general immunotoxicity. In the present study, immune regulatory functions were investigated in mice that had been exposed to ZEA (5 or 20 mg/kg BW) daily for 14 days. Results showed that sub-populations of CD4+, CD8+and CD11c+cells in the spleen and CD4+, CD8+and F4/80+cells in the mesenteric lymph nodes (MLN) of ZEA (20 mg/kg)-exposed hosts were decreased compared to those in the control mice. However, CD19+and CD11c+cells were increased in the MLN of the ZEA mice and CD4+CD25+Foxp3+cells were decreased in the spleen and MLN. There were differential changes in the immune cell populations of the small intestine of the ZEA mice as well, depending on small intestine location. Inex vivoexperiments, ZEA treatments resulted in increased proliferative capacities of mitogen-induced splenocytes and MLN cells; such changes were paralleled by significant increases in interferon (IFN)-γ production. With regard to serum isotypes, IgM levels were decreased and IgE levels were increased in the 20 mg/kg ZEA-treated mice. Mucosal IgA levels were decreased in the duodenum and vagina of these hosts. Serum analyzes also revealed that tumor necrosis factor (TNF)-α levels were decreased and interleukin (IL)-6 levels increased as a result of ZEA exposures. ZEA treatment also led to increased apoptosis in the spleen and Peyer’s patches; these changes were associated with changes in the ratios of Bax:Bcl-2. Following priming with different TLR ligands, ZEA exposure led to differentially modulated TLR signaling and variable production of pro- and anti-inflammatory cytokines in RAW 264.7 macrophage cells. Taken together, these results indicated that ZEA could alter the normal expression/function of different immune system components and this would likely lead to immunomodulationin situ. [ABSTRACT FROM AUTHOR]

Molecular detection of target molecules with high sensitivity and specificity is of great significance in bio and medical sciences. Here, we present genetically functionalized ferritin nanoparticles with a high-affinity protein binder, and their utility as a signal generator in a variety of immunoassays and imaging. As a high-affinity protein binder, human IgG-specific repebody, which is composed of LRR (Leucine-rich repeat) modules, was used. The repebody was genetically fused to the N-terminal heavy-chain ferritin, and the resulting subunits were self-assembled to the repebody-ferritin nanoparticles composed of 24 subunits. The repebody-ferritin nanoparticles were shown to have a three-order of magnitude higher binding affinity toward human IgG than free repebody mainly owing to a decreased dissociation rate constant. The repebody-ferritin nanoparticles were conjugated with fluorescent dyes, and the resulting nanoparticles were used for western blotting, cell imaging, and flow cytometric analysis. The dye-labeled repebody-ferritin nanoparticles were shown to generate about 3-fold stronger fluorescent signals in immunoassays than monovalent repebody. The repebody-functionalized ferritin nanoparticles can be effectively used for sensitive and specific immunoassays and imaging in many areas. [ABSTRACT FROM AUTHOR]

Cornea is an avascular transparent tissue. Ocular trauma caused by a corneal alkali burn induces corneal neovascularization (CNV), inflammation, and fibrosis, leading to vision loss. The purpose of this study was to examine the effects of Zerumbone (ZER) on corneal wound healing caused by alkali burns in mice. CNV was induced by alkali-burn injury in BALB/C female mice. Topical ZER (three times per day, 3 μl each time, at concentrations of 5, 15, and 30 μM) was applied to treat alkali-burned mouse corneas for 14 consecutive days. Histopathologically, ZER treatment suppressed alkali burn-induced CNV and decreased corneal epithelial defects induced by alkali burns. Corneal tissue treated with ZER showed reduced mRNA levels of pro-angiogenic genes, including vascular endothelial growth factor, matrix metalloproteinase-2 and 9, and pro-fibrotic factors such as alpha smooth muscle actin and transforming growth factor-1 and 2. Immunohistochemical analysis demonstrated that the infiltration of F4/80 and/or CCR2 positive cells was significantly decreased in ZER-treated corneas. ZER markedly inhibited the mRNA and protein levels of monocyte chemoattractant protein-1 (MCP-1) in human corneal fibroblasts and murine peritoneal macrophages. Immunoblot analysis revealed that ZER decreased the activation of signal transducer and activator of transcription 3 (STAT3), with consequent reduction of MCP-1 production by these cells. In conclusion, topical administration of ZER accelerated corneal wound healing by inhibition of STAT3 and MCP-1 production. [ABSTRACT FROM AUTHOR]

Epidemiological studies have indicated that smoking is a pivotal risk factor for the progression of several chronic diseases. Nicotine, the addictive component of cigarettes, has powerful pathophysiological properties in the body. Although the effects of cigarette smoking on corneal re-epithelialization have been studied, the effects of nicotine on corneal wound healing-related neovascularization and fibrosis have not been fully demonstrated. The aim of this study was to evaluate the effects of chronic administration of nicotine on corneal wound healing following acute insult induced by an alkali burn. BALB/C female mice randomly received either vehicle (2% saccharin) or nicotine (100 or 200 μg/ml in 2% saccharin) in drinking water ad libitum. After 1 week, animals were re-randomized and the experimental group was subjected to a corneal alkali burn, and then nicotine was administered until day 14 after the alkali burn. A corneal alkali burn model was generated by placing a piece of 2 mm-diameter filter paper soaked in 1N NaOH on the right eye. Histopathological analysis and the expression level of the pro-angiogenic genes vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP9) revealed that chronic nicotine administration enhanced alkali burn-induced corneal neovascularization. Furthermore, the mRNA expression of the pro-fibrogenic factors α-smooth muscle actin (αSMA), transforming growth factor-β (TGF-β), and collagen α1 (Col1) was enhanced in the high-concentration nicotine-treated group compared with the vehicle group after corneal injury. Immunohistochemical analysis also showed that the αSMA-positive area was increased in chronic nicotine-treated mice after corneal alkali burn. An in vitro assay found that expression of the α3, α7, and β1 nicotinic acetylcholine receptor (nAChR) subunits was significantly increased by chemical injury in human corneal fibroblast cells. Moreover, alkali-induced fibrogenic gene expression and proliferation of fibroblast cells were further increased by treatment with nicotine and cotinine. The proliferation of such cells induced by treatment of nicotine and cotinine was reduced by inhibition of the PI3K and PKC pathways using specific inhibitors. In conclusion, chronic administration of nicotine accelerated the angiogenic and fibrogenic healing processes in alkali-burned corneal tissue. [ABSTRACT FROM AUTHOR]

An Automatic tool changer (ATC) is a device used in a tapping machine to reduce process time. This paper presents the optimization of a Peak torque reduction mechanism (PTRM) for an ATC. It is necessary to reduce the fatigue load and energy consumed, which is related to the peak torque. The PTRM uses a torsion spring to reduce the peak torque and was applied to a novel ATC mechanism, which was modeled using inverse dynamics. Optimization of the PTRM is required to minimize the peak torque. The design parameters are the initial angle and stiffness of the torsion spring, and the objective function is the peak torque of the input link. The torque was simulated, and the peak torque was decreased by 10 %. The energy consumed was reduced by the optimization. [ABSTRACT FROM AUTHOR]

Background The usefulness of plasma neutrophil gelatinase-associated lipocalin (NGAL) concentration for predicting the outcome of community-acquired pneumonia (CAP) is unclear. We evaluated the prognostic value of plasma NGAL concentration for predicting disease severity in comparison with other widely used biological markers of inflammation in patients with CAP. Methods NGAL, procalcitonin, and C-reactive protein concentrations were measured in 362 patients with CAP, who were followed for up to 30 days. The Pneumonia Severity Index (PSI) and CURB-65 score were obtained for all patients. Results The median plasma NGAL concentration increased with CAP severity classified according to the PSI. Plasma NGAL concentration was higher in nonsurvivors than in survivors. The AUC for predicting mortality was highest for NGAL concentration (0.871), followed by that for PSI (0.865) and procalcitonin concentration (0.744). Multivariable logistic regression analysis showed that plasma NGAL concentration was an independent predictor of hospital mortality in CAP patients. Plasma NGAL concentration correlated positively with C-reactive protein and procalcitonin concentrations, CURB-65 score, and PSI. Conclusions Plasma NGAL concentration is a valuable biological marker in the assessment of the severity and prediction of the prognosis of patients with CAP in the emergency department. [ABSTRACT FROM AUTHOR]

Cigarette smoking in adolescents is considered to be a major cause of preventable morbidity and mortality. The purpose of this study is to investigate the role of mainstream cigarette smoke (MSCS) on the progression of nonalcoholic steatohepatitis in adolescents. Three-week-old C57BL/6 mice were fed either a methionine and choline-deficient plus high fat (MCDHF) diet for 6 weeks. Each group was exposed to MSCS (300, 600 ug/L) or fresh air for 2 h per day during the first 3 weeks of MCDHF diet feeding. MSCS increased MCDHF diet-induced NASH by increasing serum ALT/AST levels, steatosis, inflammation, and fibrosis. Furthermore, MSCS was associated with the degree of oxidative stress and hepatocellular apoptosis in NASH mice, but not prominent in controls. In vitro , cigarette smoke extract (CSE) activated Kupffer cells (KCs) to release inflammatory cytokines and oxidative stress, which induced hepatocellular apoptosis. In conclusion, MSCS exposure accelerates the progression and severity of NASH by modulating KC-mediated hepatocellular apoptosis. Our results support the regulation of CS in adolescents with steatohepatitis. [ABSTRACT FROM AUTHOR]

Aim: This study compared endotracheal intubation (ETI) performance during cardiopulmonary resuscitation (CPR) between direct laryngoscopy (DL) and video laryngoscopy (VL) (GlideScope(®)) by experienced intubators (>50 successful ETIs).Methods: This was a prospective randomized controlled study conducted in an emergency department between 2011 and 2013. Intubators who used DL or VL were randomly allocated to ETI during CPR. Data were collected from recorded video clips and rhythm sheets. The success, speed, complications, and chest compressions interruption were compared between the two devices.Results: Total 140 ETIs by experienced intubators using DL (n=69) and VL (n=71) were analysed. There were no significant differences between DL and VL in the ETI success rate (92.8% vs. 95.8%; p=0.490), first-attempt success rate (87.0% vs. 94.4%; p=0.204), and median time to complete ETI (51 [36-67] vs. 42 [34-62]s; p=0.143). In both groups, oesophageal intubation and dental injuries seldom occurred. However, longer chest compressions interruption occurred using DL (4.0 [1.0-11.0]s) compared with VL (0.0 [0.0-1.0]s) and frequent serious no-flow (interruption>10s) occurred with DL (18/69 [26.1%]) compared with VL (0/71) (p<0.001). For highly experienced intubators (>80 successful ETIs), frequent serious no-flow occurred in DL (14/55 [25.5%] vs. 0/57 in VL).Conclusions: The ETI success, speed and complications during CPR did not differ significantly between the two devices for experienced intubators. However, the VL was superior in terms of completion of ETI without chest compression interruptions.Trial Registration: Clinical Research Information Service (CRIS) in South Korea KCT0000849. [ABSTRACT FROM AUTHOR]

We present a new algorithm for application to path synthesis of a four-bar linkage with continuous variables called the Hybrid Taguchi random coordinate search algorithm (HTRCA). The HTRCA combines two algorithms of the Taguchi method (TM) and the random coordinate search algorithm (RCA). The RCA adjusts one variable simultaneously with two directions and various step sizes in random order to escape a local minimum. Since the RCA modifies one variable at a time according to the random order, the result of the RCA is sensitive to an initial condition of variables. The TM was adopted to generate nearly optimal initial conditions. Using the TM, the approximate optimal value can be found in even multi-modal functions. Also, the TM is used with different setting values to escape a local minimum point by changing two or more variables in one step. By combining the two methods, a global optimal value can be found efficiently. Seven test functions were optimized and the robust and efficient performance was verified by comparison with other hybrid optimization algorithms. Finally, path synthesis of four-bar linkage is done by the developed optimization algorithm, and the result is compared to previous works on the same problem with evolutionary algorithm. [ABSTRACT FROM AUTHOR]

This paper presents a new design methodology for crank-rocker four-bar linkages based on differential objective functions. Firstly, to avoid obtaining a mechanism with an unintended trajectory shape, we classified the trajectory of the linkage into four types of shapes. Two-step optimization for a specific shape type is proposed. In the first step, the shape of the trajectory is obtained by minimizing the root mean square error (RMSE) between the slope (first-order derivative) of the coupler point and that of the target trajectory. The size of the trajectory is then determined by minimizing the RMSE between the change in angle of slope (second-order derivative) of the coupler point and that of the desired trajectory. This new approach has three advantages: i) the desired trajectory can be set as a continuous and closed loop, ii) the optimal solution can be obtained without the possibility of generating a mechanism with an unintended coupler curve, and iii) the method can take account of the velocity of the output for each section with a constant input velocity. Three case studies were conducted to verify the advantages of the new approach based on a new index called the goodness of traceability. [ABSTRACT FROM AUTHOR]

Background Sepsis is a major cause of morbidity and mortality in the emergency department. This study aimed to evaluate the assessment of severity of sepsis by and prognostic value of plasma neutrophil gelatinase-associated lipocalin (NGAL) compared with other widely used biological markers of inflammation in patients with sepsis. Methods NGAL, procalcitonin, and C-reactive protein values were measured in 470 patients with suspected sepsis, and the Mortality in Emergency Department Sepsis (MEDS) score was obtained for all enrolled subjects, who were followed for up to 28 days. Results The median plasma NGAL value was increased with sepsis severity according to the MEDS score. The plasma NGAL value was higher in nonsurvivors than in survivors. The area under the receiver operating characteristic curve of NGAL (0.797) was greater than that of procalcitonin (0.599) and MEDS score (0.774) in predicting 28-day hospital mortality. Multivariable logistic regression found that the plasma NGAL value was an independent predictor for hospital mortality in patients with sepsis. The plasma NGAL values were positively correlated with C-reactive protein and procalcitonin levels, and MEDS scores. Conclusions Plasma NGAL is a valuable biological marker in the assessment of severity and prediction of prognosis of patients with sepsis in the emergency department. [ABSTRACT FROM AUTHOR]

During the chemical investigation of marine-derived fungus, an unusual diketopiperazine (DKP) alkaloid, haenamindole ( 1 ), was isolated from a culture of the marine-derived fungus Penicillium sp. KCB12F005. The structure of 1 , which possesses benzyl-hydroxypiperazindione and phenyl-pyrimidoindole rings system in the molecule, was elucidated by analysis of NMR and MS data. The stereochemistry of 1 was determined by ROESY and advanced Marfey’s method. [ABSTRACT FROM AUTHOR]

Carbon fibers were produced from linear low density polyethylene (LLDPE) instead of commonly used precursors, such as viscose rayon, mesophase pitch and polyacrylonitrile (PAN). Cross-linked fibers were produced at various temperatures, times and stress conditions during a sulfuric acid treatment using LLDPE fibers obtained from dry-wet spinning. The effects of cross-linking were analyzed using a range of characterization techniques, such as differential scanning calorimetry, color change, fourier transform infrared spectroscopy, elemental analysis, density, scanning electron microscopy, and single filament mechanical properties. The carbonization process of cross-linked fibers was carried out at 950 °C for 5 min in a nitrogen atmosphere. The carbon fibers with the best mechanical properties were obtained from the cross-linked fiber with the highest tensile modulus. In particular, the carbon fibers with the best mechanical properties (tensile strength and tensile modulus of 1.65 GPa and 110 GPa, respectively), similar to commercial-grade carbon fiber, were obtained from the cross-linked fiber that had undergone a carbonization process with a stress of 0.25 MPa after an acid treatment for 150 min at 140 °C and a stress of 0.26 MPa. [ABSTRACT FROM AUTHOR]

Are the first principles in the philosophy of Thomas Reid derived inductively from particular experience, or are they self-evident? Is Reid an epistemic particularist, or a methodist? Some scholars interpret him as an epistemic particularistic, while others hold that he is a methodist like other philosophers of his time. This debate was central to an exchange between Roderick Chisholm and Keith Lehrer. Taking the general belief in personal identity as an example, this paper aims to show which interpretation is more consistent with Reid's whole philosophical system. Although Reid believes that the general belief is self-evident without reasoning, it is not self-evident in the way that beliefs in particular cases are. Reid's overall philosophical method makes the self-evidence of particular beliefs more basic, the self-evidence of general beliefs being transferred from particular beliefs by means of habit. I conclude that the particularistic interpretation is more consistent with his whole philosophical system than the methodist interpretation. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the epidemiologic and clinical characteristics of renal colic in Korea.Materials and Methods: Forty-six participating emergency departments provide their essential informa­tion to the National Emergency Medical Center. We extracted the National Emergency Department Informa­tion System data from January to December 2010. We analyzed data on demographics, visit time, chief com­plaints, mode of arrival, outcome, and length of stay. A total of 23,653 patients with renal colic visited the 46 emergency departments, and this patient population comprised 1.8% of all emergency department visits.Results: The median patient age was 45 years, and the male-to-female ratio was 2:1. The peak time of inci­dence for patients with renal colic occurred between 06:00 and 10:00 h. The peak incidence occurred in Au­gust, whereas the lowest incidence occurred in winter. The most common chief complaint was flank pain, followed by abdominal pain and hematuria. The median length of stay in the emergency department was 171 min, and female patients stayed longer in the emergency department relative to male patients. The medi­an length of stay was shorter for weekend visits than for weekday visits. Most patients were discharged from the emergency department; only 6% of patients were admitted. Monday was the day with the highest ad­mission rate. The length of stay did not correlate with age, whereas the admission rate increased with age.Conclusion: The epidemiologic and clinical features derived from this study may facilitate further investigations aimed at understanding the etiology of renal colic. [ABSTRACT FROM AUTHOR]

Aim To compare the first-attempt success in endotracheal intubation (ETI) during cardiopulmonary resuscitation (CPR) using direct laryngoscopy (DL) and video laryngoscopy (VL) (GlideScope ® ) among novice emergency physicians (EPs). Methods This study is a historically controlled clinical design. From May 2011 to April 2013 out-of-hospital cardiac arrest patients were intubated during CPR by novice EPs. CPR data was automatically recorded by pre-installed video and subsequently analysed. The primary outcome was the success rate of the first-attempt at ETI. In addition, time to successful ETI from first-attempt (T-complete), duration of chest compression interruptions, and incidence of oesophageal intubation were compared. Results Of 305 patients undergoing ETI, 83 were intubated by novice EPs. The success rate of first-attempt ETI in the VL group ( n = 49) was higher than that in the DL group ( n = 34, 91.8% vs. 55.9%; p < 0.001). The median T-complete was significantly shorter with VL than with DL (37 [29–55] vs. 62 [56–110] s; p < 0.001). Oesophageal intubation was observed only in the DL group ( n = 6, 17.6%). The median duration of chest compression interruptions was greater with DL (7 [3–6] s) than with VL (0 [0–0] s). Improvements in ETI during CPR were observed in the VL group after the first 3 months, but not the DL group during regular use for 1 year. Conclusions For novice EPs, the VL could significantly improve the first-attempt success in ETI during CPR while the DL couldn’t improve it. [ABSTRACT FROM AUTHOR]

Previous studies on the dimensionless Fanning friction factor (f) and Colburn heat transfer factor (j) of offset strip fins have considered an offset ratios of 50. However, most mass-produced offset strip fins have an offset ratio of 30, while a few others have offset ratios of 20 or 10. Thus, previous correlations usually overpredicted j over the entire range of Reynolds numbers for offset ratio of 30 or lower. In this study, we numerically investigated the thermal-hydraulic characteristics of an offset strip fin relative to the offset ratio. In particular, we analyzed the difference in thermal performance subject to the offset ratio based on a 3D computational fluid dynamics analysis. The values of f and j were obtained using eight geometries with different offset ratios. New correlations for f and j were derived from the data obtained through nonlinear regression and multilinear regression. These correlations considered the offset ratio as a variable. Therefore, the heat performance was predicted to be more accurate than the previous correlations. In addition, new correlations could be used to determine the values of f and j using simple calculations. [ABSTRACT FROM AUTHOR]

The workspace, working velocity, excavating force, and load capacity of a hydraulic excavator play critical roles in the performance of the excavator for various tasks. This paper presents an optimal design of the front linkage of an excavator to maximize the performances of several indices simultaneously. A multi-objective function is defined to increase the excavator's workspace, working velocity, excavating force, and load capacity simultaneously. The workspace is defined by using four geometrical indices and the working velocity is defined by the amount of time needed to perform one cycle composed of digging and dumping. The excavating force consists of two forces, and the load capacity is defined by using the minimum values of three types with specific operations. A total of 10 indices define objective function with each weight, and pin-points of the front linkage are the design parameters, including joint positions of links and hydraulic actuators. A two-step optimization procedure is considered based on a new method called the hybrid Taguchi-random coordinate search algorithm. The results indicate a 3.43% increase in performance relative to the initial design parameters of a commercial excavator. More specifically, the excavator's workspace, working velocity, excavating force, and load capacity increase by 5.55%, 0.14%, 5.46%, and 0.33%, respectively. These improved design parameters can be applied to next generation excavators. [ABSTRACT FROM AUTHOR]

Highlights: [•] We analysed resting, awake EEG data using two qEEG methods, power spectral analysis (PSA) and detrended fluctuation analysis (DFA), and assessed their ability to yield EEG biomarkers of neurobehavioural impairment and sleepiness. [•] PSA and DFA biomarkers correlated with impaired performance and increased sleepiness, and baseline measures of the DFA scaling exponent, but not power spectra, were associated with impaired simulated driving after extended wakefulness in obstructive sleep apnea (OSA) patients. [•] The DFA scaling exponent has potential as a useful biomarker of performance failure which can be used as an alternative to conventional power spectra. [ABSTRACT FROM AUTHOR]

Large-scale sequencing of cancer genomes has revealed many novel mutations and inter-tumoral heterogeneity. Therefore, prioritizing variants according to their potential deleterious effects has become essential. We constructed a disease gene network and proposed a Bayesian ensemble approach that integrates diverse sources to predict the functional effects of missense variants. We analyzed 23,336 missense disease mutations and 36,232 neutral polymorphisms of 12,039 human proteins. The results showed successful improvement of prediction accuracy in both sensitivity and specificity, and we demonstrated the utility of the method by applying it to somatic mutations obtained from colorectal and breast cancer cell lines. The candidate genes with predicted deleterious mutations as well as known cancer genes were significantly enriched in many KEGG pathways related to carcinogenesis, supporting genetic homogeneity of cancer at the pathway level. The breast cancer-specific network increased the prediction accuracy for breast cancer mutations. This study provides a ranked list of deleterious mutations and candidate cancer genes and suggests that mutations affecting cancer may occur in important pathways and should be interpreted on the phenotype-related network or pathway. A disease gene network may be of value in predicting functional effects of novel disease-specific mutations. [ABSTRACT FROM AUTHOR]

SUMMARY Hygroscopic growth within the human respiratory tract can be significant, which may notably alter the behavior and fate of the inhaled aerosols. The objective of this study is to evaluate the hygroscopic effects upon the transport and deposition of nasally inhaled fine-regime aerosols in children. A physiologically realistic nasal-laryngeal airway model was developed based on magnetic resonance imaging of a 5-year-old boy. Temperature and relative humidity field were simulated using the low Reynolds number k − ε turbulence model and chemical specie transport model under a spectrum of four thermo-humidity conditions. Particle growth and transport were simulated using a well validated Lagrangian tracking model coupled with a user-defined hygroscopic growth module. The subsequent aerosol depositions for the four inhalation scenarios were evaluated on a multiscale basis such as total, subregional, and cellular-level depositions. Results of this study show that a supersaturated humid environment is possible in the nasal turbinate region and can lead to significant condensation growth ( d / d0 > 10) of nasally inhaled aerosols. Depositions in the nasal airway can also be greatly enhanced by condensation growth with appropriate inhalation temperature and humidity. For subsaturated and mild inhalation conditions, the hygroscopic effects were found to be nonsignificant for total depositions, while exerting a large impact upon localized depositions. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Abstract: Small modular reactors (SMRs) with integral system layout have been drawing a great deal of attention as alternative options to branch out the utilization of nuclear energy as well as to offer the inherent safety features. Serving to confirm the design basis and analyze the transient behavior of an integral reactor such as REX-10, a thermal–hydraulic system code named TAPINS (Thermal–hydraulic Analysis Program for INtegral reactor System) is developed in this study. The TAPINS supports the simple pre-processing to build up the frameworks of node diagram for the typical integral reactor configuration. The TAPINS basically consists of mathematical models for the reactor coolant system, the core, the once-through helical-coil steam generator, and the built-in steam–gas pressurizer. The hydrodynamic model of the TAPINS is formulated using the one-dimensional momentum integral model, which is based on the analytical integration of the momentum equation around the closed loop in the system. As a key contribution of the study, a dynamic model for the steam–gas pressurizer with non-condensable gas present is newly proposed and incorporated into the code. The TAPINS is validated by comparing against the experimental data from the pressurizer insurge tests conducted at MIT (Massachusetts Institute of Technology) and natural circulation tests in the RTF (REX-10 Test Facility) at RERI (Regional Energy Reactor Institute). From the comparison results, it is demonstrated that, notwithstanding a few simplifying assumptions and the undemanding solution method to facilitate solutions for transients, the TAPINS can provide a reasonable prediction on the performances and the transients of an integral reactor system operating on natural circulation. [Copyright &y& Elsevier]

Abstract: Dosimetry tools for proton therapy research have been developed to measure the properties of a therapeutic proton beam. A CCD camera–scintillation screen system, which can verify the 2D dose distribution of a scanning beam and can be used for proton radiography, was developed. Also developed were a large area parallel-plate ionization chamber and a multi-layer Faraday cup to monitor the beam current and to measure the beam energy, respectively. To investigate the feasibility of locating the distal dose falloff in real time during patient treatment, a prompt gamma measuring system composed of multi-layer shielding structures was then devised. The system worked well for a pristine proton beam. However, correlation between the distal dose falloff and the prompt gamma distribution was blurred by neutron background for a therapy beam formed by scattering method. We have also worked on the design of a Compton camera to image the 2D distribution of prompt gamma rays. [ABSTRACT FROM AUTHOR]

Abstract: Sleep electroencephalograms (EEGs) typically showed correlated fluctuations that became random-like oscillations beyond a characteristic time scale. To investigate this behavior quantitatively, the detrended fluctuation analysis (DFA) was applied to EEGs of 10 narcoleptic patients (; 6 males) and 8 healthy controls (; 5 males). The characteristic time scales of the narcoleptics and controls were estimated as and , respectively (significance level, ). We further performed DFA of the EEGs segmented into 30s epochs and found that the DFA scaling exponents increased in deep sleep stages. These results were verified with power spectrum and auto-correlation analysis, and reproduced by a mathematical model. We thus concluded that characteristics of EEGs of narcoleptic patients could be differentiated from those of healthy subjects, suggesting a potential application of DFA in diagnosing narcolepsy. [ABSTRACT FROM AUTHOR]

Abstract: Background: Although a number of association studies of gastric cancer (GC) risk have been conducted worldwide, their results have been inconsistent among different populations. The association between GC incidence and Helicobacter pylori (H. pylori) infection is somewhat of an enigma that has yet to be clearly explained. Geographically-restricted positive selection due to unique environmental pressures often result in large allele frequency differences between populations. Thus, population differences need to be investigated when attempting to identify genes that contribute to phenotypes that differ greatly between populations. Methods: We analyzed population differences in 18 polymorphisms of 12 GC-associated or immune response-related genes from 3 ethnic groups comprising 50 Koreans, 46 Indians, and 60 Caucasians; these groups differed in H. pylori seropositivity and susceptibility to GC. Results: An interleukin 10 (IL10) polymorphism demonstrated a significantly different genotype distribution (F ST =0.306, P =0.014), indicating a large difference between the Korean and Caucasian populations. The odds ratio of IL10 polymorphism allele between the populations was 38.32 (95% confidence interval, 11.49–127.83). Conclusion: This finding, taken together with previous evidence, provides a possible explanation for previous discrepant association results and supports the idea that IL10 gene polymorphisms can differentially affect GC development among populations. [Copyright &y& Elsevier]

Abstract: Protein quantification in a complex protein mixture presents a daunting task in biochemical analysis. Antibody-based immunoassays are traditional methods for protein quantification. However, there are issues associated with accuracy and specificity in these assays, especially when the changes are small (e.g., <2-fold). With recent developments in mass spectrometry, monitoring a selected peptide, thus protein, in a complex biological sample has become possible. In this study, we demonstrate a simple mass spectrometry-based method for selective measurement of a moderately low abundant protein, superoxide dismutase 1 (SOD1), in cisplatin-sensitive and cisplatin-resistant human ovarian cancer cells. Selected-reaction-monitoring (SRM) technology was employed to specifically analyze the target peptides in a pair of human ovarian cancer cell lines: 2008/2008-C13*5.25 (cisplatin-sensitive/cisplatin-resistant, respectively). The observed 1.47-fold higher expression in the resistant cell line is consistent with findings by other approaches. This robust liquid chromatography/mass spectrometry (LC/MS) method provides a powerful tool for targeted proteomic verification and/or validation studies. [Copyright &y& Elsevier]

Abstract: Objective: To examine the process of the sleep onset quantitatively and explore differences between narcoleptics and controls during the sleep onset period (SOP). Method: Dynamic detrended fluctuation analysis (DFA) was applied to electroencephalograms recorded during multiple sleep latency tests of 11 drug-free narcoleptic patients ( yrs; 8 males) and 9 healthy controls ( yrs; 6 males). The SOP of each group was estimated by fitting the time courses of the DFA scaling exponents to a parametric curve. Results: The sequence of DFA exponents showed that electrophysiological brain activity was changing rapidly across the SOP. This transition was also verified by a conventional method (i.e., dynamic spectral analysis). The SOP durations of narcoleptics and controls were estimated as s and s, respectively. Conclusions: The significantly larger SOP of narcoleptics, compared to controls, is consistent with the wake state of narcolepsy being more susceptible to sleep due to a lower barrier to transitioning to sleep. Significance: Our results suggest that electrophysiological signatures of narcolepsy could be quantified by dynamic DFA, so the method may have promise as a potential tool to help the diagnosis of narcolepsy despite the present study’s limited sample size. [Copyright &y& Elsevier]

Abstract: The steam–gas pressurizer in integrated small reactors experiences very complicated thermal-hydraulic phenomena. Especially, the condensation heat transfer with noncondensable gas under natural convection is an important factor to evaluate the pressurizer behavior. However, few studies have investigated the condensation in the presence of noncondensable gas at high pressure. In this study, therefore, a theoretical model is proposed to estimate the condensation heat transfer at high pressure using the heat and mass transfer analogy. For the high pressure effect, the steam and nitrogen gas tables are used directly to determine the density of the gas mixture and the heat and mass transfer analogy based on mass approach is applied instead of that based on the ideal gas law. A comparison of the results from the proposed model with experimental data obtained from Seoul National University indicates that the condensation heat transfer coefficients increase with increasing system pressure and with decreasing mass fraction of the nitrogen gas. The proposed model is also compared with other conventional correlations proposed in the literature. The proposed model demonstrates the capability to predict the condensation heat transfer coefficients at high pressure better than any other correlation. Finally, the condensate rate is compared to verify the application of the heat and mass transfer analogy at high pressure. The comparison results confirm that the heat and mass transfer analogy can be applied to evaluate the condensation heat and mass transfer at high pressure. [Copyright &y& Elsevier]

Loop-mediated isothermal amplification (LAMP) is a molecular diagnosis technology with the advantages of rapid results, isothermal reaction conditions, and high sensitivity. However, this diagnostic system often produces false positive results due to a high rate of non-specific reactions caused by formation of hairpin structures, self-dimers, and mismatched hybridization. The non-specific signals can be due to primers used in the methods because the utilization of multiple LAMP primers increases the possibility of self-annealing of primers or mismatches between primers and templates. In this study, we report a nanomaterial-assisted LAMP method that uses a graphene oxide–gold nanoparticles (AuNPs@GO) nanocomposite to enable the detection of foot-and-mouth disease virus (FMDV) with high sensitivity and specificity. Foot-and-mouth disease (FMD) is a highly contagious and deadly disease in cloven-hoofed animals; hence, a rapid, sensitive, and specific detection method is necessary. The proposed approach exhibited high sensitivity and successful reduction of non-specific signals compared to the traditionally established LAMP assays. Additionally, a mechanism study revealed that these results arose from the adsorption of single-stranded DNA on AuNPs@GO nanocomposite. Thus, AuNPs@GO nanocomposite is demonstrated to be a promising additive in the LAMP system to achieve highly sensitive and specific detection of diverse diseases, including FMD. [ABSTRACT FROM AUTHOR]

Abstract: A 250MeV superconducting cyclotron for the proton radiation therapy was designed at the Michigan State University (MSU) for use at the Paul Scherrer Institut. This work was based on the conceptual design carried out at the MSU in 1994. The previous design was refined to finalize the magnet configuration and to optimally arrange cyclotron elements for the actual construction. The spiral angle of the pole was reduced, the new hill-edges and valley shims being introduced. The magnetic fields were highly isochronized using a least square fitting routine involving a schematic shimming scheme. The resulting reference field was adequate for the elaborate study of beam optics. The optics simulation predicted that extraction efficiency of above 80% was achievable for a beam with the initial phase width of 20°. The vertical deflector was investigated located in the central region to control the beam intensity with tracking of beam phase spaces. Some measurement results for the constructed cyclotron were found in a good agreement with those of the optics study. [Copyright &y& Elsevier]

Abstract: A biomedical beam line has been designed for the experimental area of a proton therapy facility to deliver mm to sub-mm size beams in the energy range of 20–50MeV using the TRANSPORT/TURTLE beam optics codes and a newly-written program. The proton therapy facility is equipped with a 230MeV fixed-energy cyclotron and an energy selection system based on a degrader and slits, so that beam currents available for therapy decrease at lower energies in the therapeutic beam energy range of 70–230MeV. The new beam line system is composed of an energy-degrader, two slits, and three quadrupole magnets. The minimum beam sizes achievable at the focal point are estimated for the two energies of 50 and 20MeV. The focused FWHM beam size is approximately 0.3mm with an expected beam current of 20pA when the beam energy is reduced to 50MeV from 100MeV, and roughly 0.8mm with a current of 10pA for a 20MeV beam. [Copyright &y& Elsevier]

Abstract: Aerosol size distributions of observed mass concentration and number concentration at the Seoul National University (SNU) campus site in Korea during the non-Asian dust and the Asian dust (Hwangsa) periods have been examined using the 8-stage cascade impactor and the 8-channel airborne particle counting system, respectively. The particle size distribution of the observed mass concentration during the Asian dust period at the SNU site is compared with that observed at the Asian dust source site of Duolun in Inner Mongolia, China. The results indicate that the size distribution of both the mass concentration and the number concentration shows a bi-modal distribution that can be regressed optimally with two log-normal distribution functions. It is found that the optimally regressed probability density function of the mass concentration distribution during the non-Asian dust period at the SNU site shows two log-normal distributions with the particle mean diameters of 0.66 and 8.51μm and the standard deviations of 1.78 and 2.14μm, respectively. The probability density of the small size mode is slightly smaller than that of the large size mode. During the Asian dust period at the SNU site the estimated probability density function of the mass concentration also composes of two log-normal distributions with the particle mean diameters of 0.89 and 9.12μm and the standard deviations of 2.40 and 2.14μm, respectively. However, the high probability density is greatly shifted to the large size mode. The probability density of the small size mode is only 6% of that of the large size mode. A quite similar size distribution pattern is found in the Asian dust source region of Duolun, suggesting the high probability density at the large particle-size mode during the Asian dust period being mainly attributed to long-range transport of particles from the Asian dust source region. It is also found that the estimated probability density function of the number concentration distribution observed at the SNU site during the non-Asian dust period has a bi-modal distribution with the particle mean diameters of 0.36 and 1.12μm and the mean standard deviations of 1.48 and 1.91μm, respectively. Much higher probability density is found in the small size mode in contrast to that of the mass concentration distribution where the probability density of both modes is almost the same. [Copyright &y& Elsevier]