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Amorphous oxide semiconductor thin-film transistors (TFTs) are used as the backplane for large-screen, high-resolution OLED and LCD displays. Amorphous InGaZnO (a-IGZO) TFTs are widely used in commercialized TVs, tablets, and wearable displays for its good device performance, stability, and process controllability. Also, due to its extremely low off-current, a-IGZO TFTs are used for low refresh rate and low-power displays. Furthermore, a-IGZO TFTs have a low process temperature, enabling fabrication on various substrates (including flexible films), and also hybrid integration with other backplane technologies, such as LTPS or Si CMOS. By taking advantage of the low off-current and low process temperature, a-IGZO can be monolithically integrated in the back-end of Si CMOS for low-power applications, as well as embedded memories for long retention and non-volatile operation. There are many incentives to shorten the channel length of IGZO TFTs. First, shorter channels can boost the current without incorporating high-mobility oxides, which usually suffer from reliability issues and small process margin. When gate drivers are integrated directly onto the panel, larger currents allow smaller device footprint, thinner bezel width, and less dead space. Second, transistors with sub-micron pitch are desired to bridge the pixel gap between smartphone displays and micro-displays, and to be used for consumer AR/VR displays with > 1000 ppi. Third, reduced device length is necessary for fine-grained integration with nanoscale CMOS. However, short-channel TFTs suffer from short-channel effects (SCE). For example, threshold voltage (Vt) roll-off, where the Vt reduces for short channel lengths, causes device variability and hence, worse process tolerance. Therefore understanding and control of SCE is critical for designing and fabricating short-channel TFTs. In this paper, we study the device scalability of short-channel IGZO TFTs down to 1μm. The electrical channel length (Leff) is not the same as the gate length (Lg), and is determined by the carrier profile at the gate edges. Leff ( = Lg - ΔL) is obtained by the transmission line method (TLM), or shift-and-ratio method. Accurate ΔL extraction is important in determining the exact device mobility. Since scalability is related to the carrier concentration profile, it is strongly dependent on the process, where oxygen and hydrogen content varies with process conditions, and profiles change during thermal treatments. Devices with higher carrier concentration generally result in larger ΔL and worse SCE. Device simulations using TCAD shows the dependence on overlap (Lov), slope of carrier Gaussian decay (Xc), channel carrier concentration (Nch) on the Leff and SCE. TCAD simulation results are matched with experimental measurements for verification of the simulation models and parameters used. We define a critical carrier concentration (Ncrit) which defines the Leff. Changing the carrier profile while maintaining Ncrit results in little difference in ΔL. For devices with an underlap, similar ΔL values result in similar SCE. However, for devices with an overlap, even with the similar ΔL values, SCE is more sensitive to carrier profile at the channel edges. This study shows that SCE may be controlled through shaping of the carrier concentration profile through optimization of the device structure and process conditions allowing fabrication of short-channel TFTs with good scalability.

Control of the shape, size, internal structure, and uniformity of block copolymer (BCP) particles is crucial for determining their utility and functionality in practical applications. Here, we demonstrate a particle restructuring by solvent engineering (PRSE) strategy that combines membrane emulsification and solvent annealing processes to produce monodisperse BCP particles with controlled size, shape, and internal structure. A major advantage of the PRSE approach is the general applicability to different families of functional BCPs, including polystyrene-block-poly(1,4-butadiene) (PS-b-PB), polystyrene-block-poly(dimethylsiloxane) (PS-b-PDMS), and polystyrene-block-poly(4-vinylpyridine) (PS-b-P4VP). PRSE starts with the production of monodisperse BCP spheres in a wide range of particle sizes (from hundreds of nanometers to several tens of microns) using membrane emulsification, followed by successful transformation to shape-anisotropic BCP particles by solvent annealing under neutral wetting conditions. ...

Tungsten composites reinforced with 20 vol% of different particle sizes of ZrN and W powders were prepared by ball milling and spark plasma sintering. Correlations between the W and ZrN grain sizes, and the mechanical and ablation properties of the composites, were investigated. The improved mechanical properties of the ZrN/W composite containing fine ZrN and fine W grains is attributed to a W grain refinement effect and a ZrN particle strengthening effect. The mass ablation rate of the composites containing fine ZrN and coarse W grains significantly decreased, i.e., 36% lower that of the composite containing fine ZrN grains and fine W grains. The improved ablation resistance is attributed to better surface coverage of the ZrO2 oxide layer because of uniformly dispersed fine ZrN particles, and to less oxidation and sweeping away of the W matrix during ablation through grain boundary diffusion suppression caused by the large W grain size.

Sustainable recycling of cemented tungsten carbide (WC) is essential to solve supply issues and natural resource exhaustion caused by increasing demand. The recycling process should be efficient, ecofriendly, and economically viable, and the resulting product must have quality that is comparable or better than that of cemented WC prepared from virgin raw materials. Herein, we describe an efficient process for recycling cemented WC soft scrap using mechanochemical ball milling in the presence of sulfuric acid. The process is based on the synergetic effect of mechanical milling of scrap and chemical leaching of cobalt (Co). This method has the advantage that WC can be recovered without oxidation or phase change. The leached aqueous Co salts are precipitated as cobalt hydroxide (Co(OH)2) via pH titration, followed by reduction to obtain high-purity Co powder. The WC and Co purities were 98.04% and 98.07%, respectively. Consolidation of the recovered WC particles and Co powders provided recycled cemented WC having excellent mechanical properties.

Mechanical robustness of polymer solar cells should be ensured for the device reliability, but the brittle active layers of fullerene derivative based polymer solar cells would fracture easily causing the device failure. Therefore, mechanical properties of polymer solar cells should be investigated thoroughly in order to enhance the mechanical reliability. Herein, the mechanical properties of polymer solar cells were examined depending on the acceptor types (polymer or small molecule acceptors) and the content. In addition, the fracture behaviors were revealed in detail with various morphology analyses. This result demonstrates the importance of polymer acceptors to improve the mechanically robustness of polymer solar cells.

Development of particles that change shape in response to external stimuli has been a long-thought goal for producing bioinspired, smart materials. Herein, the temperature-driven transformation of the shape and morphology of polymer particles composed of polystyrene-b-poly(4-vinylpyridine) (PS-b-P4VP) block copolymers (BCPs) and temperature-responsive poly(N-isopropylacrylamide) (PNIPAM) surfactants is reported. PNIPAM acts as a temperature-responsive surfactant with two important roles. First, PNIPAM stabilizes oil-in-water droplets as a P4VP-selective surfactant, creating a nearly neutral interface between the PS and P4VP domains together with cetyltrimethylammonium bromide, a PS-selective surfactant, to form anisotropic PS-b-P4VP particles (i.e., convex lenses and ellipsoids). More importantly, the temperature-directed positioning of PNIPAM depending on its solubility determines the overall particle shape. Ellipsoidal particles are produced above the critical temperature, whereas convex lens-shaped particles are obtained below the critical temperature. Interestingly, given that the temperature at which particle shape change occurs depends solely on the lower critical solution temperature (LCST) of the polymer surfactants, facile tuning of the transition temperature is realized by employing other PNIPAM derivatives with different LCSTs. Furthermore, reversible transformations between different shapes of PS-b-P4VP particles are successfully demonstrated using a solvent-adsorption annealing with chloroform, suggesting great promise of these particles for sensing, smart coating, and drug delivery applications.

Background/aims The aim of this study was to investigate the role of psychosocial problems and their associations with rotating shift work in the development of functional gastrointestinal disorders. Methods In this cross-sectional observation study, survey was administered to nurses and nurse assistants in a referral hospital. In addi-tion to demographic questions, subjects were asked to complete the Rome III Questionnaire, Pittsburgh Sleep Quality Index and Rome III Psychosocial Alarm Questionnaire. Results Responses from 301 subjects were assessed. The overall prevalence of irritable bowel syndrome (IBS) and functional dyspepsia (FD) were 15.0% and 19.6%, respectively. Psychosocial alarms were prevalent in the nursing personnel (74.8% with alarm pres-ence and 23.3% with serious condition) and were more frequent among rotating shift workers (84.7% vs. 74.5% for alarm presence and 28.1% vs. 13.3% for serious condition). The prevalence of both IBS and FD significantly increased with psychoso-cial risk. An independent risk factor for IBS was serious psychosocial alarm (adjusted odds ratio [aOR], 10.75; 95% confidence interval (CI), 1.30-88.99; P = 0.028). Serious psychosocial alarm was an independent risk factor for FD (aOR, 7.84; 95% CI, 1.98-31.02; P = 0.003). Marriage (aOR 0.30; 95% CI, 0.09-0.93; P = 0.037) was associated with the decreased risk of FD. Conclusions The high prevalence of psychosocial stress among nurses who work rotating shifts is associated with the development of func-tional gastrointestinal disorders.(J Neurogastroenterol Motil 2014;20:516-522).

BACKGROUND/AIMS Hyperglycemia is associated with decreased 2-(18)[F]fluoro-2-deoxy-D-glucose (FDG) uptake by tumors assessed by positron emission tomography (PET). In this retrospective study we investigated a comparison of standardized uptake values (SUVs) in patients with primary colorectal cancers who either had diabetes mellitus (DM) or were otherwise healthy. METHODS The medical records of 397 patients who were diagnosed with colorectal cancer and underwent PET-CT between January 2006 and December 2012 were analyzed. Eighty patients with DM and 317 patients without DM were included. Clinical characteristics were reviewed and maximal standardized uptake values (SUVmax) were calculated in the primary colorectal lesions. RESULTS There was no significant difference between tumor SUVmax in DM patients (10.60±5.78) and those without DM (10.92±5.44). In addition, no significant difference was detected between tumor SUVmax in DM patients with glycated hemoglobin (HbA1c) levels

The present experiment was conducted to investigate the effects of partial substitution of soybean meal (SBM) with fermented SBM (FSBM) on immunophysiological and stress-related parameters in Holstein calves after weaning. Eighteen Holstein calves were randomly assigned to receive either SBM or FSBM (5% of SBM was replaced with FSBM) calf starter and calves were weaned at 42 d of age. It was noted that FSBM contained a lower content of trypsin inhibitor but higher crude protein, amino acids, and small-sized peptides than those of SBM. The group fed FSBM calf starter significantly increased body weight gain and intakes of both feed and milk, when compared with those fed SBM calf starter at 4 wk of age. Calves fed the FSBM calf starter had significantly lower fecal scores than those fed the SBM calf starter during both pre- and postweaning periods. Calves also had better health scores when fed the FSBM calf starter than those fed SBM during the preweaning period. Weaning challenge significantly increased proinflammatory cytokines, tumor necrosis factor α, IL-1β, and IL-6 levels at 1 d postweaning (DPW). The TNF-α and IL-6 levels of the SBM group were significantly higher compared with those of the FSBM group at 3 DPW. Acute phase proteins (serum amyloid A and haptoglobin) in the serum were increased after weaning. Concentrations of serum amyloid A and haptoglobin in calves fed FSBM calf starter were significantly lower than those fed the SBM calf starter at 3 and 5 DPW, respectively. The concentration of cortisol was significantly lower in the FSBM group than that of the SBM group at 3 DPW. Weaning stress did not cause drastic changes in the total serum immunoglobulin levels and composition of peripheral lymphocytes. Our results indicate that FSBM may not only improve growth performance, feed intake, and health conditions during the preweaning period, but also alleviate stress responses, which was indicated by reduced induction of stress hormone, proinflammatory cytokines, and acute phase proteins in Holstein calves after weaning.

During embryo implantation in pigs, the uterine endometrium undergoes dramatic morphological and functional changes accompanied with dynamic gene expression. Since the greatest amount of embryonic losses occur during this period, it is essential to understand the expression and function of genes in the uterine endometrium. Although many reports have. studied gene expression in the uterine endometrium during the estrous cycle and pregnancy, the pattern of global gene expression in the uterine endometrium in response to the presence of a conceptus (embryo/fetus and associated extraembryonic membranes) has not been completely determined. To better understand the expression of pregnancy-specific genes in the endometrium during the implantation period, we analyzed global gene expression in the endometrium on day (D) 12 and D15 of pregnancy and the estrous cycle using a microarray technique in order to identify differentially expressed endometrial genes between D12 of pregnancy and D12 of the estrous cycle and between D15 of pregnancy and D15 of the estrous cycle. Results showed that the global pattern of gene expression varied with pregnancy status. Among 23,937 genes analyzed, 99 and 213 up-regulated genes and 92 and 231 down-regulated genes were identified as differentially expressed genes (DEGs) in the uterine endometrium on D12 and D15 of pregnancy compared to D12 and D15 of the estrous cycle, respectively. Functional annotation clustering analysis showed that those DEGs included genes involved in immunity, steroidogenesis, cell-to-cell interaction, and tissue remodeling. These findings suggest that the implantation process regulates differential endometrial gene expression to support the establishment of pregnancy in pigs. Further analysis of the genes identified in this study will provide insight into the cellular and molecular bases of the implantation process in pigs.

The pig exhibits true epitheliochorial placentation, where the fetal membrane maintains attachment throughout pregnancy but does not invade into the maternal uterine endometrium. Accordingly, the expression and function of cell adhesion molecules are very important for embryo implantation and the establishment of pregnancy. In our recent microarray analysis, we found that activated leukocyte cell adhesion molecule (ALCAM) was expressed in the uterine endometrium during pregnancy in pigs. To better understand the roles of ALCAM in the establishment and maintenance of pregnancy, we examined ALCAM expression in the uterine endometrium during the estrous cycle and pregnancy in pigs. Real-time RT-PCR analysis showed that ALCAM was differentially expressed in the uterine endometrium during the estrous cycle and pregnancy, with the highest levels on D12 of pregnancy. ALCAM mRNA was localized to the luminal and glandular epithelial cells and to the trophectoderm of conceptuses during early pregnancy. The steroid hormones estrogen and progesterone had no effect on ALCAM expression in an endometrial explant culture study. Further, we found that ALCAM expression in the uterine endometrium from gilts with somatic cell nuclear transfer-derived embryos was not different from that in gilts with embryos from natural mating. ALCAM was expressed in a pregnancy stage- and cell type-specific manner in the uterine endometrium and conceptuses during pregnancy. These findings suggest that ALCAM may play a role in the establishment of pregnancy. Further analysis of ALCAM will provide insight into the implantation process and establishment of pregnancy in pigs.

Objectives: One aspect of the effects of isoflavones against fat deposition might be at least associated with the mechanism by which Wnt/β-catenin signalling inhibits adipocyte differentiation. However, it remains completely unknown as to whether isoflavones might influence Wnt signalling during commitment of pluripotent mesenchymal stem cells (MSCs) to adipose lineages. In the present study, we have investigated the mechanisms underlying effects of genistein and daidzein, the major soy isoflavones, on anti-adipogenic Wnt/β-catenin signalling. Materials and methods: Adipose tissue-derived (AD) MSCs were exposed continuously to genistein and daidzein (0.01–100 μm) during adipogenic differentiation (21 days). An oestrogen antagonist, ICI 182,780, was used to determine whether or not the isoflavones activated Wnt signalling via oestrogen receptors (ERs). Results: Genistein and daidzein suppressed adipogenic differentiation of AD-MSCs in a dose-dependent manner and inhibited expression of adipogenic markers, PPARγ, SREBP-1c and Glut 4, from mid-phase differentiation. Microarrays showed that anti-adipogenic effects of genistein were principally attributable to activation of Wnt signalling via ERs-dependent pathway, such as Erk/JNK signalling and LEF/TCF4 co-activators. These findings were supported by evidence that the effects of genistein were offset by ICI182,780. Unlike genistein, daidzein inhibited adipogenesis through stimulation of lipolysis, with for example, PKA-mediated hormone sensitive lipase. This is consistent with the increase in glycerol released from AD-MSCs. In conclusion, understanding that different sets of mechanisms of the two isoflavones on adipogenesis will help the design of novel strategies to prevent observed current epidemic levels of obesity, using isoflavones.

Calcium ions have been implicated in the establishment and maintenance of pregnancy, but the regulatory mechanisms of calcium ions in the uterine endometrium and conceptus are not well understood in pigs. Recently, we showed that TRPV6, a calcium ion channel protein associated with cellular entry of calcium ions, is highly expressed in the uterine endometrium during the implantation period in pigs. In the present study, we investigated spatial and temporal expression and regulation of TRPV6 and S100G, an intracellular calcium-regulatory molecule, in the uterine endometrium during the estrous cycle and pregnancy in pigs. TRPV6 expression was maintained at significantly higher levels in the uterine endometrium during pregnancy compared with levels during the estrous cycle. TRPV6 transcripts and proteins were localized mainly to luminal epithelial cells (LE) and weakly to glandular epithelial cells (GE) and chorionic membrane (CM) during pregnancy. TRPV6 expression was also detected in conceptuses on Day (D) 12 and D15. TRPV6 mRNA levels in the endometrium were increased by estrogen treatment. S100G expression showed a biphasic pattern of increases on D12 of pregnancy and from D60 to term pregnancy, and it localized primarily to LE during early pregnancy and to LE, GE, and CM from D30 to term pregnancy. These results indicate that spatial and temporal expression of TRPV6 and S100G is dynamically regulated in the uterine endometrium during pregnancy and that endometrial regulation of calcium ion concentration by TRPV6 and S100G may be critical for the establishment and maintenance of pregnancy in pigs.

The technique of somatic cell nuclear transfer (NT) is a useful tool to produce cloned animals for various purposes, but the efficiency to generate cloned animals using this technique is still very low. To improve the low efficiency in production of cloned pigs it is critical to understand the reprogramming process during development of cloned embryos, but it is also essential to understand the uterine function interacting with the transferred cloned embryos during implantation and placentation. Thus, to understand the uterine responsiveness to NT cloned embryos during pregnancy, we investigated expression of retinol-binding protein (RBP), osteopontin (OPN) and fibroblast growth factor 7 (FGF7), which play important roles in implantation and/or maintenance of pregnancy as a transport protein, an extracellular matrix protein and a growth factor, respectively, in the uterine endometrium in pigs. The uterine tissue samples were obtained by C-section from pigs with NT cloned normal (NT-normal) embryos and NT cloned abnormal (NT-abnormal) embryos and pigs with non-NT (Non-NT) embryos at term. Immunoblot analysis showed that expression of RBP and FGF7 decreased in the uterine endometrium of recipient gilts carrying NT embryos than in the endometrium of gilts carrying Non-NT embryos. Levels of OPN protein of 70 and 45 kDa were not different in between the uterine endometrium of gilts carrying Non-NT and NT-normal embryos, but in the uterine endometrium of gilts carrying NT-abnormal embryos 70 and 45 kDa OPN proteins increased compared to those in the endometrium of gilts carrying Non-NT embryos. Immunohistochemistry results showed that RBP expression was lower in the endometrial glandular epithelial cells, while OPN expression was higher in the endometrial luminal epithelial cells of the uterus of gilts carrying NT embryos than in the uterus of gilts carrying Non-NT embryos. Results of this study showed that maternal uterine genes were aberrantly expressed in the uterine endometrium of gilts carrying NT cloned embryos in varying degrees depending on the normality of the developing embryos. These results indicate that abnormal maternal–fetal interactions of the uterus carrying the developing NT cloned embryos may cause problems in development of cloned embryos.

Cloning by somatic cell nuclear transfer (SCNT) in pigs has great value for research and biomedical applications. However, cloning pigs is inefficient, and cloning procedures often lead to the birth of abnormal offspring because of the inadequate nuclear remodeling of donor cells as well as inadequate subsequent development. To understand the problems of the cloning process, it is necessary to understand how the uterus interacts with cloned embryo during pregnancy and supports placentation and fetal development. In this study, we compared gene expression profiles of the uterus with SCNT embryos to those of the uterus with normal embryos by natural mating. We obtained the uterine endometrial tissues on day 30 of pregnancy and conducted gene expression profiling using the Platinum Pig 13K oligonucleotide microarrays. Of the 13,610 genes analyzed, expression of 351 genes significantly increased or decreased in the uterine tissues with SCNT embryos compared to those with normal embryos. The differentially regulated genes included enzymes involved in steroidogenesis and extracellular matrix remodeling and uterine secretory proteins. Analyses of real-time reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization of selected genes confirmed the validity of the gene expression patterns observed in the microarray analysis. Results of this study showed that the transcriptional profile of the genes in the uterus with SCNT embryos was regulated differently indicating that the maternal responsiveness to the SCNT embryos was impaired, resulting in the altered gene expression in the uterus and, in turn, abnormal placental and fetal development and increased embryonic loss.

Lysophosphatidic acid (LPA), a simple phospholipid-derived mediator with diverse biological actions, acts through the specific G protein-coupled receptors endothelial differentiation gene (EDG) 2, EDG4, EDG7, and GPR23. Recent studies indicate a critical role for LPA receptor signaling in embryo implantation. To understand how LPA acts in the uterus during pregnancy in pigs, we evaluated: 1) spatial and temporal expression of LPA receptors in the uterine endometrium during the estrous cycle and pregnancy and in early-stage concepti, 2) LPA levels in uterine luminal fluids from d 12 of the estrous cycle and pregnancy, 3) effects of steroid hormones on EDG7 mRNA levels, and 4) effects of LPA on prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA levels in the uterine endometrium using explant cultures. Of the four receptors, EDG7 was dominant, and its expression was regulated by pregnancy stage and status. EDG7 expression was highest on d 12 pregnancy, and localized to the luminal and glandular epithelium, and EDG7 mRNA levels were elevated by estrogen in the endometrium. EDG7 expression was also detected in concepti of d 12 and 15. LPA with various fatty acyl groups was present in the uterine lumen on d 12 of both the estrous cycle and pregnancy. LPA increased PTGS2 mRNA abundance in the uterine endometrium. These results indicate that LPA produced in the uterine endometrium may play a critical role in uterine endometrial function and conceptus development through EDG7-mediated PTGS2 expression during implantation and establishment of pregnancy in pigs.

Methotrexate (MTX) is used to treat a variety of chronic inflammatory and neoplastic diseases. However, it can induce hepatotoxicity such as microvesicular steatosis and necrosis. To explore the mechanisms of MTX-induced hepatic steatosis, we used microarray analysis to profile the gene expression patterns of mouse liver after MTX treatment. MTX was administered orally as a single dose of 10mg/kg (low dose) or 100 mg/kg (high dose) to ICR mice, and the livers were obtained 6 h, 24 h, and 72 h after treatment. Serum alanine aminotransferase, aspartate aminotransferase and triacylglycerol levels were not significantly altered in the experimental animals. Signs of steatosis were observed at 24 h after administration of high dose of MTX. From microarray data analysis, 908 genes were selected as MTX-responsive genes (P0.05, two-way ANOVA; cutoffor =1.5-fold). Database for Annotation, Visualization and Integrated Discovery (DAVID) analysis revealed that the predominant biological processes associated with these genes are response to unfolded proteins, phosphate metabolism, and cellular lipid metabolism. Functional categorization of these genes identified 28 genes involved in lipid metabolism that was interconnected with the biological pathways of biosynthesis, catabolism, and transport of lipids and fatty acids. Taken together, these data provide a better understanding of the molecular mechanisms of MTX-induced steatogenic hepatotoxicity, and useful information for predicting hepatotoxicity through pattern recognition.

Cadmium is a naturally occurring metallic element with food and smoking being the main sources of exposure in the non-occupationally exposed population. Chronic exposure to cadmium leads to tumors in a number of tissues including lung. In the present study we investigated genes whose expression is modified by Cd exposure in human lung fibroblast WI38-VA13 cells. We employed a cDNA microarray hybridization method to identify changes in the gene expression profile. Thirty five genes were identified as cadmium-responsive. Their level of expression differed significantly from controls (significance analysis of microarray; SAM, q

Ethanol induces cumulative liver damage including steatosis, steatohepatitis and cirrhosis. The aim of this study is to investigate the global intrahepatic gene expression profile in the mouse liver treated with ethanol. A single oral dose of 0.5 or 5 g/kg ethanol was administered to male ICR mice, and liver samples were obtained after 6, 24 and 72 h. Histopathological evaluation showed typical fatty livers in the high-dose group at 24 h. Microarray analysis identified 28 genes as being ethanol responsive (two-way ANOVA; p0.05), after adjustment by the Benjamini-Hochberg multiple testing correction; these genes displayedor=2-fold induction or repression. The expression of genes that are known to be involved in fatty acid synthesis was examined. The transcript for lipogenic transcription factor, sterol regulatory element (SRE)-binding factor 1 (Srebf1), was upregulated by acute ethanol exposure. Of the genes known to contain SRE or SRE-like sequences and to be regulated by SRE-binding protein 1 (SREBP1), those encoding malic enzyme (Mod1), ATP-citrate lyase (Acly), fatty acid synthase (Fasn) and stearyl-CoA desaturase (Scd1) were induced by ethanol. Quantitative real-time PCR confirmed the changes in the expression levels of the selected genes. The change in the Srebf1 mRNA level correlates well with that of the SREBP1 protein expression as well as its binding to the promoters of the target genes. The present study identifies differentially expressed genes that can be applied to the biomarkers for alcohol-binge-induced fatty liver. These results support the hypothesis by which ethanol-induced steatosis in mice is mediated by the fatty acid synthetic pathway regulated by SREBP1.

This study aimed to provide basic information as the foundation for further studies on the assessment of velvet antler quality by investigating the changes in fatty acid, vitamin A and E, minerals and GAGs contents by development stage of antler in spotted deer (Cervus nippon). Twelve stags (aged 4 to 5 years) were divided into two groups and velvet antler harvested 40 days (FDG) and 60 days (SDG) after casting of the buttons from the previous set. Total saturated fatty acid was lower in FDG than SDG (p

Valproic acid (VPA) has been used as anticonvulsants, however, it induces hepatotoxicity such as microvesicular steatosis and necrosis in the liver. To explore the mechanisms of VPA-induced steatosis, we profiled the gene expression patterns of the mouse liver that were altered by treatment with VPA using microarray analysis. VPA was orally administered as a single dose of 100 mg/kg (low-dose) or 1000 mg/kg (high-dose) to ICR mice and the animals were killed at 6, 24, or 72 h after treatment. Serum alanine aminotransferase and aspartate aminotransferase levels were not significantly altered in the experimental animals. However, symptoms of steatosis were observed at 72 h with low-dose and at 24 h and 72 h with high-dose. After microarray data analysis, 1910 genes were selected by two-way ANOVA (P0.05) as VPA-responsive genes. Hierarchical clustering revealed that gene expression changes depended on the time rather than the dose of VPA treatment. Gene profiling data showed striking changes in the expression of genes associated with lipid, fatty acid, and steroid metabolism, oncogenesis, signal transduction, and development. Functional categorization of 1156 characteristically up- and down-regulated genes (cutoff1.5-fold) revealed that 60 genes were involved in lipid metabolism that was interconnected with biological pathways for biosynthesis of triglyceride and cholesterol, catabolism of fatty acid, and lipid transport. This gene expression profile may be associated with the known steatogenic hepatotoxicity of VPA and it may provide useful information for prediction of hepatotoxicity of unknown chemicals or new drug candidates through pattern recognition.

The uterine endometrium plays a critical role in regulating the estrous cycle and the establishment and maintenance of pregnancy in mammalian species. Many studies have investigated the expression and function of genes in the uterine endometrium, but the global expression pattern of genes and relationships among genes differentially expressed in the uterine endometrium during gestation in pigs remain unclear. Thus, this study investigated global gene expression profiles using microarray in pigs. Diverse transcriptome analyses including clustering, network, and differentially expressed gene (DEG) analyses were performed to detect endometrial gene expression changes during the different gestation stages. In total, 6,991 genes were found to be differentially expressed by comparing genes expressed on day (D) 12 of pregnancy with those on D15, D30, D60, D90 and D114 of pregnancy, and clustering analysis of detected DEGs distinguished 8 clusters. Furthermore, several pregnancy-related hub genes such as ALPPL2, RANBP17, NF1B, SPP1, and CST6 were discovered through network analysis. Finally, detected hub genes were technically validated by quantitative RT-PCR. These results suggest the complex network characteristics involved in uterine endometrial gene expression during pregnancy and indicate that diverse patterns of stage-specific gene expression and network connections may play a critical role in endometrial remodeling and in placental and fetal development to establish and maintenance of pregnancy in pigs.

Microarray analysis of RNA from diclofenac-administered mouse livers was performed to establish a global gene expression profile during injury and recovery stages at two different doses. A single dose of diclofenac at 9.5 mg/kg or 0.95 mg/kg body weight was given orally, and the liver samples were obtained after 6, 24, and 72 h. Histopathologic studies enabled the classification of the diclofenac effect into injury (6, 24 h) and recovery (72 h) stages. By using the Applied Biosystems Mouse Genome Survey Microarray, a total of 7370 out of 33,315 (22.1%) genes were found to be statistically reliable at p < 0.05 by two-way ANOVA, and 602 (1.8%) probes at false discovery rate

Tetracycline is one of a group of drugs known to induce microvesicular steatosis. In the present study, we investigated the effects of tetracycline on gene expression in mouse liver, using Applied Biosystems Mouse Genome Survey Microarrays. A single oral dose of 0.1 or 1 g/kg tetracycline was administered to male ICR mice, and liver samples were obtained after 6, 24, or 72 h. Histopathological evaluation showed microvesicular steatosis in the high-dose group at 24 h. In total, 96 genes were identified as tetracycline responsive. Their level of expression differed significantly from controls (two-way analysis of variance; p0.05), after adjustment by the Benjamini-Hochberg multiple testing correction, and displayed a twofold or greater induction or repression. The largest groups of gene products affected by tetracycline exposure were those involved in signal transduction, nucleic acid metabolism, developmental processes, and protein metabolism. The expression of genes known to be involved in lipid metabolism was examined, using two-sample Student's t-test for each treatment group versus a corresponding control group. The overall net effects on expression of lipid metabolism genes indicated an increase in cholesterol and triglyceride biosynthesis and a decrease in beta-oxidation of fatty acids. Our data support a proposed mechanism for tetracycline-induced steatogenic hepatotoxicity that involves these processes. Moreover, we demonstrated global changes in hepatic gene expression following tetracycline exposure; many of these genes have the potential to be used as biomarkers of exposure to steatogenic hepatotoxic agents.

Biological pathways can provide key information on the organization of biological systems. ArrayXPath (http://www.snubi.org/software/ArrayXPath/) is a web-based service for mapping and visualizing microarray gene-expression data for integrated biological pathway resources using Scalable Vector Graphics (SVG). By integrating major bio-databases and searching pathway resources, ArrayXPath automatically maps different types of identifiers from microarray probes and pathway elements. When one inputs gene-expression clusters, ArrayXPath produces a list of the best matching pathways for each cluster. We applied Fisher's exact test and the false discovery rate (FDR) to evaluate the statistical significance of the association between a cluster and a pathway while correcting the multiple-comparison problem. ArrayXPath produces Javascript-enabled SVGs for web-enabled interactive visualization of pathways integrated with gene-expression profiles.

This paper investigates high rate systematic punctured convolutional codes based on Forney's (1970) results. High rate systematic punctured convolutional codes of rate-2/3 with constraint length 3/spl les/K/spl les/7 and rate-3/4 through 15/16 with K=7 are derived using the rate-1/2 best known nonsystematic convolutional codes. Weight spectra of newly discovered systematic punctured convolutional codes are provided and compared with the best known nonsystematic punctured codes. Simulation results on bit-error probabilities (BEPs) are also given.

Previous attempts to predict bacteremia have focused on selecting significant variables. However, these approaches have had limitations such as poor reproducibility in prediction accuracy and inconsistency in predictor selection. Here we propose a Bayesian approach to predict bacteremia based on the statistical distributions of clinical variables of previous patients, which has recently become possible through the adoption of electronic medical records.In a derivation cohort, Bayesian prediction models were derived and their discriminative performance was compared with previous models under varying combinations of predictors. Then the Bayesian models were prospectively tested in a validation cohort. According to Bayesian probabilities of bacteremia, patients in both cohorts were grouped into bacteremia risk groups.Using the same prediction variables, the Bayesian predictions were more accurate than conventional rule-based predictions. Moreover, their better discriminative performance remained consistent despite variations in clinical variables. The receiver operating characteristic (ROC) area of the Bayesian model with 20 predictors was 0.70 ± 0.007 in the derivation cohort and 0.70 ± 0.018 in the validation cohort. The prevalence of bacteremia in groups I, II, and VI (grouped according to probability ratio) were 1.9%, 3.4%, and 20.0% in the derivation cohort, and 0.4%, 3.2%, and 18.4% in the validation cohort, respectively. The overall prevalence of bacteremia was 6.9% in both cohorts.In the present study, the Bayesian prediction model showed stable performance in predicting bacteremia and identifying risk groups, as the previous models did. The clinical significance of the Bayesian approach is expected to be demonstrated through a multicenter trial.

We investigate the undetected error probabilities for bounded-distance decoding of binary primitive BCH codes when they are used for both error correction and detection on a binary symmetric channel. We show that the undetected error probability of binary linear codes can be simplified and quantified if the weight distribution of the code is binomial-like. We obtain bounds on the undetected error probability of binary primitive BCH codes by applying the result to the code and show that the bounds are quantified by the deviation factor of the true weight distribution from the binomial-like weight distribution.

Lysophosphatidic acid (LPA), a simple phospholipid, plays a critical role in the establishment of pregnancy in pigs. LPA production is mediated by the action of ENPP2, a secreted lysophospholipase D (lysoPLD) that converts lysophosphatidylcholine to LPA. However, the mechanism that regulates LPA production by ENPP2 in the porcine uterus is not well understood. In this study, we evaluated ENPP2 expression during the estrous cycle and pregnancy in the uterine endometrium and in early stage conceptuses. We also evaluated lysoPLD activity in the uterine lumen. ENPP2 transcripts and proteins were detected in the uterine endometrium at all stages of the estrous cycle and pregnancy, with higher levels on Day (D) 12 and D15 of the estrous cycle and pregnancy. ENPP2 expression was localized mainly in luminal and glandular epithelial cells in the endometrium and was also detected in conceptuses on D12 of pregnancy. Secreted ENPP2 protein was detected in fluid flushing samples from the uterine lumen on D12 of the estrous cycle and pregnancy, with higher levels on D12 of pregnancy. LysoPLD activity was detected in uterine flushings on D12 of the estrous cycle and pregnancy, with higher levels on D12 of pregnancy. This study showed that uterine endometrium and conceptuses produce ENPP2 and secreted it into the uterine lumen where it has lysoPLD activity. These results suggest that ENPP2 may play an important role in the establishment of pregnancy in pigs by regulating LPA production at the maternal-conceptus interface.

Lysophosphatidic acid (LPA), a simple phospholipid, plays a critical role in the establishment of pregnancy in pigs. LPA production is mediated by the action of ENPP2, a secreted lysophospholipase D (lysoPLD) that converts lysophosphatidylcholine to LPA. However, the mechanism that regulates LPA production by ENPP2 in the porcine uterus is not well understood. In this study, we evaluated ENPP2 expression during the estrous cycle and pregnancy in the uterine endometrium and in early stage conceptuses. We also evaluated lysoPLD activity in the uterine lumen. ENPP2 transcripts and proteins were detected in the uterine endometrium at all stages of the estrous cycle and pregnancy, with higher levels on Day (D) 12 and D15 of the estrous cycle and pregnancy. ENPP2 expression was localized mainly in luminal and glandular epithelial cells in the endometrium and was also detected in conceptuses on D12 of pregnancy. Secreted ENPP2 protein was detected in fluid flushing samples from the uterine lumen on D12 of the estrous cycle and pregnancy, with higher levels on D12 of pregnancy. LysoPLD activity was detected in uterine flushings on D12 of the estrous cycle and pregnancy, with higher levels on D12 of pregnancy. This study showed that uterine endometrium and conceptuses produce ENPP2 and secreted it into the uterine lumen where it has lysoPLD activity. These results suggest that ENPP2 may play an important role in the establishment of pregnancy in pigs by regulating LPA production at the maternal-conceptus interface.

Successful pregnancy requires an appropriate intrauterine immune response to the conceptus, which is a semiallograft within the uterus. We reported that swine leukocyte antigen-DQA (SLA-DQA), a major histocompatibility complex (MHC) class II gene, is expressed in the uterine endometrium at the time of conceptus implantation in pigs. Because MHC molecules play critical roles in the immune system, SLA-DQ was hypothesized to be involved in immune regulation during pregnancy. Therefore, we examined expression of SLA-DQ in uterine endometrial tissues obtained during the estrous cycle and pregnancy. SLA-DQA and SLA-DQB mRNAs were detected as 1.3-kb and 1.2-kb bands, respectively. Real-time RT-PCR analysis indicated that SLA-DQA and SLA-DQB mRNA expression was affected by day and pregnancy status, with the highest expression on Day 15 of pregnancy. SLA-DQ was localized primarily to subepithelial stromal cells and endothelial cells of the uterus. Using endometrial explant cultures from Day 12 of the estrous cycle, we determined that expression of SLA-DQA and SLA-DQB mRNAs increased in response to interferon-gamma (IFNG), which is produced by pig conceptus trophectoderm between Days 14 and 18 of pregnancy. The abundance of SLA-DQ protein was less in endometria from gilts with conceptuses resulting from somatic cell nuclear transfer compared with endometria from gilts with conceptuses resulting from natural mating. These results support our hypothesis that SLA-DQ is expressed in response to IFNG from the conceptus, and likely regulates immune response at the maternal-fetal interface to support the maintenance of pregnancy in pigs.

It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether the reported intercellular mitochondrial transfer could be replicated in different types of cells or under different experimental conditions, and tried to elucidate possible mechanism. Using biochemical selection methods, we found exponentially growing cells in restrictive media (uridine(-) and bromodeoxyuridine [BrdU](+)) during the coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mitochondrial DNA (mtDNA) identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B rho(0) cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. Cytochalasin B, an inhibitor of chemotaxis and cytoskeletal assembly, blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential cell therapy-based mitochondrial restoration or mitochondrial gene therapy for human diseases caused by mitochondrial dysfunction.

Calcium ions play an important role in the establishment and maintenance of pregnancy, but molecular and cellular regulatory mechanisms of calcium ion action in the uterine endometrium are not fully understood in pigs. Previously, we have shown that calcium regulatory molecules, transient receptor potential vanilloid type 5 (TRPV6) and calbindin-D9k (S100G), are expressed in the uterine endometrium during the estrous cycle and pregnancy in a pregnancy status- and stage-specific manner, and that estrogen of conceptus origin increases endometrial TRPV6 expression. However, regulation of S100G expression in the uterine endometrium and conceptus expression of S100G has been not determined during early pregnancy. Thus, we investigated regulation of S100G expression by estrogen and interleukin-1β (IL1B) in the uterine endometrium and conceptus expression of S100G during early pregnancy in pigs. We obtained uterine endometrial tissues from day (D) 12 of the estrous cycle and treated with combinations of steroid hormones, estradiol-17β (E2) and progesterone (P4), and increasing doses of IL1B. Real-time RT-PCR analysis showed that E2 and IL1B increased S100G mRNA levels in the uterine endometrium, and conceptuses expressed S100G mRNA during early pregnancy, as determined by RT-PCR analysis. To determine if endometrial expression of S100G mRNA during the implantation period was affected by the somatic cell nuclear transfer (SCNT) procedure, we compared S100G mRNA levels in the uterine endometrium from gilts with SCNT-derived conceptuses with those from gilts with conceptuses derived from natural mating on D12 of pregnancy. Real-time RT-PCR analysis showed that levels of S100G mRNA in the uterine endometrium from gilts carrying SCNT-derived conceptuses was significantly lower than those from gilts carrying conceptuses derived from natural mating. These results showed that S100G expression in the uterine endometrium was regulated by estrogen and IL1B of conceptus origin, and affected by the SCNT procedure during early pregnancy. These suggest that conceptus signals regulate S100G, an intracellular calcium transport protein, for the establishment of pregnancy in pigs.

Successful pregnancy requires an appropriate intrauterine immune response to the conceptus, which is a semiallograft within the uterus. We reported that swine leukocyte antigen-DQA (SLA-DQA), a major histocompatibility complex (MHC) class II gene, is expressed in the uterine endometrium at the time of conceptus implantation in pigs. Because MHC molecules play critical roles in the immune system, SLA-DQ was hypothesized to be involved in immune regulation during pregnancy. Therefore, we examined expression of SLA-DQ in uterine endometrial tissues obtained during the estrous cycle and pregnancy. SLA-DQA and SLA-DQB mRNAs were detected as 1.3-kb and 1.2-kb bands, respectively. Real-time RT-PCR analysis indicated that SLA-DQA and SLA-DQB mRNA expression was affected by day and pregnancy status, with the highest expression on Day 15 of pregnancy. SLA-DQ was localized primarily to subepithelial stromal cells and endothelial cells of the uterus. Using endometrial explant cultures from Day 12 of the estrous cycle, we determined that expression of SLA-DQA and SLA-DQB mRNAs increased in response to interferon-gamma (IFNG), which is produced by pig conceptus trophectoderm between Days 14 and 18 of pregnancy. The abundance of SLA-DQ protein was less in endometria from gilts with conceptuses resulting from somatic cell nuclear transfer compared with endometria from gilts with conceptuses resulting from natural mating. These results support our hypothesis that SLA-DQ is expressed in response to IFNG from the conceptus, and likely regulates immune response at the maternal-fetal interface to support the maintenance of pregnancy in pigs.

Uterine secretions are essential for the development of the conceptus during pregnancy. In pigs, various molecules, including transport proteins, growth factors, enzymes, and extracellular matrix proteins, are secreted into the uterine lumen. Our previous work identified salivary lipocalin (SAL1), a steroidal pheromone-binding protein, as present in the porcine uterus. To initiate studies on the role of SAL1 in the porcine uterus, we evaluated 1) the spatial and temporal expression of SAL1 in the uterine endometrium during the estrous cycle and pregnancy, and in the conceptus during early pregnancy; 2) secretion of SAL1 into the uterine lumen on Day (D) 12 of the estrous cycle and pregnancy; and 3) the effects of steroid hormones and cytokines on SAL1 mRNA levels. SAL1 was localized to glandular epithelial cells (GE) in the endometrium during the estrous cycle and pregnancy, with the highest level of SAL1 expression on D12 of pregnancy. In addition, SAL1 protein secretion into the uterine lumen was detected in uterine flushings on D12 of the estrous cycle and pregnancy, with higher levels on D12 of pregnancy. SAL1 protein, but not SAL1 transcript, was also detected in the conceptuses on D12 and D15. In explant culture experiments, SAL1 mRNA levels in the endometrium were increased by interleukin 1beta. The results of a GE- and implantation stage-specific expression and uterine secretion of SAL1 in the porcine uterus suggest that SAL1 present at the maternal-fetal interface may act as a histotroph and play an important role in the establishment of pregnancy.

Motivation: The small number of samples in many microarray experiments is a challenge for the correct identification of differentially expressed gens (DEGs) by conventional statistical means. Information from public microarray databases can help more efficient identification of DEGs. To model various experimental conditions of a public microarray database, we applied Gaussian mixture model and extracted bi- or tri-modal distributions of gene expression. Prior variance of Baldi's Bayesian framework was estimate for the analysis of the small sample-sized datasets. Results: First, we estimated the prior variance of a gene expression by pooling variances obtained from mixture modeling of large samples in the public microarray database. Then, using the prior variance, we identified DEGs in small sample-sized test datasets using the Baldi's framework. For benchmark study, we generated test datasets having several samples from relatively large datasets. Our proposed method outperformed other benchmark methods in terms of detecting gold-standard DEGs from the test datasets. The results may be a challenging evidence for usage of public microarray databases in microarray data analysis. Availability: Supplementary data are available at http://www.snubi.org/publication/MixBayes Contact: juhan@snu.ac.kr