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Gastric endoscopic screening is an effective way to decide appropriate gastric cancer treatment at an early stage, reducing gastric cancer-associated mortality rate. Although artificial intelligence has brought a great promise to assist pathologist to screen digitalized endoscopic biopsies, existing artificial intelligence systems are limited to be utilized in planning gastric cancer treatment. We propose a practical artificial intelligence-based decision support system that enables five subclassifications of gastric cancer pathology, which can be directly matched to general gastric cancer treatment guidance. The proposed framework is designed to efficiently differentiate multi-classes of gastric cancer through multiscale self-attention mechanism using 2-stage hybrid vision transformer networks, by mimicking the way how human pathologists understand histology. The proposed system demonstrates its reliable diagnostic performance by achieving class-average sensitivity of above 0.85 for multicentric cohort tests. Moreover, the proposed system demonstrates its great generalization capability on gastrointestinal track organ cancer by achieving the best class-average sensitivity among contemporary networks. Furthermore, in the observational study, artificial intelligence-assisted pathologists show significantly improved diagnostic sensitivity within saved screening time compared to human pathologists. Our results demonstrate that the proposed artificial intelligence system has a great potential for providing presumptive pathologic opinion and supporting decision of appropriate gastric cancer treatment in practical clinical settings.

OBJECTIVE--Peroxisome proliferator--activated receptor (PPAR)-α/γ dual agonists have been developed to alleviate metabolic disorders. However, several PPARα/γ dual agonists are accompanied with unwanted side effects, including body weight gain, edema, and tissue failure. This study investigated the effects of a novel PPARα/γ dual agonist, CG301269, on metabolic disorders both in vitro and in vivo. RESEARCH DESIGN AND METHODS--Function of CG301269 as a PPARα/γ dual agonist was assessed in vitro by luciferase reporter assay, mammalian one-hybrid assay, and analyses of PPAR target genes. In vitro profiles on fatty acid oxidation and inflammatory responses were acquired by fatty acid oxidation assay and quantitative (q)RT-PCR of proinflammatory genes. In vivo effect of CG301269 was examined in db/db mice. Total body weight and various tissue weights were measured, and hepatic lipid profiles were analyzed. Systemic glucose and insulin tolerance were measured, and the in vivo effect of CG301269 on metabolic genes and proinflammatory genes was examined by qRT-PCR. RESULTS--CG301269 selectively stimulated the transcriptional activities of PPARα and PPARγ. CG301269 enhanced fatty acid oxidation in vitro and ameliorated insulin resistance and hyperlipidemia in vivo. In db/db mice, CG301269 reduced inflammatory responses and fatty liver, without body weight gain. CONCLUSIONS--We demonstrate that CG301269 exhibits beneficial effects on glucose and lipid metabolism by simultaneous activation of both PPARα and PPARγ. Our data suggest that CG301269 would be a potential lead compound against obesity and related metabolic disorders. Diabetes 60:496-506, 2011, Energy homeostasis is regulated by metabolic organs such as adipose tissue, liver, and muscle. Excess energy produced by surplus nutrient intake or reduced energy expenditure, or both, is mostly stored [...]

With the passing of Korea's Gifted Education Act, creativity has come to the forefront in considering the future of Korea's economic prosperity in the global economy (Korean Educational Development Institute, [...]

Aunque el oxigenador extracorpóreo de membrana venoarterial (ECMO-VA) proporciona un soporte cardiocirculatorio eficaz en pacientes con miocarditis fulminante, no se sabe con certeza cuál es el momento adecuado para iniciar la descarga del ventrículo izquierdo (VI). El objetivo del estudio fue investigar el beneficio de la descarga precoz del VI en pacientes con miocarditis fulminante sometidos a ECMO-VA.

Brpf-histone acetyltransferase (HAT) complexes have important roles in embryonic development and regulating differentiation in ESCs. Among Brpf family, Brpf3 is a scaffold protein of Myst2 histone acetyltransferase complex that plays crucial roles in gene regulation, DNA replication, development as well as maintaining pluripotency in embryonic stem cells (ESCs). However, its biological functions in ESCs are not elucidated. In this study, we find out that Brpf3 protein level is critical for Myst2 stability and E3 ligase Huwe1 functions as a novel negative regulator of Myst2 via ubiquitin-mediated degradation. Importantly, Brpf3 plays an antagonistic role in Huwe1-mediated degradation of Myst2, suggesting that protein–protein interaction between Brpf3 and Myst2 is required for retaining Myst2 stability. Further, Brpf3 overexpression causes the aberrant upregulation of Myst2 protein levels which in turn induces the dysregulated cell-cycle progression and also delay of early embryonic development processes such as embryoid-body formation and lineage commitment of mouse ESCs. The Brpf3 overexpression-induced phenotypes can be reverted by Huwe1 overexpression. Together, these results may provide novel insights into understanding the functions of Brpf3 in proper differentiation as well as cell-cycle progression of ESCs via regulation of Myst2 stability by obstructing Huwe1-mediated ubiquitination. In addition, we suggest that this is a useful report which sheds light on the function of an unknown gene in ESC field.

Anaemia is an important health-care burden globally, and screening for anaemia is crucial to prevent multi-organ injury, irreversible complications, and life-threatening adverse events. We aimed to establish whether a deep learning algorithm (DLA) that enables non-invasive anaemia screening from electrocardiograms (ECGs) might improve the detection of anaemia.

Huntington’s disease (HD) is caused by an expanded CAG trinucleotide repeat in the first exon of the huntingtin gene (HTT). Since the entire course of the disease starts from this dominant gain-of-function mutation, lowering total or mutant huntingtin mRNA/protein has emerged as an appealing therapeutic strategy. We reasoned that endogenous mechanisms underlying HTTgene regulation may inform strategies to target the source of the disease. As part of our investigation to understand how the expression of HTTis controlled, we performed (1) complete sequencing analysis for mutant HTT3′-UTR and (2) unbiased screening assays to identify naturally-occurring miRNAs that could lower the HTTmRNA levels. By sequencing HD families inheriting the major European mutant haplotype, we determined the full sequence of HTT3′-UTRs of the most frequent mutant (i.e., hap.01) and normal (i.e., hap.08) haplotypes, revealing 5 sites with alternative alleles. In subsequent miRNA activity assays using the full-length hap.01 and hap.08 3′-UTR reporter vectors and follow-up validation experiments, hsa-miR-4324 and hsa-miR-4756-5p significantly reduced HTT3′-UTR reporter activity and endogenous HTT protein levels. However, those miRNAs did not show strong haplotype-specific effects. Nevertheless, our data highlighting full sequences of HTT3′-UTR haplotypes, effects of miRNAs on HTTlevels, and potential interaction sites provide rationale and promising targets for total and mutant-specific HTTlowering intervention strategies using endogenous and artificial miRNAs, respectively.

NADPH oxidase (NOX) is a key source of reactive oxygen species (ROS). This study aimed to verify NOX2 and NOX4 expression levels in hepatocellular carcinoma (HCC). A total of 134 matched pairs of HCC cells and non-tumour hepatocytes from 134 patients were examined by immunohistochemical staining, and the association of NOX2 and NOX4 expression with clinicopathological parameters was analysed. Western blotting in four HCC cell lines and reverse transcription digital droplet polymerase chain reaction (RT-ddPCR) in 20 pairs of HCC and non-tumour tissue samples were also performed to detect NOX4. Cytoplasmic NOX2 and nuclear NOX4 expression levels were shown by immunohistochemistry to be higher in HCC cells than in non-tumour hepatocytes (p<0.001 each). The western blotting results for NOX4 in four HCC cell lines were consistent with the immunohistochemical results. Increased cytoplasmic expression of NOX2 and NOX4 in HCC cells was significantly correlated with liver cirrhosis (p<0.001 and p<0.031, respectively). However, decreased cytoplasmic expression of NOX2 and NOX4 was significantly correlated with advanced pathological TNM stage (p<0.029 and p<0.007, respectively). Multivariate analysis with clinicopathological parameters showed that high nuclear and low cytoplasmic NOX4 expression levels are correlated with short overall survival (p=0 .021). Our findings imply that cytoplasmic NOX2 and nuclear NOX4 expression is upregulated during HCC development. In particular, NOX4 translocation into the nucleus may affect the development and progression of HCC. NOX2 and NOX4 could be diagnostic markers and have therapeutic implications in HCC.

An inverse agonist of estrogen-related receptor-γ (ERRγ), an orphan nuclear receptor encoded by Esrrg, enhances sodium iodide symporter-mediated radioiodine uptake in anaplastic thyroid cancer (ATC) cells, thereby facilitating responsiveness to radioiodine therapy in vitro. We synthesized potent, selective, and orally bioavailable ERRγ-inverse agonists and evaluated their activity by analyzing in vitro pharmacology and absorption, distribution, metabolism, excretion, and toxicity profiles. X-ray crystallographic analysis of the ligand and ERRγ complex showed that 35completely binds to the target protein (PDB 6A6K). Our results showed improved radioiodine avidity in ATC cells through compound 35-mediated upregulation of iodide-handling genes, leading to enhanced responsiveness to radioiodine therapy in vitro. Importantly, in vivo 124I-positron emission tomography/computed tomography imaging revealed that 35increases radioiodine avidity in CAL62 tumors. Collectively, these results demonstrated that 35can be developed as a promising treatment for ERRγ-related cancer in the future.

We aimed to determine the effect of fibronectin (FN)-immobilized microgrooved titanium (Ti) on human gingival fibroblast proliferation, gene expression and protein expression. Photolithography was used to fabricate the microgrooved Ti, and amine funtionalization (silanization) was used for FN immobilization on titanium surfaces. Cell proliferation, gene expression and protein expression were analyzed, followed by multiple regression analysis for determining the influential factors on cell proliferation. FN-immobilized microgrooved Ti significantly enhanced the fibroblast proliferation in various timelines of culture, among which a burst of fivefold increase is induced at 96 h of culture compared to that on the control smooth Ti. We suggest a presence of the synergistic promotion effect of microgrooves and FN immobilization on fibroblast proliferation. Through a series of analyses on the expression of various genes and proteins involved in cell adhesion and proliferation, cyclin-dependent kinase 6, cyclin D1, integrin α5, oncogene c-Src, osteonectin, paxillin and talin-2 were determined as influential factors on promoting fibroblast proliferation induced by FN-immobilized microgrooved Ti. FN-immobilized microgrooved Ti can act as an effective surface for enhancing fibroblast proliferation, and can be used for promoting soft tissue response on the connective tissue attachment zone of biomaterial surfaces.

Supplemental Digital Content is available in the text.Membranous nephropathy (MGN) is the most common cause of the nephrotic syndrome in adults. Most cases of MGN are primary, but secondary MGN are frequently encountered. Determination of secondary MGN is crucial for initiation of appropriate treatment. The diagnostic performance of the phospholipase A2 receptor (PLA2R) and immunoglobulin G4 (IgG4) detection based on immunohistochemistry were evaluated using biopsy tissues of 59 primary and 56 secondary MGN cases for discrimination between primary MGN and secondary MGN. The PLA2R and IgG4 detection based on immunohistochemistry were dominantly positive in primary MGN cases. Sensitivity and specificity values for identification of primary MGN were 83% and 88% for PLA2R, and 76% and 86% for IgG4. Both PLA2R and IgG4 positivity showed a high specificity of 96.4% for identifying primary MGN. A meta-analysis was performed for analysis of the diagnostic accuracy of histologic PLA2R and IgG4 deposition for differentiation of primary from secondary MGN. The overall sensitivity, specificity, and area under curve of summary receiver operating characteristics were 76%, 86%, 0.93 for histologic PLA2R deposition, and 80%, 69%, 0.82 for histologic IgG4 deposition. PLA2R and IgG4 detection based on immunohistochemistry can be useful for differentiation of primary MGN from secondary MGN.

Partitioning defective (Par) proteins regulate cell polarity and differentiation. Par3, Par6β, and protein kinase Cζ (PKCζ), which are PAR complex members, have been shown to be associated with oncogenesis and progression. Herein, we report the expression pattern and clinical relevance of Par3, Par6β, and PKCζ in colorectal adenocarcinoma (CRAC). A total of 393 primary CRACs, 41 primary-metastatic CRAC pairs, 41 adenomas with low-grade dysplasia, and 41 nontumor colorectal tissue samples were examined by immunohistochemistry and Western blot assays for Par3, Par6β, and PKCζ protein expressions. The association Par3, Par6β, and PKCζ expressions and clinicopathologic factors, including patient survival, was evaluated. Primary CRACs and adenomas demonstrated higher levels of Par3, Par6β, and PKCζ than in nontumor colorectal epithelia. The expressions of Par3, Par6β, and PKCζ were higher in primary CRACs as compared to adenomas or in metastatic CRACs. Among primary CRACs, decreased Par3 expression was found to correlate with a high proliferation rate and poor histologic differentiation, decreased PKCζ expression was correlated with pathologic TNM stage (I-II vs III-IV) and lymph node metastasis, and decreased Par6β and PKCζ expressions were correlated with shortened overall survivals. In metastatic CRACs, decreased PKCζ expression was correlated with a shortened metastasis-free survival. While increased Par3, Par6β, and PKCζ expressions were implicated in tumorigenesis, decreased expressions of Par3, Par6β, and PKCζ were found to be associated with worse clinicopathologic factors in CRAC. In particular, the results of our study suggest that PKCζ down-expression is an independent poor prognostic and metastatic factor for CRAC.

Girdin is an actin-binding Akt substrate that is an integral component of the PI3K/Akt signalling pathway. However, the clinicopathological significance of Girdin expression in breast cancer has not been clarified. The purpose of this study was to characterise the clinicopathological implication of Girdin expression in breast cancer. Immunohistochemistry-based protein expression analyses of 892 human breast cancer tissues showed that Girdin was expressed in 289 (32.4%) cases. Girdin expression was significantly associated with larger tumour size, frequent lymph node invasion, advanced cancer stage, and expression of oestrogen and progesterone receptors. Patients who had breast cancer with Girdin expression experienced significantly poorer overall survival (OS) (p=0.021) and disease-free survival (DFS) (p=0.002) than those without Girdin expression. In subtype analyses, Girdin expression was significantly correlated with poorer OS and DFS in HER2 subtype (p=0.004 and p=0.034, respectively). In triple negative breast cancer (TNBC) subtype, Girdin expression was significantly correlated with poorer DFS (p=0.035), and there was a trend toward poorer OS (p=0.060) in TNBC patients with Girdin expression. Multivariate analysis revealed that Girdin expression was an independent prognostic factor for OS (p=0.022) and DFS (p=0.030) in patients with breast cancer. In HER2 subtype under multivariate analysis, Girdin expression retained its role as an independent prognostic predictor for worse OS (p=0.023), and there was a trend toward poorer DFS (p=0.086) in patients with HER2 subtype expressing Girdin. Girdin expression may serve as a useful prognostic factor for invasive breast cancer, especially for the HER2 subtype.

Antimicrobial stewardship programs (ASPs) have been a challenge in less resourceful health care settings. Medical smartphone applications (apps) can be accessible tools to support ASPs under such circumstances. A hospital-specific ASP app was prepared and the acceptance and usability of the study ASP app were evaluated by physicians and pharmacists in 2 community-based academic hospitals.

Preoperative chemoradiotherapy (CRT) is generally performed for locally advanced rectal cancer (LARC, cStage 2 or 3) to improve local disease control and patient survival. The pathological tumor response to CRT is a surrogate marker that is associated with oncological outcome. Thus, markers that predict the response to CRT would be valuable for individualizing treatment for LARC patients. The current study used metabolomics-based approaches to identify molecular markers that predict the response to CRT. Seventy-six patients with LARC who received pelvic radiotherapy and concurrent chemotherapy using tegafur-uracil and leucovorin were enrolled. Radical surgery was performed 6–8 weeks after the completion of CRT. The postsurgical pathological CRT response was evaluated using the ypStage or tumor regression grade. Profiling patterns of low-mass ions (LMIs) in the pretreatment sera were obtained from all patients using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Our previously developed two-step algorithms, which showed a powerful diagnostic capability during colorectal cancer screening, were then used to screen for meaningful LMIs with discriminatory power. One combination consisting of seven LMIs was identified, whose discriminatory score separated a good CRT response (ypStage 0–1) from a poor CRT response (ypStage 3–4) successfully. However, each individual LMI alone showed insignificant discriminatory power. This finding suggests that analysis of the LMIs in pretreatment serum could serve as a predictive marker of the CRT response in patients with LARC.

The aim of this study was to form a scaffold-free coculture spheroid model of colonic adenocarcinoma cells (CACs) and normal colonic fibroblasts (NCFs) and to use the spheroids to investigate the role of NCFs in the tumorigenicity of CACs in nude mice. We analysed three-dimensional (3D) scaffold-free coculture spheroids of CACs and NCFs. CAC Matrigel invasion assays and tumorigenicity assays in nude mice were performed to examine the effect of NCFs on CAC invasive behaviour and tumorigenicity in 3D spheroids. We investigated the expression pattern of fibroblast activation protein-α (FAP-α) by immunohistochemical staining. CAC monocultures did not form densely-packed 3D spheroids, whereas cocultured CACs and NCFs formed 3D spheroids. The 3D coculture spheroids seeded on a Matrigel extracellular matrix showed higher CAC invasiveness compared to CACs alone or CACs and NCFs in suspension. 3D spheroids injected into nude mice generated more and faster-growing tumors compared to CACs alone or mixed suspensions consisting of CACs and NCFs. FAP-α was expressed in NCFs-CACs cocultures and xenograft tumors, whereas monocultures of NCFs or CACs were negative for FAP-α expression. Our findings provide evidence that the interaction between CACs and NCFs is essential for the tumorigenicity of cancer cells as well as for tumor propagation.

Background:Huntington’s disease (HD) is a dominantly inherited disease caused by a CAG expansion mutation in HTT. The age at onset of clinical symptoms is determined primarily by the length of this CAG expansion but is also influenced by other genetic and/or environmental factors.Objective:Recently, through genome-wide association studies (GWAS) aimed at discovering genetic modifiers, we identified loci associated with age at onset of motor signs that are significant at the genome-wide level. However, many additional HD modifiers may exist but may not have achieved statistical significance due to limited power.Methods:In order to disseminate broadly the entire GWAS results and make them available to complement alternative approaches, we have developed the internet website “GeM MOA” where genetic association results can be searched by gene name, SNP ID, or genomic coordinates of a region of interest.Results:Users of the Genetic Modifiers of Motor Onset Age (GeM MOA) site can therefore examine support for association between any gene region and age at onset of HD motor signs. GeM MOA’s interactive interface also allows users to navigate the surrounding region and to obtain association p-values for individual SNPs.Conclusions:Our website conveys a comprehensive view of the genetic landscape of modifiers of HD from the existing GWAS, and will provide the means to evaluate the potential influence of genes of interest on the onset of HD. GeM MOA is freely available at https://www.hdinhd.org/.

This issue emphasizes students' stories--from the stories of students based on their perceptions of different classes (Gentry and Owen), to the stories of two students learning mathematics in different ways [...]

AbstractA 45-year-old man with dyspnoea and palpitations exhibited a unique systemic-to-pulmonary veno-venous connection on preoperative CT images. A window of 31.5-mm diameter was evident between the superior caval vein and the middle pulmonary vein, which was normally connected to the left atrium via a 30-mm-diameter orifice. The atrial septum was intact.

AbstractIn Korea, mass mortality of Quercus mongolicatrees has become obvious since 2004. Raffaelea quercus-mongolicaeis believed to be a causal fungus contributing the mortality. To evaluate the pathogenicity of the fungus to the trees, the fungus was multiple- and single-inoculated to the seedlings and twigs of the mature trees, respectively. In both the inoculations, the fungus was reisolated from more than 50% of inoculated twigs and seedlings. In the single inoculations, proportions of the transverse area of non-conductive sapwood at inoculation points and vertical lengths of discoloration expanded from the points were significantly different between the inoculation treatment and the control. In the multiple inoculations, no mortality was confirmed among the seedlings examined. These results showed that R. quercus-mongolicaecan colonize sapwood, contribute to sapwood discoloration and disrupt sap flows around inoculation sites of Q. mongolica, although the pathogenicity of the fungus was not proven.

Thrombocytopenia is caused by insufficient production and excessive destruction of platelets. Recent improvement of automated blood cell analyzers has allowed measurement of several platelet parameters, providing better understanding of the underlying mechanisms of thrombocytopenia. We investigated the significance of platelet parameters in thrombocytopenic patients. Thrombocytopenic patients (platelet <100×103l) who were newly diagnosed with acute myeloid leukemia and primary immune thrombocytopenia were enrolled, and platelet, mean platelet volume, platelet distribution width, platelet crit, mean platelet component, mean platelet mass, and large platelet count were measured, and the percentages of large platelets were calculated. The parameters were also measured in the reference population. The mean values of each parameter were as follows: platelet, 259×103l; mean platelet volume, 7.9 fl; platelet distribution width, 51.3; platelet crit, 0.20; mean platelet component, 26.0gdl; mean platelet mass, 1.9 pg; large platelet, 4.7×103l; large platelet percentage, 1.7. In comparison with acute myeloid leukemia patients, patients with primary immune thrombocytopenia showed significantly higher mean platelet volume, platelet distribution width, mean platelet component, mean platelet mass, large platelet, and large platelet (P<0.05). Because of increased destruction of platelets, primary immune thrombocytopenia patients have increased mean platelet volume, platelet distribution width, mean platelet component, mean platelet mass, large platelet, and large platelet percentage compared with acute myeloid leukemia patients who have ineffective platelet production. Parameters measured by automated analyzer provide better understanding of thrombopoiesis in the bone marrow and the status of the peripheral blood in the clinical field.

Panax ginseng, the most famous medicinal herb, has a highly duplicated genome structure. However, the genome duplication of P. ginsenghas not been characterized at the sequence level. Multiple band patterns have been consistently observed during the development of DNA markers using unique sequences in P. ginseng.

Korean ginseng (Panax ginseng) and American ginseng (Panax quinquefolius) are widely used medicinal plants with similar morphology but different medicinal efficacy. Roots, flowers, and processed products of Korean and American ginseng can be difficult to differentiate from each other, leading to illegal trade in which one species is sold as the other. This study was carried out to develop convenient and reliable chloroplast genome-derived DNA markers for authentication of Korean and American ginseng in commercial processed products. One codominant marker could reproducibly identify both species and intentional mixtures of the two species. We further developed a set of species-unique dominant DNA markers. Each species-specific dominant marker could detect 1% cross contamination with other species by low resolution agarose gel electrophoresis or quantitative polymerase chain reaction. Both markers were successfully applied to evaluate the original species from various processed ginseng products purchased from markets in Korea and China. We believe that high-throughput application of this marker system will eradicate illegal trade and promote confident marketing for both species to increase the value of Korean as well as American ginseng in Korea and worldwide.

Background:Various biologic mediators, including matrix metalloproteinases (MMPs), that are implicated in periodontal tissue breakdown can be induced by cytokines. MMPs are known to degrade periodontal ligament attachment, and bone matrix proteins and tissue inhibitors of metalloproteinase (TIMPs) inhibit the activity of MMPs. The aim of this study is to investigate the effect of tumor necrosis factor (TNF)‐α on the expression of MMPs in human periodontal ligament (PDL) cells in vitro and establish which MMPs are expressed specifically in response to that stimulus. Methods:Cultured PDL cells were stimulated with TNF‐α and analyzed with an MMP antibody array. Real‐time polymerase chain reaction (PCR), enzyme‐linked immunosorbent assay (ELISA), and western blot with cell lysate and zymography were used to measure messenger RNA (mRNA) and protein levels of MMP‐3, ‐10, and ‐13. To examine TNF receptor (TNFR) expression, PDL cells were examined by flow cytometry, and expression of MMP‐3, ‐10, and ‐13 was observed after blocking the TNFR with an antagonist. Results from real‐time PCR, ELISA, and western blot were analyzed by paired ttest. Results:The antibody array showed that the protein most strongly upregulated by TNF‐α stimulation was MMP‐3, followed by MMP‐13 and MMP‐10. The TNF‐α receptor blocker specifically inhibited expression of MMP‐3 and ‐13. In addition, TNF‐α increased levels of MMP mRNAs in MMP‐3, ‐13, and ‐10 (in decreasing order). However, ELISAs showed that MMP‐13 was the most upregulated protein, followed by MMP‐10 and MMP‐3. Western blotting indicated that TNF‐α increased MMP‐3 and ‐13 levels but had no significant effect on the level of MMP‐10, and zymography showed that TNF‐α increased the activities of all forms of MMP‐3 and ‐13, but MMP‐10 was not detected. Flow cytometry demonstrated that the majority of PDL cells expressed TNFR1. Conclusions:TNF‐α (10 ng/mL) upregulates levels of MMP‐3, ‐10, and ‐13 in human PDL cells. These results suggest that these proteins play an important role in the inflammation of PDLs.

Project Clarion, a Jacob K. Javits-funded project, focused on the scale-up of primary-grade science curricula. Curriculum units, based on an Integrated Curriculum Model (ICM), were developed for high-ability learners, but tried out with all students in Title I settings to study the efficacy of the units with all learners. The units focus on the development of students’ conceptual understanding to undergird science content attainment. Teaching and learning models, such as concept formation and concept mapping were used to scaffold science learning and reasoning for appropriate curriculum differentiation. Science content mastery was measured using the Metropolitan Achievement Tests. Reasoning skills were measured using the Test of Critical Thinking. Understanding of macro-concepts and content attainment were measured by curriculum-embedded performance-based assessments. Students with the ICM outperformed students without the specialized curriculum in science content and reasoning skills, and showed greater growth in both conceptual understanding and content attainment.

AbstractObjective:Estrogen is the final key factor that triggers the onset of puberty. The raised sensitivity of estrogen receptor, which may be caused by an estrogen receptor α(ERα) gene mutation or polymorphism, has been implicated in the etiology of precocious puberty. The aim of this study is to identify ERα gene mutations or polymorphisms in girls with central precocious puberty (CPP).Methods:A total of 204 Korean girls with CPP were included in this study along with 102 healthy Korean female adults as controls. All coding exons and exon-intron boundaries of the ERαgene were sequenced. The relationship between identified sequence variations and CPP were evaluated via comparison of allele frequencies between the two groups.Results:Eight polymorphisms were identified in the ERαgene. Among the eight polymorphisms in this study, five have been previously reported, whereas the other three were novel polymorphisms. Two of the three novel polymorphisms, p.G145S in exon 1 and p.R555H in exon 8 were only identified in the patient group. The subgroup with p.G145S showed a significantly higher level of peak luteinizing hormone than the subgroup without p.G145S in girls with CPP.Conclusion:The scanning and typing of ERαpolymorphism has uncovered several potentially meaningful polymorphisms. However, no solid conclusion can be made from this study and further studies are necessary to validate the function of these polymorphisms.

B-type natriuretic peptide (BNP) is a useful biomarker of cardiac function in patients with mitral regurgitation (MR). However, the change in BNP in association with rhythm status after corrective surgery has not been studied.

Preoperative chemoradiotherapy has become a standard treatment modality for locally advanced rectal cancer. Favorable long-term outcomes have been reported for patients with good responses to chemoradiotherapy. Therefore, predictive factors for chemoradiotherapy responses can be useful for their applicability to risk-adaptive therapy in patients with colorectal cancer.

The purpose of this study was to determine the differentially expressed genes in human gingival fibroblasts (HGFs) cultured on titanium (Ti) substrata with topographies presenting microgrooves and acid-etched roughness. Microgrooves were fabricated with a truncated V-shape in cross-section at 15/3.5, 30/10, and 60/10 μm (width/depth) by photolithography. Subsequent acid etching was applied to the entire surface of the fabricated Ti substratum to generate etched microgrooves and ridges (designated as E15/3.5, E30/10, and E60/10). Both smooth and acidetched-only Ti were used as controls (designated as NE0 and E0). Large-scale gene expression analyses were performed using differential display PCR, and the results were confirmed using RT-PCR and quantitative real-time PCR. Of the 21 genes with altered expression determined by differential display PCR and sequencing, we verified through RT-PCR that MTDH and TIMP1 were up-regulated and TGF-β1, TPM1, and VIM were down-regulated in the HGFs cultured on E60/10 versus NE0. We also confirmed, by quantitative real-time PCR, that MTDH and TIMP1 expression in HGFs on E60/10 was significantly up-regulated compared to HGFs on the other Ti substrata. This study indicates that acid-etched ridges and microgrooves on Ti with a width and depth of 60 and 10 μm (E60/10) induce alterations in the expression of genes involved in cell adhesion, proliferation, and regulation of the cytoskeleton in HGFs.

Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication, such as axons, dendrites and synapses, which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autophagic activity is frequently observed in selective neuronal populations afflicted in common neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis. These observations have provoked controversy regarding whether the increase in autophagosomes observed in the degenerating neurons play a protective role or instead contribute to pathogenic neuronal cell death. It is still unknown what factors may determine whether active autophagy is beneficial or pathogenic during neurodegeneration. In this review, we consider both the normal and pathophysiological roles of neuronal autophagy and its potential therapeutic implications for common neurodegenerative diseases.

The ambrosia beetle, Platypus koryoensis, is a serious pest of oak trees in Korea. In this study we investigated filamentous fungi present in the body of the beetle. Fourteen genera of filamentous fungi belonging to Ascomycota and Basidiomycota were isolated. Among the isolated fungi, some were able to produce wood degrading enzymes. This is first report of fungi associated with P. koryoensis.

Use of ecliptic pHluorin-fused ER46 and TIRFM identifies ER46 as a type I transmembrane protein in live human ECs. The transmembrane mutant ER46-Ile386Cys obscures the N-terminal ectodomain and effects a marked reduction in membrane-impermeant estrogen binding, with diminished rapid eNOS activation and NO production.

The diagnosis and management of paradoxical low-flow (PLF) aortic stenosis (AS) is challenging in clinical practice. In addition, its pathophysiology has not been fully understood. The aim of this study was to test the hypothesis that left ventricular (LV) myocardial function is deteriorated in PLF AS and that it is closely related to global LV afterload.

Creativity is a very complex interaction among a person, a field, and a culture (Csikszentmihalyi, 1988). People vary in their native capacity for creativity; however, an individual's interaction with the macrocosm can foster creative expression. East Asian cultures, which include Korean culture, are based upon the principals of Confucianism. The impact of Confucianism on creativity is reviewed and the relationship between Confucianism and creativity was explored in the present study. The study involved comparing 184 Korean educators' scores on a measure of Confucianism (Eastern-Western Perspective Scale) with their scores on a measure of creativity (Torrance Tests of Creative Thinking-Figural). The results indicate that Confucianism is negatively related to creativity. Specifically, some elements of Confucianism, Unconditional Obedience, Gender Inequality, Gender Role Expectations, and Suppression of Expression, may present cultural blocks to creativity. Further, Confucianism was found to be negatively related to Adaptive creative type and Creative Streangths, but not Innovative creative type, which indicates that Adaptive creative type may be more sensitive to, and thus more influenced by, culture.

There is disagreement among researchers about whether IQ tests or divergent thinking (DT) tests are better predictors of creative achievement. Resolving this dispute is complicated by the fact that some research has shown a relationship between IQ and DT test scores (e.g., Runco & Albert, 1986; Wallach, 1970). The present study conducted meta-analyses of the relationships between creative achievement and both IQ and DT test scores. The analyses included 17 studies (with 5,544 participants) that established the correlation coefficients between IQ and creative achievement and 27 studies (with 47,197 participants) that established the correlation coefficients between DT test scores and creative achievement. Marginal, but statistically significant, Fisher's Z-transformed correlation coefficients were revealed. The analysis found a significantly higher relationship between DT test scores and creative achievement (r = .216) than between IQ test scores and creative achievement (r = .167). The differences in the correlation coefficients were explained by differences in DT tests, creative achievement types, predicted time periods, and creativity subscales. The significant independent moderator effect for different DT tests indicates that the Torrance Tests of Creative Thinking (TTCT) predict creative achievement better than any other DT test included in this study. Among the creative achievement types, music is predicted the best by IQ and all others are predicted best by DT tests. Among the time periods evaluated, the relationship between DT test scores and creative achievement had the highest correlation at the period of 11–15 years.

Recently, Platypus koryoensis has been reported as a major pest of oak trees in Korea which can introduce the pathogenic fungus (Raffaelea sp.) by making galleries into the heartwood of the tree. As the beetle has developed its effective drilling mouthpart enough to make tunnels, we have analyzed the fine structural aspects of the mouthpart using the field emission scanning electron microscopy (FESEM) to reveal its mechano-dynamic characteristics. The mouthparts of this ambrosia beetle which consist of a labrum, a pair of mandibles, a pair of maxillae and the labium exhibit typical morphology of mycophagous coleopteran beetles and have those characteristics of chewing mouthparts that can excavate galleries in the hardwood. Both of maxillary and labial palpi have the functions of direct the food to the mouth and hold it while the mandibles chew the food. The distal ends of these palpi are flattened and have shovel-like setae. Females have larger maxillary palpi and a larger gular region than males in general.

Abstract: Saccharomyces cerevisiae CY phytase-producing cells were immobilized in calcium alginate beads and used for the degradation of phylate. The maximum activity and immobilization yield of the immobilized phytase reached 280 mU/g-bead and 43%, respectively. The optimal pH of the immobilized cell phytase was not different from that of the free cells. However, the optimum temperature for the immobilized phytase was 50°C, which was 10°C higher than that of the free cells; pH and thermal stability were enhanced as a consequence of immobilization. Using the immobilized phytase, phytate was degraded in a stirred tank bioreactor. Phytate degradation, both in a buffer solution and in soybean-curd whey mixture, showed very similar trends. At an enzyme dosage of 93.9 mU/g-phytate, half of the phytate was degraded after 1 h of hydrolysis. The operational stability of the immobilized beads was examined with repeated batchwise operations. Based on 50% conversion of the phytate and five times of reuse of the immobilized beads, the specific degradation (g phytate/g dry cell weight) for the immobilized phytase increased 170% compared to that of the free phytase.

According to Csikszentmihalyi (1988), creativity is a very complex interaction among a person, a field, and a culture. In keeping with this approach, a look at Asian culture in relation to its impact on creativity is in order. While people may vary in their native capacity for creativity, it is in the individual's interaction with the macrocosm where creative expression can be found. Therefore, this paper will explore the four principles of Confucianism, and how they compare to creativity research in order to discover how Asian culture influences creativity; and what we can do to enhance our students' creative capacity.

The production of prostaglandin E2 (PGE2), a key proinflammatory mediator, is regulated by the availability of its substrate, arachidonic acid (AA), and the activity of the enzyme cyclooxygenase (COX). Increased PGE2 production and COX-2 expression have been observed frequently in specimens from lung cancer patients. Agents that decrease PGE2 production may prevent the initiation and progression of lung cancer. We, therefore, tested the effects of alpha-tocopherol (αTOL) analogs on PGE2 production in human lung epithelial cells. Alpha-tocopheryl succinate (αTOS), but not αTOL or alpha-tocopheryl acetate (αTOA), inhibited the phorbol 12-myristate 13-acetate (PMA)-stimulated PGE2 production in three human lung epithelial cell lines (BEAS-2B, H460 and A549 cells). The effect of these compounds on PGE2 production was not correlated with their antioxidant activities, since αTOS alone did not inhibit PMA-induced generation of reactive oxygen species. αTOS had no effect on PMA-induced AA release or COX-2 expression, although post-incubation with αTOS inhibited COX activity and prostaglandin (PGE2 and PGF2α) production in PMA-stimulated cells. αTOS also blocked the COX activity in A549 cells with endogenous high levels of COX enzymes in the absence of PMA stimulation. In addition, the ability of αTOS to inhibit COX was affected by AA concentration, suggesting that αTOS may compete with AA for interaction with COX proteins. These results suggest that αTOS inhibits COX activity, thereby inhibiting PGE2 production in human lung epithelial cells, despite the lack of antioxidant activity. Administration of αTOS may block inflammatory responses mediated by PGE2, thereby inhibiting the initiation and progression of lung cancer.

Regulation of osteoclast differentiation is key to understanding the pathogenesis and to developing treatments for bone diseases such as osteoporosis. To gain insight into the mechanism of the receptor activator of nuclear factor (NF)–κB ligand (RANKL)–specific induction of the osteoclast differentiation program, we took a suppression-subtractive hybridization screening approach to identify genes specifically induced via the RANKL-Rac1 signaling pathway. Among identified targets, we show that RANKL selectively induces cyclooxygenase (COX) 2 expression via Rac1 that results in turn in production of prostaglandin E2 (PGE2) in RAW 264.7 cells. By using transient transfection assays, we found that the –233/–206 region of the COX-2 promoter gene was critical for RANKL-induced promoter activity. This RANKL-responsive region contained an NF-κB site that, when mutated, completely abolished the induction of NF-κB DNA-binding activity by RANKL. Blockade of COX-2 by celecoxib inhibits differentiation of bone marrow-derived monocyte/macrophage precursor cells (BMMs) into tartrate-resistant acid phosphatase-positive (TRAP+) osteoclastic cells. This inhibition can be rescued by the addition of exogenous PGE2, suggesting that COX-2–dependent PGE2 induction by RANKL in osteoclast precursors is required for osteoclast differentiation.

Since late July, 2000, fruiting bodies of Rhizina undulata, an ascomycetous fungus which causes root rot on coniferous trees, began to develop after a forest fire in the eastern coastal pine forests of Korea. In a survey conducted in August, they were abundantly developed in the fire-damaged pine forests. The occurrence frequency of the fruiting bodies seemed to be correlated with the degree of damage by the forest fire. That is, in severely damaged or completely burned areas, fruiting bodies were found around trees with abundant frequency, whereas moderate or slightly damaged areas showed a relatively low occurrence frequency. In addition, pine seedlings transplanted just after the fire outbreak were infected and killed by this fungus, producing typical symptoms on the infected roots. These phenomena present a warning that Rhizina root rot may cause severe damage on still-alive pine trees after being burnt in fire-damaged forests. This disease also may attack pine seedlings which are transplanted to restore the symbiotic relationships with the mycelium of pine mushroom, Tricholoma matsutake, just after a forest fire.

Some research has shown that creativity test scores are independent from IQ scores, whereas other research has shown a relationship between the two. To clarify the cumulative evidence in this field, a quantitative review of the relationship between creativity test scores and IQ scores was conducted. Moderating influences of IQ tests, IQ score levels, creativity tests, creativity subscales, creativity test types, gender, age, and below and above the threshold (IQ 120) were examined. Four hundred forty-seven correlation coefficients from 21 studies and 45,880 participants were retrieved. The mean correlation coefficient was small (r= .174; 95% CI = .165 - .183), but heterogeneous; this correlation coefficient indicates that the relationship between creativity test scores and IQ scores is negligible. Age contributed to the relationship between intelligence and creativity the most; different creativity tests contributed to it secondly. This study does not support threshold theory.

The effect of aluminum substitution on superconductivity in Mg11B2prepared under a high pressure (HP) of P≈3 GPa was compared with that in (Mg1−xAlx)B2prepared at ambient pressure (AP). In both the HP and the AP samples, the superconducting transition temperature (Tc) tended to decrease in the same way due to the substitution, but the width of the superconducting transition (90%–10%), ΔTc, decreased more drastically in the HP sample (HPS) than it did in the AP sample (APS). Moreover, bulk superconductivity lasted up to x=0.3 for the HPS, which is not the case for the APS. A systematic change in the lattice constants due to the substitution of Al for Mg was observed by X-ray diffraction. A scanning electron microscopic image showed that the grains were compactly connected in the HPS, thus explaining the reduced normal-state resistivity.