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Sample records for k4 increased significantly

  1. Inflammatory genes TNFα and IL6 display no signs of increased H3K4me3 in circulating monocytes from untreated rheumatoid arthritis patients.

    Science.gov (United States)

    Messemaker, T C; Mikkers, H M M; Huizinga, T W; Toes, R E M; van der Helm-van Mil, A H M; Kurreeman, F

    2017-09-01

    Innate immune cells, such as monocytes, can adopt a long-lasting pro-inflammatory phenotype, a phenomenon called 'trained immunity'. In trained immunity, increased cytokine levels of genes, like interleukin (IL)-6 and tumor necrosis factor (TNF)-α, are observed, which are associated with increased histone 3 lysine 4 trimethylation (H3K4me3) in the promoter region. As systemic IL6 and TNFα levels are increased in rheumatoid arthritis (RA) patients and monocytes are known to be the primary producers of TNFα and IL6, we hypothesized that 'trained immunity' signals may be observed at these genes in monocytes from RA patients. CD14+ monocytes were isolated from untreated RA patients and paired age-matched healthy controls. H3K4me3, mRNA, protein and serum levels of IL6 and TNFα were evaluated by chromatin immunoprecipitation, reverse-transcription quantitative PCR and enzyme-linked immunosorbent assays. Despite elevated serum levels of TNFα and IL6 in the tested RA patients (P<0.05), ex vivo isolated monocytes displayed similar H3K4me3 levels to healthy controls in the promoter region of TNFα and IL6. Concordantly, mRNA and protein levels of IL6 and TNFα were similar before and after lipopolysaccharide stimulation between patients and controls. Together, with the current number of individuals tested we have not detected enhanced trained immunity signals in circulating monocytes from untreated RA patients, despite increased IL6 and TNFα serum levels.

  2. ESSEA K-4 Online Course: Polar Connections

    Science.gov (United States)

    Blaney, L.; Myers, R. J.; Schwerin, T.

    2007-12-01

    The Earth System Science Education Alliance (ESSEA) is a National Science Foundation-supported program implemented by the Institute for Global Environmental Strategies (IGES) to improve the quality of geoscience instruction for pre-service, middle, and high school teachers. ESSEA increases teachers' access to quality materials, standards-based instructional methods and content knowledge. Started in 2000 and based on a trio of online courses (for elementary, middle, and high school teachers), the courses have been used by 40 faculty at 20 institutions educating over 1,700 teachers in Earth system science. Program evaluation of original course participants indicated that the courses had significant impact on teachers Earth system content knowledge and beliefs about teaching and learning. Seventeen of the original participating institutions have continued to use the courses and many have developed new programs that incorporate the courses in Earth science education opportunities for teachers. Today the ESSEA program lists nearly 40 colleges and universities as participants. The original K-4 course and modules have been revised to include topics and resources focusing on the International Polar Year. The new K-4 Land, Living Things, Water and Air modules contain inquiry-based investigations exploring our polar regions. Each module lists a set of essential questions that guide teachers and their students as they build content knowledge. The course structure requires teachers to work individually and in teams to build content knowledge and pedagogical understanding of how their students learn. This group investigation approach and a "Teacher as Researcher" theme promote reflection and collaboration to develop criteria for effective concept building. By exploring the characteristics of polar landscapes, atmosphere, and polar life, teachers and their students will develop new understandings about the interactions and dependencies of the Earth spheres and our polar regions

  3. Coal exporters win significant price increases

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-04-01

    Coal exports won a 3 dollars/t or almost 8% rise in hard coking coal prices to lift the benchmark Goonyella brand to 42.75 dollars/t. This was followed by major price increases for semi-hard coking coal with the prices of some grades increased by 8 dollars/t or by more than 23%. The new prices will come into effect for the year beginning April, 2001 and acre then first price rises in two years. The article reviews the major Asia countries with their coal supply information. 1 tab., 4 photos.

  4. CNOOC Reports Significant Increase in 2006 Profits

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    @@ China National Offshore Oil Corporation (CNOOC), the country's No.3 oil producer,recently announced pretax profits jumped 24 percent to 48.1 billion yuan (US$6.2 billion) in 2006. The offshore oil giant reported 60.1 percent increase in pretax profits, totaling 38.8 billion yuan (US$5 billion) in 2005. Analysts said the dropped oil prices in the second half of last year had greatly affected the company's profit growth.

  5. Effects of nickel treatment on H3K4 trimethylation and gene expression.

    Directory of Open Access Journals (Sweden)

    Kam-Meng Tchou-Wong

    Full Text Available Occupational exposure to nickel compounds has been associated with lung and nasal cancers. We have previously shown that exposure of the human lung adenocarcinoma A549 cells to NiCl(2 for 24 hr significantly increased global levels of trimethylated H3K4 (H3K4me3, a transcriptional activating mark that maps to the promoters of transcribed genes. To further understand the potential epigenetic mechanism(s underlying nickel carcinogenesis, we performed genome-wide mapping of H3K4me3 by chromatin immunoprecipitation and direct genome sequencing (ChIP-seq and correlated with transcriptome genome-wide mapping of RNA transcripts by massive parallel sequencing of cDNA (RNA-seq. The effect of NiCl(2 treatment on H3K4me3 peaks within 5,000 bp of transcription start sites (TSSs on a set of genes highly induced by nickel in both A549 cells and human peripheral blood mononuclear cells were analyzed. Nickel exposure increased the level of H3K4 trimethylation in both the promoters and coding regions of several genes including CA9 and NDRG1 that were increased in expression in A549 cells. We have also compared the extent of the H3K4 trimethylation in the absence and presence of formaldehyde crosslinking and observed that crosslinking of chromatin was required to observe H3K4 trimethylation in the coding regions immediately downstream of TSSs of some nickel-induced genes including ADM and IGFBP3. This is the first genome-wide mapping of trimethylated H3K4 in the promoter and coding regions of genes induced after exposure to NiCl(2. This study may provide insights into the epigenetic mechanism(s underlying the carcinogenicity of nickel compounds.

  6. Unifiability in extensions of K4

    NARCIS (Netherlands)

    Gencer, Ç.; de Jongh, D.

    2009-01-01

    We extend and generalize the work on unifiability of [8]. We give a semantic characterization for unifiability and non-unifiability in the extensions of K4. We apply this in particular to extensions of KD4, GL and K4.3 to obtain a syntactic characterization and give a concrete decision procedure for

  7. Climate impacts of oil extraction increase significantly with oilfield age

    Science.gov (United States)

    Masnadi, Mohammad S.; Brandt, Adam R.

    2017-08-01

    Record-breaking temperatures have induced governments to implement targets for reducing future greenhouse gas (GHG) emissions. Use of oil products contributes ~35% of global GHG emissions, and the oil industry itself consumes 3-4% of global primary energy. Because oil resources are becoming increasingly heterogeneous, requiring different extraction and processing methods, GHG studies should evaluate oil sources using detailed project-specific data. Unfortunately, prior oil-sector GHG analysis has largely neglected the fact that the energy intensity of producing oil can change significantly over the life of a particular oil project. Here we use decades-long time-series data from twenty-five globally significant oil fields (>1 billion barrels ultimate recovery) to model GHG emissions from oil production as a function of time. We find that volumetric oil production declines with depletion, but this depletion is accompanied by significant growth--in some cases over tenfold--in per-MJ GHG emissions. Depletion requires increased energy expenditures in drilling, oil recovery, and oil processing. Using probabilistic simulation, we derive a relationship for estimating GHG increases over time, showing an expected doubling in average emissions over 25 years. These trends have implications for long-term emissions and climate modelling, as well as for climate policy.

  8. Solubility increases associated with crystalline drug nanoparticles: methodologies and significance.

    Science.gov (United States)

    Van Eerdenbrugh, Bernard; Vermant, Jan; Martens, Johan A; Froyen, Ludo; Humbeeck, Jan Van; Van den Mooter, Guy; Augustijns, Patrick

    2010-10-01

    In this manuscript, the determination of solubility of crystalline drug nanosuspensions by a range of methods is critically investigated. As the determinations of solubility were performed in the presence of the solubilizing nanosuspension stabilizer d-α-tocopherol polyethylene glycol 1000 succinate (TPGS), the potential effects of this excipient on the measurements were studied first. Solubility data of nanosuspensions of itraconazole, loviride, phenytoin and naproxen were generated using different methodologies. Data obtained using separation-based methodologies (centrifugation, filtration and ultracentrifugation) proved to be of limited use, due to poor nanoparticle separation efficiencies and/or significant adsorption of TPGS onto the nanoparticle surfaces. Light scattering and turbidity were found to be more suitable for the determination of nanosuspension solubility. The obtained data show that, unlike earlier reports, the solubility increases due to nanosizing are small, with measured increases of only 15%. These solubility increases are in fair agreement with what would be predicted based on the Ostwald-Freundlich equation.

  9. Teaching Strategies for K-4 General Music.

    Science.gov (United States)

    Teaching Music, 1999

    1999-01-01

    Provides a strategy, from the book entitled "Strategies for Teaching K-4 General Music," that addresses Standard 6A of the National Standards for Music Education. Explains that students will identify characteristics that enables them to make decisions about the form of the composition in listening examples longer than classroom songs. (CMK)

  10. Stromal p16 expression is significantly increased in endometrial carcinoma.

    Science.gov (United States)

    Yoon, Gun; Koh, Chang Won; Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

    2017-01-17

    p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC.

  11. Neocortical RELN promoter methylation increases significantly after puberty.

    Science.gov (United States)

    Lintas, Carla; Persico, Antonio M

    2010-01-27

    Reelin plays a pivotal role in neurodevelopment. Excessive RELN promoter methylation and/or decreased RELN gene expression have been described in schizophrenia and autism. We assessed RELN promoter methylation in post-mortem temporocortical tissue (Brodmann Area 41/42) of three prepuberal and six postpuberal normal individuals. The former display very little or no methylation, whereas most postpuberal individuals are heavily methylated, especially at CpG positions located between -131 and -98 bp (prepuberal vs. postpuberal, P<0.05). Sex hormones thus seemingly boost DNA methylation at the RELN promoter. This physiological change could significantly contribute to the onset of schizophrenia and the worsening of autistic behaviors, both typically occurring at puberty.

  12. Significant increase of chromosomal damage in protein energy malnutrition.

    Science.gov (United States)

    el-Ghazali, S; Mikhail, M; Awadallah, M; Shatla, H

    1990-12-01

    The present study attempts to investigate the impact of protein energy malnutrition (PEM) on chromosomes. Twenty infants suffering from marasmus and kwashiorkor were chosen from the in-patient paediatric hospital of Ain Shams University. They were matched by age and sex and socioeconomic status to ten healthy infants (controls). Whole blood lymphocytic cultures were set up for every infant and harvested after 48 h incubation. The frequency of chromosomal aberrations was found to be nearly nine times greater among infants with PEM compared to controls (6.7% versus 0.7% respectively); the difference was statistically highly significant, P less than 0.001. The recorded aberrations were mainly chromatid gaps and isogaps. In addition, chromatid breaks, dicentrics and acentric fragments were observed. Moreover, the younger the age of the infant the greater the frequency of chromosomal aberrations. The results direct our attention to the genetic risk effect of PEM.

  13. Mitogen-activated protein kinase kinase 4 (MAP2K4 promotes human prostate cancer metastasis.

    Directory of Open Access Journals (Sweden)

    Janet M Pavese

    Full Text Available Prostate cancer (PCa is the second leading cause of cancer death in the US. Death from PCa primarily results from metastasis. Mitogen-activated protein kinase kinase 4 (MAP2K4 is overexpressed in invasive PCa lesions in humans, and can be inhibited by small molecule therapeutics that demonstrate favorable activity in phase II studies. However, MAP2K4's role in regulating metastatic behavior is controversial and unknown. To investigate, we engineered human PCa cell lines which overexpress either wild type or constitutive active MAP2K4. Orthotopic implantation into mice demonstrated MAP2K4 increases formation of distant metastasis. Constitutive active MAP2K4, though not wild type, increases tumor size and circulating tumor cells in the blood and bone marrow. Complementary in vitro studies establish stable MAP2K4 overexpression promotes cell invasion, but does not affect cell growth or migration. MAP2K4 overexpression increases the expression of heat shock protein 27 (HSP27 protein and protease production, with the largest effect upon matrix metalloproteinase 2 (MMP-2, both in vitro and in mouse tumor samples. Further, MAP2K4-mediated increases in cell invasion are dependent upon heat shock protein 27 (HSP27 and MMP-2, but not upon MAP2K4's immediate downstream targets, p38 MAPK or JNK. We demonstrate that MAP2K4 increases human PCa metastasis, and prolonged over expression induces long term changes in cell signaling pathways leading to independence from p38 MAPK and JNK. These findings provide a mechanistic explanation for human studies linking increases in HSP27 and MMP-2 to progression to metastatic disease. MAP2K4 is validated as an important therapeutic target for inhibiting human PCa metastasis.

  14. CCM key comparison CCM.D-K4 'Hydrometer'

    Science.gov (United States)

    Lorefice, S.; Becerra, L. O.; Lenard, E.; Lee, Y. J.; Lee, W. G.; Madec, T.; Meury, P. A.; Caceres, J.; Santos, C.; Vamossy, C.; Man, J.; Fen, K.; Toda, K.; Wright, J.; Bettin, H.; Toth, H.

    2016-01-01

    This report presents the comparison philosophy, methodology, analysis and the results of the designed CCM.D-K4 key comparison that covered the calibration of high resolution hydrometers for liquid and alcoholometers in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20°C. The main purpose of this comparison was not only to evaluate the degree of equivalence in the calibration of high accuracy hydrometers between NMI participants, but also to link, were it is possible, the results of previous comparisons to Key Comparison Reference Values (KCRVs) of CCM.D-K4. Eleven NMI laboratories took part in the CCM.D-K4 divided in two groups (petals). With the CCM.D-K4 purpose, two similar sets consisting of three hydrometers for liquid density determinations and an alcoholometer were circulated to the NMI participants as a travelling standard in the time interval from January 2011 to April 2012. Twelve Key Comparison Reference Values (KCRVs) for each petal have been obtained at the density values related to the tested density marks of the transfer standards by the results of participants. The KCRVs and corresponding uncertainties were calculated by the weighted mean in the case of consistent results, otherwise the median was used. The degree of equivalence (DoE) with respect to the corresponding KCRV was determined for each participant and, in this particular comparison, the Weighted Least Squares (WLS) method was used to link the individual DoE of each participant by a continuous function. Significant drift of the transfer standards was not detected. This report also gives instructions on calculating pair-wise degrees of equivalence, with the addition of any information on correlations that may be necessary to estimate more accurately as well as the procedure for linking international comparisons to the CCM.D-K4. Finally an example of linkage to the CCM.D-K4 is given by dealing with the results of the bilateral comparison between INRiM and NMIA, which was

  15. Significant increase of Echinococcus multilocularis prevalencein foxes, but no increased predicted risk for humans

    NARCIS (Netherlands)

    Maas, M.; Dam-Deisz, W.D.C.; Roon, van A.M.; Takumi, K.; Giessen, van der J.W.B.

    2014-01-01

    The emergence of the zoonotic tapeworm Echinococcus multilocularis, causative agent ofalveolar echinococcosis (AE), poses a public health risk. A previously designed risk mapmodel predicted a spread of E. multilocularis and increasing numbers of alveolar echinococ-cosis patients in the province of L

  16. Increasing vaginal progesterone gel supplementation after frozen-thawed embryo transfer significantly increases the delivery rate

    DEFF Research Database (Denmark)

    Alsbjerg, Birgit; Polyzos, Nikolaos P; Elbaek, Helle Olesen

    2013-01-01

    The aim of this study was to evaluate the reproductive outcome in patients receiving frozen-thawed embryo transfer before and after doubling of the vaginal progesterone gel supplementation. The study was a retrospective study performed in The Fertility Clinic, Skive Regional Hospital, Denmark....... A total of 346 infertility patients with oligoamenorrhoea undergoing frozen-thawed embryo transfer after priming with oestradiol and vaginal progesterone gel were included. The vaginal progesterone dose was changed from 90 mg (Crinone) once a day to twice a day and the reproductive outcome during the two...... rate (8.7% versus 20.5%, respectively; P=0.002). Doubling of the vaginal progesterone gel supplementation during frozen-thawed embryo transfer cycles decreased the early pregnancy loss rate, resulting in a significantly higher delivery rate. This study evaluated the reproductive outcome of 346 women...

  17. Reading, Writing & Rings: Science Literacy for K-4 Students

    Science.gov (United States)

    McConnell, S.; Spilker, L.; Zimmerman-Brachman, R.

    2007-12-01

    Scientific discovery is the impetus for the K-4 Education program, "Reading, Writing & Rings." This program is unique because its focus is to engage elementary students in reading and writing to strengthen these basic academic skills through scientific content. As science has been increasingly overtaken by the language arts in elementary classrooms, the Cassini Education Program has taken advantage of a new cross-disciplinary approach to use language arts as a vehicle for increasing scientific content in the classroom. By utilizing the planet Saturn and the Cassini-Huygens mission as a model in both primary reading and writing students in these grade levels, young students can explore science material while at the same time learning these basic academic skills. Content includes reading, thinking, and hands-on activities. Developed in partnership with the Cassini-Huygens Education and Public Outreach Program, the Bay Area Writing Project/California Writing Project, Foundations in Reading Through Science & Technology (FIRST), and the Caltech Pre-College Science Initiative (CAPSI), and classroom educators, "Reading, Writing & Rings" blends the excitement of space exploration with reading and writing. All materials are teacher developed, aligned with national science and language education standards, and are available from the Cassini-Huygens website: http://saturn.jpl.nasa.gov/education/edu-k4.cfm Materials are divided into two grade level units. One unit is designed for students in grades 1 and 2 while the other unit focuses on students in grades 3 and 4. Each includes a series of lessons that take students on a path of exploration of Saturn using reading and writing prompts.

  18. Parity, cycle space, and K4-subdivisions in graphs

    DEFF Research Database (Denmark)

    Thomassen, Carsten

    1999-01-01

    . Zang). We prove the new result that every $4$-connected graph with at least three triangles contains a totally odd $K_4$-subdivision if and only if it does notcontain a vertex whose deletion results in a bipartite graph.In particular, every $4$-connected planar graph contains a totally odd $K_4...

  19. Peaked and Smooth Solitons for K*(4,1 Equation

    Directory of Open Access Journals (Sweden)

    Yongan Xie

    2013-01-01

    Full Text Available This paper is contributed to explore all possible single peak solutions for the K*(4,1 equation ut=uxu2+2α(uuxxx+2uxuxx. Our procedure shows that the K*(4,1 equation either has peakon, cuspon, and smooth soliton solutions when sitting on a nonzero constant pedestal limξ→±∞u=A≠0 or possesses compacton solutions only when limξ→±∞u=A=0. We present a new smooth soliton solution in an explicit form. Mathematical analysis and numeric graphs are provided for those soliton solutions of the K*(4,1 equation.

  20. The Role of GluK4 in Synaptic Plasticity and Affective Behavior in Mice

    Science.gov (United States)

    Catches, Justin Samuel

    Kainate receptors (KARs) are glutamate-gated ion channels that signal through both ionotropic and metabotropic pathways (Contractor et al., 2011). Combinations of five KAR subunits (GluK1-5) form tetrameric receptors with GluK1, GluK2, and GluK3 able to form functional homomeric channels. The high-affinity subunits, GluK4 and GluK5, do not form homomeric channels but modify the properties of heteromeric receptors. Expression of the GluK4 receptor subunit in the forebrain is restricted to the CA3 region of the hippocampus and dentate gyrus regions where KARs modulate synaptic plasticity. In this study, ablation of Grik4, which encodes GluK4, in mice reduced KAR synaptic currents and altered activation properties of postsynaptic receptors but left two forms of presynaptic short-term plasticity intact. Disruption of both Grik4 and Grik5 caused complete loss of the postsynaptic ionotropic KAR current and impaired presynaptic frequency facilitation. Additionally, KAR surface expression was altered at pre- and postsynaptic sites at the MF synapse. Despite the loss of ionotropic signaling, KAR-mediated inhibition of the slow afterhyperpolarization current, which is dependent on metabotropic signaling, was intact in CA3 neurons. Long-term potentiation at the MF-CA3 synapse was reduced, likely through a loss of KAR modulation of excitability of the presynaptic MF axons. Genetic variants in the human GRIK4 gene alter the susceptibility for affective disorders (Bloss and Hunter, 2010). We found that ablation of Grik4 in mice resulted in reduced anxiety and an antidepressant-like phenotype. In the elevated zero-maze, a test for anxiety and risk taking behavior, and in two anxiogenic tests, marble-burying and novelty-induced suppression of feeding, anxiety-like behavior was consistently reduced in knockout animals. In the forced swim, a test of learned helplessness used to determine depression-like behavior, knockout mice demonstrated significantly less immobility suggesting

  1. 调控因子SlyA和RfaH在E.coli K4合成果糖软骨素中的生理作用%Effects of overexpression of transcriptional regulators SlyA and RfaH on fructosylated chondroitin production in E coli K4

    Institute of Scientific and Technical Information of China (English)

    杨爱华; 刘佳; 张震宇; 刘立明

    2015-01-01

    To enhance K4CPS production of E. coli K4,the transcriptional factor SlyA and RfaH were over expressed in E. coli K4 to create E. coli pTH⁃slyA,E. coli pTH⁃rfaH and co⁃expression strain E. coli pTH⁃slyA⁃rfaH. The over⁃expression of SlyA and RfaH significantly enhanced K4CPS production. The K4CPS concentration for E. coli pTH⁃slyA,E. coli pTH⁃rfaH and E. coli pTH⁃slyA⁃rfaH was increased by 81�8%、46�5% and 153�8%, compared with that of E. coli K4, respectively. The glycerol consumption rate of recombinant strain decreased by 12�5%、18�8% and 31�3% than that of E. coli K4. Moreover, the concentration of acetic acid decreased by 98�6%、39�7%and 91�6%compared with that of E. coli K4� The overexpression of slyA and rfaH could significantly enhanced K4CPS production.%利用基因工程手段过量表达E. coli K4荚膜多糖( K4CPS)合成途径中相关代谢调控因子SlyA和RfaH,以构建高效合成K4CPS的菌株。结果发现:slyA和rfaH基因的单独过量表达和共表达重组菌的K4CPS的产量较对照菌分别提高了81�8%、46�5%和153�8%;甘油比消耗速率较对照菌降低了12�5%、18�8%和31�3%,而乙酸含量则较对照菌降低了98�6%、39�7%和91�6%。因此,调控蛋白SlyA和RfaH的过量表达能够大幅度提高E�coli K4K4CPS合成,并增强菌体对甘油的利用率,而乙酸合成明显降低。而与单独表达策略相比,共表达策略能够更加有效地增强菌体合成K4CPS的能力。

  2. Inducible Deletion of Protein Kinase Map4k4 in Obese Mice Improves Insulin Sensitivity in Liver and Adipose Tissues.

    Science.gov (United States)

    Danai, Laura V; Flach, Rachel J Roth; Virbasius, Joseph V; Menendez, Lorena Garcia; Jung, Dae Young; Kim, Jong Hun; Kim, Jason K; Czech, Michael P

    2015-07-01

    Studies in vitro suggest that mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) attenuates insulin signaling, but confirmation in vivo is lacking since Map4k4 knockout is lethal during embryogenesis. We thus generated mice with floxed Map4k4 alleles and a tamoxifen-inducible Cre/ERT2 recombinase under the control of the ubiquitin C promoter to induce whole-body Map4k4 deletion after these animals reached maturity. Tamoxifen administration to these mice induced Map4k4 deletion in all tissues examined, causing decreased fasting blood glucose concentrations and enhanced insulin signaling to AKT in adipose tissue and liver but not in skeletal muscle. Surprisingly, however, mice generated with a conditional Map4k4 deletion in adiponectin-positive adipocytes or in albumin-positive hepatocytes displayed no detectable metabolic phenotypes. Instead, mice with Map4k4 deleted in Myf5-positive tissues, including all skeletal muscles tested, were protected from obesity-induced glucose intolerance and insulin resistance. Remarkably, these mice also showed increased insulin sensitivity in adipose tissue but not skeletal muscle, similar to the metabolic phenotypes observed in inducible whole-body knockout mice. Taken together, these results indicate that (i) Map4k4 controls a pathway in Myf5-positive cells that suppresses whole-body insulin sensitivity and (ii) Map4k4 is a potential therapeutic target for improving glucose tolerance and insulin sensitivity in type 2 diabetes.

  3. Phosphorus K4 Crystal: A New Stable Allotrope

    Science.gov (United States)

    Liu, Jie; Zhang, Shunhong; Guo, Yaguang; Wang, Qian

    2016-11-01

    The intriguing properties of phosphorene motivate scientists to further explore the structures and properties of phosphorus materials. Here, we report a new allotrope named K4 phosphorus composed of three-coordinated phosphorus atoms in non-layered structure which is not only dynamically and mechanically stable, but also possesses thermal stability comparable to that of the orthorhombic black phosphorus (A17). Due to its unique configuration, K4 phosphorus exhibits exceptional properties: it possesses a band gap of 1.54 eV which is much larger than that of black phosphorus (0.30 eV), and it is stiffer than black phosphorus. The band gap of the newly predicted phase can be effectively tuned by appling hydrostastic pressure. In addition, K4 phosphorus exibits a good light absorption in visible and near ultraviolet region. These findings add additional features to the phosphorus family with new potential applications in nanoelectronics and nanomechanics.

  4. Isolation of an Escherichia coli K4 kfoC mutant over-producing capsular chondroitin

    Directory of Open Access Journals (Sweden)

    De Rosa Mario

    2010-05-01

    Full Text Available Abstract Background Chondroitin sulphate is a complex polysaccharide having important structural and protective functions in animal tissues. Extracted from animals, this compound is used as a human anti-inflammatory drug. Among bacteria, Escherichia coli K4 produces a capsule containing a non-sulphate chondroitin and its development may provide an efficient and cheap fermentative production of the polysaccharide. Results A random N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis was performed on E. coli K4 to isolate mutants showing an increased production of chondroitin. Several mutants were isolated, one of which, here named VZ15, produced about 80% more chondroitin than the wild type E. coli. We found that the mutant has a missense mutation in the codon 313 of kfoC, the gene encoding chondroitin polymerase (K4CP, with a change from arginine to glutamine. A docking analysis to explain the increased productivity of the K4CP enzyme is presented. Conclusion The enhanced chondroitin production by the E. coli K4 mutant reported here shows the validity of the strain improvement strategy for more cost-friendly fermentative processes in the production of this pharmaceutically important but so-far expensive polysaccharide.

  5. Properties of atomic intercalated carbon K4 crystals

    OpenAIRE

    Itoh, Masahiro; Takami, Seiichi; Kawazoe, Yoshiyuki; Adschiri, Tadafumi

    2009-01-01

    The stability of atomic intercalated carbon $K_{4}$ crystals, XC$_{2}$ (X=H, Li, Be, B, C, N, O, F, Na, Mg, Al, Si, P, S, Cl, K, Ca, Ga, Ge, As, Se, Br, Rb or Sr) is evaluated by geometry optimization and frozen phonon analysis based on first principles calculations. Although C $K_{4}$ is unstable, NaC$_{2}$ and MgC$_{2}$ are found to be stable. It is shown that NaC$_{2}$ and MgC$_{2}$ are metallic and semi conducting, respectively.

  6. The existence spectrum of Meta(K4(3)>K4(3)-e)

    Institute of Scientific and Technical Information of China (English)

    LO; FARO; Giovanni; TRIPODI; Antoinette

    2010-01-01

    Let H and J1 be both t-uniform hypergraphs. Let J2 be a sub-hypergraph of J1. In this paper, the metamorphosis of a hypergraph decomposition is introduced, denoted by (H, J1 > J2)-design, which is a generalization of the concept of metamorphosis of a graph decomposition. Let Meta(J1>J2) denote the set of all integers v such that there exists a (Kv((3)), J1>J2)-design. We completely determine the set Meta(K4((3))>K4((3))-e).

  7. Cost of wound treatment to increase significantly in Denmark over the next decade

    DEFF Research Database (Denmark)

    Hjort, Anne Mette; Gottrup, F

    2010-01-01

    To demonstrate that changes in demography, life expectancy and incidence of background diseases (including type 2 diabetes mellitus) during the period 2009-2020 will significantly increase the costs of wound care in Denmark.......To demonstrate that changes in demography, life expectancy and incidence of background diseases (including type 2 diabetes mellitus) during the period 2009-2020 will significantly increase the costs of wound care in Denmark....

  8. Continuous background light significantly increases flashing-light enhancement of photosynthesis and growth of microalgae.

    Science.gov (United States)

    Abu-Ghosh, Said; Fixler, Dror; Dubinsky, Zvy; Iluz, David

    2015-01-01

    Under specific conditions, flashing light enhances the photosynthesis rate in comparison to continuous illumination. Here we show that a combination of flashing light and continuous background light with the same integrated photon dose as continuous or flashing light alone can be used to significantly enhance photosynthesis and increase microalgae growth. To test this hypothesis, the green microalga Dunaliella salina was exposed to three different light regimes: continuous light, flashing light, and concomitant application of both. Algal growth was compared under three different integrated light quantities; low, intermediate, and moderately high. Under the combined light regime, there was a substantial increase in all algal growth parameters, with an enhanced photosynthesis rate, within 3days. Our strategy demonstrates a hitherto undescribed significant increase in photosynthesis and algal growth rates, which is beyond the increase by flashing light alone.

  9. Simple exercises that significantly increase cerebral blood flow and cerebral oxygenation

    CERN Document Server

    Gersten, Alexander; Raz, Amir; Fried, Robert

    2011-01-01

    We tested the hypothesis that simple exercises may significantly increase cerebral blood flow (CBF) and/or cerebral oxygenation. Eighteen subjects ranging in age from nineteen to thirty nine participated in a four-stage study during which measurements of end tidal CO_2 (EtCO2 - by capnometer) and local brain oxygenation (by near-infrared spectroscopy (NIRS) sensor) were taken. The four stages were 1) baseline, 2) breathing exercises, 3) solving an arithmetic problem, and 4) biofeedback. During the breathing exercises there was a significant increase in EtCO2 indicating a significant increase in global CBF. The increase in global CBF was estimated on the basis of a theoretical model. During the arithmetic and biofeedback tasks there was a significant increase in the local (Fp1) oxygenation, but it varied between the different participants. The results may lead to new clinical applications of CBF and brain oxygenation monitoring and behavioral control. We foresee future more detailed investigations in the contr...

  10. An acoustical pump capable of significantly increasing pressure ratio of thermoacoustic heat engines

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    Pressure ratio is one of the important parameters for evaluating a thermoacoustic heat engine. A so-called acoustical pump, which is capable of significantly increasing pressure ratio of a thermoacoustic heat engine, is proposed. Its operating principle is given. Also, a verification experiment is done with nitrogen gas in the energy-focused thermoacoustic heat engine, showing that the pressure ratio increased from 1.25 to 1.47.

  11. THE SMALL BUT SIGNIFICANT AND NONTRANSITORY INCREASE IN PRICES (SSNIP TEST

    Directory of Open Access Journals (Sweden)

    Liviana Niminet

    2008-12-01

    Full Text Available The Small but Significant Nontransitory Increase in Price Test was designed to define the relevant market by concepts of product, geographical area and time. This test, also called the ,,hypothetical monopolistic test” is the subject of many researches both economical and legal as it deals with economic concepts as well as with legally aspects.

  12. Increase of the Antarctic Sea Ice Extent is highly significant only in the Ross Sea

    Science.gov (United States)

    Yuan, Naiming; Ding, Minghu; Ludescher, Josef; Bunde, Armin

    2017-01-01

    In the context of global warming, the question of why Antarctic sea ice extent (SIE) has increased is one of the most fundamental unsolved mysteries. Although many mechanisms have been proposed, it is still unclear whether the increasing trend is anthropogenically originated or only caused by internal natural variability. In this study, we employ a new method where the underlying natural persistence in the Antarctic SIE can be correctly accounted for. We find that the Antarctic SIE is not simply short-term persistent as assumed in the standard significance analysis, but actually characterized by a combination of both short- and long-term persistence. By generating surrogate data with the same persistence properties, the SIE trends over Antarctica (as well as five sub-regions) are evaluated using Monte-Carlo simulations. It is found that the SIE trends over most sub-regions of Antarctica are not statistically significant. Only the SIE over Ross Sea has experienced a highly significant increasing trend (p = 0.008) which cannot be explained by natural variability. Influenced by the positive SIE trend over Ross Sea, the SIE over the entire Antarctica also increased over the past decades, but the trend is only at the edge of being significant (p = 0.034).

  13. Significant alterations in reported clinical practice associated with increased oversight of organ transplant center performance.

    Science.gov (United States)

    Schold, Jesse D; Arrington, Charlotte J; Levine, Greg

    2010-09-01

    In the past several years, emphasis on quality metrics in the field of organ transplantation has increased significantly, largely because of the new conditions of participation issued by the Centers for Medicare and Medicaid Services. These regulations directly associate patients' outcomes and measured performance of centers with the distribution of public funding to institutions. Moreover, insurers and marketing ventures have used publicly available outcomes data from transplant centers for business decision making and advertisement purposes. We gave a 10-question survey to attendees of the Transplant Management Forum at the 2009 meeting of the United Network for Organ Sharing to ascertain how centers have responded to the increased oversight of performance. Of 63 responses, 55% indicated a low or near low performance rating at their center in the past 3 years. Respondents from low-performing centers were significantly more likely to indicate increased selection criteria for candidates (81% vs 38%, P = .001) and donors (77% vs 31%, P < .001) as well as alterations in clinical protocols (84% vs 52%, P = .007). Among respondents indicating lost insurance contracts (31%), these differences were also highly significant. Based on respondents' perceptions, outcomes of performance evaluations are associated with significant changes in clinical practice at transplant centers. The transplant community and policy makers should practice vigilance that performance evaluations and regulatory oversight do not inadvertently lead to diminished access to care among viable candidates or decreased transplant volume.

  14. Analysis of the Mitogen-activated protein kinase kinase 4 (MAP2K4 tumor suppressor gene in ovarian cancer

    Directory of Open Access Journals (Sweden)

    Ryland Georgina L

    2011-05-01

    Full Text Available Abstract Background MAP2K4 is a putative tumor and metastasis suppressor gene frequently found to be deleted in various cancer types. We aimed to conduct a comprehensive analysis of this gene to assess its involvement in ovarian cancer. Methods We screened for mutations in MAP2K4 using High Resolution Melt analysis of 149 primary ovarian tumors and methylation at the promoter using Methylation-Specific Single-Stranded Conformation Polymorphism analysis of 39 tumors. We also considered the clinical impact of changes in MAP2K4 using publicly available expression and copy number array data. Finally, we used siRNA to measure the effect of reducing MAP2K4 expression in cell lines. Results In addition to 4 previously detected homozygous deletions, we identified a homozygous 16 bp truncating deletion and a heterozygous 4 bp deletion, each in one ovarian tumor. No promoter methylation was detected. The frequency of MAP2K4 homozygous inactivation was 5.6% overall, and 9.8% in high-grade serous cases. Hemizygous deletion of MAP2K4 was observed in 38% of samples. There were significant correlations of copy number and expression in three microarray data sets. There was a significant correlation between MAP2K4 expression and overall survival in one expression array data set, but this was not confirmed in an independent set. Treatment of JAM and HOSE6.3 cell lines with MAP2K4 siRNA showed some reduction in proliferation. Conclusions MAP2K4 is targeted by genetic inactivation in ovarian cancer and restricted to high grade serous and endometrioid carcinomas in our cohort.

  15. Properties of atomic intercalated boron nitride K4 type crystals

    OpenAIRE

    Itoh, Masahiro; Takami, Seiichi; Kawazoe, Yoshiyuki; Adschiri, Tadafumi

    2010-01-01

    The stability of atomic intercalated boron nitride K4 crystal structures, XBN (X=H, Li, Be, B, C, N, O, F, Na, Mg, Al, Si, P, S, Cl, K, Ca, Ga, Ge, As, Se, Br, Rb or Sr) is evaluated by the geometric optimization and frozen phonon calculations based on the first principles calculations. NaBN, MgBN, GaBN, FBN and ClBN are found to be stable. NaBN, GaBN, FBN and ClBN are metallic, whereas MgBN is semiconducting.

  16. Endotracheal tube cuff pressure increases significantly during anterior cervical fusion with the Caspar instrumentation system.

    Science.gov (United States)

    Sperry, R J; Johnson, J O; Apfelbaum, R I

    1993-06-01

    To determine whether endotracheal tube cuff pressure increases significantly with surgical retraction and cervical spine distraction during anterior cervical spine surgery with Caspar instrumentation, we prospectively studied 10 patients undergoing this procedure. The tracheas of all patients were intubated with a Mallinckrodt Hi-Lo endotracheal tube. Tracheal tube cuff pressures measured with a transducer system were 42.4 mm Hg +/- 7.0 mm Hg (SEM) after intubation and cuff inflation. Air was removed from the endotracheal tube cuff until the trachea was just barely sealed at a cuff pressure of 15.2 mm Hg +/- 1.6 mm Hg. The endotracheal tube cuff pressure was readjusted to "just-seal" pressure before the surgeons introduced the Caspar instrumentation. The cuff pressure with traction and distraction was 43.2 mm Hg +/- 5.0 mm Hg. This pressure was significantly increased from the "just-seal" pressure, and from the cuff pressure after instrumentation was discontinued (9.8 mm Hg +/- 2.3 mm Hg). We conclude that anterior cervical spine surgery with Caspar instrumentation is associated with a significant increase in endotracheal tube cuff pressure.

  17. St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats.

    Science.gov (United States)

    Yang, Shih-Ying; Juang, Shin-Hun; Tsai, Shang-Yuan; Chao, Pei-Dawn Lee; Hou, Yu-Chi

    2012-08-15

    St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC(0-t) and C(max) of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC(0-t) of MTX by 55%. In addition, diclofenac enhanced the C(max) of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution.

  18. Significant increase of summertime ozone at Mount Tai in Central Eastern China

    Science.gov (United States)

    Sun, Lei; Xue, Likun; Wang, Tao; Gao, Jian; Ding, Aijun; Cooper, Owen R.; Lin, Meiyun; Xu, Pengju; Wang, Zhe; Wang, Xinfeng; Wen, Liang; Zhu, Yanhong; Chen, Tianshu; Yang, Lingxiao; Wang, Yan; Chen, Jianmin; Wang, Wenxing

    2016-08-01

    Tropospheric ozone (O3) is a trace gas playing important roles in atmospheric chemistry, air quality and climate change. In contrast to North America and Europe, long-term measurements of surface O3 are very limited in China. We compile available O3 observations at Mt. Tai - the highest mountain over the North China Plain - during 2003-2015 and analyze the decadal change of O3 and its sources. A linear regression analysis shows that summertime O3 measured at Mt. Tai has increased significantly by 1.7 ppbv yr-1 for June and 2.1 ppbv yr-1 for the July-August average. The observed increase is supported by a global chemistry-climate model hindcast (GFDL-AM3) with O3 precursor emissions varying from year to year over 1980-2014. Analysis of satellite data indicates that the O3 increase was mainly due to the increased emissions of O3 precursors, in particular volatile organic compounds (VOCs). An important finding is that the emissions of nitrogen oxides (NOx) have diminished since 2011, but the increase of VOCs appears to have enhanced the ozone production efficiency and contributed to the observed O3 increase in central eastern China. We present evidence that controlling NOx alone, in the absence of VOC controls, is not sufficient to reduce regional O3 levels in North China in a short period.

  19. Significant yield increases from control of leaf diseases in maize - an overlooked problem?!

    DEFF Research Database (Denmark)

    Jørgensen, Lise Nistrup

    2012-01-01

    The area of maize has increased in several European countries in recent years. In Denmark, the area has increased from 10,000 ha in 1980 to 185,000 ha in 2011. Initially only silage maize was cultivated in Denmark, but in more recent years the area of grain maize has also increased. Farms growing...... maize have often grown maize consecutively for several years. This leads to significant amounts of debris building up in the fields, which serves as an important source of inoculum for diseases when new crops are grown. In recent years, leaf diseases have caused production problems over several seasons....... Two major diseases have been identified: Eyespot (Kabatiella zeae) and Northern leaf blotch (Exserohilum turcicum). Other diseases, including Southern maize leaf blight or maydis leaf blight, caused by Bipolaris maydis, and Northern corn leaf spot, caused by Bipolaris zeicola, may potentially play...

  20. Hydrologic effects of large southwestern USA wildfires significantly increase regional water supply: fact or fiction?

    Science.gov (United States)

    Wine, M. L.; Cadol, D.

    2016-08-01

    In recent years climate change and historic fire suppression have increased the frequency of large wildfires in the southwestern USA, motivating study of the hydrological consequences of these wildfires at point and watershed scales, typically over short periods of time. These studies have revealed that reduced soil infiltration capacity and reduced transpiration due to tree canopy combustion increase streamflow at the watershed scale. However, the degree to which these local increases in runoff propagate to larger scales—relevant to urban and agricultural water supply—remains largely unknown, particularly in semi-arid mountainous watersheds co-dominated by winter snowmelt and the North American monsoon. To address this question, we selected three New Mexico watersheds—the Jemez (1223 km2), Mogollon (191 km2), and Gila (4807 km2)—that together have been affected by over 100 wildfires since 1982. We then applied climate-driven linear models to test for effects of fire on streamflow metrics after controlling for climatic variability. Here we show that, after controlling for climatic and snowpack variability, significantly more streamflow discharged from the Gila watershed for three to five years following wildfires, consistent with increased regional water yield due to enhanced infiltration-excess overland flow and groundwater recharge at the large watershed scale. In contrast, we observed no such increase in discharge from the Jemez watershed following wildfires. Fire regimes represent a key difference between the contrasting responses of the Jemez and Gila watersheds with the latter experiencing more frequent wildfires, many caused by lightning strikes. While hydrologic dynamics at the scale of large watersheds were previously thought to be climatically dominated, these results suggest that if one fifth or more of a large watershed has been burned in the previous three to five years, significant increases in water yield can be expected.

  1. Breast cancer-associated metastasis is significantly increased in a model of autoimmune arthritis

    Science.gov (United States)

    Das Roy, Lopamudra; Pathangey, Latha B; Tinder, Teresa L; Schettini, Jorge L; Gruber, Helen E; Mukherjee, Pinku

    2009-01-01

    Introduction Sites of chronic inflammation are often associated with the establishment and growth of various malignancies including breast cancer. A common inflammatory condition in humans is autoimmune arthritis (AA) that causes inflammation and deformity of the joints. Other systemic effects associated with arthritis include increased cellular infiltration and inflammation of the lungs. Several studies have reported statistically significant risk ratios between AA and breast cancer. Despite this knowledge, available for a decade, it has never been questioned if the site of chronic inflammation linked to AA creates a milieu that attracts tumor cells to home and grow in the inflamed bones and lungs which are frequent sites of breast cancer metastasis. Methods To determine if chronic inflammation induced by autoimmune arthritis contributes to increased breast cancer-associated metastasis, we generated mammary gland tumors in SKG mice that were genetically prone to develop AA. Two breast cancer cell lines, one highly metastatic (4T1) and the other non-metastatic (TUBO) were used to generate the tumors in the mammary fat pad. Lung and bone metastasis and the associated inflammatory milieu were evaluated in the arthritic versus the non-arthritic mice. Results We report a three-fold increase in lung metastasis and a significant increase in the incidence of bone metastasis in the pro-arthritic and arthritic mice compared to non-arthritic control mice. We also report that the metastatic breast cancer cells augment the severity of arthritis resulting in a vicious cycle that increases both bone destruction and metastasis. Enhanced neutrophilic and granulocytic infiltration in lungs and bone of the pro-arthritic and arthritic mice and subsequent increase in circulating levels of proinflammatory cytokines, such as macrophage colony stimulating factor (M-CSF), interleukin-17 (IL-17), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and tumor necrosis factor

  2. Association of common genetic variants in the MAP4K4 locus with prediabetic traits in humans.

    Directory of Open Access Journals (Sweden)

    Tina Sartorius

    Full Text Available Mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4 is expressed in all diabetes-relevant tissues and mediates cytokine-induced insulin resistance. We investigated whether common single nucleotide polymorphisms (SNPs in the MAP4K4 locus associate with glucose intolerance, insulin resistance, impaired insulin release, or elevated plasma cytokines. The best hit was tested for association with type 2 diabetes. Subjects (N = 1,769 were recruited from the Tübingen Family (TÜF study for type 2 diabetes and genotyped for tagging SNPs. In a subgroup, cytokines were measured. Association with type 2 diabetes was tested in a prospective case-cohort study (N = 2,971 derived from the EPIC-Potsdam study. Three SNPs (rs6543087, rs17801985, rs1003376 revealed nominal and two SNPs (rs11674694, rs11678405 significant associations with 2-hour glucose levels. SNPs rs6543087 and rs11674694 were also nominally associated with decreased insulin sensitivity. Another two SNPs (rs2236936, rs2236935 showed associations with reduced insulin release, driven by effects in lean subjects only. Three SNPs (rs11674694, rs13003883, rs2236936 revealed nominal associations with IL-6 levels. SNP rs11674694 was significantly associated with type 2 diabetes. In conclusion, common variation in MAP4K4 is associated with insulin resistance and β-cell dysfunction, possibly via this gene's role in inflammatory signalling. This variation's impact on insulin sensitivity may be more important since its effect on insulin release vanishes with increasing BMI.

  3. Exam anxiety induces significant blood pressure and heart rate increase in college students.

    Science.gov (United States)

    Zhang, Zhihong; Su, Hai; Peng, Qiang; Yang, Qing; Cheng, Xiaoshu

    2011-01-01

    To investigate the relationship between the anxiety and blood pressure (BP) and heart rate (HR) increase in peri-exam period. Sixty-four college students(20.0 ± 0.1 year old) were included in this study. The BP and HR were measured in the morning and in the evening for 3 days during the prereview (ba), review, and exam periods. The BP and HR increase amplitudes (HRIA) of review and exam periods were from the difference of corresponding values and basic values, and the BPIA/baBP and HRIA/baHR were calculated. All of the students completed the Self-Rating Anxiety score (SAS) questionnaire the first day of the exam period. Scores over 50 points were used as the standard for anxiety. From the prereview to exam periods, the BP and HR increased gradually. The exam SBPIA (4.3 ± 1.3 vs. 0.3 ± 0.5 mmHg, P family hypertension group had higher anxiety score; meanwhile, their exam BPIAs and HRIAs were significantly higher than their corresponding group. The BP and HR increase in the review and exam period, anxiety is an important factor of BP and HR increase.

  4. Significantly Increasing the Ductility of High Performance Polymer Semiconductors through Polymer Blending.

    Science.gov (United States)

    Scott, Joshua I; Xue, Xiao; Wang, Ming; Kline, R Joseph; Hoffman, Benjamin C; Dougherty, Daniel; Zhou, Chuanzhen; Bazan, Guillermo; O'Connor, Brendan T

    2016-06-08

    Polymer semiconductors based on donor-acceptor monomers have recently resulted in significant gains in field effect mobility in organic thin film transistors (OTFTs). These polymers incorporate fused aromatic rings and have been designed to have stiff planar backbones, resulting in strong intermolecular interactions, which subsequently result in stiff and brittle films. The complex synthesis typically required for these materials may also result in increased production costs. Thus, the development of methods to improve mechanical plasticity while lowering material consumption during fabrication will significantly improve opportunities for adoption in flexible and stretchable electronics. To achieve these goals, we consider blending a brittle donor-acceptor polymer, poly[4-(4,4-dihexadecyl-4H-cyclopenta[1,2-b:5,4-b']dithiophen-2-yl)-alt-[1,2,5]thiadiazolo[3,4-c]pyridine] (PCDTPT), with ductile poly(3-hexylthiophene). We found that the ductility of the blend films is significantly improved compared to that of neat PCDTPT films, and when the blend film is employed in an OTFT, the performance is largely maintained. The ability to maintain charge transport character is due to vertical segregation within the blend, while the improved ductility is due to intermixing of the polymers throughout the film thickness. Importantly, the application of large strains to the ductile films is shown to orient both polymers, which further increases charge carrier mobility. These results highlight a processing approach to achieve high performance polymer OTFTs that are electrically and mechanically optimized.

  5. Potential therapeutic significance of increased expression of aryl hydrocarbon receptor in human gastric cancer

    Institute of Scientific and Technical Information of China (English)

    TieLi Peng; Jie Chen; Wei Mao; Xin Liu; Yu Tao; Lian-Zhou Chen; Min-Hu Chen

    2009-01-01

    AIM: To determine the functional significance of aryl hydrocarbon receptor (AhR) in gastric carcinogenesis, and to explore the possible role of AhR in gastric cancer (GC) treatment. METHODS: RT-PCR, real-time PCR, and Western blotting were performed to detect AhR expression in 39 GC tissues and five GC cell lines. AhR protein was detected by immunohistochemistry (IHC) in 190 samples: 30 chronic superficial gastritis (CSG), 30 chronic atrophic gastritis (CAG), 30 intestinal metaplasia (IM), 30 atypical hyperplasia (AH), and 70 GC. The AhR agonist tetrachlorodibenzo-para-dioxin (TCDD) was used to treat AGS cells. MTT assay and flow cytometric analysis were performed to measure the viability, cell cycle and apoptosis of AGS cells. RESULTS: AhR expression was significantly increased in GC tissues and GC cell lines. IHC results indicated that the levels of AhR expression gradually increased, with the lowest levels in CSG, followed by CAG, IM, AH and GC. AhR expression and nuclear translocation were significantly higher in GC than in precancerous tissues. TCDD inhibited proliferation of AGS cells via induction of growth arrest at the G1-S phase. CONCLUSION: AhR plays an important role in gastric carcinogenesis. AhR may be a potential therapeutic target for GC treatment.

  6. Iontophoresis significantly increases the trans-dentinal delivery of osteoprotegerin, alendronate, and calcitonin.

    Science.gov (United States)

    Kitchens, James A; Schwartz, Scott A; Schindler, William G; Hargreaves, Kenneth M

    2007-10-01

    The purpose of this study was to evaluate the delivery of alendronate, calcitonin, and osteoprotegerin (OPG) through human dentin by both diffusion and iontophoresis for the potential treatment of invasive cervical resorption. Radiolabeled alendronate, calcitonin, and OPG were added to the top of a split chamber device that contained 1-mm thick dentin disks devoid of a smear layer. Transdentinal movement of medicaments by either random diffusion or application of an iontophoretic current was measured by analysis of gamma emission of effluent fractions. In addition, calcitonin delivery was evaluated at differing magnitudes of current (0-4 mA) by using the aforementioned chamber. Diffusion of all 3 medicaments was minimal. In contrast, the application of a 3-mA iontophoretic gradient significantly increased delivery for all 3 compounds at 10-, 20-, and 30-minute intervals. In addition, a linear increase in permeability was seen for calcitonin as milliamperes were increased from 0 to 4 (r = 0.947), with more than a 100-fold increase in delivery observed with iontophoresis. Delivery of the tested medicaments by using iontophoresis might prove to be a useful technique for treatment of invasive cervical resorption.

  7. [A significant increase in intraoperative flash visual evoked potential amplitude during craniopharyngioma surgery-case report].

    Science.gov (United States)

    Kawaguchi, Tomohiro; Ogawa, Yoshikazu; Fujiwara, Satoru; Tominaga, Teiji

    2015-04-01

    The flash visual evoked potential (VEP) is a useful diagnostic modality for visual preservation during surgery. Decreased VEP amplitude is recognized to indicate visual deterioration;however, whether intraoperative VEP can detect visual improvement remains unclear. We describe a craniopharyngioma case with a significant increase in VEP amplitude during surgery. A 67-year-old woman presented with progressive gait disturbance and impaired consciousness. Head magnetic resonance imaging demonstrated a sellar-suprasellar tumor compressing the optic chiasm upward with significant ventricular dilation. Her Glasgow Coma Scale was E3V3M5. Visual fields and acuity could not be examined because of impaired consciousness, and she could not see/recognize objects on a table. Preoperative VEP showed reproducible waveforms. Tumor removal by the extended transsphenoidal approach was performed with VEP monitoring. Increased VEP amplitude was observed after dural incision and persisted until the surgery ended. Postoperative VEP waveforms were also reproducible, but visual fields/acuity could not be examined because of cognitive dysfunction. Useful visual function was restored, and she became independent in daily life. The histological diagnosis was craniopharyngioma. The patient underwent ventriculo-peritoneal shunting for hydrocephalus 16 days after tumor removal. The postoperative course was uneventful and she was transferred to another hospital for rehabilitation. Intraoperative VEP may indicate visual improvement during surgery, which is a useful objective assessment for visual function in patients with impaired consciousness and cognitive dysfunction.

  8. Significant increase in ecosystem C can be achieved with sustainable forest management in subtropical plantation forests.

    Directory of Open Access Journals (Sweden)

    Xiaohua Wei

    Full Text Available Subtropical planted forests are rapidly expanding. They are traditionally managed for intensive, short-term goals that often lead to long-term yield decline and reduced carbon sequestration capacity. Here we show how it is possible to increase and sustain carbon stored in subtropical forest plantations if management is switched towards more sustainable forestry. We first conducted a literature review to explore possible management factors that contribute to the potentials in ecosystem C in tropical and subtropical plantations. We found that broadleaves plantations have significantly higher ecosystem C than conifer plantations. In addition, ecosystem C increases with plantation age, and reaches a peak with intermediate stand densities of 1500-2500 trees ha⁻¹. We then used the FORECAST model to simulate the regional implications of switching from traditional to sustainable management regimes, using Chinese fir (Cunninghamia lanceolata plantations in subtropical China as a study case. We randomly simulated 200 traditional short-rotation pure stands and 200 sustainably-managed mixed Chinese fir--Phoebe bournei plantations, for 120 years. Our results showed that mixed, sustainably-managed plantations have on average 67.5% more ecosystem C than traditional pure conifer plantations. If all pure plantations were gradually transformed into mixed plantations during the next 10 years, carbon stocks could rise in 2050 by 260.22 TgC in east-central China. Assuming similar differences for temperate and boreal plantations, if sustainable forestry practices were applied to all new forest plantation types in China, stored carbon could increase by 1,482.80 TgC in 2050. Such an increase would be equivalent to a yearly sequestration rate of 40.08 TgC yr⁻¹, offsetting 1.9% of China's annual emissions in 2010. More importantly, this C increase can be sustained in the long term through the maintenance of higher amounts of soil organic carbon and the production

  9. Significant increase in ecosystem C can be achieved with sustainable forest management in subtropical plantation forests.

    Science.gov (United States)

    Wei, Xiaohua; Blanco, Juan A

    2014-01-01

    Subtropical planted forests are rapidly expanding. They are traditionally managed for intensive, short-term goals that often lead to long-term yield decline and reduced carbon sequestration capacity. Here we show how it is possible to increase and sustain carbon stored in subtropical forest plantations if management is switched towards more sustainable forestry. We first conducted a literature review to explore possible management factors that contribute to the potentials in ecosystem C in tropical and subtropical plantations. We found that broadleaves plantations have significantly higher ecosystem C than conifer plantations. In addition, ecosystem C increases with plantation age, and reaches a peak with intermediate stand densities of 1500-2500 trees ha⁻¹. We then used the FORECAST model to simulate the regional implications of switching from traditional to sustainable management regimes, using Chinese fir (Cunninghamia lanceolata) plantations in subtropical China as a study case. We randomly simulated 200 traditional short-rotation pure stands and 200 sustainably-managed mixed Chinese fir--Phoebe bournei plantations, for 120 years. Our results showed that mixed, sustainably-managed plantations have on average 67.5% more ecosystem C than traditional pure conifer plantations. If all pure plantations were gradually transformed into mixed plantations during the next 10 years, carbon stocks could rise in 2050 by 260.22 TgC in east-central China. Assuming similar differences for temperate and boreal plantations, if sustainable forestry practices were applied to all new forest plantation types in China, stored carbon could increase by 1,482.80 TgC in 2050. Such an increase would be equivalent to a yearly sequestration rate of 40.08 TgC yr⁻¹, offsetting 1.9% of China's annual emissions in 2010. More importantly, this C increase can be sustained in the long term through the maintenance of higher amounts of soil organic carbon and the production of timber products

  10. The chronicity of tonsillitis is significantly correlated with an increase in an LTi cell portion.

    Science.gov (United States)

    Chang, Jung Hyun; Kim, Soochan; Koo, Jihye; Lane, Peter J L; Yoon, Sun Och; Park, Ah Young; Kim, Kyung-Su; Kim, Mi-Yeon

    2014-02-01

    The current study explored the relationship between lymphoid tissue inducer (LTi) cells and patients' clinical and immunological status. LTi cells are critical for lymphoid tissue development and maintenance of CD4 T cell-dependent immune responses. The percentage of CD117+CD3-CD56-CD127+ RORγ+ LTi cells isolated from human tonsils was determined and correlated with changes in other immune subsets and clinical factors. We found that the portion of LTi and CD4 T cells was significantly increased in chronic tonsillitis compared to non-inflamed tonsils. Additionally, the expression of OX40 by memory CD4 T cells and OX40 ligand (OX40L) and interleukin (IL)-22 by LTi cells was higher in chronically inflamed tonsils. The treatment for tonsillitis with ibuprofen did not alter LTi cell viability and the expression of OX40L and IL-22. These results demonstrate that during chronic inflammation, LTi cells are increased and express higher levels of OX40L and IL-22, and this is correlated with an increase in memory CD4 T cells.

  11. Pedi-cap color change precedes a significant increase in heart rate during neonatal resuscitation.

    Science.gov (United States)

    Blank, Doug; Rich, Wade; Leone, Tina; Garey, Donna; Finer, Neil

    2014-11-01

    Heart rate is the most important indicator of infant well-being during neonatal resuscitation. The Nellcor Pedi-Cap turns gold when exposed to exhaled gas with CO₂>15 mmHg. The aim of this study was to determine if Pedi-Cap gold color change during neonatal resuscitation precedes an increase in heart rate in babies with bradycardia receiving mask ventilation. This was a single-center retrospective review of video recordings and physiologic data of newborns with bradycardia receiving mask positive pressure ventilation during neonatal resuscitation. Subjects were included if the baby's HRCap gold color change compared to the HR after Pedi-Cap gold color change. Forty-one newborns during the study period had HRCap. The median heart rate 10s prior to Pedi-Cap gold color change was 75 BPM (IQR 62-85) and increased to 136 BPM (IQR 113-158) 30 s after gold color change (pCap gold color change to 52 ± 17% 30s after gold color change (p=0.001). Colorimetric CO₂ detection during mask positive pressure ventilation in neonatal resuscitation precedes a significant increase in heart rate and SpO₂. The Pedi-Cap can be easily applied during resuscitation, requires no electricity, provides immediate feedback and may be a useful, simple tool early in resuscitation and may be especially useful in resource limited settings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  12. Adenovirus respiratory infection: significant increase in diagnosis using PCR comparing with antigen detection and culture methods

    Directory of Open Access Journals (Sweden)

    Elenice Stroparo

    2010-12-01

    Full Text Available Adenovirus (AdV respiratory infections are usually described as being associated with high mortality rates. Laboratory diagnosis is essential for the establishment of the appropriate therapy, and for guiding the implementation of preventive measures in order to prevent the spread of the infection. Aiming to analyze the sensitivity and specificity of the laboratorial diagnosis methods available, we compared antigen detection by indirect immunofluorescence assay (IF, and a specific nested polymerase chain reaction (PCR, to detect AdV in respiratory samples collected from patients admitted to hospital with acute respiratory disease. Positive samples were inoculated into a cell culture to confirm the results. We analyzed 381 samples from the nasopharyngeal aspirates collected during the year 2008; of these, 2.6% tested were positive for adenovirus through IF and 10% through PCR; positive isolation was obtained in 40% and 26% of these cases, respectively. Most infected patients were children under six months of age, and despite of the fact that a significant number of patients required intensive care, the mortality rate was low (5%. In conclusion, molecular methods were found to be useful for rapid diagnosis of adenovirus infections with higher sensitivity than antigen detection; their introduction permitted a significant increase in diagnoses of adenovirus infections.

  13. [Significant increase in the colonisation of Staphylococcus aureus among medical students during their hospital practices].

    Science.gov (United States)

    Rodríguez-Avial, Carmen; Alvarez-Novoa, Andrea; Losa, Azucena; Picazo, Juan J

    2013-10-01

    Staphylococcus aureus is a pathogen of major concern. The emergence of methicillin-resistant S. aureus (MRSA) has increasingly complicated the therapeutic approach of hospital-acquired infections. Surveillance of MRSA and control measures must be implemented in different healthcare settings, including screening programs for carriers. Our first aim was to determine the prevalence of methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage in medical students from the Clínico San Carlos Hospital (Madrid). As the MRSA carrier rate in healthcare workers is higher than in the general population, we hypothesised that carrier rate could be increased during their clinical practice in their last three years. We performed an epidemiologic al study of the prevalence of S. aureus colonisation among a group of medical students, who were sampled in 2008 in their third-year, and in 2012 when this class was in its sixth year. We have found a significant increase in MSSA carriage, from 27% to 46%. There were no MRSA colonisations in the third-year, but one was found in the sixth-year group. The large majority of strains (89%) of strains were resistant to penicillin, and 27% to erythromycin and clindamycin. As 19 coagulase-negative Staphylococcus MR were also identified, a horizontal transfer of genes, such as mecA gene to S. aureus, could have occurred. Medical students are both, at risk for acquiring, and a potential source of nosocomial pathogens, mainly MSSA. Therefore, they should take special care for hygienic precautions, such as frequent and proper hand washing, while working in the hospital. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  14. Inhibition of H3K4me2 Demethylation Protects Auditory Hair Cells from Neomycin-Induced Apoptosis.

    Science.gov (United States)

    He, Yingzi; Yu, Huiqian; Cai, Chengfu; Sun, Shan; Chai, Renjie; Li, Huawei

    2015-08-01

    Aminoglycoside-induced hair cell loss is a major cause of hearing impairment in children and deserves more attention in medical research. Epigenetic mechanisms have been shown to protect hair cells from ototoxic drugs. In this study, we focused on the role of dimethylated histone H3K4 (H3K4me2) in hair cell survival. To investigate the effects of lysine-specific demethylase 1 (LSD1)--the histone demethylase primarily responsible for demethylating H3K4me2--on neomycin-induced hair cell loss, isolated cochleae were pretreated with LSD1 inhibitors followed by neomycin exposure. There was a severe loss of hair cells in the organ of Corti after neomycin exposure, and inhibition of LSD1 significantly protected against neomycin-induced hair cell loss. H3K4me2 expression in the nuclei of hair cells decreased after exposure to neomycin, and blocking the decreased expression of H3K4me2 with LSD1 inhibitors prevented hair cell loss. Local delivery of these inhibitors in vivo also protected hair cells from neomycin-induced ototoxicity and maintained the hearing threshold in mice as determined by auditory brain stem response. This inhibition of neomycin-induced apoptosis occurs via reduced caspase-3 activation. Together, our findings demonstrate the protective role for H3K4me2 against neomycin-induced hair cell loss and hearing loss.

  15. Subcurative radiation significantly increases cell proliferation, invasion, and migration of primary glioblastoma multiforme in vivo

    Institute of Scientific and Technical Information of China (English)

    Adarsh Shankar; Robert A. Knight; Stephen Brown; Ali S. Arbab; Sanath Kumar; Asm Iskander; Nadimpalli RS Varma; Branislava Janic; Ana deCarvalho; Tom Mikkelsen; Joseph A. Frank; Meser M. Ali

    2014-01-01

    Tumor cellproliferation, infiltration, migration, and neovascularization are known causes of treatment resistance in glioblastoma multiforme (GBM). The purpose of this study was to determine the effect of radiation on the growth characteristics of primary human GBM developed in a nude rat. Primary GBM cells grown from explanted GBM tissues were implanted orthotopically in nude rats. Tumor growth was confirmed by magnetic resonance imaging on day 77 (baseline) after implantation. The rats underwent irradiation to a dose of 50 Gy delivered subcuratively on day 84 postimplantation (n= 8), or underwent no radiation (n= 8). Brain tissues were obtained on day 112 (nonirradiated) or day 133 (irradiated). Immunohistochemistry was performed to determine tumor cell proliferation (Ki-67) and to assess the expression of infiltration marker (matrix metalloproteinase-2, MMP-2) and cell migration marker (CD44). Tumor neovascularization was assessed by microvessel density using von-Willebrand factor (vWF) staining. Magnetic resonance imaging showed well-developed, infiltrative tumors in 11 weeks postimplantation. The proportion of Ki-67-positive cells in tumors undergoing radiation was (71 ± 15)%compared with (25 ± 12)%in the nonirradiated group (P=0.02). The number of MMP-2-positive areas and proportion of CD44-positive cells were also high in tumors receiving radiation, indicating great invasion and infiltration. Microvessel density analysis did not show a significant difference between nonirradiated and irradiated tumors. Taken together, we found that subcurative radiation significantly increased proliferation, invasion, and migration of primary GBM. Our study provides insights into possible mechanisms of treatment resistance fol owing radiation therapy for GBM.

  16. Myriocin significantly increases the mortality of a non-mammalian model host during Candida pathogenesis.

    Directory of Open Access Journals (Sweden)

    Nadja Rodrigues de Melo

    Full Text Available Candida albicans is a major human pathogen whose treatment is challenging due to antifungal drug toxicity, drug resistance and paucity of antifungal agents available. Myrocin (MYR inhibits sphingosine synthesis, a precursor of sphingolipids, an important cell membrane and signaling molecule component. MYR also has dual immune suppressive and antifungal properties, potentially modulating mammalian immunity and simultaneously reducing fungal infection risk. Wax moth (Galleria mellonella larvae, alternatives to mice, were used to establish if MYR suppressed insect immunity and increased survival of C. albicans-infected insects. MYR effects were studied in vivo and in vitro, and compared alone and combined with those of approved antifungal drugs, fluconazole (FLC and amphotericin B (AMPH. Insect immune defenses failed to inhibit C. albicans with high mortalities. In insects pretreated with the drug followed by C. albicans inoculation, MYR+C. albicans significantly increased mortality to 93% from 67% with C. albicans alone 48 h post-infection whilst AMPH+C. albicans and FLC+C. albicans only showed 26% and 0% mortalities, respectively. MYR combinations with other antifungal drugs in vivo also enhanced larval mortalities, contrasting the synergistic antifungal effect of the MYR+AMPH combination in vitro. MYR treatment influenced immunity and stress management gene expression during C. albicans pathogenesis, modulating transcripts putatively associated with signal transduction/regulation of cytokines, I-kappaB kinase/NF-kappaB cascade, G-protein coupled receptor and inflammation. In contrast, all stress management gene expression was down-regulated in FLC and AMPH pretreated C. albicans-infected insects. Results are discussed with their implications for clinical use of MYR to treat sphingolipid-associated disorders.

  17. Free ammonia pre-treatment of secondary sludge significantly increases anaerobic methane production.

    Science.gov (United States)

    Wei, Wei; Zhou, Xu; Wang, Dongbo; Sun, Jing; Wang, Qilin

    2017-07-01

    Energy recovery in the form of methane from sludge/wastewater is restricted by the poor and slow biodegradability of secondary sludge. An innovative pre-treatment technology using free ammonia (FA, i.e. NH3) was proposed in this study to increase anaerobic methane production. The solubilisation of secondary sludge was significantly increased after FA pre-treatment at up to 680 mg NH3-N/L for 1 day, under which the solubilisation (i.e. 0.4 mg SCOD/mg VS; SCOD: soluble chemical oxygen demand; VS: volatile solids) was >10 times higher than that without FA pre-treatment (i.e. 0.03 mg SCOD/mg VS). Biochemical methane potential assays showed that FA pre-treatment at above 250 mg NH3-N/L is effective in improving anaerobic methane production. The highest improvement in biochemical methane potential (B0) and hydrolysis rate (k) was achieved at FA concentrations of 420-680 mg NH3-N/L, and was determined as approximately 22% (from 160 to 195 L CH4/kg VS added) and 140% (from 0.22 to 0.53 d(-1)) compared to the secondary sludge without pre-treatment. More analysis revealed that the FA induced improvement in B0 and k could be attributed to the rapidly biodegradable substances rather than the slowly biodegradable substances. Economic and environmental analyses showed that the FA-based technology is economically favourable and environmentally friendly. Since this FA technology aims to use the wastewater treatment plants (WWTPs) waste (i.e. anaerobic digestion liquor) to enhance methane production from the WWTPs, it will set an example for the paradigm shift of the WWTPs from 'linear economy' to 'circular economy'. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Significantly increased risk of carotid atherosclerosis with arsenic exposure and polymorphisms in arsenic metabolism genes

    Energy Technology Data Exchange (ETDEWEB)

    Hsieh, Yi-Chen [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Lien, Li-Ming [Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Medicine, Taipei Medical University, Taipei, Taiwan (China); Department of Neurology, Shin Kong WHS Memorial Hospital, Taipei, Taiwan (China); Chung, Wen-Ting [Department of Neurology, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan (China); Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan (China); Hsieh, Fang-I; Hsieh, Pei-Fan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Graduate Institute of Basic Medicine, College of Medicine, Fu-Jen Catholic University, Taipei, Taiwan (China); Tseng, Hung-Pin [Department of Neurology, Lotung Poh-Ai Hospital, I-Lan, Taiwan (China); Chiou, Hung-Yi, E-mail: hychiou@tmu.edu.tw [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, 250 Wusing St., Taipei 11031, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2011-08-15

    Individual susceptibility to arsenic-induced carotid atherosclerosis might be associated with genetic variations in arsenic metabolism. The purpose of this study is to explore the interaction effect on risk of carotid atherosclerosis between arsenic exposure and risk genotypes of purine nucleoside phosphorylase (PNP), arsenic (+3) methyltransferase (As3MT), and glutathione S-transferase omega 1 (GSTO1) and omega 2 (GSTO2). A community-based case-control study was conducted in northeastern Taiwan to investigate the arsenic metabolic-related genetic susceptibility to carotid atherosclerosis. In total, 863 subjects, who had been genotyped and for whom the severity of carotid atherosclerosis had been determined, were included in the present study. Individual well water was collected and arsenic concentration determined using hydride generation combined with flame atomic absorption spectrometry. The result showed that a significant dose-response trend (P=0.04) of carotid atherosclerosis risk associated with increasing arsenic concentration. Non-significant association between genetic polymorphisms of PNP Gly51Ser, Pro57Pro, As3MT Met287Thr, GSTO1 Ala140Asp, and GSTO2 A-183G and the risk for development of carotid atherosclerosis were observed. However, the significant interaction effect on carotid atherosclerosis risk was found for arsenic exposure (>50 {mu}g/l) and the haplotypes of PNP (p=0.0115). A marked elevated risk of carotid atherosclerosis was observed in subjects with arsenic exposure of >50 {mu}g/l in drinking water and those who carried the PNP A-T haplotype and at least either of the As3MT risk polymorphism or GSTO risk haplotypes (OR, 6.43; 95% CI, 1.79-23.19). In conclusion, arsenic metabolic genes, PNP, As3MT, and GSTO, may exacerbate the formation of atherosclerosis in individuals with high levels of arsenic concentration in well water (>50 {mu}g/l). - Highlights: {yields}Arsenic metabolic genes might be associated with carotid atherosclerosis. {yields

  19. Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.

    Science.gov (United States)

    Arlt, W; Haas, J; Callies, F; Reincke, M; Hübler, D; Oettel, M; Ernst, M; Schulte, H M; Allolio, B

    1999-06-01

    The most abundant human steroids, dehydroepiandrosterone (DHEA) and its sulfate ester DHEAS, may have a multitude of beneficial effects, but decline with age. DHEA possibly prevents immunosenescence, and as a neuroactive steroid it may influence processes of cognition and memory. Epidemiological studies revealed an inverse correlation between DHEAS levels and the incidence of cardiovascular disease in men, but not in women. To define a suitable dose for DHEA substitution in elderly men we studied pharmacokinetics and biotransformation of orally administered DHEA in 14 healthy male volunteers (mean age, 58.8 +/- 5.1 yr; mean body mass index, 25.5 +/- 1.5 kg/m2) with serum DHEAS concentrations below 4.1 micromol/L (1500 ng/mL). Diurnal blood sampling was performed on 3 occasions in a single dose, randomized, cross-over design (oral administration of placebo, 50 mg DHEA, or 100 mg DHEA). The intake of 50 mg DHEA led to an increase in serum DHEAS to mean levels of young adult men, whereas 100 mg DHEA induced supraphysiological concentrations [placebo vs. 50 mg DHEA vs. 100 mg DHEA; area under the curve (AUC) 0-12 h (mean +/- SD) for DHEA, 108 +/- 22 vs. 252 +/- 45 vs. 349 +/- 72 nmol/L x h; AUC 0-12 h for DHEAS, 33 +/- 9 vs. 114 +/- 19 vs. 164 +/- 36 micromol/L x h]. Serum testosterone and dihydrotestosterone remained unchanged after DHEA administration. In contrast, 17beta-estradiol and estrone significantly increased in a dose-dependent manner to concentrations still within the upper normal range for men [placebo vs. 50 mg DHEA vs. 100 mg DHEA; AUC 0-12 h for 17beta-estradiol, 510 +/- 198 vs. 635 +/- 156 vs. 700 +/- 209 pmol/L x h (P DHEA seems to be a suitable substitution dose in elderly men, as it leads to serum DHEAS concentrations usually measured in young healthy adults. The DHEA-induced increase in circulating estrogens may contribute to beneficial effects of DHEA in men.

  20. Scaling of surface-plasma reactors with a significantly increased energy density for NO conversion.

    Science.gov (United States)

    Malik, Muhammad Arif; Xiao, Shu; Schoenbach, Karl H

    2012-03-30

    Comparative studies revealed that surface plasmas developing along a solid-gas interface are significantly more effective and energy efficient for remediation of toxic pollutants in air than conventional plasmas propagating in air. Scaling of the surface plasma reactors to large volumes by operating them in parallel suffers from a serious problem of adverse effects of the space charges generated at the dielectric surfaces of the neighboring discharge chambers. This study revealed that a conductive foil on the cathode potential placed between the dielectric plates as a shield not only decoupled the discharges, but also increased the electrical power deposited in the reactor by a factor of about forty over the electrical power level obtained without shielding and without loss of efficiency for NO removal. The shield had no negative effect on efficiency, which is verified by the fact that the energy costs for 50% NO removal were about 60 eV/molecule and the energy constant, k(E), was about 0.02 L/J in both the shielded and unshielded cases.

  1. Penguins significantly increased phosphine formation and phosphorus contribution in maritime Antarctic soils.

    Science.gov (United States)

    Zhu, Renbin; Wang, Qing; Ding, Wei; Wang, Can; Hou, Lijun; Ma, Dawei

    2014-11-14

    Most studies on phosphorus cycle in the natural environment focused on phosphates, with limited data available for the reduced phosphine (PH3). In this paper, matrix-bound phosphine (MBP), gaseous phosphine fluxes and phosphorus fractions in the soils were investigated from a penguin colony, a seal colony and the adjacent animal-lacking tundra and background sites. The MBP levels (mean 200.3 ng kg(-1)) in penguin colony soils were much higher than those in seal colony soils, animal-lacking tundra soils and the background soils. Field PH3 flux observation and laboratory incubation experiments confirmed that penguin colony soils produced much higher PH3 emissions than seal colony soils and animal-lacking tundra soils. Overall high MBP levels and PH3 emissions were modulated by soil biogeochemical processes associated with penguin activities: sufficient supply of the nutrients phosphorus, nitrogen, and organic carbon from penguin guano, high soil bacterial abundance and phosphatase activity. It was proposed that organic or inorganic phosphorus compounds from penguin guano or seal excreta could be reduced to PH3 in the Antarctic soils through the bacterial activity. Our results indicated that penguin activity significantly increased soil phosphine formation and phosphorus contribution, thus played an important role in phosphorus cycle in terrestrial ecosystems of maritime Antarctica.

  2. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels

    Energy Technology Data Exchange (ETDEWEB)

    Kucharski, TJ; Ferralis, N; Kolpak, AM; Zheng, JO; Nocera, DG; Grossman, JC

    2014-04-13

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol(-1), and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

  3. Templated assembly of photoswitches significantly increases the energy-storage capacity of solar thermal fuels.

    Science.gov (United States)

    Kucharski, Timothy J; Ferralis, Nicola; Kolpak, Alexie M; Zheng, Jennie O; Nocera, Daniel G; Grossman, Jeffrey C

    2014-05-01

    Large-scale utilization of solar-energy resources will require considerable advances in energy-storage technologies to meet ever-increasing global energy demands. Other than liquid fuels, existing energy-storage materials do not provide the requisite combination of high energy density, high stability, easy handling, transportability and low cost. New hybrid solar thermal fuels, composed of photoswitchable molecules on rigid, low-mass nanostructures, transcend the physical limitations of molecular solar thermal fuels by introducing local sterically constrained environments in which interactions between chromophores can be tuned. We demonstrate this principle of a hybrid solar thermal fuel using azobenzene-functionalized carbon nanotubes. We show that, on composite bundling, the amount of energy stored per azobenzene more than doubles from 58 to 120 kJ mol(-1), and the material also maintains robust cyclability and stability. Our results demonstrate that solar thermal fuels composed of molecule-nanostructure hybrids can exhibit significantly enhanced energy-storage capabilities through the generation of template-enforced steric strain.

  4. Factors associated with an increased risk of vertebral fracture in monoclonal gammopathies of undetermined significance.

    Science.gov (United States)

    Piot, J M; Royer, M; Schmidt-Tanguy, A; Hoppé, E; Gardembas, M; Bourrée, T; Hunault, M; François, S; Boyer, F; Ifrah, N; Renier, G; Chevailler, A; Audran, M; Chappard, D; Libouban, H; Mabilleau, G; Legrand, E; Bouvard, B

    2015-08-28

    Monoclonal gammopathies of undetermined significance (MGUS) have been shown to be associated with an increased risk of fractures. This study describes prospectively the bone status of MGUS patients and determines the factors associated with vertebral fracture. We included prospectively 201 patients with MGUS, incidentally discovered, and with no known history of osteoporosis: mean age 66.6±12.5 years, 48.3% women, 51.7% immunoglobulin G (IgG), 33.3% IgM and 10.4% IgA. Light chain was kappa in 64.2% patients. All patients had spinal radiographs and bone mineral density measurement in addition to gammopathy assessment. At least one prevalent non-traumatic vertebral fracture was discovered in 18.4% patients and equally distributed between men and women. Fractured patients were older, had a lower bone density and had also more frequently a lambda light chain isotype. Compared with patients with κ light chain, the odds ratio of being fractured for patients with λ light chain was 4.32 (95% confidence interval 1.80-11.16; P=0.002). These results suggest a high prevalence of non-traumatic vertebral fractures in MGUS associated with lambda light chain isotype and not only explained by low bone density.

  5. Processes involved in assisted reproduction technologies significantly increase sperm DNA fragmentation and phosphatidylserine translocation.

    Science.gov (United States)

    Balasuriya, A; Serhal, P; Doshi, A; Harper, J C

    2014-03-01

    Sperm preparation techniques in assisted reproduction technologies (ART) are potential generators of exogenous stresses that cause additional DNA damage. DNA fragmentation tests, such as the sperm chromatin structure assay, involve freezing sperm samples in the absence of cryoprotectant. Thermal, oxidative stress (OS) and freezing are detrimental to sperm DNA fragmentation and phosphatidylserine (PS) translocation. The primary aim of this study was to subject mature sperm to environmental insults that normally occur during ART. We tested the hypotheses that OS, thermal stress and freeze-thawing caused sperm nuclear and membrane damage and that a positive correlation exists between PS translocation and DNA fragmentation. Sperm DNA integrity deteriorates in semen samples from men with advancing age and a sperm concentration of DNA fragmentation at 37 °C after merely 1 h is important clinically as semen liquefaction and short-term sperm storage in an ART cycle involve incubating samples at this temperature. Freezing without a cryoprotectant significantly increases the level of sperm nuclear damage, so it is important not to freeze neat semen prior to DNA fragmentation testing. This study highlights the importance of minimising the production of exogenous stresses during sperm preparation in ART. © 2012 Blackwell Verlag GmbH.

  6. Penguins significantly increased phosphine formation and phosphorus contribution in maritime Antarctic soils

    Science.gov (United States)

    Zhu, Renbin; Wang, Qing; Ding, Wei; Wang, Can; Hou, Lijun; Ma, Dawei

    2014-01-01

    Most studies on phosphorus cycle in the natural environment focused on phosphates, with limited data available for the reduced phosphine (PH3). In this paper, matrix-bound phosphine (MBP), gaseous phosphine fluxes and phosphorus fractions in the soils were investigated from a penguin colony, a seal colony and the adjacent animal-lacking tundra and background sites. The MBP levels (mean 200.3 ng kg−1) in penguin colony soils were much higher than those in seal colony soils, animal-lacking tundra soils and the background soils. Field PH3 flux observation and laboratory incubation experiments confirmed that penguin colony soils produced much higher PH3 emissions than seal colony soils and animal-lacking tundra soils. Overall high MBP levels and PH3 emissions were modulated by soil biogeochemical processes associated with penguin activities: sufficient supply of the nutrients phosphorus, nitrogen, and organic carbon from penguin guano, high soil bacterial abundance and phosphatase activity. It was proposed that organic or inorganic phosphorus compounds from penguin guano or seal excreta could be reduced to PH3 in the Antarctic soils through the bacterial activity. Our results indicated that penguin activity significantly increased soil phosphine formation and phosphorus contribution, thus played an important role in phosphorus cycle in terrestrial ecosystems of maritime Antarctica. PMID:25394572

  7. The Role of H3K4me3 in Transcriptional Regulation Is Altered in Huntington's Disease.

    Directory of Open Access Journals (Sweden)

    Xianjun Dong

    Full Text Available Huntington's disease (HD is an autosomal-dominant neurodegenerative disorder resulting from expansion of CAG repeats in the Huntingtin (HTT gene. Previous studies have shown mutant HTT can alter expression of genes associated with dysregulated epigenetic modifications. One of the most widely studied chromatin modifications is trimethylated lysine 4 of histone 3 (H3K4me3. Here, we conducted the first comprehensive study of H3K4me3 ChIP-sequencing in neuronal chromatin from the prefrontal cortex of six HD cases and six non-neurologic controls, and its association with gene expression measured by RNA-sequencing. We detected 2,830 differentially enriched H3K4me3 peaks between HD and controls, with 55% of them down-regulated in HD. Although H3K4me3 signals are expected to be associated with mRNA levels, we found an unexpected discordance between altered H3K4me3 peaks and mRNA levels. Gene ontology (GO term enrichment analysis of the genes with differential H3K4me3 peaks, revealed statistically significantly enriched GO terms only in the genes with down-regulated signals in HD. The most frequently implicated biological process terms are organ morphogenesis and positive regulation of gene expression. More than 9,000 H3K4me3 peaks were located not near any recognized transcription start sites and approximately 36% of these "distal" peaks co-localized to known enhancer sites. Six transcription factors and chromatin remodelers are differentially enriched in HD H3K4me3 distal peaks, including EZH2 and SUZ12, two core subunits of the polycomb repressive complex 2 (PRC2. Moreover, PRC2 repressive state was significantly depleted in HD-enriched peaks, suggesting the epigenetic role of PRC2 inhibition associated with up-regulated H3K4me3 in Huntington's disease. In summary, our study provides new insights into transcriptional dysregulation of Huntington's disease by analyzing the differentiation of H3K4me3 enrichment.

  8. Association of MAP4K4 gene single nucleotide polymorphism with mastitis and milk traits in Chinese Holstein cattle.

    Science.gov (United States)

    Bhattarai, Dinesh; Chen, Xing; Ur Rehman, Zia; Hao, Xingjie; Ullah, Farman; Dad, Rahim; Talpur, Hira Sajjad; Kadariya, Ishwari; Cui, Lu; Fan, Mingxia; Zhang, Shujun

    2017-02-01

    The objective of the studies presented in this Research Communication was to investigate the association of single nucleotide polymorphisms present in the MAP4K4 gene with different milk traits in dairy cows. Based on previous QTL fine mapping results on bovine chromosome 11, the MAP4K4 gene was selected as a candidate gene to evaluate its effect on somatic cell count and milk traits in ChineseHolstein cows. Milk production traits including milk yield, fat percentage, and protein percentage of each cow were collected using 305 d lactation records. Association between MAP4K4 genotype and different traits and Somatic Cell Score (SCS) was performed using General Linear Regression Model of R. Two SNPs at exon 18 (c.2061T > G and c.2196T > C) with genotype TT in both SNPs were found significantly higher for somatic SCS. We found the significant effect of exon 18 (c.2061T > G) on protein percentage, milk yield and SCS. We identified SNPs at different location of MAP4K4 gene of the cattle and several of them were significantly associated with the somatic cell score and other different milk traits. Thus, MAP4K4 gene could be a useful candidate gene for selection of dairy cattle against mastitis and the identified polymorphisms might potentially be strong genetic markers.

  9. The H3K4me3/2 histone demethylase RBR-2 controls axon guidance by repressing the actin-remodeling gene wsp-1

    DEFF Research Database (Denmark)

    Mariani, Luca; Lussi, Yvonne C.; Vandamme, Julien;

    2016-01-01

    . Here, we show that RBR-2, the sole homolog of the KDM5 family of H3K4me3/2 demethylases in Caenorhabditis elegans, ensures correct axon guidance by controlling the expression of the actin regulator wsp-1. Loss of rbr-2 results in increased levels of H3K4me3 at the transcriptional start site of wsp-1...

  10. Significant increase in residual DNA damage as a possible mechanism of radiosensitization by gemcitabine

    Energy Technology Data Exchange (ETDEWEB)

    Weiss, C. [Dept. of Radiation Oncology, Friedrich Alexander Univ. of Erlangen-Nuernberg, Erlangen (Germany); Div. of Radiobiology, Friedrich Alexander Univ. of Erlangen-Nuernberg, Erlangen (Germany); Grabenbauer, G.G.; Sauer, R. [Dept. of Radiation Oncology, Friedrich Alexander Univ. of Erlangen-Nuernberg, Erlangen (Germany); Distel, L. [Div. of Radiobiology, Friedrich Alexander Univ. of Erlangen-Nuernberg, Erlangen (Germany)

    2003-02-01

    Purpose: To investigate the effect of gemcitabine (dFdC), a promising radiosensitizing nucleoside analog, on the induction and repair of DNA double-strand breaks (dsbs) after ionizing radiation (RT) in a pancreatic tumor cell line. Material and Methods: BxPC3 pancreatic tumor cells were treated using different concentrations of gemcitabine with and without subsequent irradiation. DNA dsbs were detected by constant-field gel electrophoresis under neutral conditions. Results: With the addition of gemcitabine (0.5-1,000 {mu}mol/l for 2 h prior to RT) to RT (0-75 Gy), a considerable and dose-dependent increase of remaining DNA damage after 24 h (5.4-fold for 0.5 {mu}mol/l dFdC, 12.2-fold for 1,000 {mu}mol/l dFdC at 25 Gy) was noted. Enhancement factors were inversely correlated with increasing X-ray dose (7.8-fold for 0.5 {mu}mol/l dFdC at 1 Gy decreasing to 1.6-fold at 75 Gy). Conversely, the induction of DNA dsbs was not affected. Gemcitabine alone lead to a slight increase of initial DNA dsbs and only a modest elevation of residual DNA damage. Conclusion: These findings strengthen the hypothesis of DNA repair inhibition as a major mechanism of radiosensitization by gemcitabine. (orig.)

  11. Gene-gene interaction and RNA splicing profiles of MAP2K4 gene in rheumatoid arthritis.

    Science.gov (United States)

    Shchetynsky, Klementy; Protsyuk, Darya; Ronninger, Marcus; Diaz-Gallo, Lina-Marcela; Klareskog, Lars; Padyukov, Leonid

    2015-05-01

    We performed gene-gene interaction analysis, with HLA-DRB1 shared epitope (SE) alleles for 195 SNPs within immunologically important MAP2K, MAP3K and MAP4K gene families, in 2010 rheumatoid arthritis (RA) patients and 2280 healthy controls. We found a significant statistical interaction for rs10468473 with SE alleles in autoantibody-positive RA. Individuals heterozygous for rs10468473 demonstrated higher expression of total MAP2K4 mRNA in blood, compared to A-allele homozygous. We discovered a novel, putatively translated, "cassette exon" RNA splice form of MAP2K4, differentially expressed in peripheral blood mononuclear cells from 88 RA cases and controls. Within the group of RA patients, we observed a correlation of MAP2K4 isoform expression with carried SE alleles, autoantibody, and rheumatoid factor profiles. TNF-dependent modulation of isoform expression pattern was detected in the Jurkat cell line. Our data suggest a genetic interaction between MAP2K4 and HLA-DRB1, and the importance of rs10468473 and MAP2K4 splice variants in the development of autoantibody-positive RA.

  12. Differential dynamics of histone H3 methylation at positions K4 and K9 in the mouse zygote

    Directory of Open Access Journals (Sweden)

    Walter Jörn

    2004-09-01

    Full Text Available Abstract Background In the mouse zygote the paternal genome undergoes dramatic structural and epigenetic changes. Chromosomes are decondensed, protamines replaced by histones and DNA is rapidly and actively demethylated. The epigenetic asymmetry between parental genomes remains at least until the 2-cell stage suggesting functional differences between paternal and maternal genomes during early cleavage stages. Results Here we analyzed the timing of histone deposition on the paternal pronucleus and the dynamics of histone H3 methylation (H3/K4mono-, H3/K4tri- and H3/K9di-methylation immediately after fertilization. Whereas maternal chromatin maintains all types of histone H3 methylation throughout the zygotic development, paternal chromosomes acquire new and unmodified histones shortly after fertilization. In the following hours we observe a gradual increase in H3/K4mono-methylation whereas H3/K4tri-methylation is not present before latest pronuclear stages. Histone H3/K9di-methylation is completely absent from the paternal pronucleus, including metaphase chromosomes of the first mitotic stage. Conclusion Parallel to the epigenetic asymmetry in DNA methylation, chromatin modifications are also different between both parental genomes in the very first hours post fertilization. Whereas methylation at H3/K4 gradually becomes similar between both genomes, H3/K9 methylation remains asymmetric.

  13. Over-expression of histone H3K4 demethylase gene JMJ15 enhances salt tolerance in Arabidopsis

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    Yuan eShen

    2014-06-01

    Full Text Available Histone H3 lysine 4 trimethylation (H3K4me3 has been shown to be involved in stress-responsive gene expression and gene priming in plants. However, the role of H3K4me3 resetting in the processes is not clear. In this work we studied the expression and function of Arabidopsis H3K4 demethylase gene JMJ15. We show that the expression of JMJ15 was relatively low and was limited to a number of tissues during vegetative growth but was higher in young floral organs. Over-expression of the gene in gain-of-function mutants reduced the plant height with accumulation of lignin in stems, while the loss-of-function mutation did not produce any visible phenotype. The gain-of-function mutants showed enhanced salt tolerance, whereas the loss-of-function mutant was more sensitive to salt compared to the wild type. Transcriptomic analysis revealed that over-expression of JMJ15 down-regulated many genes which are preferentially marked by H3K4me3 and H3K4me2. Many of the down-regulated genes encode transcription regulators involved in stress responses. The data suggest that increased JMJ15 levels may regulate the gene expression program that enhances stress tolerance.

  14. Strong Selection Significantly Increases Epistatic Interactions in the Long-Term Evolution of a Protein.

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    Aditi Gupta

    2016-03-01

    Full Text Available Epistatic interactions between residues determine a protein's adaptability and shape its evolutionary trajectory. When a protein experiences a changed environment, it is under strong selection to find a peak in the new fitness landscape. It has been shown that strong selection increases epistatic interactions as well as the ruggedness of the fitness landscape, but little is known about how the epistatic interactions change under selection in the long-term evolution of a protein. Here we analyze the evolution of epistasis in the protease of the human immunodeficiency virus type 1 (HIV-1 using protease sequences collected for almost a decade from both treated and untreated patients, to understand how epistasis changes and how those changes impact the long-term evolvability of a protein. We use an information-theoretic proxy for epistasis that quantifies the co-variation between sites, and show that positive information is a necessary (but not sufficient condition that detects epistasis in most cases. We analyze the "fossils" of the evolutionary trajectories of the protein contained in the sequence data, and show that epistasis continues to enrich under strong selection, but not for proteins whose environment is unchanged. The increase in epistasis compensates for the information loss due to sequence variability brought about by treatment, and facilitates adaptation in the increasingly rugged fitness landscape of treatment. While epistasis is thought to enhance evolvability via valley-crossing early-on in adaptation, it can hinder adaptation later when the landscape has turned rugged. However, we find no evidence that the HIV-1 protease has reached its potential for evolution after 9 years of adapting to a drug environment that itself is constantly changing. We suggest that the mechanism of encoding new information into pairwise interactions is central to protein evolution not just in HIV-1 protease, but for any protein adapting to a changing

  15. Longer duration of asthma is significantly associated with increased RV/TLC ratio.

    Science.gov (United States)

    Tiwari, Anupama; Rahman, Kazi; Abejie, Belayneh; Jain, Vipul V; Vempilly, Jose Joseph

    2017-03-01

    Although FEV1/FVC ratio has been shown to be negatively associated with longer duration of asthma; an association between RV/TLC ratio and longer duration of asthma has not been explored. Patients with established asthma for more than a year and met inclusion and exclusion criteria were recruited. Data obtained by questionnaire after informed consent was obtained, Pulmonary function tests and laboratory results were collected through chart review. Correlation and multiple linear regressions were used to analyze the data. Among the 93 subjects, 61 were women. The mean age of patients was 58 ± 15 years, and the mean duration of asthma was 21 ± 18 years. The ethnic composition included: Caucasians 64%, Hispanics 28% and other groups 8%. The FEV1/FVC ratio was not significantly associated with duration of asthma (R2 = 0.15, p = 0.05). However, the RV/TLC ratio was significantly associated with duration of asthma (R2 = 0.46, p TLC ratio may be a better indicator than FEV1/FVC ratio to detect airway obstruction related to longer duration of asthma. Lung volume measurements should be done in addition to spirometry to detect changes related to airway obstruction in patients with longer duration of asthma. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Rerouting end-face-TIR capable rays to significantly increase evanescent wave signal power

    Institute of Scientific and Technical Information of China (English)

    Jianjun Ma; Yasser Chiniforooshan; Huacai Chen; Jiahua Chen; Wojtek J. Bock; Andrea Cusano

    2011-01-01

    The critical findings associated with end-face total internal reflection (TIR) phenomemon we proved before are reported. In particular, these findings reveal that the end-face-TIR capable rays experience enormous mode mixing when encountering a roughened end face. As a result, 94% of the overall detectable power is contributed by this effect. With a smooth fiber end face, this figure is mere 52%. We interpret the mechanism behind these unusual phenomena and its significance for the performance enhancement of fiber optic evanescent wave sensor.%@@ The critical findings associated with end-face total internal reflection (TIR) phenomemon we proved before are reported, In particular, these findings reveal that the end-face-TIR capable rays experience enormous mode mixing when encountering a roughened end face.As a result, 94Vo of the overall detectable poweris contributed by this effect.With a smooth fiber end face, this figure is mere 52%.We interpret the mechanism behind these unusual phenomena and its significance for the performance enhancement of fiber optic evanescent wave sensor.

  17. Stromal p16 expression is significantly increased in malignant ovarian neoplasms.

    Science.gov (United States)

    Yoon, Nara; Yoon, Gun; Park, Cheol Keun; Kim, Hyun-Soo

    2016-10-04

    Alterations in p16 protein expression have been reported to be associated with tumor development and progression. However, p16 expression status in the peritumoral stroma has been rarely investigated. We investigated the stromal p16 expression in ovarian neoplasms using immunohistochemistry, and differences in the expression status depending on the degree of malignancy and histological type were analyzed. This study included 24, 21, and 46 cases of benign, borderline, and malignant ovarian lesions, respectively, of which 29, 25, and 32 cases were serous, mucinous, and endometriosis-associated lesions. Most benign lesions showed negative or weak expression, whereas borderline lesions showed focal, moderate expression. Malignant lesions showed markedly elevated stromal p16 expression compared with benign or borderline lesions. There were significant differences in stromal p16 expression between benign and borderline lesions (P p16 expression among the histological types were not significant. Stromal p16 expression in ovarian neoplasms was absent or weak in benign and focal, moderate in borderline lesions, whereas malignant lesions exhibited diffuse, moderate-to-strong p16 immunoreactivity. Our observations suggest that stromal p16 expression is involved in the development of ovarian carcinoma. Further studies are necessary to confirm our preliminary results.

  18. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication.

    Science.gov (United States)

    Atkinson, Helen C; Marsh, Julie A; Rath, Shoshana R; Kotecha, Rishi S; Gough, Hazel; Taylor, Mandy; Walwyn, Thomas; Gottardo, Nicholas G; Cole, Catherine H; Choong, Catherine S

    2015-01-01

    Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

  19. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication

    Directory of Open Access Journals (Sweden)

    Helen C. Atkinson

    2015-01-01

    Full Text Available Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL and treated with modern COG protocols (n=80 to determine longitudinal changes in body mass index (BMI and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5% were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P<0.004 for females but remained relatively unchanged for males (9.8% to 13.7%, P=0.7. Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P=0.0005, disease risk (P<0.0001, age (P=0.0001, and BMI z-score (P<0.0001 at diagnosis and total dose of steroid during maintenance (P=0.01. Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL.

  20. Significant increase of aerosol number concentrations in air masses crossing a densely trafficked sea area

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    Simonas Kecorius

    2016-01-01

    Full Text Available In this study, we evaluated 10 months data (September 2009 to June 2010 of atmospheric aerosol particle number size distribution at three atmospheric observation stations along the Baltic Sea coast: Vavihill (upwind, Sweden, Utö (upwind, Finland, and Preila (downwind, Lithuania. Differences in aerosol particle number size distributions between the upwind and downwind stations during situations of connected atmospheric flow, when the air passed each station, were used to assess the contribution of ship emissions to the aerosol number concentration (diameter interval 50–400 nm in the Lithuanian background coastal environment. A clear increase in particle number concentration could be noticed, by a factor of 1.9 from Utö to Preila (the average total number concentration at Utö was 791 cm−3, and by a factor of 1.6 from Vavihill to Preila (the average total number concentration at Vavihill was 998 cm−3. The simultaneous measurements of absorption Ångström exponents close to unity at Preila supported our conclusion that ship emissions in the Baltic Sea contributed to the increase in particle number concentration at Preila.

  1. Big data integration shows Australian bush-fire frequency is increasing significantly

    Science.gov (United States)

    Dutta, Ritaban; Das, Aruneema; Aryal, Jagannath

    2016-01-01

    Increasing Australian bush-fire frequencies over the last decade has indicated a major climatic change in coming future. Understanding such climatic change for Australian bush-fire is limited and there is an urgent need of scientific research, which is capable enough to contribute to Australian society. Frequency of bush-fire carries information on spatial, temporal and climatic aspects of bush-fire events and provides contextual information to model various climate data for accurately predicting future bush-fire hot spots. In this study, we develop an ensemble method based on a two-layered machine learning model to establish relationship between fire incidence and climatic data. In a 336 week data trial, we demonstrate that the model provides highly accurate bush-fire incidence hot-spot estimation (91% global accuracy) from the weekly climatic surfaces. Our analysis also indicates that Australian weekly bush-fire frequencies increased by 40% over the last 5 years, particularly during summer months, implicating a serious climatic shift. PMID:26998312

  2. Continuous Collection of Adeno-Associated Virus from Producer Cell Medium Significantly Increases Total Viral Yield.

    Science.gov (United States)

    Benskey, Matthew J; Sandoval, Ivette M; Manfredsson, Fredric P

    2016-02-01

    The ability to efficiently produce large amounts of high-titer recombinant adeno-associated virus (AAV) is a prerequisite to the continued success of AAV as a gene therapy tool targeted toward large-animal preclinical studies or human clinical therapeutics. Current manufacturing procedures necessitate laborious and time-consuming purification procedures to obtain AAV particles of sufficient titer and purity for these demanding biomedical applications. The finding that AAV can be harvested and purified from producer cell medium may represent an efficient alternative to purifying AAV from cellular lysates. Here we sought to determine the maximum duration of time, and frequency within which AAV can be harvested from producer cell medium, in order to maximize the yield obtained from a single transfection preparation. Human embryonic kidney 293T cells were transfected with polyethylenimine to produce AAV2/5 expressing green fluorescent protein (GFP), and cellular medium was harvested every 2 days until a maximum duration of 19 days posttransfection. AAV2/5-GFP was released into producer cell medium at a steady state until 7 days posttransfection, at which time titers dropped dramatically. Harvesting medium every two days resulted in the maximum yield of AAV from a single preparation, and the cumulative yield of AAV harvested from the producer cell medium was 4-fold higher than the yield obtained from a traditional purification of AAV from cellular lysates. The AAV2/5 harvested from medium within the 7-day collection time-course mediated high levels of transduction in vivo, comparable to AAV2/5 harvested from cellular lysates. AAV purified from cell lysates showed increasing amounts of empty particles at 5 and 7 days posttransfection, whereas AAV purified from cell medium did not show an increase in the amount of empty particles throughout the 7-day time course. Finally, we extended these findings to AAV2/9, demonstrating that a comparable ratio of AAV2/9 particles are

  3. Break dance significantly increases static balance in 9 years-old soccer players.

    Science.gov (United States)

    Ricotti, Leonardo; Ravaschio, Andrea

    2011-03-01

    Static balance in young athletes is an important ability that has a relevant influence on their present and future sport performances, as well as on the reduction in risk of injury. The present study reports data collected on three homogeneous groups of 9 years-old athletes (n=10 for each group), whose static balance was monitored every two months during an overall period of six months. At the beginning of the study, all of the children in each of the three groups were performing soccer activity with a frequency (three times a week) that was kept constant during the observation period. During the six months, group 1 maintained only the soccer activity, group 2 also performed swimming activity (twice a week) in parallel with the soccer activity, while group 3 started, at month 2, to perform soccer activity with a break dance course (twice a week). Double leg stance (with eyes open and closed) and single leg stance (on dominant and non-dominant leg) tests were performed using a force platform, and the COP area calculated for each trial. Results show a clear decrease in the "soccer+break dance" players COP area values during the six months, suggesting an improvement in their static balance. The difference was significantly greater with respect to that of soccer players and "soccer+swimming" players. This was evident in all the tests performed starting from two months after the break dance activity began.

  4. Increase of energy balance significantly alters major lipogenic gene expression in lactation ewes.

    Science.gov (United States)

    Laliotis, George P; Bizelis, Iosif; Vitsa, Alkistis; Rogdakis, Emmanuel

    2012-01-01

    The objective of the present study was to examine changes observed in the expression of cytosolic NADP isocitrate dehydrogenase (ICDH) and glucose 6-phosphate dehydrogenase (G6PD) genes, the major implicated genes in ruminant lipogenesis in terms of produce NADPH, during the early post-weaning period in dairy ewes in respect to energy intake, and to further correlate the noted changes with their respective enzymatic activities. A total of 21 subcutaneous adipose tissue samples were obtained from seven lactating (2nd lactation period) dairy ewes of the Chios breed. Adipose tissue samples were taken from the tail head region at weeks 1, 2, and 4 after weaning (45 days after parturition). Dairy ewes were in negative energy balance during weeks 1 and 2 after weaning and they moved into a strong positive energy balance at week 4 after weaning. Expression of ICDH and G6PD genes and their respective enzymatic activity was determined. Results showed that both genes' expression and enzymatic activities were significantly minimal at week 1 after weaning, reaching a maximum level at week 4 after weaning (P gene expression (P energy intake changes. Almost similar changes were observed for enzymatic activities, rendering these enzymes as potential biochemical markers of ovine lipogenesis. Copyright © Taylor & Francis Group, LLC

  5. Delaying diagnostic procedure significantly increases mortality in patients with invasive mucormycosis.

    Science.gov (United States)

    Jeong, Su Jin; Lee, Ji Un; Song, Young Goo; Lee, Kyoung Hwa; Lee, Min Joo

    2015-12-01

    Invasive mucormycosis is an uncommon but increasing life-threatening fungal infection. The present study investigated clinical characteristics and mortality among patients diagnosed as invasive mucormycosis infection. We retrospectively reviewed a total of 24 histologically proven cases of invasive mucormycosis at two tertiary care referral hospitals between November 2005 and February 2014. Overall survival was 50% (n = 12). The time between onset of symptom and diagnostic procedure proved to be associated with mortality (P = 0.009). In addition, preexisting renal failure and thrombocytopenia demonstrated trends toward a poor outcome in our study (P = 0.089 and 0.065, respectively). On multivariate regression analysis, delayed diagnostic procedure (more than 16 days after the onset of symptoms) was an independent predictor of mortality (OR= 12.34, 95% CI, 1.43-10.64; P = 0.022). Mucormycosis is a destructive fungal infection that is associated with high mortality rates, ranging from 40% to 100% depending on the form of disease. When a clinician suspects invasive mucormycosis infection, an early diagnostic procedure performed within 16 days from the onset of symptom and early initiation of antifungal therapy will lead to successful management of this highly fatal disease.

  6. Elicitor Mixtures Significantly Increase Bioactive Compounds, Antioxidant Activity, and Quality Parameters in Sweet Bell Pepper

    Directory of Open Access Journals (Sweden)

    Lina Garcia-Mier

    2015-01-01

    Full Text Available Sweet bell peppers are greatly appreciated for their taste, color, pungency, and aroma. Additionally, they are good sources of bioactive compounds with antioxidant activity, which can be improved by the use of elicitors. Elicitors act as metabolite-inducing factors (MIF by mimic stress conditions. Since plants rarely experience a single stress condition one by one but are more likely to be exposed to simultaneous stresses, it is important to evaluate the effect of elicitors on plant secondary metabolism as mixtures. Jasmonic acid (JA, hydrogen peroxide (HP, and chitosan (CH were applied to fruits and plants of bell pepper as mixtures. Bioactive compounds, antioxidant activity, and quality parameters were evaluated. The assessed elicitor cocktail leads to an increase in the variables evaluated (P ≤ 0.05 when applied to mature fruits after harvest, whereas the lowest values were observed in the treatment applied to immature fruits. Therefore, the application of the elicitor cocktail to harvested mature fruits is recommended in order to improve bioactive compounds and the antioxidant activity of sweet bell peppers.

  7. Significance of Increasing n-3 PUFA Content in Pork on Human Health.

    Science.gov (United States)

    Ma, Xianyong; Jiang, Zongyong; Lai, Chaoqiang

    2016-01-01

    Evidence for the health-promoting effects of food rich in n-3 polyunsaturated fatty acids (n-3 PUFA) is reviewed. Pork is an important meat source for humans. According to a report by the US Department of Agriculture ( http://www.ers.usda.gov/topics ), the pork consumption worldwide in 2011 was about 79.3 million tons, much higher than that of beef (48.2 million tons). Pork also contains high levels of unsaturated fatty acids relative to ruminant meats (Enser, M., Hallett, K., Hewett, B., Fursey, G. A. J. and Wood, J. D. (1996) . Fatty acid content and composition of English beef, lamb, and pork at retail. Meat Sci. 44:443-458). The available literature indicates that the levels of eicosatetraenoic and docosahexaenoic in pork may be increased by fish-derived or linseed products, the extent of which being dependent on the nature of the supplementation. Transgenic pigs and plants show promise with high content of n-3 PUFA and low ratio of n-6/n-3 fatty acids in their tissues. The approaches mentioned for decreasing n-6/n-3 ratios have both advantages and disadvantages. Selected articles are critically reviewed and summarized.

  8. Epigenetics and sex differences in the brain: A genome-wide comparison of histone-3 lysine-4 trimethylation (H3K4me3) in male and female mice.

    Science.gov (United States)

    Shen, Erica Y; Ahern, Todd H; Cheung, Iris; Straubhaar, Juerg; Dincer, Aslihan; Houston, Isaac; de Vries, Geert J; Akbarian, Schahram; Forger, Nancy G

    2015-06-01

    Many neurological and psychiatric disorders exhibit gender disparities, and sex differences in the brain likely explain some of these effects. Recent work in rodents points to a role for epigenetics in the development or maintenance of neural sex differences, although genome-wide studies have so far been lacking. Here we review the existing literature on epigenetics and brain sexual differentiation and present preliminary analyses on the genome-wide distribution of histone-3 lysine-4 trimethylation in a sexually dimorphic brain region in male and female mice. H3K4me3 is a histone mark primarily organized as 'peaks' surrounding the transcription start site of active genes. We microdissected the bed nucleus of the stria terminalis and preoptic area (BNST/POA) in adult male and female mice and used ChIP-Seq to compare the distribution of H3K4me3 throughout the genome. We found 248 genes and loci with a significant sex difference in H3K4me3. Of these, the majority (71%) had larger H3K4me3 peaks in females. Comparisons with existing databases indicate that genes and loci with increased H3K4me3 in females are associated with synaptic function and with expression atlases from related brain areas. Based on RT-PCR, only a minority of genes with a sex difference in H3K4me3 has detectable sex differences in expression at baseline conditions. Together with previous findings, our data suggest that there may be sex biases in the use of epigenetic marks. Such biases could underlie sex differences in vulnerabilities to drugs or diseases that disrupt specific epigenetic processes. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. Factors affecting early elementary (K--4) teachers' introduction of the nature of science: A national survey

    Science.gov (United States)

    Sweeney, Sophia Jean

    A researcher-developed questionnaire regarding the importance and developmental appropriateness of 12 specific elements of the nature of science (Alshamrani, 2008) for early elementary (kindergarten through fourth grade [K-4]) science instruction was mailed to a random sample of U.S. K-4 teachers. At least half (N = 377) of the respondents reported introducing the inferential, empirical, creative, collaborative, tentative, and cultural aspects of the nature of science (NOS) during the current school year, as well as the idea that no single step-by-step scientific method exists. Over 90% of respondents identified the inferential, empirical, and creative aspects of the NOS as developmentally appropriate for the grade level taught. Based on a 5 point scale (0=not at all important and 4 =very important), the mean scores of eight NOS elements were above a value of three, which corresponded with the descriptor somewhat important to include in K-4 science instruction: the inferential, empirical, creative, collaborative, cultural, and tentative NOS, along with the ideas that replication is an important aspect of experimental research and that no single stepwise scientific method exists. A series of binary logistic regression analyses were used to explore the impact of three predictor variables (developmental appropriateness, importance, and presence in state standards) on teachers' self-reported introduction of each of the NOS elements during the 2009-2010 school year. The data for the presence of the NOS elements in state standards were extracted from a previous study (McComas, Lee, & Sweeney, 2009). Developmental appropriateness was a significant predictor of teachers' introduction of the NOS element for all except the collaborative, empirical and inferential aspects of NOS. Importance was a significant predictor for all 12 NOS elements of interest. A NOS element's presence in the state standards significantly predicted teachers' introduction of that NOS element for only

  10. Analisis Cakupan Antenatal Care K4 Program Kesehatan Ibu dan Anak di Wilayah Kerja Dinas Kesehatan Kabupaten Padang Pariaman

    Directory of Open Access Journals (Sweden)

    Elmispendriya Gusna

    2016-01-01

    objective of this study was to analyze K4 antenatal care scope of maternal and child program in Padang Pariaman health department working area. This is a mixed of quantitative and qualitative study. The subject of quantitative study was 49 village midwives and informant of qualitative study was: chief of family health and chief of maternal child health of  Padang Pariaman health department; chief, maternal and child program coordinator, and administrator midwife of Sungai Limau public health care. The results of this study were more than half (53.1% of village midwives have low levels of motivation, while more than half (67.3% of coordinator midwives have been doing supervision to village midwives. There was no significant relationship of village midwives motivation and coordinator midwives supervision with K4 antenatal care scope (p < 0.05. Analysis of the result showed K4 antenatal care scope of maternal and child program in Padang Pariaman has not succeded yet caused by lack of active role of village midwives, minimum monitoring and evaluation from health department and public health care of Padang Pariaman and coordinator midwives, lack of optimalized role of human resources and lack of infrastructure. Keywords: complete visits (K4 antenatal care scope, motivation, supervision

  11. Impaired removal of H3K4 methylation affects cell fate determination and gene transcription

    DEFF Research Database (Denmark)

    Lussi, Yvonne C; Mariani, Luca; Rundsten, Carsten Friis;

    2016-01-01

    implicated in development, but how the regulation of H3K4me3 level controls developmental processes is not fully established. Here, we show that the H3K4 demethylase RBR-2, the unique member of the KDM5 family in C. elegans, acts cell-autonomously and in a catalytic-dependent manner to control vulva...

  12. The GluK4 kainate receptor subunit regulates memory, mood, and excitotoxic neurodegeneration.

    Science.gov (United States)

    Lowry, E R; Kruyer, A; Norris, E H; Cederroth, C R; Strickland, S

    2013-04-01

    Though the GluK4 kainate receptor subunit shows limited homology and a restricted expression pattern relative to other kainate receptor subunits, its ablation results in distinct behavioral and molecular phenotypes. GluK4 knockout mice demonstrated impairments in memory acquisition and recall in a Morris water maze test, suggesting a previously unreported role for kainate receptors in spatial memory. GluK4 knockout mice also showed marked hyperactivity and impaired pre-pulse inhibition, thereby mirroring two of the hallmark endophenotypes of patients with schizophrenia and bipolar disorder. Furthermore, we found that GluK4 is a key mediator of excitotoxic neurodegeneration: GluK4 knockout mice showed robust neuroprotection in the CA3 region of the hippocampus following intrahippocampal injection of kainate and widespread neuroprotection throughout the hippocampus following hypoxia-ischemia. Biochemical analysis of kainate- or sham-treated wild-type and GluK4 knockout hippocampal tissue suggests that GluK4 may act through the JNK pathway to regulate the molecular cascades that lead to excitotoxicity. Together, our findings suggest that GluK4 may be relevant to the understanding and treatment of human neuropsychiatric and neurodegenerative disorders.

  13. [Synthesis, spectral analysis and photocatalysis of Ag/K4Nb6,O17 heterojunction catalysts].

    Science.gov (United States)

    Zhang, Feng-li; Cao, Yan-ning; Ying, Song; Chen, Rong; Zhang, Han-hui; Zheng, Qi

    2010-10-01

    K4Nb6O17 photocatalyst was successfully synthesized by low-temperature hydrothermal method with layer structure. Considering that a large number of hydroxyl (Nb-OH) and oxygen species (Nb==O, Nb--O-) exist on the surface of K4Nb6O17 synthesized by hydrothermal method, Ag(en)2+ precursors were employed to synthesize Ag/K4Nb6O17 heterostructure photo-catalysts with highly dispersed Ag. Photocatalytic performance evaluation results show that the photodegradation rate of MO for K4Nb6O17 was remarkably improved when a small amont of Ag was loaded. The best loading dose of Ag is 0.5 at%. Based on various characterizations results of XRD, FTIR, UV-Vis DRS, XRF and TEM, the photocatalytic mechanism of Ag/ K4Nb6O17 heterostructure catalysts was illuminated in detail and the conclusions were drawn as follows: (1) K4Nb6O17 nanocrystals serve as electron and hole sources for degradation of an organic dye; (2) Ag nanoparticles on the surface of K4Nb6O17 nanocrystals act as a sink for the electrons, promote interfacial charge-transfer kinetics between the metal and semiconductor, improve the separation of photogenerated electron-hole pairs, and thus enhance the photocatalytic activity of Ag/K4Nb6O17 photocatalyst.

  14. Re-patterning of H3K27me3, H3K4me3 and DNA methylation during fibroblast conversion into induced cardiomyocytes

    Directory of Open Access Journals (Sweden)

    Ziqing Liu

    2016-03-01

    Full Text Available Direct conversion of fibroblasts into induced cardiomyocytes (iCMs offers an alternative strategy for cardiac disease modeling and regeneration. During iCM reprogramming, the starting fibroblasts must overcome existing epigenetic barriers to acquire the CM-like chromatin pattern. However, epigenetic dynamics along this reprogramming process have not been studied. Here, we took advantage of our recently generated polycistronic system and determined the dynamics of two critical histone marks, H3K27me3 and H3K4me3, in parallel with gene expression at a set of carefully selected cardiac and fibroblast loci during iCM reprogramming. We observed reduced H3K27me3 and increased H3K4me3 at cardiac promoters as early as day 3, paralleled by a rapid significant increase in their mRNA expression. In contrast, H3K27me3 at loci encoding fibroblast marker genes did not increase until day 10 and H3K4me3 progressively decreased along the reprogramming process; these changes were accompanied by a gradual decrease in the mRNA expression of fibroblast marker genes. Further analyses of fibroblast-enriched transcription factors revealed a similarly late deposition of H3K27me3 and decreased mRNA expression of Sox9, Twist1 and Twist2, three important players in epithelial−mesenchymal transition. Our data suggest early rapid activation of the cardiac program and later progressive suppression of fibroblast fate at both epigenetic and transcriptional levels. Additionally, we determined the DNA methylation states of representative cardiac promoters and found that not every single CpG was equally demethylated during early stages of iCM reprogramming. Rather, there are specific CpGs, whose demethylation states correlated tightly with transcription activation, that we propose are the major contributing CpGs. Our work thus reveals a differential re-patterning of H3K27me3, H3K4me3 at cardiac and fibroblast loci during iCM reprogramming and could provide future genome

  15. Light Fractionation Significantly Increases the Efficacy of Photodynamic Therapy Using BF-200 ALA in Normal Mouse Skin.

    NARCIS (Netherlands)

    H.S. de Bruijn (Riette); S. Brooks (Sander); A. van der Ploeg-van den Heuvel (Angélique); T.L.M. ten Hagen (Timo); E.R.M. de Haas (Ellen); D.J. Robinson (Dominic)

    2016-01-01

    markdownabstractBACKGROUND: Light fractionation significantly increases the efficacy of 5-aminolevulinic acid (ALA) based photodynamic therapy (PDT) using the nano-emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several

  16. DVIG ENERGETSKE UČINKOVITOSTI PREMOGOVNEGA KOTLA K4 V TOVARNI VIPAP

    OpenAIRE

    Lekše, Aleš

    2014-01-01

    Diplomsko delo se nanaša na znižanje lastne rabe energije na postrojenju kotla K4 ter na dvig deleža pridobljene energije iz OVE v podjetju Vipap Videm Krško. Na podlagi ugotovitev, da so izvedeni ukrepi znižali lastno rabo električne energije, večji delež OVE v strukturi goriva pa je zagotovil željeno toplotno moč kotla K4, nam zaključni del naloge potrjuje, da so vsi izvedeni ukrepi upravičili ekonomsko in ekološko upravičenost posodobitve postrojenja kotla K4.

  17. On a $\\{K_4,L(Q_3)\\}_{K_3}$-ultrahomogeneous graph

    CERN Document Server

    Dejter, Italo J

    2010-01-01

    A construction based on the Biggs-Smith graph is shown to produce an edge-disjoint union of 102 copies of $K_4$ forming a $\\{K_4,L(Q_3)\\}_{K_3}$-ultrahomogeneous graph as well as the non-line-graphical Menger graph of a self-dual $(102_4)$-configuration. This stands in contrast to and is a follow-up of the self-dual $(42_4)$-configuration of \\cite{D1}, whose Menger graph is a non-line-graphical $\\{K_4,$ $K_{2,2,2}\\}_{K_2}$-ultrahomogeneous graph.

  18. Characterization and analysis of Devonian shales as related to release of gaseous hydrocarbons. Well K-4 Johnson County, Kentucky

    Energy Technology Data Exchange (ETDEWEB)

    Kalyoncu, R.S.; Snyder, M.J.

    1979-08-15

    Various characterization tasks were performed on 54 cored shale samples from Johnson County, Kentucky. Core samples were obtained from depths of 967 to 1510 feet. A total of 126 samples were canned for several DOE contractors, including Battelle Columbus. Free gas analyses indicate the presence of significant quantities of higher chain hydrocarbon gases in the K-4 shales. Hydrocarbon gas release rates and kinetic studies indicate that diffusion coefficients are inversely proportional to the square root of the molecular weight of diffusing species. Although wide scatter is observed in the chemical and physical characterization data, good correlations exist between the hydrocarbon gas contents and various laboratory characterization values (physical and chemical). A number of one-to-one relationships are pointed out and discussed. Lithologically, inorganic portions of K-4 shales are composed predominantly of quartz and illite with small quantities of pyrite and various carbonate minerals.

  19. Triglyceride content in remnant lipoproteins is significantly increased after food intake and is associated with plasma lipoprotein lipase.

    Science.gov (United States)

    Nakajima, Katsuyuki; Tokita, Yoshiharu; Sakamaki, Koji; Shimomura, Younosuke; Kobayashi, Junji; Kamachi, Keiko; Tanaka, Akira; Stanhope, Kimber L; Havel, Peter J; Wang, Tao; Machida, Tetsuo; Murakami, Masami

    2017-02-01

    Previous large population studies reported that non-fasting plasma triglyceride (TG) reflect a higher risk for cardiovascular disease than TG in the fasting plasma. This is suggestive of the presence of higher concentration of remnant lipoproteins (RLP) in postprandial plasma. TG and RLP-TG together with other lipids, lipoproteins and lipoprotein lipase (LPL) in both fasting and postprandial plasma were determined in generally healthy volunteers and in patients with coronary artery disease (CAD) after consuming a fat load or a more typical moderate meal. RLP-TG/TG ratio (concentration) and RLP-TG/RLP-C ratio (particle size) were significantly increased in the postprandial plasma of both healthy controls and CAD patients compared with those in fasting plasma. LPL/RLP-TG ratio demonstrated the interaction correlation between RLP concentration and LPL activity The increased RLP-TG after fat consumption contributed to approximately 90% of the increased plasma TG, while approximately 60% after a typical meal. Plasma LPL in postprandial plasma was not significantly altered after either type of meal. Concentrations of RLP-TG found in the TG along with its particle size are significantly increased in postprandial plasma compared with fasting plasma. Therefore, non-fasting TG determination better reflects the presence of higher RLP concentrations in plasma. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  20. St. John's wort significantly increased the systemic exposure and toxicity of methotrexate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Shih-Ying [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China); Juang, Shin-Hun [Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China); Tsai, Shang-Yuan; Chao, Pei-Dawn Lee [School of Pharmacy, China Medical University, Taichung, Taiwan (China); Hou, Yu-Chi, E-mail: hou5133@gmail.com [School of Pharmacy, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical University Hospital, Taichung, Taiwan (China)

    2012-08-15

    St. John's wort (SJW, Hypericum perforatum) is one of the popular nutraceuticals for treating depression. Methotrexate (MTX) is an immunosuppressant with narrow therapeutic window. This study investigated the effect of SJW on MTX pharmacokinetics in rats. Rats were orally given MTX alone and coadministered with 300 and 150 mg/kg of SJW, and 25 mg/kg of diclofenac, respectively. Blood was withdrawn at specific time points and serum MTX concentrations were assayed by a specific monoclonal fluorescence polarization immunoassay method. The results showed that 300 mg/kg of SJW significantly increased the AUC{sub 0−t} and C{sub max} of MTX by 163% and 60%, respectively, and 150 mg/kg of SJW significantly increased the AUC{sub 0−t} of MTX by 55%. In addition, diclofenac enhanced the C{sub max} of MTX by 110%. The mortality of rats treated with SJW was higher than that of controls. In conclusion, coadministration of SJW significantly increased the systemic exposure and toxicity of MTX. The combined use of MTX with SJW would need to be with caution. -- Highlights: ► St. John's wort significantly increased the AUC{sub 0−t} and C{sub max} of methotrexate. ► Coadministration of St. John's wort increased the exposure and toxicity of methotrexate. ► The combined use of methotrexate with St. John's wort will need to be with caution.

  1. Significant social events and increasing use of life-sustaining treatment: trend analysis using extracorporeal membrane oxygenation as an example.

    Science.gov (United States)

    Chen, Yen-Yuan; Chen, Likwang; Huang, Tien-Shang; Ko, Wen-Je; Chu, Tzong-Shinn; Ni, Yen-Hsuan; Chang, Shan-Chwen

    2014-03-04

    Most studies have examined the outcomes of patients supported by extracorporeal membrane oxygenation as a life-sustaining treatment. It is unclear whether significant social events are associated with the use of life-sustaining treatment. This study aimed to compare the trend of extracorporeal membrane oxygenation use in Taiwan with that in the world, and to examine the influence of significant social events on the trend of extracorporeal membrane oxygenation use in Taiwan. Taiwan's extracorporeal membrane oxygenation uses from 2000 to 2009 were collected from National Health Insurance Research Dataset. The number of the worldwide extracorporeal membrane oxygenation cases was mainly estimated using Extracorporeal Life Support Registry Report International Summary July 2012. The trend of Taiwan's crude annual incidence rate of extracorporeal membrane oxygenation use was compared with that of the rest of the world. Each trend of extracorporeal membrane oxygenation use was examined using joinpoint regression. The measurement was the crude annual incidence rate of extracorporeal membrane oxygenation use. Each of the Taiwan's crude annual incidence rates was much higher than the worldwide one in the same year. Both the trends of Taiwan's and worldwide crude annual incidence rates have significantly increased since 2000. Joinpoint regression selected the model of the Taiwan's trend with one joinpoint in 2006 as the best-fitted model, implying that the significant social events in 2006 were significantly associated with the trend change of extracorporeal membrane oxygenation use following 2006. In addition, significantly social events highlighted by the media are more likely to be associated with the increase of extracorporeal membrane oxygenation use than being fully covered by National Health Insurance. Significant social events, such as a well-known person's successful extracorporeal membrane oxygenation use highlighted by the mass media, are associated with the use of

  2. A study on directions of significant efficiency increase of rock fracture by tools equipped with super hard inserts from composite

    Science.gov (United States)

    Dvornikov, L. T.; Klishin, V. I.; Nikitenko, S. M.; Korneyev, V. A.; Korneyev, P. A.

    2016-10-01

    In the paper the directions of a significant increase in effectiveness of mine rocks destruction by tools equipped with super hard inserts from composite materials are reviewed and justified. Designs of mining drill bits with the cutting insert in the form of elliptical Cassinian oval and the asymmetric ring cleaves are suggested. Versions of laboratory stand constructions are developed in order to determine the power consumption of rock destruction.

  3. Depletion of CD25+ cells during acute toxoplasmosis does not significantly increase mortality in Swiss OF1 mice

    Directory of Open Access Journals (Sweden)

    Haroon Akbar

    2012-03-01

    Full Text Available The interleukin (IL-2R alpha chain (CD25 is expressed on regulatory T cells (Treg, which constitute more than 85% of the CD25+ T cell population in a naïve mouse. CD25 is also expressed on effector T cells in mice suffering from an acute infection by the obligate intracellular protozoan parasite, Toxoplasma gondii. Lethal toxoplasmosis is accompanied by a significant loss of Treg in mice naturally susceptible to toxoplasmosis. The present study was done to explore the role of Treg cells using an anti-CD25 antibody-mediated depletion in mice naturally resistant to toxoplasmosis. Although a significant decrease in the percentage of Treg cells was observed following anti-CD25 monoclonal antibody injections, the depletion of CD25+ cells during acute toxoplasmosis did not significantly increase the mortality of Swiss OF1 mice and no significant difference was observed in the brain parasitic load between the mice in the depleted-infected and isotype-infected groups. We found no significant difference between the titres of total IgG in the sera of the mice from the two groups in the chronic phase. However, CD25+ cells depletion was followed by significantly higher levels of IL-12 in the serum of depleted mice than in that of mice injected with the isotype control antibody.

  4. Cellular Membrane Composition Requirement by Antimicrobial and Anticancer Peptide GA-K4.

    Science.gov (United States)

    Mishig-Ochir, Tsogbadrakh; Gombosuren, Davaadulam; Jigjid, Altanchimeg; Tuguldur, Badamkhatan; Chuluunbaatar, Galbadrakh; Urnukhsaikhan, Enerelt; Pathak, Chinar; Lee, Bong-Jin

    2017-01-01

    Naturally occurring antimicrobial peptides important for innate immunity are widely studied for their antimicrobial and anticancer activity. The primary target of these AMPs is believed to be the bacterial cytoplasmic membrane. However, the interaction between cytoplasmic membrane and the antimicrobial peptides remains poorly understood. Therefore to focus on the target membrane composition that is required by AMPs to interact with membranes, we have examined the interaction of the antimicrobial and anticancer active 11-residue GA-K4 (FLKWLFKWAKK) peptide with model and intact cell membranes. Effect on the structural conformational properties of GA-K4 peptide was investigated by means of far-UV CD and fluorescence spectroscopic methods. The different conformation of GA-K4 peptide in large unilamellar vesicles (LUV) bilayer and micelle environment suggest that the curvature has an influence on the secondary structure acquired by the peptide. Furthermore, the leakage experiment result confirmed that GA-K4 induced the leakage of cytoplasmic membrane in Staphylococcus аureus bacterial cells. Fluorescence data revealed the interfacial location of GA-K4 peptide in the model membranes. The blue-shift in emission wavelength by tryptophan residues in fluorescence data indicated the penetration of GA-K4 peptide in micelles and phospholipid bilayers. These results showed that the GA-K4 peptide is a membrane-active peptide and its activity depends on membrane curvature and lipid composition. Although further studies are required to confirm the mechanism of action, the data suggest mechanism of toroidal pore formation for the interaction of GA-K4 peptide with membranes. Our studies will be helpful in better understanding of the membrane requirment of peptides to express their therapeutic effects. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  5. Weissella paramesenteroides WpK4 reduces gene expression of intestinal cytokines, and hepatic and splenic injuries in a murine model of typhoid fever.

    Science.gov (United States)

    Alvim, L B; Sandes, S H C; Silva, B C; Steinberg, R S; Campos, M H A; Acurcio, L B; Arantes, R M E; Nicoli, J R; Neumann, E; Nunes, Á C

    2016-02-01

    Diarrhoea in piglets by Salmonella and other pathogens can be a serious health problem. Non-drug treatments such as probiotic microorganisms have various effects on the gastrointestinal microbiota dysbiosis and host immune system modulation. The aim of this study was to demonstrate the suitable use of Weissella paramesenteroides WpK4 strain isolated from healthy piglets as an alternative prophylactic or therapeutic treatment against Salmonella Typhimurium. Out of 37 lactic acid bacteria isolates, 24 strains belonging to the Weissella and Lactobacillus genera were analysed in vitro for desirable probiotic characteristics. The W. paramesenteroides WpK4 strain fulfilled all in vitro tests: resistance to acidic pH and bile salts, hydrophobic cell surface, antagonism against bacterial pathogens, H2O2 production and exopolysaccharide secretion, and non-transferable resistance to antibiotics. Mice fed with WpK4 showed no signs of bacterial translocation to the liver or spleen and decreased Salmonella translocation to these organs. Significantly, WpK4 intake attenuated the weight loss, fostered the preservation of intestinal architecture and integrity, and promoted survival in mice following infection with Salmonella Typhimurium. In addition, WpK4 modulated immune cellular response by inhibiting the production of pro-inflammatory cytokines and inducing anti-inflammatory mediators. These findings validate the probiotic properties of W. paramesenteroides WpK4 strain, and its eventual use in piglets.

  6. CFP1 Regulates Histone H3K4 Trimethylation and Developmental Potential in Mouse Oocytes

    Directory of Open Access Journals (Sweden)

    Chao Yu

    2017-08-01

    Full Text Available Trimethylation of histone H3 at lysine-4 (H3K4me3 is associated with eukaryotic gene promoters and poises their transcriptional activation during development. To examine the in vivo function of H3K4me3 in the absence of DNA replication, we deleted CXXC finger protein 1 (CFP1, the DNA-binding subunit of the SETD1 histone H3K4 methyltransferase, in developing oocytes. We find that CFP1 is required for H3K4me3 accumulation and the deposition of histone variants onto chromatin during oocyte maturation. Decreased H3K4me3 in oocytes caused global downregulation of transcription activity. Oocytes lacking CFP1 failed to complete maturation and were unable to gain developmental competence after fertilization, due to defects in cytoplasmic lattice formation, meiotic division, and maternal-zygotic transition. Our study highlights the importance of H3K4me3 in continuous histone replacement for transcriptional regulation, chromatin remodeling, and normal developmental progression in a non-replicative system.

  7. Acyclic chromatic indices of K4-minor free graphs%没有K4-图子式的图的无圈边色数

    Institute of Scientific and Technical Information of China (English)

    王维凡; 舒巧君

    2011-01-01

    一个图G的无圈k-边染色是指G的一个正常的不产生双色圈的k-边染色.G的无圈边色数a1(G)定义为使得G有一个无圈k-边染色的最小的整数k.本文完全刻画了最大度不为4的没有K4-图子式的图的无圈边色数.%An acyclic edge coloring of a graph G is a proper edge coloring such that no Dichromatic cycles are produced. The acyclic chromatic index a'(G) of G is the smallest integer k such that G has an acyclic edge coloring using k colors. In this paper, we determine completely the acyclic chromatic indices of K4-minor free graphs with maximum degree not equal to 4.

  8. Reduced brain levels of DHEAS in hepatic coma patients: significance for increased GABAergic tone in hepatic encephalopathy.

    Science.gov (United States)

    Ahboucha, Samir; Talani, Giuseppe; Fanutza, Tomas; Sanna, Enrico; Biggio, Giovanni; Gamrani, Halima; Butterworth, Roger F

    2012-07-01

    Increased neurosteroids with allosteric modulatory activity on GABA(A) receptors such as 3α-5α tertrahydroprogesterone; allopregnanolone (ALLO), are candidates to explain the phenomenon of "increased GABAergic tone" in hepatic encephalopathy (HE). However, it is not known how changes of other GABA(A) receptor modulators such as dehydroepiandrosterone sulfate (DHEAS) contribute to altered GABAergic tone in HE. Concentrations of DHEAS were measured by radioimmunoassay in frontal cortex samples obtained at autopsy from 11 cirrhotic patients who died in hepatic coma and from an equal number of controls matched for age, gender, and autopsy delay intervals free from hepatic or neurological diseases. To assess whether reduced brain DHEAS contributes to increased GABAergic tone, in vitro patch clamp recordings in rat prefrontal cortex neurons were performed. A significant reduction of DHEAS (5.81±0.88 ng/g tissue) compared to control values (9.70±0.79 ng/g, puremic coma (12.56 ng/g tissue) were within the control range. Increasing ALLO enhances GABAergic tonic currents concentration-dependently, but increasing DHEAS reduces these currents. High concentrations of DHEAS (50 μM) reduce GABAergic tonic currents in the presence of ALLO, whereas reduced concentrations of DHEAS (1 μM) further stimulate these currents. These findings demonstrate that decreased concentrations of DHEAS together with increased brain concentrations of ALLO increase GABAergic tonic currents synergistically; suggesting that reduced brain DHEAS could further increase GABAergic tone in human HE. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. K4, K9 and K18 in human histone H3 are targets for biotinylation by biotinidase.

    Science.gov (United States)

    Kobza, Keyna; Camporeale, Gabriela; Rueckert, Brian; Kueh, Alice; Griffin, Jacob B; Sarath, Gautam; Zempleni, Janos

    2005-08-01

    Histones are modified post-translationally, e.g. by methylation of lysine and arginine residues, and by phosphorylation of serine residues. These modifications regulate processes such as gene expression, DNA repair, and mitosis and meiosis. Recently, evidence has been provided that histones are also modified by covalent binding of the vitamin biotin. The aims of this study were to identify biotinylation sites in histone H3, and to investigate the crosstalk among histone biotinylation, methylation and phosphorylation. Synthetic peptides based on the sequence of human histone H3 were used as substrates for enzymatic biotinylation by biotinidase; biotin in peptides was probed using streptavidin peroxidase. These studies provided evidence that K4, K9 and K18 in histone H3 are good targets for biotinylation; K14 and K23 are relatively poor targets. Antibodies were generated to histone H3, biotinylated either at K4, K9 or K18. These antibodies localized to nuclei in human placental cells in immunocytochemistry and immunoblotting experiments, suggesting that lysines in histone H3 are biotinylated in vivo. Dimethylation of R2, R8 and R17 increased biotinylation of K4, K9 and K18, respectively, by biotinidase; phosphorylation of S10 abolished biotinylation of K9. These observations are consistent with crosstalk between biotinylation of histones and other known modifications of histones. We speculate that this crosstalk provides a link to known roles for biotin in gene expression and cell proliferation.

  10. Significantly increased concentration of soluble urokinase-type plasminogen activator receptor in the blood of patients with pelvic inflammatory disease.

    Science.gov (United States)

    Yeh, Yuan-Hung; Wang, Po-Hui; Lin, Long-Yau; Tee, Yi-Torng; Chou, Ming-Chih; Yang, Shun-Fa; Tsai, Hsiu-Ting

    2013-01-16

    To determine expression levels of urokinase-type plasminogen activator (uPA), soluble urokinase-type plasminogen activator receptor (suPAR), plasminogen activator inhibitor-1 (PAI-1) in plasma and to identify gene polymorphisms specific to patients with pelvic inflammatory disease (PID) and healthy controls. Enzyme-linked immunosorbent assay and polymerase chain reaction-restriction fragment length polymorphism were used to measure plasma levels and polymorphisms in uPA, suPAR, and PAI-1 among seventy healthy controls and 64 PID patients before and after they received routine treatment protocols. The levels of plasma uPA (ng/ml) and soluble suPAR (pg/ml) were significantly increased in PID patients (uPA: 0.57±0.03; suPAR: 1372.04±68.20) when compared to that in normal controls (uPA: 0.55±0.06, p=0.002; suPAR: 1192.46±51.98, p=0.04); moreover, suPAR decreased significantly after treatment when compared to levels noted in the same patients (1220.06±58.14; p=0.003) after they received treatment. The increased expression of suPAR was significantly correlated with WBC counts (r=0.382, p=0.002, n=64) in blood as well as the plasma levels of CRP (r=0.441, ppelvic inflammatory disease. Copyright © 2012. Published by Elsevier B.V.

  11. Analysis of a large dataset of mycorrhiza inoculation field trials on potato shows highly significant increases in yield.

    Science.gov (United States)

    Hijri, Mohamed

    2016-04-01

    An increasing human population requires more food production in nutrient-efficient systems in order to simultaneously meet global food needs while reducing the environmental footprint of agriculture. Arbuscular mycorrhizal fungi (AMF) have the potential to enhance crop yield, but their efficiency has yet to be demonstrated in large-scale crop production systems. This study reports an analysis of a dataset consisting of 231 field trials in which the same AMF inoculant (Rhizophagus irregularis DAOM 197198) was applied to potato over a 4-year period in North America and Europe under authentic field conditions. The inoculation was performed using a liquid suspension of AMF spores that was sprayed onto potato seed pieces, yielding a calculated 71 spores per seed piece. Statistical analysis showed a highly significant increase in marketable potato yield (ANOVA, P < 0.0001) for inoculated fields (42.2 tons/ha) compared with non-inoculated controls (38.3 tons/ha), irrespective of trial year. The average yield increase was 3.9 tons/ha, representing 9.5 % of total crop yield. Inoculation was profitable with a 0.67-tons/ha increase in yield, a threshold reached in almost 79 % of all trials. This finding clearly demonstrates the benefits of mycorrhizal-based inoculation on crop yield, using potato as a case study. Further improvements of these beneficial inoculants will help compensate for crop production deficits, both now and in the future.

  12. Water in Comet 2/2003 K4 (LINEAR) with Spitzer

    CERN Document Server

    Woodward, Charles E; Bockelee-Morvan, Dominique; Gehrz, R D

    2007-01-01

    We present sensitive 5.5 to 7.6 micron spectra of comet C/2003 K4 (LINEAR) obtained on 16 July 2004 (r_{h} = 1.760 AU, Delta_{Spitzer} = 1.409 AU, phase angle 35.4 degrees) with the Spitzer Space Telescope. The nu_{2} vibrational band of water is detected with a high signal-to-noise ratio (> 50). Model fitting to the best spectrum yields a water ortho-to-para ratio of 2.47 +/- 0.27, which corresponds to a spin temperature of 28.5^{+6.5}_{-3.5} K. Spectra acquired at different offset positions show that the rotational temperature decreases with increasing distance from the nucleus, which is consistent with evolution from thermal to fluorescence equilibrium. The inferred water production rate is (2.43 +/- 0.25) \\times 10^{29} molec. s^{-1}. The spectra do not show any evidence for emission from PAHs and carbonate minerals, in contrast to results reported for comets 9P/Tempel 1 and C/1995 O1 (Hale-Bopp). However, residual emission is observed near 7.3 micron the origin of which remains unidentified.

  13. GSTT1 Null Genotype Significantly Increases the Susceptibility to Urinary System Cancer: Evidences from 63,876 Subjects.

    Science.gov (United States)

    Wang, Ying; He, Jing; Ma, Tian-Jiao; Lei, Wei; Li, Feng; Shen, Han; Shen, Zhen-Ya

    2016-01-01

    GSTT1 gene plays an important role in detoxification and clearance of reactive oxygen species(ROS). A null variant in this gene has been demonstrated to confer cancer susceptibility. Although many studies have demonstrated the association between GSTT1 null polymorphism and urinary system cancer susceptibility, several publications reported opposite conclusions. For better understanding the effects of this polymorphism on the risk of urinary system cancer, a updated meta-analysis was performed with a total of 26,666 cases and 37,210 controls extracted from 117 studies, by following the latest meta-analysis guidelines (PRISMA). The results suggested that the GSTT1 null genotype was significantly associated with an increased risk of urinary system cancer (OR=1.13, 95%CI=1.05-1.22). Furthermore, stratified analyses by the type of cancer, ethnicity, source of control and quality score presented a significantly increased risk associated with GSTT1 null genotype in bladder and prostate cancer subgroup, Caucasians and Indians subgroup, population-based(PB) subgroup, medium quality and low quality subgroup. Overall, our meta-analysis suggested that GSTT1 null genotype is a potential cancer susceptibility variant. Well-designed and large-cohort studies are needed to confirm the association between GSTT1 null genotype and urinary system cancer risk.

  14. Significance of increasing poverty levels for determining late-stage breast cancer diagnosis in 1990 and 2000.

    Science.gov (United States)

    Barry, Janis; Breen, Nancy; Barrett, Michael

    2012-08-01

    We examine the association between late-stage breast cancer diagnosis and residential poverty in Detroit, Atlanta, and San Francisco in 1990 and 2000. We tested whether residence in census tracts with increasing levels of poverty were associated with increased odds of a late-stage diagnosis in 1990 and 2000 and found that it was. To test this, we linked breast cancer cases from the Surveillance, Epidemiology, and End Results cancer registries with poverty data from the census. Tracts were grouped into low, moderate, and high poverty based on the percentage of households reporting income below the poverty level. While late-stage breast cancer rates and the number of women living in high and moderate-poverty areas declined absolutely between 1990 and 2000, estimates from our combined three-city model showed that odds of a late-stage diagnosis remained stubbornly elevated in increasingly poor areas in both years. Non-Hispanic black women faced higher odds of a late-stage diagnosis relative to non-Hispanic white women in both years. In separate regressions for each city, the odds ratios affirm that combining data across cities may be misleading. In 1990 and 2000, only women living in moderately poor neighborhoods of San Francisco faced elevated odds, while in Detroit women in both moderate- and high-poverty areas faced increased likelihood of late-stage diagnosis. In Atlanta, none of the poverty measures were significant in 1990 or 2000. In our test of physician supply on stage, an increase in the number of neighborhood primary care doctor's offices was associated with decreased odds of a late-stage diagnosis only for Detroit residents and for non-Hispanic whites in the three-city model.

  15. The adipokine leptin increases skeletal muscle mass and significantly alters skeletal muscle miRNA expression profile in aged mice

    Energy Technology Data Exchange (ETDEWEB)

    Hamrick, Mark W., E-mail: mhamrick@mail.mcg.edu [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Herberg, Samuel; Arounleut, Phonepasong [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); He, Hong-Zhi [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Shiver, Austin [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Qi, Rui-Qun [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Zhou, Li [Henry Ford Immunology Program, Henry Ford Health System, Detroit, MI (United States); Department of Dermatology, Henry Ford Health System, Detroit, MI (United States); Department of Internal Medicine, Henry Ford Health System, Detroit, MI (United States); Isales, Carlos M. [Department of Cellular Biology and Anatomy, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); Department of Orthopaedic Surgery, Institute of Molecular Medicine and Genetics, Medical College of Georgia, Augusta, GA (United States); and others

    2010-09-24

    Research highlights: {yields} Aging is associated with muscle atrophy and loss of muscle mass, known as the sarcopenia of aging. {yields} We demonstrate that age-related muscle atrophy is associated with marked changes in miRNA expression in muscle. {yields} Treating aged mice with the adipokine leptin significantly increased muscle mass and the expression of miRNAs involved in muscle repair. {yields} Recombinant leptin therapy may therefore be a novel approach for treating age-related muscle atrophy. -- Abstract: Age-associated loss of muscle mass, or sarcopenia, contributes directly to frailty and an increased risk of falls and fractures among the elderly. Aged mice and elderly adults both show decreased muscle mass as well as relatively low levels of the fat-derived hormone leptin. Here we demonstrate that loss of muscle mass and myofiber size with aging in mice is associated with significant changes in the expression of specific miRNAs. Aging altered the expression of 57 miRNAs in mouse skeletal muscle, and many of these miRNAs are now reported to be associated specifically with age-related muscle atrophy. These include miR-221, previously identified in studies of myogenesis and muscle development as playing a role in the proliferation and terminal differentiation of myogenic precursors. We also treated aged mice with recombinant leptin, to determine whether leptin therapy could improve muscle mass and alter the miRNA expression profile of aging skeletal muscle. Leptin treatment significantly increased hindlimb muscle mass and extensor digitorum longus fiber size in aged mice. Furthermore, the expression of 37 miRNAs was altered in muscles of leptin-treated mice. In particular, leptin treatment increased the expression of miR-31 and miR-223, miRNAs known to be elevated during muscle regeneration and repair. These findings suggest that aging in skeletal muscle is associated with marked changes in the expression of specific miRNAs, and that nutrient

  16. High cell density cultivation of Escherichia coli K4 in a microfiltration bioreactor: a step towards improvement of chondroitin precursor production

    Directory of Open Access Journals (Sweden)

    De Rosa Mario

    2011-02-01

    Full Text Available Abstract Background The bacteria Escherichia coli K4 produces a capsular polysaccharide (K4 CPS whose backbone is similar to the non sulphated chondroitin chain. The chondroitin sulphate is one of the major components of the extra-cellular matrix of the vertebrate connective tissues and a high value molecule, widely employed as active principle in the treatment of osteoarthritis. It is usually obtained by extraction from animal tissues, but the risk of virus contaminations, as well as the scarceness of raw material, makes this productive process unsafe and unable to satisfy the growing market demand. In previous studies a new biotechnological process to produce chondroitin from Escherichia coli K4 capsular polysaccharide was investigated and a 1.4 g·L-1 K4 CPS concentration was reached using fed-batch fermentation techniques. In this work, on the trail of these results, we exploited new fermentation strategies to further improve the capsular polysaccharide production. Results The inhibitory effect of acetate on the bacterial cells growth and K4 CPS production was studied in shake flask conditions, while a new approach, that combined the optimization of the feeding profiles, the improvement of aeration conditions and the use of a microfiltration bioreactor, was investigated in three different types of fermentation processes. High polysaccharide concentrations (4.73 ± 0.2 g·L-1, with corresponding average yields (0.13 ± 0.006 gK4 CPS·gcdw-1, were obtained; the increase of K4 CPS titre, compared to batch and fed-batch results, was of 16-fold and 3.3-fold respectively, while average yield was almost 3.5 and 1.4 fold higher. Conclusion The increase of capsular polysaccharide titre confirmed the validity of the proposed fermentation strategy and opened the way to the use of the microfiltration bioreactor for the biotechnological production of chondroitin.

  17. Medication of /-tetrahydropalmatine significantly ameliorates opiate craving and increases the abstinence rate in heroin users: a pilot study

    Institute of Scientific and Technical Information of China (English)

    Zheng YANG; Yong-cong SHAO; Shi-jiang LI; Jian-lin QI; Mei-jie ZHANG; Wei HAO; Guo-zhang JIN

    2008-01-01

    Aim: Drug addiction is a chronic brain disease with constant relapse requiring long-term treatment. New pharmacological strategies focus on the development of an effective antirelapse drug. This study examines the effects of levo-tetrahydropalmatine (l-THP) on reducing heroin craving and increasing the absti-nence rate among heroin-dependent patients. Methods: In total, 120 heroin-de-pendent patients participated in the randomized, double-blinded, and placebo-controlled study using l-THP treatment. The participants remained in a ward during a 4-week period of l-THP treatment, followed by 4 weeks of observation after treatment. The patients were followed for 3 months after discharge. Out-come measures are the measured severity of the protracted abstinence withdrawal syndrome (PAWS) and the abstinence rate. Results: Four weeks of l-THP treat-ment significantly ameliorated the severity of PAWS, specifically, somatic syndrome, mood states, insomnia, and drug craving, in comparison to the placebo group. Based on the 3 month follow-up observation, participants who survived the initial 2 weeks of I-THP medication and remained in the trial program had a significantly higher abstinence rate of 47.8% (95% confidence interval [CI]: 33%-67%) than the 15.2% in the placebo group (95% CI: 7%-25%), according to a log-rank test (P<0.0005). Conclusion: l-THP significantly ameliorated PAWS, espe-cially reducing drug craving. Furthermore, it increased the abstinence rate among heroin users. These results support the potential use of l-THP for the treatment of heroin addiction.

  18. Effect of fexofenadine,a mast cell blocker,in infertile men with significantly increased testicular mast cells

    Institute of Scientific and Technical Information of China (English)

    CayaS; ApaDD

    2002-01-01

    Aim:To investigate the role of fexofenadine,a mast cell blocker,on semen quality in the treatment of infertile men.Methods:The study included 16 Turkish idiopathic infertile men with azoospermia or oligozoospermia who underwent testicular biopsy to examine maxt cells containing tryptase.In all patients,a complete metical history,clinical examination,semen analysis and serum hormone assay were carried out.The biopsy specimens were immunohistochemically stained with antihuman tryptase for mast cells.The number of total mast cells per seminiferous tubule was calculated and recorded as mast cell index.The patients were divided into two groups according to their mast cell index:the higher (≥1,n=9) and the lower (<1,n=7) index groups.Fexofenadine was administered orally at a dose of 180mg/day for 4 to 9 months.Pre-and post-treatment semen parameters,including total motile sperm counts(TMC) were recorded and compared.spontaneous pregnancies after the treatment were registered.Results:There was no statistically significant difference in TMC between the pre-treatment and post-treatment values in patients with higher and lower mast cell index(P≥0.05).In both groups,nobody had a significant response to the treatment and there was no spontaneous pregnancy after the treatment.Conclusion:Althought testicular dysfunction is closely associated with increased number of testicular mast cells,fexofenadine,a mast cell blocker,appears not having any benefit in the treatment of Turkish infertile men with a significant increase in testicular mast cells.

  19. Prognostic significance of increased bone marrow microcirculation in newly diagnosed multiple myeloma: results of a prospective DCE-MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Merz, Maximilian; Hillengass, Jens [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Moehler, Thomas M.; Ritsch, Judith; Delorme, Stefan [Department of Radiology, German Cancer Research Center, Heidelberg (Germany); Baeuerle, Tobias [University of Erlangen-Nuremberg, Department of Radiology, Erlangen (Germany); Zechmann, Christian M. [Rinecker Proton Therapy, Muenchen (Germany); Wagner, Barbara; Hose, Dirk [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); Jauch, Anna [University of Heidelberg, Institute of Human Genetics, Heidelberg (Germany); Kunz, Christina; Hielscher, Thomas [German Cancer Research Center, Department of Biostatistics, Heidelberg (Germany); Laue, Hendrik [Fraunhofer MEVIS, Bremen (Germany); Goldschmidt, Hartmut [University of Heidelberg, Department of Hematology, Oncology and Rheumatology, Heidelberg (Germany); National Center for Tumor Diseases, Heidelberg (Germany)

    2016-05-15

    Aim of this prospective study was to investigate prognostic significance of increased bone marrow microcirculation as detected by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for survival and local complications in patients with multiple myeloma (MM). We performed DCE-MRI of the lumbar spine in 131 patients with newly diagnosed MM and analysed data according to the Brix model to acquire amplitude A and exchange rate constant k{sub ep}. In 61 patients a second MRI performed after therapy was evaluated to assess changes in vertebral height and identify vertebral fractures. Correlation analysis revealed significant positive association between beta2-microglobulin as well as immunoparesis with DCE-MRI parameters A and k{sub ep}. Additionally, A was negatively correlated with haemoglobin levels and k{sub ep} was positively correlated with LDH levels. Higher baseline k{sub ep} values were associated with decreased vertebral height in a second MRI (P = 0.007) and A values were associated with new vertebral fractures in the lower lumbar spine (P = 0.03 for L4). Pre-existing lytic bone lesions or remission after therapy had no impact on the occurrence of vertebral fractures. Multivariate analysis revealed that amplitude A is an independent adverse risk factor for overall survival. DCE-MRI is a non-invasive tool with significance for systemic prognosis and vertebral complications. (orig.)

  20. Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism.

    Science.gov (United States)

    Torres, Anthony R; Westover, Jonna B; Gibbons, Cole; Johnson, Randall C; Ward, David C

    2012-10-01

    Killer-cell immunoglobulin-like receptor (KIR) proteins are expressed on natural killer (NK) cells and appear important in innate and adaptive immunity. There are about 14 KIR genes on chromosome 19q13.4, composed of those that inhibit and those that activate NK cell killing. Haplotypes have different combinations of these genes meaning that not all genes are present in a subject. There are two main classes of cognate human leukocyte antigen (HLA) ligands (HLA-Bw4 and HLA-C1/C2) that bind to the inhibitory/activating receptors. As a general rule, the inhibitory state is maintained except when virally infected or tumor cells are encountered; however, both increased activation and inhibition states have been associated with susceptibility and protection against numerous disease states including cancer, arthritis, and psoriasis. Utilizing DNA from 158 Caucasian subjects with autism and 176 KIR control subjects we show for the first time a highly significant increase in four activating KIR genes (2DS5, 3DS1, 2DS1 and 2DS4) as measured by chi square values and odds ratios. In addition, our data suggests a highly significant increase in the activating KIR gene 2DS1 and its cognate HLA-C2 ligand (2DS1+C2; p = 0.00003 [Odds ratio = 2.87]). This information ties together two major immune gene complexes, the human leukocyte complex and the leukocyte receptor complex, and may partially explain immune abnormalities observed in many subjects with autism.

  1. Neurite outgrowth is significantly increased by the simultaneous presentation of Schwann cells and moderate exogenous electric fields.

    Science.gov (United States)

    Koppes, Abigail N; Seggio, Angela M; Thompson, Deanna M

    2011-08-01

    Axonal extension is influenced by a variety of external guidance cues; therefore, the development and optimization of a multi-faceted approach is probably necessary to address the intricacy of functional regeneration following nerve injury. In this study, primary dissociated neonatal rat dorsal root ganglia neurons and Schwann cells were examined in response to an 8 h dc electrical stimulation (0-100 mV mm(-1)). Stimulated samples were then fixed immediately, immunostained, imaged and analyzed to determine Schwann cell orientation and characterize neurite outgrowth relative to electric field strength and direction. Results indicate that Schwann cells are viable following electrical stimulation with 10-100 mV mm(-1), and retain a normal morphology relative to unstimulated cells; however, no directional bias is observed. Neurite outgrowth was significantly enhanced by twofold following exposure to either a 50 mV mm(-1) electric field (EF) or co-culture with unstimulated Schwann cells by comparison to neurons cultured alone. Neurite outgrowth was further increased in the presence of simultaneously applied cues (Schwann cells + 50 mV mm(-1) dc EF), exhibiting a 3.2-fold increase over unstimulated control neurons, and a 1.2-fold increase over either neurons cultured with unstimulated Schwann cells or the electrical stimulus alone. These results indicate that dc electric stimulation in combination with Schwann cells may provide synergistic guidance cues for improved axonal growth relevant to nerve injuries in the peripheral nervous system.

  2. Increased expression of long intergenic non-coding RNA LINC00152 in gastric cancer and its clinical significance.

    Science.gov (United States)

    Pang, Qianqian; Ge, Jiaxin; Shao, Yongfu; Sun, Weiliang; Song, Haojun; Xia, Tian; Xiao, Bingxiu; Guo, Junming

    2014-06-01

    It has been known that differential expression of long non-coding RNA (lncRNA) plays critical roles in carcinogenesis. However, the significance of lncRNA, especially long intergenic ncRNA (lincRNA, the main type of lncRNA family), in the diagnosis of gastric cancer is largely unknown. The aim of this study was to determine the expression level of LINC00152, a newfound lincRNA, in gastric carcinoma and its clinical association. The expression of LINC00152 in 71 pairs of tumorous and adjacent normal tissues from patients with gastric cancer was detected by quantitative real-time reverse transcription-polymerase chain reaction. And then, the potential associations between its level in gastric cancer tissue and the clinicopathological features were analyzed. Finally, a receiver operating characteristic (ROC) curve was constructed for differentiating patients with gastric cancer from patients with benign gastric diseases. The results showed that the expression level of LINC00152 in gastric carcinoma was significantly increased, compared with matched normal tissue (P=0.045) and normal mucosa from health control (P=0.004), respectively. Levels of LINC00152 in gastric cancer cell lines, BGC-823, MGC-803, and SGC-7901, were significantly higher than those in human normal gastric epithelial cell line GES-1. In addition, high expression of LINC00152 was correlated with invasion (P=0.042). LINC00152 levels in gastric juice from patients with gastric cancer were further found significantly higher than those from normal controls (P=0.002). Moreover, the area under the ROC curve (AUC) was up to 0.645 (95 % CI=0.559-0.740, P=0.003). This study highlights that lincRNA LINC00152 might be a novel biomarker for predicting gastric cancer.

  3. The GIP/GIPR axis is functionally linked to GH-secretion increase in a significant proportion of gsp(-) somatotropinomas.

    Science.gov (United States)

    Regazzo, Daniela; Losa, Marco; Albiger, Nora; Terreni, Maria Rosa; Vazza, Giovanni; Ceccato, Filippo; Emanuelli, Enzo; Denaro, Luca; Scaroni, Carla; Occhi, Gianluca

    2017-02-08

    Objective: Glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion of gsp(-) somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load. Design and Methods: This study was aimed at linking the GIP/GIPR pathway to GH secretion in 25 somatotropinomas-derived primary cultures and correlating molecular with clinical features in acromegalic patients. Given the impairment of the GIPR/GIPR axis in acromegaly, an additional aim was to assess the effect of GH/IGF-1 stimulation on GIP expression in the enteroendocrine cell line STC-1. Results: nearly 80% of GIPR-expressing somatotropinomas, all of them negative for gsp mutations, show increased GH secretion upon GIP stimulation, higher sensitivity to forskolin but not to somatostatin analogues. Beside increased frequency of GH-PI, GIPR overexpression does not appear to affect acromegalic patients' clinical features. In STC-1 cells transfected with GIP promoter-driven luciferase vector, IGF-1 but not GH induced dose-dependent increase in luciferase activity. Conclusions: we demonstrate that GIPR mediates the GH-PI in a significant proportion of gsp(-) acromegalic patients. In these cases the stimulatory effect of IGF-I on GIP promoter support the hypothesis of a functional GH-IGF1-GIP axis. Further studies based on larger cohorts and the development of a stable transgenic model with inducible GIPR overexpression targeted to pituitary somatotroph lineage will be mandatory to establish the real role of GIPR in the pathogenesis of somatotropinomas.

  4. HIV-1 structural proteins serve as PAMPs for TLR2 heterodimers significantly increasing infection and innate immune activation

    Directory of Open Access Journals (Sweden)

    Kenneth Lee Rosenthal

    2015-08-01

    Full Text Available Immune activation is critical to HIV infection and pathogenesis; however, our understanding of HIV innate immune activation remains incomplete. Recently we demonstrated that soluble TLR2 (sTLR2 physically inhibited HIV-induced, NFκB activation and inflammation, as well as HIV-1 infection. In light of these findings, we hypothesized that HIV-1 structural proteins may serve as pathogen-associated molecular patterns (PAMPs for cellular TLR2 heterodimers. These studies made use of primary human T cells and TZMbl cells stably transformed to express TLR2 (TZMbl-2. Our results demonstrated that cells expressing TLR2 showed significantly increased proviral DNA compared to cells lacking TLR2, and mechanistically this may be due to a TLR2-mediated increased CCR5 expression. Importantly, we show that HIV-1 structural proteins, p17, p24, and gp41 act as viral PAMPs signalling through TLR2 and its heterodimers leading to significantly increased immune activation via the NFκB signaling pathway. Using co-immunoprecipitation and a dot blot method, we demonstrated direct protein interactions between these viral PAMPs and TLR2, while only p17 and gp41 bound to TLR1. Specifically, TLR2/1 heterodimer recognized p17 and gp41, while p24 lead to immune activation through TLR2/6. These results were confirmed using TLR2/1 siRNA knock down assays which ablated p17 and gp41-induced cellular activation and through studies of HEK293 cells expressing selected TLRs. Interestingly, our results show in the absence of TLR6, p24 bound to TLR2 and blocked p17 and gp41-induced activation, thus providing a novel mechanism by which HIV-1 can manipulate innate sensing. Taken together, our results identified, for the first time, novel HIV-1 PAMPs that play a role in TLR2-mediated cellular activation and increased proviral DNA. These findings have important implications for our fundamental understanding of HIV-1 immune activation and pathogenesis, as well as HIV-1 vaccine development.

  5. Increase of electrodermal activity of heart meridian during physical exercise: the significance of electrical values in acupuncture and diagnostic importance.

    Science.gov (United States)

    Pontarollo, Francesco; Rapacioli, Giuliana; Bellavite, Paolo

    2010-08-01

    Electric field measurements of skin potential and electrical currents are physiological indicators of electrodermal activity (EDA) and have been associated with a variety of sensory, cognitive and emotional stimuli. The aim of this study was to investigate the EDA at some hand acupoints before, during and after a physical exercise. EDA of eight points located at the corner of fingernails of hands was measured in 10 healthy young volunteers before, during and after a 14-min acute exercise in a bicycle ergometer. In pre-exercise resting state the parameters were stable and similar between the 8 different tested points, while during exercise a significant increase of current (from 1000-2000 to 4000-8000 nA) was observed, with the maximal values related to the point located on the ulnar side of the little finger, at the base of the nail, corresponding to the Shao chong (HT9) of heart meridian. Copyright 2010 Elsevier Ltd. All rights reserved.

  6. Effect of stearic acid on the properties of metronidazole/methocel K4M floating matrices

    Directory of Open Access Journals (Sweden)

    Belem Lara-Hernández

    2009-09-01

    Full Text Available The properties of metronidazole/Methocel K4M sustained release floating tablets have been studied varying the proportion of the lubricant, stearic acid, on formulations with and without sodium bicarbonate. The variables studied include technological properties of the tablets such as tablet hardness and ejection pressure, the drug release profile, the hydration kinetics and the floating behaviour. The presence of stearic acid and sodium bicarbonate improves the floating behaviour for more than 8 hours. The hydration volume, the tablet hardness and the ejection pressure decrease as the stearic acid content increases and the polymer content decreases. Drug dissolution increases with increasing proportions of stearic acid and decreasing proportions of the polymer in the tablets. The presence of sodium bicarbonate extends the differences in dissolution produced by stearic acid. These results are attributed to decreasing matrices coherence with an increasing quantity of stearic acid and a reducing polymer proportion. The carbon dioxide bubbles produced by sodium bicarbonate expand the matrices facilitating the dissolution, although their presence obstructs also the diffusion path through the hydrated gel layer.Estudaram-se as propriedades de comprimidos flutuantes de metronidazol/Methocel K4M de liberação controlada, variando-se a proporção do lubrificante, ácido esteárico, nas formulações com e sem bicarbonato de sódio. As variáveis estudadas incluem propriedades tecnológicas dos comprimidos, tais como dureza, pressão de ejeção, perfil de liberação do fármaco, cinética de hidratação e comportamento de flutuação. A presença de ácido esteárico e do bicarbonato de sódio melhora o comportamento de flutuação para mais de 8 horas. O volume de hidratação, a dureza e a pressão de ejeção do comprimido decrescem à medida que o conteúdo de ácido esteárico e de polímero diminui. A dissolução do fármaco aumenta com o

  7. The presence of a sponsoring embryo in a batch of poor quality thawed embryos significantly increases pregnancy and implantation rate.

    Science.gov (United States)

    Lightman, A; Kol, S; Wayner, V; Vertman, D; Manor, D; Itskovitz-Eldor, J

    1997-04-01

    To evaluate quantitatively the effect of one good-quality (sponsoring) embryo in a batch of low-quality thawed embryos on the implantation and pregnancy rates (PR). Retrospective analysis of data. Tertiary care center IVF clinic affiliated with a university medical school. Between March 1988 and April 1995, 392 IVF patients underwent a total of 440 thawing and ET cycles of 1,436 multicellular embryos. Implantation, clinical pregnancy, and multiple pregnancy rates. In the absence of sponsoring embryos in the thawed batch of embryos, a PR of 9.8% with an implantation rate of 3.1% was achieved. In the presence of a single sponsoring embryo, the PR nearly doubled (18.2%), with a significantly higher implantation rate of 7.0%. Only singleton pregnancies were achieved in the absence of sponsoring embryos compared with 21.7% multiple pregnancies in the single sponsoring embryo group. The presence of a sponsoring embryo in a batch of poor quality thawed embryos is an important factor that significantly increased pregnancy and implantation rates. The optimal strategy for planning batches of multicellular frozen embryos is to include at least one sponsoring embryo in each batch when possible. We speculate that the sponsoring embryo may favorably influence the chances of low-quality embryos to undergo successful implantation.

  8. Exploring PHD fingers and H3K4me0 interactions with molecular dynamics simulations and binding free energy calculations: AIRE-PHD1, a comparative study.

    Directory of Open Access Journals (Sweden)

    Dimitrios Spiliotopoulos

    Full Text Available PHD fingers represent one of the largest families of epigenetic readers capable of decoding post-translationally modified or unmodified histone H3 tails. Because of their direct involvement in human pathologies they are increasingly considered as a potential therapeutic target. Several PHD/histone-peptide structures have been determined, however relatively little information is available on their dynamics. Studies aiming to characterize the dynamic and energetic determinants driving histone peptide recognition by epigenetic readers would strongly benefit from computational studies. Herein we focus on the dynamic and energetic characterization of the PHD finger subclass specialized in the recognition of histone H3 peptides unmodified in position K4 (H3K4me0. As a case study we focused on the first PHD finger of autoimmune regulator protein (AIRE-PHD1 in complex with H3K4me0. PCA analysis of the covariance matrix of free AIRE-PHD1 highlights the presence of a "flapping" movement, which is blocked in an open conformation upon binding to H3K4me0. Moreover, binding free energy calculations obtained through Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA methodology are in good qualitative agreement with experiments and allow dissection of the energetic terms associated with native and alanine mutants of AIRE-PHD1/H3K4me0 complexes. MM/PBSA calculations have also been applied to the energetic analysis of other PHD fingers recognizing H3K4me0. In this case we observe excellent correlation between computed and experimental binding free energies. Overall calculations show that H3K4me0 recognition by PHD fingers relies on compensation of the electrostatic and polar solvation energy terms and is stabilized by non-polar interactions.

  9. One of the 10 cells of AA Injection Kicker K4

    CERN Multimedia

    1979-01-01

    The 3.5 GeV/c Antiproton Accumulator (AA) had 2 delay-line type injection kickers, K3 (12 cells) and K4 (10 cells). Here we see one of the K4 cells, with ferrite between stainless-steel plates. Pulse voltage: 61 kV; rise/fall-time 86 ns; flat-top 460 ns; top flatness +-2%. During injection, the open side of the C-shaped kickers was closed off with a fast shutter, so that their stray field would not perturb the stack of already accumulated antiprotons.

  10. The Histone Demethylase Jarid1b Ensures Faithful Mouse Development by Protecting Developmental Genes from Aberrant H3K4me3

    DEFF Research Database (Denmark)

    Albert, Mareike; Schmitz, Sandra U; Kooistra, Susanne M

    2013-01-01

    of the H3K4me2/3 histone demethylase Jarid1b (Kdm5b/Plu1) results in major neonatal lethality due to respiratory failure. Jarid1b knockout embryos have several neural defects including disorganized cranial nerves, defects in eye development, and increased incidences of exencephaly. Moreover, in line...... with an overlap of Jarid1b and Polycomb target genes, Jarid1b knockout embryos display homeotic skeletal transformations typical for Polycomb mutants, supporting a functional interplay between Polycomb proteins and Jarid1b. To understand how Jarid1b regulates mouse development, we performed a genome-wide analysis...... of histone modifications, which demonstrated that normally inactive genes encoding developmental regulators acquire aberrant H3K4me3 during early embryogenesis in Jarid1b knockout embryos. H3K4me3 accumulates as embryonic development proceeds, leading to increased expression of neural master regulators like...

  11. Unequivocal detection of ozone recovery in the Antarctic Ozone Hole through significant increases in atmospheric layers with minimum ozone

    Science.gov (United States)

    de Laat, Jos; van Weele, Michiel; van der A, Ronald

    2015-04-01

    An important new landmark in present day ozone research is presented through MLS satellite observations of significant ozone increases during the ozone hole season that are attributed unequivocally to declining ozone depleting substances. For many decades the Antarctic ozone hole has been the prime example of both the detrimental effects of human activities on our environment as well as how to construct effective and successful environmental policies. Nowadays atmospheric concentrations of ozone depleting substances are on the decline and first signs of recovery of stratospheric ozone and ozone in the Antarctic ozone hole have been observed. The claimed detection of significant recovery, however, is still subject of debate. In this talk we will discuss first current uncertainties in the assessment of ozone recovery in the Antarctic ozone hole by using multi-variate regression methods, and, secondly present an alternative approach to identify ozone hole recovery unequivocally. Even though multi-variate regression methods help to reduce uncertainties in estimates of ozone recovery, great care has to be taken in their application due to the existence of uncertainties and degrees of freedom in the choice of independent variables. We show that taking all uncertainties into account in the regressions the formal recovery of ozone in the Antarctic ozone hole cannot be established yet, though is likely before the end of the decade (before 2020). Rather than focusing on time and area averages of total ozone columns or ozone profiles, we argue that the time evolution of the probability distribution of vertically resolved ozone in the Antarctic ozone hole contains a better fingerprint for the detection of ozone recovery in the Antarctic ozone hole. The advantages of this method over more tradition methods of trend analyses based on spatio-temporal average ozone are discussed. The 10-year record of MLS satellite measurements of ozone in the Antarctic ozone hole shows a

  12. Hypoalbuminemia is significantly associated with increased clearance time of high dose methotrexate in patients being treated for lymphoma or leukemia.

    Science.gov (United States)

    Reiss, Samantha N; Buie, Larry W; Adel, Nelly; Goldman, Debra A; Devlin, Sean M; Douer, Dan

    2016-12-01

    As a weak acid, methotrexate (MTX) is bound to serum albumin and has variable protein binding. The purpose of this study was to assess serum albumin's relationship with MTX pharmacokinetics by comparing MTX clearance and toxicities between patients with normal serum albumin to those with hypoalbuminemia. This single-center retrospective study included adult patients with leukemia or lymphoma who received their first MTX at a dose ≥1 g/m(2). Hypoalbuminemia was defined as serum albumin ≤3.4 g/dL. MTX clearance was defined as the first documented time the MTX level ≤0.05 μM. Fisher's exact tests and Wilcoxon rank sum tests were used to examine differences in toxicities, and Cox proportional hazard regression was used to assess relationship with time to clearance. Of 523 patients identified, 167 patients were evaluable. One hundred thirty-five patients had normal serum albumin and 32 had hypoalbuminemia. Hypoalbuminemia was associated with a higher proportion of patients experiencing edema, ascites or pleural effusions (34 vs. 12 %, p = 0.006), and the concomitant use of nephrotoxic agents (41 vs. 20 %, p = 0.021). Hypoalbuminemia was associated with a significantly longer time to MTX clearance (median 96 vs. 72 h, p = 0.004). In addition, patients with hypoalbuminemia had a higher proportion of hyperbilirubinemia and significantly longer hospitalization (median 14 vs. 5 days, p clearance and increased length of hospitalization. High dose MTX is safe to administer in patients with low albumin levels, with appropriate leucovorin rescue, and good supportive care.

  13. The Amazing COS FUV (1320 - 1460 A) Spectrum of (lambda) Vel (K4Ib-II)

    Science.gov (United States)

    Carpenter, Kenneth

    2010-01-01

    The FUV spectrum (1320-1460 A) of the K4 lb-11 supergiant (lambda) Vel was observed with the Cosmic Origins Spectrograph (COS) on HST, as part of the Ayres and Redfield Cycle 17 SNAP program "SNAPing Coronal Iron". This spectrum covers a region not previously recorded in (lambda) Vel at high resolution and, in a mere 20 minutes of exposure, reveals a treasure trove of information. It shows a wide variety of strong emission lines, superposed on a bright continuum, with contributions from both atomic and molecular species. Multiple absorptions, including numerous Ni II and Fe II lines, are visible over this continuum, which is likely generated in the chromosphere of the star. Evidence of the stellar wind is seen in the P Cygni profiles of the CII lines near 1335 A and the results of fluorescence processes are visible throughout the region. The spectrum has remarkable similarities to that of (alpha) Boo (K1.5 III), but significant differences as well, including substantial FUV continuum emission, reminiscent of the M2 Iab supergiant (alpha) Ori, but minus the CO fundamental absorption bands seen in the spectrum of the latter star. However, fluoresced CO emission is present, as in the K-giant stars (alpha) Boo and (alpha) Tau (K5 III). The presence of hot plasma in the atmosphere of the star, indicated by previous GHRS observations of Si III] and C III] lines near 1900 A and FUSE observations of O VI 1032 A, is further confirmed by the detection in this COS spectrum of the Si IV UV 1 lines near 1400 A, though both lines are contaminated by overlying fluorescent H2 emission. We present the details of this spectrum, in comparison with stars of similar temperature or luminosity and discuss the implications for the structure of, and the radiative processes active in, the outer atmospheres of these stars.

  14. Morphed and moving: TNFα-driven motility promotes cell dissemination through MAP4K4-induced cytoskeleton remodeling

    Directory of Open Access Journals (Sweden)

    Min Ma

    2014-04-01

    Full Text Available Cell dissemination from an initial site of growth is a highly coordinated and controlled process that depends on cell motility. The mechanistic principles that orchestrate cell motility, namely cell shape control, traction and force generation, are highly conserved between cells of different origins. Correspondingly, the molecular mechanisms that regulate these critical aspects of migrating cells are likely functionally conserved too. Thus, cell motility deregulation of unrelated pathogenesis could be caused and maintained by similar mechanistic principles. One such motility deregulation disorder is the leukoproliferative cattle disease Tropical Theileriosis, which is caused by the intracellular, protozoan parasite Theileria annulata. T. annulata transforms its host cell and promotes the dissemination of parasite-infected cells throughout the body of the host. An analogous condition with a fundamentally different pathogenesis is metastatic cancer, where oncogenically transformed cells disseminate from the primary tumor to form distant metastases. Common to both diseases is the dissemination of motile cells from the original site. However, unlike metastatic cancer, host cell transformation by Theileria parasites can be reverted by drug treatment and cell signaling be analyzed under transformed and non-transformed conditions. We have used this reversible transformation model and investigated parasite control of host cell motile properties in the context of inflammatory signaling in Ma M. et al. [PLoS Pathog (2014 10: e1004003]. We found that parasite infection promotes the production of the inflammatory cytokine TNFα in the host macrophage. We demonstrated that increased TNFα triggers motile and invasive properties by enhancing actin cytoskeleton remodeling and cell motility through the ser/thr kinase MAP4K4. We concluded that inflammatory conditions resulting in increased TNFα could facilitate cell dissemination by activating the actin

  15. Levels of vitamin C In the blood plasma patients treated with coronary artery bypass grafting increases significantly after surgery.

    Science.gov (United States)

    Kleszczewski, Tomasz; Modzelewska, Beata; Lisowska, Anna; Buzun, Leszek; Kleszczewska, Ewa

    2017-01-01

    One strong risk factor of coronary artery disease (CAD), which affects the levels of vitamin C in the blood is cigarette smoking. The supplementary effects of coronary artery bypass grafting (CABG) is smoking cessation by patients. Therefore, the aim of this study was to examine the level of vitamin C in the blood plasma one day before and one month after CABG. Human blood were collected from 20 patients (men); 1day before and 1 month after CABG. All patients were smoker and after CABG they declared their not smoking. The concentration of vitamin C in the blood plasma was assayed by FIA method with spectrophotometric detection. The mean value of the vitamin C concentration 1day before CABG was 12.36±2.84μmol/L (mean±SD), 1 month after CABG 40.07±10.95μmol/L (mean±SD). The average increase in the concentration of vitamin C was 3.27±0.73 times (mean±SD) and showed significant positive correlations (Pearson r=0.657, p=0.002). It should be consider incorporating the recommendations of preoperative smoking cessation for at least one month prior to CABG and/or additional supplementation. In addition it would be relevant to monitor the level of vitamin C in the patients' blood in the preoperative period.

  16. Edge effect and significant increase of the superconducting transition onset temperature of 2D superconductors in flat and curved geometries

    Science.gov (United States)

    Wong, Chi Ho; Lortz, Rolf

    2016-02-01

    In this paper, we present a simple method to model the curvature activated phonon softening in a 2D superconducting layer. The superconducting transition temperature Tc in the case of a 2D rectangular sheet, a hollow cylinder and a hollow sphere of one coherence length thickness is calculated by the quantum mechanical electron-phonon scattering matrix, and a series of collective lattice vibrations in the surface state. We will show that being extremely thin in a flat rectangular shape is not enough to significantly enhance the Tc through phonon softening. However, if a curvature is added, Tc can be strongly enhanced. The increase in Tc with respect to the bulk is greatest in a hollow sphere, intermediate in a hollow cylinder and weakest for the rectangular sheet, when systems of identical length scale are considered. In addition, we find that the edge effect of such a 2D sheet has a strong broadening effect on Tc in addition to the effect of order parameter phase fluctuations.

  17. Increasing significance of advanced physical/chemical processes in the development and application of sustainable wastewater treatment systems

    Institute of Scientific and Technical Information of China (English)

    Wim RULKENS

    2008-01-01

    The awareness of the problem of the scarcity of water of high quality has strongly changed the approach of wastewater treatment. Currently, there is an increasing need for the beneficial reuse of treated wastewater and to recover valuable products and energy from the wastewater. Because microbiological treatment methods are, only to a limited part, able to satisfy these needs, the role and significance of physical/chemical pro-cesses in wastewater treatment are gaining more and more interest. The specific future role and aim of the various physical/chemical treatment processes can be categorized in five groups: improvement of the perform-ance of microbiological treatment processes, achieve-ment of the high quality required for reuse of the effluent, recovery of valuable components and energy from the wastewater for beneficial reuse, desalination of brackish water and seawater, and treatment of con-centrated liquid or solid waste residues produced in a wastewater treatment process. Development of more environmentally sustainable wastewater treatment chains in which physical/chemical processes play a cru-cial role, also requires application of process control and modeling strategies. This is briefly introduced by the elaboration of treatment scenarios for three specific wastewaters.

  18. H3K4 demethylase activities repress proliferative and postmitotic aging

    Science.gov (United States)

    Alvares, Stacy M; Mayberry, Gaea A; Joyner, Ebony Y; Lakowski, Bernard; Ahmed, Shawn

    2014-01-01

    Homeostasis of postmitotic and proliferating cells is maintained by pathways that repress stress. We found that the Caenorhabditis elegans histone 3 lysine 4 (H3K4) demethylases RBR-2 and SPR-5 promoted postmitotic longevity of stress-resistant daf-2 adults, altered pools of methylated H3K4, and promoted silencing of some daf-2 target genes. In addition, RBR-2 and SPR-5 were required for germ cell immortality at a high temperature. Transgenerational proliferative aging was enhanced for spr-5; rbr-2 double mutants, suggesting that these histone demethylases may function sequentially to promote germ cell immortality by targeting distinct H3K4 methyl marks. RBR-2 did not play a comparable role in the maintenance of quiescent germ cells in dauer larvae, implying that it represses stress that occurs as a consequence of germ cell proliferation, rather than stress that accumulates in nondividing cells. We propose that H3K4 demethylase activities promote the maintenance of chromatin states during stressful growth conditions, thereby repressing postmitotic aging of somatic cells as well as proliferative aging of germ cells. PMID:24134677

  19. Purification of chondroitin precursor from Escherichia coli K4 fermentation broth using membrane processing.

    Science.gov (United States)

    Schiraldi, Chiara; Carcarino, Immacolata Loredana; Alfano, Alberto; Restaino, Odile Francesca; Panariello, Andrea; De Rosa, Mario

    2011-04-01

    Recently the possibility of producing the capsular polysaccharide K4, a fructosylated chondroitin, in fed-batch experiments was assessed. In the present study, a novel downstream process to obtain chondroitin from Escherichia coli K4 fermentation broth was developed. The process is simple, scalable and economical. In particular, downstream procedures were optimized with a particular aim of purifying a product suitable for further chemical modifications, in an attempt to develop a biotechnological platform for chondroitin sulfate production. During process development, membrane devices (ultrafiltration/diafiltration) were exploited, selecting the right cassette cut-offs for different phases of purification. The operational conditions (cross-flow rate and transmembrane pressure) used for the process were determined on an ÄKTA cross-flow instrument (GE Healthcare, USA), a lab-scale automatic tangential flow filtration system. In addition, parameters such as selectivity and throughput were calculated based on the analytical quantification of K4 and defructosylated K4, as well as the major contaminants. The complete downstream procedure yielded about 75% chondroitin with a purity higher than 90%.

  20. Research-Based Methods of Reading Instruction for English Language Learners, Grades K-4

    Science.gov (United States)

    Vaughn, Sharon; Linan-Thompson, Sylvia

    2007-01-01

    At last, a truly helpful, practical guide for K-4 teachers who want to ensure that their approach to teaching young English language learners is based on research and grounded in proven classroom practices. The authors of ASCD's best-selling book "Research-Based Methods of Reading Instruction, Grades K-3" explain how you can help the English…

  1. Research-Based Methods of Reading Instruction for English Language Learners, Grades K-4

    Science.gov (United States)

    Vaughn, Sharon; Linan-Thompson, Sylvia

    2007-01-01

    At last, a truly helpful, practical guide for K-4 teachers who want to ensure that their approach to teaching young English language learners is based on research and grounded in proven classroom practices. The authors of ASCD's best-selling book "Research-Based Methods of Reading Instruction, Grades K-3" explain how you can help the English…

  2. From Inception to Reflection: Ohio's K-4 Content-Enriched Mandarin Chinese Curriculum

    Science.gov (United States)

    Robinson, Deborah W.

    2009-01-01

    In 2006 the Ohio Department of Education (ODE) submitted and received a three-year Foreign Language Assistance Program grant from the U.S. Department of Education to write and pilot a K-4 content-enriched Mandarin curriculum and to build online professional development modules to support the curriculum. Once funded, ODE formed an advisory…

  3. Epigenetic Profiling of H3K4Me3 Reveals Herbal Medicine Jinfukang-Induced Epigenetic Alteration Is Involved in Anti-Lung Cancer Activity.

    Science.gov (United States)

    Lu, Jun; Zhang, Xiaoli; Shen, Tingting; Ma, Chao; Wu, Jun; Kong, Hualei; Tian, Jing; Shao, Zhifeng; Zhao, Xiaodong; Xu, Ling

    2016-01-01

    Traditional Chinese medicine Jinfukang (JFK) has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci.

  4. Marrying Step Feed with Secondary Clarifier Improvements to Significantly Increase Peak Wet Weather Treatment Capacity: An Integrated Methodology.

    Science.gov (United States)

    Daigger, Glen T; Siczka, John S; Smith, Thomas F; Frank, David A; McCorquodale, J A

    2017-08-01

      The need to increase the peak wet weather secondary treatment capacity of the City of Akron, Ohio, Water Reclamation Facility (WRF) provided the opportunity to test an integrated methodology for maximizing the peak wet weather secondary treatment capacity of activated sludge systems. An initial investigation, consisting of process modeling of the secondary treatment system and computational fluid dynamics (CFD) analysis of the existing relatively shallow secondary clarifiers (3.3 and 3.7 m sidewater depth in 30.5 m diameter units), indicated that a significant increase in capacity from 416 000 to 684 000 m3/d or more was possible by adding step feed capabilities to the existing bioreactors and upgrading the existing secondary clarifiers. One of the six treatment units at the WRF was modified, and an extensive 2-year testing program was conducted to determine the total peak wet weather secondary treatment capacity achievable. The results demonstrated that a peak wet weather secondary treatment capacity approaching 974 000 m3/d is possible as long as secondary clarifier solids and hydraulic loadings could be separately controlled using the step feed capability provided. Excellent sludge settling characteristics are routinely experienced at the City of Akron WRF, raising concerns that the identified peak wet weather secondary treatment capacity could not be maintained should sludge settling characteristics deteriorate for some reason. Computational fluid dynamics analysis indicated that the impact of the deterioration of sludge settling characteristics could be mitigated and the identified peak wet weather secondary treatment capacity maintained by further use of the step feed capability provided to further reduce secondary clarifier solids loading rates at the identified high surface overflow rates. The results also demonstrated that effluent limits not only for total suspended solids (TSS) and five-day carbonaceous biochemical oxygen demand (cBOD5) could be

  5. The Intracranial Volume Pressure Response in Increased Intracranial Pressure Patients: Clinical Significance of the Volume Pressure Indicator

    Science.gov (United States)

    2016-01-01

    Background For patients suffering from primary brain injury, monitoring intracranial pressure alone is not enough to reflect the dynamic intracranial condition. In our previous study, a segment of the pressure-volume curve can be expressed by the parabolic regression model with single indicator “a”. The aim of this study is to evaluate if the indicator “a” can reflect intracranial conditions. Methods Patients with traumatic brain injury, spontaneous intracranial hemorrhage, and/or hydrocephalus who had external ventricular drainage from January 2009 to February 2010 were included. The successive volume pressure response values were obtained by successive drainage of cerebral spinal fluid from intracranial pressure 20–25 mm Hg to 10 mm Hg. The relationship between withdrawn cerebral spinal fluid volume and intracranial pressure was analyzed by the parabolic regression model with single parameter “a”. Results The overall mean for indicator “a” was 0.422 ± 0.046. The mean of “a” in hydrocephalus was 0.173 ± 0.024 and in severe intracranial mass with slender ventricle, it was 0.663 ± 0.062. The two extreme intracranial conditions had a statistical significant difference (phydrocephalus. Brain computed tomography should be performed early if a rapid elevation of indicator “a” is detected, as it can reveal some ongoing intracranial pathology prior to clinical deterioration. Increased intracranial pressure was frequently observed in patients with intracranial pathology. The progression can be differentiated using the pattern of the volume pressure indicator. PMID:27723794

  6. Minimal (C4,K4;7)-P-graphs%极小(C4,K4;7)-平面图

    Institute of Scientific and Technical Information of China (English)

    段春燕

    2014-01-01

    An (H1 ,H2;n)-P-graph is a graph with order n,which does not contain a subgraph isomorphic to H1 ,and its complement has no subgraph isomorphic to H2 .G is a minimal (H1 ,H2;n)-P-graph,if G is an (H1 ,H2;n)-P-graph and G′obtained by deleting any one edge from G is not an (H1 ,H2;n)-P-graph.In this paper,the minimal (C4 ,K4;7 )-P-graphs are given.%若平面图G没有与H1同构的子图,且G珔没有与H2同构的子图,则G称为(H1,H2)-平面图。(H1,H2;n)-平面图表示n阶的(H1,H2)-平面图。若G是(H1,H2;n)-平面图,去掉G的任意一条边,都不再是(H1,H2;n)-平面图,则G称为极小(H1,H2;n)-平面图。本文给出了所有的极小(C4,K4;7)-平面图,有助于证明PR(C4,K8)。

  7. Altered expression of BRG1 and histone demethylases, and aberrant H3K4 methylation in less developmentally competent embryos at the time of embryonic genome activation.

    Science.gov (United States)

    Glanzner, Werner G; Wachter, Audrey; Coutinho, Ana Rita S; Albornoz, Marcelo S; Duggavathi, Raj; GonÇAlves, Paulo B D; Bordignon, Vilceu

    2017-01-01

    Epigenetics is a fundamental regulator underlying many biological functions, such as development and cell differentiation. Epigenetic modifications affect key chromatin regulation, including transcription and DNA repair, which are critical for normal embryo development. In this study, we profiled the expression of epigenetic modifiers and patterns of epigenetic changes in porcine embryos around the period of embryonic genome activation (EGA). We observed that Brahma-related gene 1 (BRG1) and Lysine demethylase 1A (KDM1A), which can alter the methylation status of lysine 4 in histone 3 (H3K4), localize to the nucleus at Day 3-4 of development. We then compared the abundance of epigenetic modifiers between early- and late-cleaving embryos, which were classified based on the time to the first cell cleavage, to investigate if their nuclear localization contributes to developmental competence. The mRNA abundance of BRG1, KDM1A, as well as other lysine demethylases (KDM1B, KDM5A, KDM5B, and KDM5C), were significantly higher in late- compared to early-cleaving embryos near the EGA period, although these difference disappeared at the blastocyst stage. The abundance of H3K4 mono- (H3K4me) and di-methylation (H3K4me2) during the EGA period was reduced in late-cleaving and less developmentally competent embryos. By contrast, BRG1, KDM1A, and H3K4me2 abundance was greater in embryos with more than eight cells at Day 3-4 of development compared to those with fewer than four cells. These findings suggest that altered epigenetic modifications of H3K4 around the EGA period may affect the developmental capacity of porcine embryos to reach the blastocyst stage. Mol. Reprod. Dev. 84: 19-29, 2017. © 2016 Wiley Periodicals, Inc.

  8. Note: significant increase to the temporal resolution of 2D X-ray detectors using a novel beam chopper system.

    Science.gov (United States)

    Küchemann, Stefan; Mahn, Carsten; Samwer, Konrad

    2014-01-01

    The investigation of short time dynamics using X-ray scattering techniques is commonly limited either by the read out frequency of the detector or by a low intensity. In this paper, we present a chopper system, which can increase the temporal resolution of 2D X-ray detectors by a factor of 13. This technique only applies to amorphous or polycrystalline samples due to their circular diffraction patterns. Using the chopper, we successfully increased the temporal resolution up to 5.1 ms during synchrotron experiments. For the construction, we provide a mathematical formalism, which, in principle, allows an even higher increase of the temporal resolution.

  9. Electrochemical Catalysis of Inorganic Complex K4[Fe(CN)6] by Shewanella oneidensis MR-1

    DEFF Research Database (Denmark)

    Zheng, Zhiyong; Wu, Ranran; Xiao, Yong

    to the redox proteins localized to the outer-membrane, for example, the MtrC, MtrB,MtrA and CymA2. Here we investigate its electrochemical properties towards redox inorganic redox compounds. It shows strong electrocatalysis toward electrochemical oxidation of K4[Fe(CN)6]. As a redox molecule, K4[Fe(CN)6] gives...... on the selectivity and electrocatalysis mechanisms of Shewanella oneidensis MR-1 are under investigation. The ability of Shewanella oneidensis MR-1 to catalyze redox action of inorganic metal complex compounds will provide an insight on metal cycles in nature....... disappearance of the cathodic peak and strengthen of the anodic peak, which is a typical catalysis feature of electrochemical oxidation. Further experiments show that Shewanella oneidensis MR-1 does not give such electrocatalysis to redox compounds such as Ru[(NH3)6]Cl3 and Resorufin. Systematic study...

  10. Timing of transcriptional quiescence during gametogenesis is controlled by global histone H3K4 demethylation.

    Science.gov (United States)

    Xu, Mengshu; Soloveychik, Maria; Ranger, Mathieu; Schertzberg, Michael; Shah, Zarna; Raisner, Ryan; Venkatasubrahmanyan, Shivkumar; Tsui, Kyle; Gebbia, Marinella; Hughes, Tim; van Bakel, Harm; Nislow, Corey; Madhani, Hiten D; Meneghini, Marc D

    2012-11-13

    Gametes are among the most highly specialized cells produced during development. Although gametogenesis culminates in transcriptional quiescence in plants and animals, regulatory mechanisms controlling this are unknown. Here, we confirm that gamete differentiation in the single-celled yeast Saccharomyces cerevisiae is accompanied by global transcriptional shutoff following the completion of meiosis. We show that Jhd2, a highly conserved JARID1-family histone H3K4 demethylase, activates protein-coding gene transcription in opposition to this programmed transcriptional shutoff, sustaining the period of productive transcription during spore differentiation. Moreover, using genome-wide nucleosome, H3K4me, and transcript mapping experiments, we demonstrate that JHD2 globally represses intergenic noncoding transcription during this period. The widespread transcriptional defects of JHD2 mutants are associated with precocious differentiation and the production of stress-sensitive spores, demonstrating that Jhd2 regulation of the global postmeiotic transcriptional program is critical for the production of healthy meiotic progeny.

  11. 不再当大男孩儿 KIA K4

    Institute of Scientific and Technical Information of China (English)

    张伟平

    2014-01-01

    东风悦达·起亚K系家族给我留下的印象,就好比是一群大男孩儿,各个都拥有一副帅气的容貌且充满活力。不过从今天开始,K系家族出现了一名"另类",一款相对成熟、稳重的车型——K4!

  12. Supplement to CCM.D-K4 'Hydrometer' report: linkage of EURAMET.M.D-K4 comparison, SIM.M.D-K4 comparison and the supplementary SIM.M.D-S2 to CCM.D-K4 'Hydrometer'

    Science.gov (United States)

    Lorefice, S.; Becerra, L. O.

    2017-01-01

    Evaluation of different types of comparisons to a common set of reference values of a CIPM key comparison is essential to satisfy the concept of the CIPM Mutual Recognition Arrangement (CIPM MRA), where the DoEs of any participant who took part in comparisons should be within the Calibration and Measurement Capability (CMC) section of the CIPM MRA Key Comparison Data Base. The subject of this supplementary report is therefore to present the equivalence of each National Metrological Institute (NMI) participant in the CCM.D-K4 'Hydrometer' key comparison, which was performed in the density range 600 kg/m3 to 2000 kg/m3 at the temperature of 20 °C, and the linkage of the European and Inter-American NMI results performed in the RMO.M.D-K4 comparisons as well as those of the supplementary SIM.M.D-S2 to the common set of KCRVs of the CCM.D-K4 'Hydrometer'. The linking procedure has been obtained by numerical simulation, based on the Monte Carlo method, in which the differences in the results of the different comparison between the intended laboratory and one or more linking laboratory/ies, which took part in both comparisons, are correlated with a continuous function describing the DoEs of the linking laboratory/ies with respect to the common set of KCRVs of the CCM.D-K4. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  13. Drosophila KDM2 is a H3K4me3 demethylase regulating nucleolar organization

    Directory of Open Access Journals (Sweden)

    Birchler James A

    2009-10-01

    Full Text Available Abstract Background CG11033 (dKDM2 is the Drosophila homolog of the gene KDM2B. dKDM2 has been known to possess histone lysine demethylase activity towards H3K36me2 in cell lines and it regulates H2A ubiquitination. The human homolog of the gene has dual activity towards H3K36me2 as well as H3K4me3, and plays an important role in cellular senescence. Findings We have used transgenic flies bearing an RNAi construct for the dKDM2 gene. The knockdown of dKDM2 gene was performed by crossing UAS-RNAi-dKDM2 flies with actin-Gal4 flies. Western blots of acid extracted histones and immunofluoresence analysis of polytene chromosome showed the activity of the enzyme dKDM2 to be specific for H3K4me3 in adult flies. Immunofluoresence analysis of polytene chromosome also revealed the presence of multiple nucleoli in RNAi knockdown mutants of dKDM2 and decreased H3-acetylation marks associated with active transcription. Conclusion Our findings indicate that dKDM2 is a histone lysine demethylase with specificity for H3K4me3 and regulates nucleolar organization.

  14. Presence of anomalous coronary seen on angiogram is not associated with increased risk of significant coronary artery disease.

    Science.gov (United States)

    Suryanarayana, Prakash; Kollampare, Shubha; Riaz, Irbaz Bin; Lee, Justin; Husnain, Muhammad; Luni, Faraz Khan; Movahed, Mohammad Reza

    2014-12-01

    It is unclear if anomalous coronary arteries are at higher risk for atherosclerosis. The link between anomalous coronary artery and early coronary artery disease has been suggested. The aim of this study is to determine whether the coronary artery anomaly predisposes to development of significant coronary disease. Using retrospective chart review, patients with documented anomalous coronary arteries recognized during coronary angiography between years 2000 to 2007 were analyzed. Prevalence of significant atherosclerotic coronary artery disease (defined as more than 50% luminal narrowing) was compared between normal and anomalous coronaries. A total of 147 patients with anomalous coronary arteries were found. Right coronary artery was the most common anomalous artery 128 of 148 (86.5%) in our dataset. There was no difference in the occurrence of atherosclerosis between anomalous and nonanomalous coronaries. Significant atherosclerosis was present in 59 of the 148 anomalous coronary arteries (37.8%), and 112 of the 293 nonanomalous coronary arteries (38.2%, p = 0.9). On the basis of our study, there is no evidence that anomalous coronary arteries predispose to significant coronary artery disease in comparison to normal coronary arteries.

  15. Increasing significance of advanced physical/chemical processes in the development and application of sustainable wastewater treatment systems

    NARCIS (Netherlands)

    Rulkens, W.H.

    2008-01-01

    The awareness of the problem of the scarcity of water of high quality has strongly changed the approach of wastewater treatment. Currently, there is an increasing need for the beneficial reuse of treated wastewater and to recover valuable products and energy from the wastewater. Because microbiologi

  16. An adverse lipid profile and increased levels of adiposity significantly predict clinical course after a first demyelinating event.

    Science.gov (United States)

    Tettey, Prudence; Simpson, Steve; Taylor, Bruce; Ponsonby, Anne-Louise; Lucas, Robyn M; Dwyer, Terence; Kostner, Karam; van der Mei, Ingrid Af

    2017-05-01

    To investigate the prospective associations between adiposity and lipid-related variables and conversion to multiple sclerosis (MS), time to subsequent relapse and progression in disability. A cohort of 279 participants with a first clinical diagnosis of central nervous system demyelination was prospectively followed to 5-year review. Height, weight, waist and hip circumference were measured, and serum samples taken for measurement of lipids and apolipoproteins. Survival analysis was used for conversion to MS and time to relapse, and linear regression for annualised change in disability (Expanded Disability Status Scale). Higher body mass index (BMI; adjusted HR (aHR): 1.22 (1.04 to 1.44) per 5 kg/m(2) increase), hip circumference (aHR: 1.32 (1.12 to 1.56) per 10 cm increase) and triglyceride levels (aHR: 1.20 (1.03 to 1.40) per unit increase) were associated with increased risk of subsequent relapse, while adiposity and lipid-related measures were not associated with conversion to MS. In addition, higher BMI (β: 0.04 (0.01 to 0.07) per 5 kg/m(2) increase), hip circumference (β: 0.04 (0.02 to 0.08) per 10 cm increase), waist circumference (β: 0.04 (0.02 to 0.07) per 10 cm increase), total cholesterol to high-density lipoprotein ratio (TC/HDL ratio; β: 0.05 (0.001 to 0.10) and non-HDL; β: 0.04 (0.001 to 0.08) at study entry) were associated with a higher subsequent annual change in disability. Higher levels of adiposity, non-HDL and TC/HDL ratio were prospectively associated with a higher rate of disability progression, and higher adiposity and triglycerides were associated with relapse but not with conversion to MS. Improving the lipid profile and losing weight into the healthy range could reduce the accumulation of disability. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  17. Regulated expression of an isopentenyltransferase gene (IPT) in peanut significantly improves drought tolerance and increases yield under field conditions.

    Science.gov (United States)

    Qin, Hua; Gu, Qiang; Zhang, Junling; Sun, Li; Kuppu, Sundaram; Zhang, Yizheng; Burow, Mark; Payton, Paxton; Blumwald, Eduardo; Zhang, Hong

    2011-11-01

    Isopentenyltransferase (IPT) is a critical enzyme in the cytokinin biosynthetic pathway. The expression of IPT under the control of a maturation- and stress-induced promoter was shown to delay stress-induced plant senescence that resulted in an enhanced drought tolerance in both monocot and dicot plants. This report extends the earlier findings in tobacco and rice to peanut (Arachis hypogaea L.), an important oil crop and protein source. Regulated expression of IPT in peanut significantly improved drought tolerance in both laboratory and field conditions. Transgenic peanut plants maintained higher photosynthetic rates, higher stomatal conductance and higher transpiration than wild-type control plants under reduced irrigation conditions. More importantly, transgenic peanut plants produced significantly higher yields than wild-type control plants in the field, indicating a great potential for the development of crops with improved performance and yield in water-limited areas of the world.

  18. Love is the triumph of the imagination: Daydreams about significant others are associated with increased happiness, love and connection.

    Science.gov (United States)

    Poerio, Giulia L; Totterdell, Peter; Emerson, Lisa-Marie; Miles, Eleanor

    2015-05-01

    Social relationships and interactions contribute to daily emotional well-being. The emotional benefits that come from engaging with others are known to arise from real events, but do they also come from the imagination during daydreaming activity? Using experience sampling methodology with 101 participants, we obtained 371 reports of naturally occurring daydreams with social and non-social content and self-reported feelings before and after daydreaming. Social, but not non-social, daydreams were associated with increased happiness, love and connection and this effect was not solely attributable to the emotional content of the daydreams. These effects were only present when participants were lacking in these feelings before daydreaming and when the daydream involved imagining others with whom the daydreamer had a high quality relationship. Findings are consistent with the idea that social daydreams may function to regulate emotion: imagining close others may serve the current emotional needs of daydreamers by increasing positive feelings towards themselves and others.

  19. Tumorigenic lung tumorospheres exhibit stem-like features with significantly increased expression of CD133 and ABCG2

    OpenAIRE

    Zhao, Wensi; Luo, Yi; Li, Boyi; Zhang, Tao

    2016-01-01

    Accumulating evidence supports the existence of cancer stem cells (CSCs) in human tumors, and the successful certification of CSCs may lead to the identification of therapeutic targets, which are more effective for the treatment of cancer. The use of spherical cancer models has increased in popularity in cancer stem cell investigations. Tumorospheres, which are used as a model of CSCs and are established in serum-free medium supplemented with growth factors under non-adherent conditions, are ...

  20. 'Knowledge for better health' revisited - the increasing significance of health research systems: a review by departing Editors-in-Chief.

    Science.gov (United States)

    Hanney, Stephen R; González-Block, Miguel A

    2017-10-02

    How can nations organise research investments to obtain the best bundle of knowledge and the maximum level of improved health, spread as equitably as possible? This question was the central focus of a major initiative from WHO led by Prof Tikki Pang, which resulted in a range of developments, including the publication of a conceptual framework for national health research systems - Knowledge for better health - in 2003, and in the founding of the journal Health Research Policy and Systems (HARPS). As Editors-in-Chief of the journal since 2006, we mark our retirement by tracking both the progress of the journal and the development of national health research systems. HARPS has maintained its focus on a range of central themes that are key components of a national health research system in any country. These include building capacity to conduct and use health research, identifying appropriate priorities, securing funds and allocating them accountably, producing scientifically valid research outputs, promoting the use of research in polices and practice in order to improve health, and monitoring and evaluating the health research system. Some of the themes covered in HARPS are now receiving increased attention and, for example, with the assessment of research impact and development of knowledge translation platforms, the journal has covered their progress throughout that expansion of interest. In addition, there is increasing recognition of new imperatives, including the importance of promoting gender equality in health research if benefits are to be maximised. In this Editorial, we outline some of the diverse and developing perspectives considered within each theme, as well as considering how they are held together by the growing desire to build effective health research systems in all countries.From 2003 until mid-June 2017, HARPS published 590 articles on the above and related themes, with authors being located in 76 countries. We present quantitative data tracing

  1. Significantly increased risk of cardiovascular disease among patients with gallstone disease: a population-based cohort study.

    Directory of Open Access Journals (Sweden)

    Muideen Tunbosun Olaiya

    Full Text Available OBJECTIVE: To investigate whether gallstone disease (GD increases the risk of developing cardiovascular disease (CVD in a large population-based cohort. METHODS: A study population including 6,981 patients with GD was identified from The Taiwan National Health Insurance Research Database between 2004 and 2005. GD patients were defined as patients with principal discharge diagnoses of cholelithiasis using the ICD-9-CM code 574. 27,924 patients without GD were randomly selected and matched for age and gender. All patients were followed for 6 years or until diagnosis for CVD. Cox proportional hazards regression model was used to assess the risk of developing CVD with adjustment for age, gender and co-morbid conditions. RESULTS: During the six years follow-up period, 935 patients with GD and 2,758 patients without GD developed CVD. Patients with GD had an elevated risk of CVD (HR, 1.32; 95% CI, 1.22-1.43 when compared with those without GD. Similar relationship was observed when CVD was categorized i.e. stroke (HR, 1.15; 95% CI, 1.01-1.32, coronary heart disease (HR, 1.42; 95% CI, 1.28-1.58 and heart failure (HR, 1.31; 95% CI, 1.00-1.73. When GD was classified according to the level of severity, using patients without GD as reference, the risks of CVD were elevated in patients with non-severe GD (HR, 1.34; 95% CI, 1.24-1.46 as well as those with severe GD (HR, 1.20, 95% CI, 1.02-1.40, after adjusting for age, gender and comorbidities. In age-stratified analysis, patients aged 18-40 years with GD were at higher risk of developing CVD (HR, 1.42; 95% CI, 1.09-1.84 than older GD patients. CONCLUSION: This study found an increased risk of CVD in patients diagnosed with GD. The excess risk was particularly high in younger GD patients. Prevention of GD could help reduce the risk of developing CVD, and the better effect could be achieved for the younger age groups.

  2. Recombinant interleukin-2 significantly increases the survival of mice with peritonitis, but not acute Staphylococcus aureus peritoneal infection.

    Science.gov (United States)

    Shadrin, O V; Kaufman, O Y; Dronova, O M; Bykovskaya, S N

    1992-09-01

    The effect of recombinant interleukin 2 (rIL-2) on survival of mice with peritonitis and acute Staphylococcus aureus strain 5/2 infection was studied. rIL-2 was ineffective in the case of acute infection when administered simultaneously with LD95 dose of bacteria. The antibiotics (gentamycin or a combination of penicillin and streptomycin) administered in the same fashion cured 100% of animals. rIL-2 proved to be a potent healing agent in the two of three models of S aureus peritonitis. In this case animals received bacteria at days 0 and 2, 4, or 6. rIL-2 was injected at day 0 (group 1), days 0 and 2 (group 2), and days 0, 2, and 4 (group 3). Treatment with rIL-2 was ineffective in group 1; however, in groups 2 and 3 rIL-2 increased the survival up to 90% (in comparison with 30% in the untreated animals of group 2 and 64% in group 3). On the contrary, administration of antibiotics instead of rIL-2 in the group 3 decreased survival to 25%. The perspectives of rIL-2 use in the treatment of bacterial peritonitis, including purous ones, and the cases complicated by immunodepression, are discussed.

  3. Genomic distribution of CHD7 on chromatin tracks H3K4 methylation patterns.

    Science.gov (United States)

    Schnetz, Michael P; Bartels, Cynthia F; Shastri, Kuntal; Balasubramanian, Dheepa; Zentner, Gabriel E; Balaji, Ravishankar; Zhang, Xiaodong; Song, Lingyun; Wang, Zhenghe; Laframboise, Thomas; Crawford, Gregory E; Scacheri, Peter C

    2009-04-01

    CHD7 is a member of the chromodomain helicase DNA binding domain family of ATP-dependent chromatin remodeling enzymes. De novo mutation of the CHD7 gene is a major cause of CHARGE syndrome, a genetic disease characterized by a complex constellation of birth defects (Coloboma of the eye, Heart defects, Atresia of the choanae, severe Retardation of growth and development, Genital abnormalities, and Ear abnormalities). To gain insight into the function of CHD7, we mapped the distribution of the CHD7 protein on chromatin using the approach of chromatin immunoprecipitation on tiled microarrays (ChIP-chip). These studies were performed in human colorectal carcinoma cells, human neuroblastoma cells, and mouse embryonic stem (ES) cells before and after differentiation into neural precursor cells. The results indicate that CHD7 localizes to discrete locations along chromatin that are specific to each cell type, and that the cell-specific binding of CHD7 correlates with a subset of histone H3 methylated at lysine 4 (H3K4me). The CHD7 sites change concomitantly with H3K4me patterns during ES cell differentiation, suggesting that H3K4me is part of the epigenetic signature that defines lineage-specific association of CHD7 with specific sites on chromatin. Furthermore, the CHD7 sites are predominantly located distal to transcription start sites, most often contained within DNase hypersensitive sites, frequently conserved, and near genes expressed at relatively high levels. These features are similar to those of gene enhancer elements, raising the possibility that CHD7 functions in enhancer mediated transcription, and that the congenital anomalies in CHARGE syndrome are due to alterations in transcription of tissue-specific genes normally regulated by CHD7 during development.

  4. High Dose Atorvastatin Associated with Increased Risk of Significant Hepatotoxicity in Comparison to Simvastatin in UK GPRD Cohort.

    Directory of Open Access Journals (Sweden)

    Alan T Clarke

    Full Text Available Occasional risk of serious liver dysfunction and autoimmune hepatitis during atorvastatin therapy has been reported. We compared the risk of hepatotoxicity in atorvastatin relative to simvastatin treatment.The UK GPRD identified patients with a first prescription for simvastatin [164,407] or atorvastatin [76,411] between 1997 and 2006, but with no prior record of liver disease, alcohol-related diagnosis, or liver dysfunction. Incident liver dysfunction in the following six months was identified by biochemical value and compared between statin groups by Cox regression model adjusting for age, sex, year treatment started, dose, alcohol consumption, smoking, body mass index and comorbid conditions.Moderate to severe hepatotoxicity [bilirubin >60μmol/L, AST or ALT >200U/L or alkaline phosphatase >1200U/L] developed in 71 patients on atorvastatin versus 101 on simvastatin. Adjusted hazard ratio [AHR] for all atorvastatin relative to simvastatin was 1.9 [95% confidence interval 1.4-2.6]. High dose was classified as 40-80mg daily and low dose 10-20mg daily. Hepatotoxicity occurred in 0.44% of 4075 patients on high dose atorvastatin [HDA], 0.07% of 72,336 on low dose atorvastatin [LDA], 0.09% of 44,675 on high dose simvastatin [HDS] and 0.05% of 119,732 on low dose simvastatin [LDS]. AHRs compared to LDS were 7.3 [4.2-12.7] for HDA, 1.4 [0.9-2.0] for LDA and 1.5 [1.0-2.2] for HDS.The risk of hepatotoxicity was increased in the first six months of atorvastatin compared to simvastatin treatment, with the greatest difference between high dose atorvastatin and low dose simvastatin. The numbers of events in the analyses were small.

  5. Synthesis and characterization of the ternary telluroargentate K4[Ag18Te11

    KAUST Repository

    Davaasuren, Bambar

    2014-10-19

    The ternary potassium telluroargentate(I), K4[Ag18Te11], was prepared by solvothermal synthesis in ethylenediamine at 160 °C. It crystallizes in the cubic space group Fm3¯ m (no. 225) with the cell parameter a = 18.6589(6) Å. The crystal structure can be described as a [Ag18Te11]4- three-dimensional anionic framework with the voids accommodating potassium cations. Chemical bonding analysis reveals polar covalent Ag-Te bonds and considerable Ag-Ag interactions, which support the complex anionic character of the structure. The compound is thermally stable up to 450 °C in an inert atmosphere.

  6. Structural insight into the recognition of the H3K4me3 mark by the TFIID subunit TAF3

    NARCIS (Netherlands)

    van Ingen, H.|info:eu-repo/dai/nl/297054651; van Schaik, F.M.A.; Wienk, H.|info:eu-repo/dai/nl/203884884; Ballering, J.|info:eu-repo/dai/nl/325784876; Rehmann, H.; Dechesne, A.C.|info:eu-repo/dai/nl/304841684; Kruijzer, J.A.W.; Liskamp, R.M.J.|info:eu-repo/dai/nl/069091315; Timmers, H.T.M.; Boelens, R.|info:eu-repo/dai/nl/070151407

    2008-01-01

    Trimethylation of lysine residue K4 of histone H3 (H3K4me3) strongly correlates with active promoters for RNA polymerase II-transcribed genes. Several reader proteins, including the basal transcription factor TFIID, for this nucleosomal mark have been identified. Its TAF3 subunit specifically binds

  7. Electrochemical Catalysis of Inorganic Complex K4[Fe(CN)6] by Shewanellaoneidensis MR-1

    DEFF Research Database (Denmark)

    Zheng, Zhiyong; Wu, Ranran; Xiao, Yong

    The interaction between metal and bacteria is a universal and important biogeochemical processin environment. As a dissimilatory metal reduction bacterium, the electrochemically activebacteriium Shewanella oneidensis MR-1 can transfer intracellular electrons to minerals. This ability is attribute...... andelectrocatalysis mechanisms of S. oneidensis MR-1 are under investigation. The ability of S. oneidensis MR-1 to catalyze redoxaction of inorganic metal complex compounds will provide an insight on metal cycles in nature....... to the redox proteins localized on the outer-membrane, for example, the MtrC, MtrB, MtrA and CymA2. Here we investigate its electrochemical properties towards redoxinorganic redox compounds. It shows strong electrocatalysis toward electrochemical oxidation of K4[Fe(CN)6]. As a redox molecule, K4[Fe(CN)6] gives......, with almost disappearance of the cathodic peak and strengthen of the anodic peak, which is a typical catalysis feature of electrochemical oxidation. Further experiments show that S. oneidensis MR-1 does not give such electrocatalysis toredox compounds such as Ru[(NH3)6]Cl3and Resorufin. Selectivity...

  8. KEY COMPARISON: Final report on key comparison APMP.QM-K4.1: Ethanol in nitrogen

    Science.gov (United States)

    Kato, Kenji; Maruyama, Masaaki; Seog Kim, Jin; Hyub, Oh Sang; Woo, Jin-Chun; Kim, Yongdoo; Bae, Hyunkil; Han, Qiao; Zhou, Zeyi

    2008-01-01

    The aim of this comparison was to compare capabilities for the preparation and value assignment of gas mixture standards for ethanol in nitrogen, maintained at national metrology institutes (NMIs). The measurements in this key comparison took place in 2006. There were three participants and one coordinating laboratory. The key comparison reference value (KCRV) was based on the gravimetric preparation for all components. The range of the nominal amount-of-substance fractions of the comparison standard is 100 µmol/mol to 130 µmol/mol. The Chemical Evaluation Research Institute (CERI, Japan) prepared gravimetric mixture samples of ethanol in nitrogen in 10 L aluminium cylinders and the homogeneity and long-term stability of these samples were evaluated at CERI before and after the shipment of the cylinders to the participants. Each participating laboratory was shipped one cylinder to be analyzed and then returned to the CERI. Each sample was reanalyzed to verify whether the contents were stable throughout the comparison. These measurements showed no significant change in the amount fraction within the estimated uncertainty of the measurements. Two of the three participants submitted results that were within 0.1% of the relevant reference value. In these cases, the estimated uncertainty was larger than the deviation from the reference value. CERI was the link laboratory between CCQM-K4 and APMP.QM-K4. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCQM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  9. Changes in rocket salad phytochemicals within the commercial supply chain: Glucosinolates, isothiocyanates, amino acids and bacterial load increase significantly after processing.

    Science.gov (United States)

    Bell, Luke; Yahya, Hanis Nadia; Oloyede, Omobolanle Oluwadamilola; Methven, Lisa; Wagstaff, Carol

    2017-04-15

    Five cultivars of Eruca sativa and a commercial variety of Diplotaxis tenuifolia were grown in the UK (summer) and subjected to commercial growth, harvesting and processing, with subsequent shelf life storage. Glucosinolates (GSL), isothiocyanates (ITC), amino acids (AA), free sugars, and bacterial loads were analysed throughout the supply chain to determine the effects on phytochemical compositions. Bacterial load of leaves increased significantly over time and peaked during shelf life storage. Significant correlations were observed with GSL and AA concentrations, suggesting a previously unknown relationship between plants and endemic leaf bacteria. GSLs, ITCs and AAs increased significantly after processing and during shelf life. The supply chain did not significantly affect glucoraphanin concentrations, and its ITC sulforaphane significantly increased during shelf life in E. sativa cultivars. We hypothesise that commercial processing may increase the nutritional value of the crop, and have added health benefits for the consumer.

  10. MoSET1 (Histone H3K4 Methyltransferase in Magnaporthe oryzae Regulates Global Gene Expression during Infection-Related Morphogenesis.

    Directory of Open Access Journals (Sweden)

    Kieu Thi Minh Pham

    2015-07-01

    Full Text Available Here we report the genetic analyses of histone lysine methyltransferase (KMT genes in the phytopathogenic fungus Magnaporthe oryzae. Eight putative M. oryzae KMT genes were targeted for gene disruption by homologous recombination. Phenotypic assays revealed that the eight KMTs were involved in various infection processes at varying degrees. Moset1 disruptants (Δmoset1 impaired in histone H3 lysine 4 methylation (H3K4me showed the most severe defects in infection-related morphogenesis, including conidiation and appressorium formation. Consequently, Δmoset1 lost pathogenicity on wheat host plants, thus indicating that H3K4me is an important epigenetic mark for infection-related gene expression in M. oryzae. Interestingly, appressorium formation was greatly restored in the Δmoset1 mutants by exogenous addition of cAMP or of the cutin monomer, 16-hydroxypalmitic acid. The Δmoset1 mutants were still infectious on the super-susceptible barley cultivar Nigrate. These results suggested that MoSET1 plays roles in various aspects of infection, including signal perception and overcoming host-specific resistance. However, since Δmoset1 was also impaired in vegetative growth, the impact of MoSET1 on gene regulation was not infection specific. ChIP-seq analysis of H3K4 di- and tri-methylation (H3K4me2/me3 and MoSET1 protein during infection-related morphogenesis, together with RNA-seq analysis of the Δmoset1 mutant, led to the following conclusions: 1 Approximately 5% of M. oryzae genes showed significant changes in H3K4-me2 or -me3 abundance during infection-related morphogenesis. 2 In general, H3K4-me2 and -me3 abundance was positively associated with active transcription. 3 Lack of MoSET1 methyltransferase, however, resulted in up-regulation of a significant portion of the M. oryzae genes in the vegetative mycelia (1,491 genes, and during infection-related morphogenesis (1,385 genes, indicating that MoSET1 has a role in gene repression either

  11. Se14, encoding a JmjC domain-containing protein, plays key roles in long-day suppression of rice flowering through the demethylation of H3K4me3 of RFT1.

    Directory of Open Access Journals (Sweden)

    Takayuki Yokoo

    Full Text Available Floral transition from the vegetative to the reproductive growth phase is a major change in the plant life cycle and a key factor in reproductive success. In rice (Oryza sativa L., a facultative short-day plant, numerous flowering time and flower formation genes that control floral transition have been identified and their physiological effects and biochemical functions have been clarified. In the present study, we used a Se14-deficient mutant line (HS112 and other flowering mutant lines to investigate the photoperiodic response, chromosomal location and function in the photoperiod sensitivity of the Se14 gene. We also studied the interactive effects of this locus with other crucial flowering time genes. We found that Se14 is independent of the known photoperiod-sensitive genes, such as Hd1 and Ghd7, and is identical to Os03g0151300, which encodes a Jumonji C (JmjC domain-containing protein. Expression analysis revealed that the expressions of RFT1, a floral initiator known as a "florigen-like gene", and Ehd1 were up-regulated in HS112, whereas this up-regulation was not observed in the original variety of 'Gimbozu'. ChIP assays of the methylation states of histone H3 at lysine 4 (H3K4 revealed that the trimethylated H3K4 in the promoter region of the RFT1 chromatin was significantly increased in HS112. We conclude that Se14 is a novel photoperiod-sensitivity gene that has a suppressive effect on floral transition (flowering time under long day-length conditions through the modification of chromatin structure by H3K4me3 demethylation in the promoter region of RFT1.

  12. 关于多重多部图λKn(t)的(K4-e,λ)—分解%Decomposition of Complete Multipartite Multi-graph λKn(t) into K4-e

    Institute of Scientific and Technical Information of China (English)

    赵彤

    2001-01-01

    Hoffman在文献[6]中已经完全解决了多重完全图λKn(t)的(K4-e,λ)一分解问题.本文将Hoffman的结果从多重完全图推广到多重多部图,证明了λKn(t)的(K4-e,λ)-分解存在的充分必要条件.

  13. Epigenetic Profiling of H3K4Me3 Reveals Herbal Medicine Jinfukang-Induced Epigenetic Alteration Is Involved in Anti-Lung Cancer Activity

    Directory of Open Access Journals (Sweden)

    Jun Lu

    2016-01-01

    Full Text Available Traditional Chinese medicine Jinfukang (JFK has been clinically used for treating lung cancer. To examine whether epigenetic modifications are involved in its anticancer activity, we performed a global profiling analysis of H3K4Me3, an epigenomic marker associated with active gene expression, in JFK-treated lung cancer cells. We identified 11,670 genes with significantly altered status of H3K4Me3 modification following JFK treatment (P<0.05. Gene Ontology analysis indicates that these genes are involved in tumor-related pathways, including pathway in cancer, basal cell carcinoma, apoptosis, induction of programmed cell death, regulation of transcription (DNA-templated, intracellular signal transduction, and regulation of peptidase activity. In particular, we found that the levels of H3K4Me3 at the promoters of SUSD2, CCND2, BCL2A1, and TMEM158 are significantly altered in A549, NCI-H1975, NCI-H1650, and NCI-H2228 cells, when treated with JFK. Collectively, these findings provide the first evidence that the anticancer activity of JFK involves modulation of histone modification at many cancer-related gene loci.

  14. Differential expression of K4-AP currents and Kv3.1 potassium channel transcripts in cortical neurons that develop distinct firing phenotypes.

    Science.gov (United States)

    Massengill, J L; Smith, M A; Son, D I; O'Dowd, D K

    1997-05-01

    Maturation of electrical excitability during early postnatal development is critical to formation of functional neural circuitry in the mammalian neocortex. Little is known, however, about the changes in gene expression underlying the development of firing properties that characterize different classes of cortical neurons. Here we describe the development of cortical neurons with two distinct firing phenotypes, regular-spiking (RS) and fast-spiking (FS), that appear to emerge from a population of immature multiple-spiking (IMS) neurons during the first two postnatal weeks, both in vivo (within layer IV) and in vitro. We report the expression of a slowly inactivating, 4-AP-sensitive potassium current (K4-AP) at significantly higher density in FS compared with RS neurons. The same current is expressed at intermediate levels in IMS neurons. The kinetic, voltage-dependent, and pharmacological properties of the K4-AP current are similar to those observed by heterologous expression of Kv3.1 potassium channel mRNA. Single-cell RT-PCR analysis demonstrates that PCR products representing Kv3.1 transcripts are amplified more frequently from FS than RS neurons, with an intermediate frequency of Kv3.1 detection in neurons with immature firing properties. Taken together, these data suggest that the Kv3.1 gene encodes the K4-AP current and that expression of this gene is regulated in a cell-specific manner during development. Analysis of the effects of 4-AP on firing properties suggests that the K4-AP current is important for rapid action potential repolarization, fast after-hyperpolarization, brief refractory period, and high firing frequency characteristic of FS GABAergic interneurons.

  15. Improved immunoelectron microscopic method for localizing cytoskeletal proteins in Lowicryl K4M embedded tissues.

    Science.gov (United States)

    Loesser, K E; Doane, K J; Wilson, F J; Roisen, F J; Malamed, S

    1986-11-01

    We have modified the Lowicryl K4M low-temperature dehydration and embedding procedure for immunoelectron microscopy to provide improved ultrastructural detail and facilitate the localization of actin and tubulin in isolated rat adrenocortical cells, chick spinal cord with attached dorsal root ganglia (SC-DRG), and cultured dorsal root ganglia (DRG). Cells and tissues were fixed for immunocytochemistry either in a mixture of 2% paraformaldehyde and 0.25% glutaraldehyde (0.1 M PIPES buffer, pH 7.3) or in a mixture of 0.3% glutaraldehyde and 1.0% ethyldimethylaminopropylcarbodiimide (0.1 M phosphate buffered saline, pH 7.3). Dehydration was in ethanol at progressively lower temperatures to -35 degrees C. Infiltration at -35 degrees C was followed by ultraviolet polymerization at -20 degrees C. Comparable samples were fixed in glutaraldehyde and osmium tetroxide and embedded in Epon 812 or Epon-Araldite. Post-embedding immunostaining of thin sections utilized commercially available monoclonal antibodies to tubulin and actin followed by the protein A-gold technique (Roth et al., Endocrinology 108:247, 1981). Actin immunoreactivity was observed at the periphery of mitochondria and between mitochondria and lipid droplets in rat adrenocortical cells and at the periphery of neuronal cell processes of SC-DRG. Tubulin immunoreactivity was associated with microtubules throughout neurites of cultured DRG. Our modified technique allows preservation of ultrastructural details as well as localization of antigens by immunoelectron microscopy.

  16. RSV-Induced H3K4 Demethylase KDM5B Leads to Regulation of Dendritic Cell-Derived Innate Cytokines and Exacerbates Pathogenesis In Vivo.

    Directory of Open Access Journals (Sweden)

    Catherine Ptaschinski

    2015-06-01

    Full Text Available Respiratory syncytial virus (RSV infection can result in severe disease partially due to its ability to interfere with the initiation of Th1 responses targeting the production of type I interferons (IFN and promoting a Th2 immune environment. Epigenetic modulation of gene transcription has been shown to be important in regulating inflammatory pathways. RSV-infected bone marrow-derived DCs (BMDCs upregulated expression of Kdm5b/Jarid1b H3K4 demethylase. Kdm5b-specific siRNA inhibition in BMDC led to a 10-fold increase in IFN-β as well as increases in IL-6 and TNF-α compared to control-transfected cells. The generation of Kdm5bfl/fl-CD11c-Cre+ mice recapitulated the latter results during in vitro DC activation showing innate cytokine modulation. In vivo, infection of Kdm5bfl/fl-CD11c-Cre+ mice with RSV resulted in higher production of IFN-γ and reduced IL-4 and IL-5 compared to littermate controls, with significantly decreased inflammation, IL-13, and mucus production in the lungs. Sensitization with RSV-infected DCs into the airways of naïve mice led to an exacerbated response when mice were challenged with live RSV infection. When Kdm5b was blocked in DCs with siRNA or DCs from Kdm5bfl/fl-CD11c-CRE mice were used, the exacerbated response was abrogated. Importantly, human monocyte-derived DCs treated with a chemical inhibitor for KDM5B resulted in increased innate cytokine levels as well as elicited decreased Th2 cytokines when co-cultured with RSV reactivated CD4+ T cells. These results suggest that KDM5B acts to repress type I IFN and other innate cytokines to promote an altered immune response following RSV infection that contributes to development of chronic disease.

  17. Ag 插层 K4Nb6O17复合光催化剂降解水中有机污染物%The Degradation of Organic Pollutants in Water on The Ag-intercalated K4Nb6O17 Composite Photocatalyst

    Institute of Scientific and Technical Information of China (English)

    穆晨帆; 梁英华; 刘利; 胡金山; 崔文权

    2015-01-01

    Ag-intercalated layered niobate (denoted as K4Nb6O17/Ag) was synthesized via a micr-owave-assisted ion-exchange method. The high enhanced activity of the composite photocatalyst was observed during the degradation of methylene blue (MB). Also, the degradation rate of MB by K4Nb6O17/Ag was higher when the solution pH increased. The composite photocatalyst showed the high enhanced activity with the different concentration of MB. In the same condition, K4Nb6O17/Ag showed higher photocatalysis than Ag-loaded K4Nb6O17 and Ag-loaded TiO2 composite photocat-alysts.%介绍了通过微波辅助的离子交换法制备 Ag 插层 K4Nb6O17复合光催化剂。复合光催化剂在降解水体中亚甲基蓝的过程中呈现出很高的光催化活性,并且插层复合光催化剂对亚基蓝在碱性条件下能发挥更高效的降解作用且对不同初始浓度的亚甲基蓝均具有较好的移除降解效率。在相同的反应条件下, Ag 插层复合光催化剂要比等量的 Ag 负载 K4Nb6O17, Ag 负载 TiO2复合光催化剂活性高很多,使 Ag 插层 K4Nb6O17复合光催化剂在净化水体污染物方面表现出更显著的优势。

  18. Comparative analyses of H3K4 and H3K27 trimethylations between the mouse cerebrum and testis.

    Science.gov (United States)

    Cui, Peng; Liu, Wanfei; Zhao, Yuhui; Lin, Qiang; Zhang, Daoyong; Ding, Feng; Xin, Chengqi; Zhang, Zhang; Song, Shuhui; Sun, Fanglin; Yu, Jun; Hu, Songnian

    2012-04-01

    The global features of H3K4 and H3K27 trimethylations (H3K4me3 and H3K27me3) have been well studied in recent years, but most of these studies were performed in mammalian cell lines. In this work, we generated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChIP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLiD technology. We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression, function and development. Moreover, we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes, which contradicts the findings in previous studies. Finally, we observed that bivalent domains, with both H3K4me3 and H3K27me3, existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes. However, the bivalent domains tend towards a "winner-takes-all" approach to regulate the expression of associated genes. We also verified the above results in mouse ES cells. As expected, the results in ES cells are consistent with those in cerebrum and testis. In conclusion, we present two very important findings. One is that H3K4me3 and H3K27me3 rarely occur in silent genes. The other is that bivalent domains may adopt a "winner-takes-all" principle to regulate gene expression. Copyright © 2012 Beijing Institute of Genomics, Chinese Academy of Sciences. Published by Elsevier Ltd. All rights reserved.

  19. Predicting the probability of H3K4me3 occupation at a base pair from the genome sequence context.

    Science.gov (United States)

    Ha, Misook; Hong, Soondo; Li, Wen-Hsiung

    2013-05-01

    Histone modifications regulate chromatin structure and gene expression. Although nucleosome formation is known to be affected by primary DNA sequence composition, no sequence signature has been identified for histone modifications. It is known that dense H3K4me3 nucleosome sites are accompanied by a low density of other nucleosomes and are associated with gene activation. This observation suggests a different sequence composition of H3K4me3 from other nucleosomes. To understand the relationship between genome sequence and chromatin structure, we studied DNA sequences at histone modification sites in various human cell types. We found sequence specificity for H3K4me3, but not for other histone modifications. Using the sequence specificities of H3 and H3K4me3 nucleosomes, we developed a model that computes the probability of H3K4me3 occupation at each base pair from the genome sequence context. A comparison of our predictions with experimental data suggests a high performance of our method, revealing a strong association between H3K4me3 and specific genomic DNA context. The high probability of H3K4me3 occupation occurs at transcription start and termination sites, exon boundaries and binding sites of transcription regulators involved in chromatin modification activities, including histone acetylases and enhancer- and insulator-associated factors. Thus, the human genome sequence contains signatures for chromatin modifications essential for gene regulation and development. Our method may be applied to find new sequence elements functioning by chromatin modulation. Software and supplementary data are available at Bioinformatics online.

  20. Comparative Analyses of H3K4 and H3K27 Trimethylations Between the Mouse Cerebrum and Testis

    KAUST Repository

    Cui, Peng

    2012-06-08

    The global features of H3K4 and H3K27 trimethylations (H3K4me3 and H3K27me3) have been well studied in recent years, but most of these studies were performed in mammalian cell lines. In this work, we generated the genome-wide maps of H3K4me3 and H3K27me3 of mouse cerebrum and testis using ChIP-seq and their high-coverage transcriptomes using ribominus RNA-seq with SOLiD technology. We examined the global patterns of H3K4me3 and H3K27me3 in both tissues and found that modifications are closely-associated with tissue-specific expression, function and development. Moreover, we revealed that H3K4me3 and H3K27me3 rarely occur in silent genes, which contradicts the findings in previous studies. Finally, we observed that bivalent domains, with both H3K4me3 and H3K27me3, existed ubiquitously in both tissues and demonstrated an invariable preference for the regulation of developmentally-related genes. However, the bivalent domains tend towards a “winner-takes-all” approach to regulate the expression of associated genes. We also verified the above results in mouse ES cells. As expected, the results in ES cells are consistent with those in cerebrum and testis. In conclusion, we present two very important findings. One is that H3K4me3 and H3K27me3 rarely occur in silent genes. The other is that bivalent domains may adopt a “winner-takes-all” principle to regulate gene expression.

  1. Predicting the probability of H3K4me3 occupation at a base pair from the genome sequence context

    Science.gov (United States)

    Ha, Misook; Hong, Soondo; Li, Wen-Hsiung

    2013-01-01

    Motivation: Histone modifications regulate chromatin structure and gene expression. Although nucleosome formation is known to be affected by primary DNA sequence composition, no sequence signature has been identified for histone modifications. It is known that dense H3K4me3 nucleosome sites are accompanied by a low density of other nucleosomes and are associated with gene activation. This observation suggests a different sequence composition of H3K4me3 from other nucleosomes. Approach: To understand the relationship between genome sequence and chromatin structure, we studied DNA sequences at histone modification sites in various human cell types. We found sequence specificity for H3K4me3, but not for other histone modifications. Using the sequence specificities of H3 and H3K4me3 nucleosomes, we developed a model that computes the probability of H3K4me3 occupation at each base pair from the genome sequence context. Results: A comparison of our predictions with experimental data suggests a high performance of our method, revealing a strong association between H3K4me3 and specific genomic DNA context. The high probability of H3K4me3 occupation occurs at transcription start and termination sites, exon boundaries and binding sites of transcription regulators involved in chromatin modification activities, including histone acetylases and enhancer- and insulator-associated factors. Thus, the human genome sequence contains signatures for chromatin modifications essential for gene regulation and development. Our method may be applied to find new sequence elements functioning by chromatin modulation. Availability: Software and supplementary data are available at Bioinformatics online. Contact: misook.ha@samsung.com or wli@uchicago.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23511541

  2. Macrohistone Variants Preserve Cell Identity by Preventing the Gain of H3K4me2 during Reprogramming to Pluripotency

    Directory of Open Access Journals (Sweden)

    María J. Barrero

    2013-04-01

    Full Text Available Transcription-factor-induced reprogramming of somatic cells to pluripotency is a very inefficient process, probably due to the existence of important epigenetic barriers that are imposed during differentiation and that contribute to preserving cell identity. In an effort to decipher the molecular nature of these barriers, we followed a genome-wide approach, in which we identified macrohistone variants (macroH2A as highly expressed in human somatic cells but downregulated after reprogramming to pluripotency, as well as strongly induced during differentiation. Knockdown of macrohistone variants in human keratinocytes increased the efficiency of reprogramming to pluripotency, whereas overexpression had opposite effects. Genome-wide occupancy profiles show that in human keratinocytes, macroH2A.1 preferentially occupies genes that are expressed at low levels and are marked with H3K27me3, including pluripotency-related genes and bivalent developmental regulators. The presence of macroH2A.1 at these genes prevents the regain of H3K4me2 during reprogramming, imposing an additional layer of repression that preserves cell identity.

  3. Aberrant intracellular localization of H3k4me3 demonstrates an early epigenetic phenomenon in Alzheimer’s disease

    Science.gov (United States)

    Mastroeni, Diego; Delvaux, Elaine; Nolz, Jennifer; Tan, Yuyan; Grover, Andrew; Oddo, Salvatore; Coleman, Paul D.

    2016-01-01

    We have previously reported in Alzheimer’s disease (AD) the mislocalization of epigenetic molecules between the cell nucleus and the cytoplasm. We have extended our finding to include the aberrant localization of histone 3 trimethylation on lysine 4 (H3k4me3), an epigenetic mark associated with actively transcribing genes as well as those poised for transcription. These findings raise the question of where the ectopic localization of H3k4me3 fits within the cascade of cell biological events in the progression of AD. We, therefore, examined the expression and intracellular location of H3k4me3 as a function of Braak stage and also in relation to a series of tau markers that are indicative of disease state. Both lines of evidence showed that ectopic localization of H3k4me3 is early in the course of disease. Because of the known role of H3k4me3 in the expression of synaptic genes, our data suggest an epigenetic role in synaptic deficits early in the course of AD. PMID:26553823

  4. Aberrant intracellular localization of H3k4me3 demonstrates an early epigenetic phenomenon in Alzheimer's disease.

    Science.gov (United States)

    Mastroeni, Diego; Delvaux, Elaine; Nolz, Jennifer; Tan, Yuyan; Grover, Andrew; Oddo, Salvatore; Coleman, Paul D

    2015-12-01

    We have previously reported in Alzheimer's disease (AD) the mislocalization of epigenetic molecules between the cell nucleus and the cytoplasm. We have extended our finding to include the aberrant localization of histone 3 trimethylation on lysine 4 (H3k4me3), an epigenetic mark associated with actively transcribing genes as well as those poised for transcription. These findings raise the question of where the ectopic localization of H3k4me3 fits within the cascade of cell biological events in the progression of AD. We, therefore, examined the expression and intracellular location of H3k4me3 as a function of Braak stage and also in relation to a series of tau markers that are indicative of disease state. Both lines of evidence showed that ectopic localization of H3k4me3 is early in the course of disease. Because of the known role of H3k4me3 in the expression of synaptic genes, our data suggest an epigenetic role in synaptic deficits early in the course of AD. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Transcriptional regulation of the differentiation-linked human K4 promoter is dependent upon esophageal-specific nuclear factors.

    Science.gov (United States)

    Opitz, O G; Jenkins, T D; Rustgi, A K

    1998-09-11

    The stratified squamous epithelium comprises actively proliferating basal cells that undergo a program of differentiation accompanied by morphological, biochemical, and genetic changes. The transcriptional regulatory signals and the genes that orchestrate this switch from proliferation to differentiation can be studied through the keratin gene family. Given the localization of keratin 4 (K4) to the early differentiated suprabasal compartment and having previously demonstrated that targeted disruption of this gene in murine embryonic stem cells results in impairment of the normal differentiation program in esophageal and corneal epithelial cells, we studied the transcriptional regulation of the human K4 promoter. A panel of K4 promoter deletions were found in transient transfection assays to be predominantly active in esophageal and corneal cell lines. A critical cis-regulatory element resides between -163 and -140 bp and contains an inverted CACACCT motif. A site-directed mutated version of this motif within the K4 promoter renders it inactive, whereas the wild-type version is active in a heterologous promoter system. It specifically binds esophageal-specific zinc-dependent transcriptional factors. Our studies demonstrate that regulation of the human K4 promoter is in part mediated through tissue-specific transcriptional factors.

  6. Stage and gene specific signatures defined by histones H3K4me2 and H3K27me3 accompany mammalian retina maturation in vivo.

    Science.gov (United States)

    Popova, Evgenya Y; Xu, Xuming; DeWan, Andrew T; Salzberg, Anna C; Berg, Arthur; Hoh, Josephine; Zhang, Samuel S; Barnstable, Colin J

    2012-01-01

    The epigenetic contribution to neurogenesis is largely unknown. There is, however, growing evidence that posttranslational modification of histones is a dynamic process that shows many correlations with gene expression. Here we have followed the genome-wide distribution of two important histone H3 modifications, H3K4me2 and H3K27me3 during late mouse retina development. The retina provides an ideal model for these studies because of its well-characterized structure and development and also the extensive studies of the retinal transcriptome and its development. We found that a group of genes expressed only in mature rod photoreceptors have a unique signature consisting of de-novo accumulation of H3K4me2, both at the transcription start site (TSS) and over the whole gene, that correlates with the increase in transcription, but no accumulation of H3K27me3 at any stage. By in silico analysis of this unique signature we have identified a larger group of genes that may be selectively expressed in mature rod photoreceptors. We also found that the distribution of H3K4me2 and H3K27me3 on the genes widely expressed is not always associated with their transcriptional levels. Different histone signatures for retinal genes with the same gene expression pattern suggest the diversities of epigenetic regulation. Genes without H3K4me2 and H3K27me3 accumulation at any stage represent a large group of transcripts never expressed in retina. The epigenetic signatures defined by H3K4me2 and H3K27me3 can distinguish cell-type specific genes from widespread transcripts and may be reflective of cell specificity during retina maturation. In addition to the developmental patterns seen in wild type retina, the dramatic changes of histone modification in the retinas of mutant animals lacking rod photoreceptors provide a tool to study the epigenetic changes in other cell types and thus describe a broad range of epigenetic events in a solid tissue in vivo.

  7. Stage and gene specific signatures defined by histones H3K4me2 and H3K27me3 accompany mammalian retina maturation in vivo.

    Directory of Open Access Journals (Sweden)

    Evgenya Y Popova

    Full Text Available The epigenetic contribution to neurogenesis is largely unknown. There is, however, growing evidence that posttranslational modification of histones is a dynamic process that shows many correlations with gene expression. Here we have followed the genome-wide distribution of two important histone H3 modifications, H3K4me2 and H3K27me3 during late mouse retina development. The retina provides an ideal model for these studies because of its well-characterized structure and development and also the extensive studies of the retinal transcriptome and its development. We found that a group of genes expressed only in mature rod photoreceptors have a unique signature consisting of de-novo accumulation of H3K4me2, both at the transcription start site (TSS and over the whole gene, that correlates with the increase in transcription, but no accumulation of H3K27me3 at any stage. By in silico analysis of this unique signature we have identified a larger group of genes that may be selectively expressed in mature rod photoreceptors. We also found that the distribution of H3K4me2 and H3K27me3 on the genes widely expressed is not always associated with their transcriptional levels. Different histone signatures for retinal genes with the same gene expression pattern suggest the diversities of epigenetic regulation. Genes without H3K4me2 and H3K27me3 accumulation at any stage represent a large group of transcripts never expressed in retina. The epigenetic signatures defined by H3K4me2 and H3K27me3 can distinguish cell-type specific genes from widespread transcripts and may be reflective of cell specificity during retina maturation. In addition to the developmental patterns seen in wild type retina, the dramatic changes of histone modification in the retinas of mutant animals lacking rod photoreceptors provide a tool to study the epigenetic changes in other cell types and thus describe a broad range of epigenetic events in a solid tissue in vivo.

  8. SET DOMAIN GROUP701 encodes a H3K4-methytransferase and regulates multiple key processes of rice plant development.

    Science.gov (United States)

    Liu, Kunpeng; Yu, Yu; Dong, Aiwu; Shen, Wen-Hui

    2017-07-01

    Chromatin-based epigenetic information plays an important role in developmental gene regulation, in response to environment, and in natural variation of gene expression levels. Histone H3 lysine 4 di/trimethylation (H3K4me2/3) is abundant in euchromatin and is generally associated with transcriptional activation. Strikingly, however, enzymes catalyzing H3K4me2/3 remain poorly characterized in crops so far. Here, we investigated the function of the rice SET DOMAIN GROUP 701 (SDG701) gene by molecular and biochemical characterization of the gene product, and by studying effects of its loss or gain of function on plant growth and development. We demonstrated that SDG701 encodes a methytransferase specifically catalyzing H3K4 methylation. Overexpression and knockdown experiments showed that SDG701 is crucial for proper sporophytic plant development as well as for gametophytic transmission that directly impacts rice grain production. In-depth analysis of plant flowering time revealed that SDG701 promotes rice flowering under either long-day or short-day photoperiods. Consistently, the SDG701 protein was found to bind chromatin to promote H3K4me3 and to enhance expression of the rice Hd3a and RFT1 florigens. Collectively, our results establish SDG701 as a major rice H3K4-specific methyltransferase and provide important insights into function of H3K4me3 deposition in transcription activation of florigens in promoting plant flowering. © 2017 The Authors. New Phytologist © 2017 New Phytologist Trust.

  9. Significant Increase in Hydrogen Photoproduction Rates and Yields by Wild-Type Algae is Detected at High Photobioreactor Gas Phase Volume (Fact Sheet)

    Energy Technology Data Exchange (ETDEWEB)

    2012-07-01

    This NREL Hydrogen and Fuel Cell Technical Highlight describes how hydrogen photoproduction activity in algal cultures can be improved dramatically by increasing the gas-phase to liquid-phase volume ratio of the photobioreactor. NREL, in partnership with subcontractors from the Institute of Basic Biological Problems in Pushchino, Russia, demonstrated that the hydrogen photoproduction rate in algal cultures always decreases exponentially with increasing hydrogen partial pressure above the culture. The inhibitory effect of high hydrogen concentrations in the photobioreactor gas phase on hydrogen photoproduction by algae is significant and comparable to the effect observed with some anaerobic bacteria.

  10. Aberrant intracellular localization of H3k4me3 demonstrates an early epigenetic phenomenon in Alzheimer’s disease

    OpenAIRE

    Mastroeni, Diego; Delvaux, Elaine; Nolz, Jennifer; Tan, Yuyan; Grover, Andrew; Oddo, Salvatore; Coleman, Paul D.

    2015-01-01

    We have previously reported in Alzheimer’s disease (AD) the mislocalization of epigenetic molecules between the cell nucleus and the cytoplasm. We have extended our finding to include the aberrant localization of histone 3 trimethylation on lysine 4 (H3k4me3), an epigenetic mark associated with actively transcribing genes as well as those poised for transcription. These findings raise the question of where the ectopic localization of H3k4me3 fits within the cascade of cell biological events i...

  11. Editorial Commentary: Big Data Suggest That Because of a Significant Increased Risk of Postoperative Infection, Steroid Injection Is Not Recommended After Ankle Arthroscopy.

    Science.gov (United States)

    Brand, Jefferson C

    2016-02-01

    A recent study addressing infection rate after intra-articular steroid injection during ankle arthroscopy gives pause to this practice, with an odds ratio of 2.2 in the entire population that was injected with a steroid simultaneously with ankle arthroscopy compared with patients who did not receive an ankle injection. Big data, used in the study upon which the Editor comments here, suggest that because of a significant increased risk of postoperative infection, steroid injection is not recommended after ankle arthroscopy.

  12. Endosperm-specific co-expression of recombinant soybean ferritin and Aspergillus phytase in maize results in significant increases in the levels of bioavailable iron.

    Science.gov (United States)

    Drakakaki, Georgia; Marcel, Sylvain; Glahn, Raymond P; Lund, Elizabeth K; Pariagh, Sandra; Fischer, Rainer; Christou, Paul; Stoger, Eva

    2005-12-01

    We have generated transgenic maize plants expressing Aspergillus phytase either alone or in combination with the iron-binding protein ferritin. Our aim was to produce grains with increased amounts of bioavailable iron in the endosperm. Maize seeds expressing recombinant phytase showed enzymatic activities of up to 3 IU per gram of seed. In flour paste prepared from these seeds, up to 95% of the endogenous phytic acid was degraded, with a concomitant increase in the amount of available phosphate. In seeds expressing ferritin in addition to phytase, the total iron content was significantly increased. To evaluate the impact of the recombinant proteins on iron absorption in the human gut, we used an in vitro digestion/Caco-2 cell model. We found that phytase in the maize seeds was associated with increased cellular iron uptake, and that the rate of iron uptake correlated with the level of phytase expression regardless of the total iron content of the seeds. We also investigated iron bioavailability under more complex meal conditions by adding ascorbic acid, which promotes iron uptake, to all samples. This resulted in a further increase in iron absorption, but the effects of phytase and ascorbic acid were not additive. We conclude that the expression of recombinant ferritin and phytase could help to increase iron availability and enhance the absorption of iron, particularly in cereal-based diets that lack other nutritional components.

  13. Infection Exposure Promotes ETV6-RUNX1 Precursor B-cell Leukemia via Impaired H3K4 Demethylases.

    Science.gov (United States)

    Rodríguez-Hernández, Guillermo; Hauer, Julia; Martín-Lorenzo, Alberto; Schäfer, Daniel; Bartenhagen, Christoph; García-Ramírez, Idoia; Auer, Franziska; González-Herrero, Inés; Ruiz-Roca, Lucia; Gombert, Michael; Okpanyi, Vera; Fischer, Ute; Chen, Cai; Dugas, Martin; Bhatia, Sanil; Linka, René Martin; Garcia-Suquia, Marta; Rascón-Trincado, María Victoria; Garcia-Sanchez, Angel; Blanco, Oscar; García-Cenador, Maria Begoña; García-Criado, Francisco Javier; Cobaleda, César; Alonso-López, Diego; De Las Rivas, Javier; Müschen, Markus; Vicente-Dueñas, Carolina; Sánchez-García, Isidro; Borkhardt, Arndt

    2017-08-15

    ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B-cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here, we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/precursor cells (HSC/PC) and postnatal infections for human-like pB-ALL. In our model, ETV6-RUNX1 conferred a low risk of developing pB-ALL after exposure to common pathogens, corroborating the low incidence observed in humans. Murine preleukemic ETV6-RUNX1 pro/preB cells showed high Rag1/2 expression, known for human ETV6-RUNX1 pB-ALL. Murine and human ETV6-RUNX1 pB-ALL revealed recurrent genomic alterations, with a relevant proportion affecting genes of the lysine demethylase (KDM) family. KDM5C loss of function resulted in increased levels of H3K4me3, which coprecipitated with RAG2 in a human cell line model, laying the molecular basis for recombination activity. We conclude that alterations of KDM family members represent a disease-driving mechanism and an explanation for RAG off-target cleavage observed in humans. Our results explain the genetic basis for clonal evolution of an ETV6-RUNX1 preleukemic clone to pB-ALL after infection exposure and offer the possibility of novel therapeutic approaches. Cancer Res; 77(16); 4365-77. ©2017 AACR. ©2017 American Association for Cancer Research.

  14. Role of RbBP5 and H3K4me3 in the vicinity of Snail transcription start site during epithelial-mesenchymal transition in prostate cancer cell.

    Science.gov (United States)

    Li, Dong; Sun, Hui; Sun, Wen-Jing; Bao, Hong-Bo; Si, Shu-Han; Fan, Jia-Lin; Lin, Ping; Cui, Rong-Jun; Pan, Yu-Jia; Wen, Si-Min; Zheng, Xiu-Lan; Yu, Xiao-Guang

    2016-10-04

    EMT (epithelial-mesenchymal transition) occurs in a wide range of tumor types, and has been shown to be crucial for metastasis. Epigenetic modifications of histones contribute to chromatin structure and result in the alterations in gene expression. Tri-methylation of histone H3 lysine 4 (H3K4me3) is associated with the promoters of actively transcribed genes and can serve as a transcriptional on/off switch. RbBP5 is a component of the COMPASS/ -like complex, which catalyzes H3K4me3 formation. In this study, we found that in the process of TGF-Beta1 induced EMT in the prostate cancer cell line DU145, H3K4me3 enrichment and RbBP5 binding increased in the vicinity of Snail (SNAI1) transcription start site. Knocking-down of RbBP5 notably decreased Snail expression and EMT. Recruitment of RbBP5 and formation of H3K4me3 at Snail TSS during EMT depend on binding of SMAD2/3 and CBP at Snail TSS. This study links the SMAD2/3 signal with Snail transcription via a histone modification - H3K4me3. Furthermore, our research also demonstrates that RbBP5 and even WRAD may be a promising therapeutic candidates in treating prostate cancer metastasis, and that DU145 cells maintain their incomplete mesenchymal state in an auto/ paracrine manner.

  15. Significant association between glycemic status and increased estimated postglomerular resistance in nondiabetic subjects - study of inulin and para-aminohippuric acid clearance in humans.

    Science.gov (United States)

    Yasumoto, Mari; Tsuda, Akihiro; Ishimura, Eiji; Uedono, Hideki; Ohno, Yoshiteru; Ichii, Mitsuru; Ochi, Akinobu; Nakatani, Shinya; Mori, Katsuhito; Uchida, Junji; Emoto, Masanori; Nakatani, Tatsuya; Inaba, Masaaki

    2015-03-01

    We investigated whether glomerular hemodynamic parameters in nondiabetic subjects, including healthy subjects, are associated with glycemic status indices, by simultaneous measurement of inulin (Cin) and para-aminohippuric acid (CPHA) clearance. Twenty-six subjects (age 49.5 ± 13.3 years; 13 men and 13 women; 14 healthy subjects and 12 subjects with mild proteinuria) were enrolled. Cin and CPAH were measured simultaneously. All 26 subjects were nondiabetics. Estimated preglomerular resistance, estimated postglomerular resistance, and estimated glomerular hydrostatic pressure (Pglo) were calculated according to Gomez' formula. Pglo correlated significantly and positively with hemoglobin A1c (HbA1c) in both healthy subjects (r = 0.532, P = 0.0498) and subjects with mild proteinuria (r = 0.681, P = 0.015). While there was no significant correlation between estimated preglomerular resistance and HbA1c, estimated postglomerular resistance correlated significantly and positively with HbA1c both in healthy subjects (r = 0.643, P = 0.013) and subjects with mild proteinuria (r = 0.589, P = 0.044). Glomerular filtration fraction, estimated Pglo and estimated postglomerular resistance in total subjects were associated significantly with HbA1c after adjustment for age, gender, and body mass index. These results demonstrate that, even in nondiabetic subjects, glycemic status is associated with estimated postglomerular resistance, but not estimated preglomerular resistance. It is suggested that increased estimated postglomerular resistance associated with higher HbA1c levels, even within the normal range, causes increased estimated Pglo, leading to increased FF. Thus, hemodynamic abnormalities associated with higher HbA1c levels may be related to glomerular hypertension, even in nondiabetic subjects.

  16. Draft Genome Sequence of Halomonas elongata Strain K4, an Endophytic Growth-Promoting Bacterium Enhancing Salinity Tolerance In Planta

    KAUST Repository

    Lafi, Feras Fawzi

    2016-11-04

    Halomonas elongata strain K4 is an endophytic bacterial strain that was isolated from roots of Cyperus conglomeratus collected at the Red Sea coast in Thuwal, Saudi Arabia. Here, we present a draft genome sequence of this strain, highlighting a number of pathways involved in plant growth promotion under salt stress.

  17. Draft Genome Sequence of Halomonas elongata Strain K4, an Endophytic Growth-Promoting Bacterium Enhancing Salinity Tolerance In Planta

    Science.gov (United States)

    Lafi, Feras F.; Ramirez-Prado, Juan S.; Alam, Intikhab; Bajic, Vladimir B.

    2016-01-01

    Halomonas elongata strain K4 is an endophytic bacterial strain that was isolated from roots of Cyperus conglomeratus collected at the Red Sea coast in Thuwal, Saudi Arabia. Here, we present a draft genome sequence of this strain, highlighting a number of pathways involved in plant growth promotion under salt stress. PMID:27811099

  18. An efficient solvent-free synthesis of imidazolines and benzimidazoles using K 4[Fe(CN 6] catalysis

    Directory of Open Access Journals (Sweden)

    Kabeer A. Shaikh

    2012-01-01

    Full Text Available Imidazolines and Benzimidazoles have been efficiently synthesized in high yields by treatment of 1,2-diamine with aldehydes using the metal co-ordinate complex K 4[Fe(CN 6] as a catalysis. The method was carried out under solvent free condition via oxidation of carbon-nitrogen bond. The process is green, mild and inexpensive.

  19. The Structure of a High-Affinity Kainate Receptor: GluK4 Ligand-Binding Domain Crystallized with Kainate.

    Science.gov (United States)

    Kristensen, Ole; Kristensen, Lise Baadsgaard; Møllerud, Stine; Frydenvang, Karla; Pickering, Darryl S; Kastrup, Jette Sandholm

    2016-09-01

    Ionotropic glutamate receptors play a key role in fast neurotransmission in the CNS and have been linked to several neurological diseases and disorders. One subfamily is the kainate receptors, which are grouped into low-affinity (GluK1-3) and high-affinity (GluK4-5) receptors based on their affinity for kainate. Although structures of the ligand-binding domain (LBD) of all low-affinity kainate receptors have been reported, no structures of the high-affinity receptor subunits are available. Here, we present the X-ray structure of GluK4-LBD with kainate at 2.05 Å resolution, together with thermofluor and radiolabel binding affinity data. Whereas binding-site residues in GluK4 are most similar to the AMPA receptor subfamily, the domain closure and D1-D2 interlobe contacts induced by kainate are similar to the low-affinity kainate receptor GluK1. These observations provide a likely explanation for the high binding affinity of kainate at GluK4-LBD.

  20. Computational inference of H3K4me3 and H3K27ac domain length

    Directory of Open Access Journals (Sweden)

    Julian Zubek

    2016-03-01

    Full Text Available Background. Recent epigenomic studies have shown that the length of a DNA region covered by an epigenetic mark is not just a byproduct of the assaying technologies and has functional implications for that locus. For example, expanded regions of DNA sequences that are marked by enhancer-specific histone modifications, such as acetylation of histone H3 lysine 27 (H3K27ac domains coincide with cell-specific enhancers, known as super or stretch enhancers. Similarly, promoters of genes critical for cell-specific functions are marked by expanded H3K4me3 domains in the cognate cell type, and these can span DNA regions from 4–5kb up to 40–50kb in length. These expanded H3K4me3 domains are known as buffer domains or super promoters. Methods. To ask what correlates with—and potentially regulates—the length of loci marked with these two important histone marks, H3K4me3 and H3K27ac, we built Random Forest regression models. With these models, we computationally identified genomic and epigenomic patterns that are predictive for the length of these marks in seven ENCODE cell lines. Results. We found that certain epigenetic marks and transcription factors explain the variability of the length of H3K4me3 and H3K27ac marks across different cell types, which implies that the lengths of these two epigenetic marks are tightly regulated in a given cell type. Our source code for the regression models and data can be found at our GitHub page: https://github.com/zubekj/broad_peaks. Discussion. Our Random Forest based regression models enabled us to estimate the individual contribution of different epigenetic marks and protein binding patterns to the length of H3K4me3 and H3K27ac deposition patterns, therefore potentially revealing genomic signatures at cell specific regulatory elements.

  1. The Application of Red Pigments from Streptomyces K-4B and Dayak Onions (Eleutherine palmifolia (L.) Merr.) In Colouring Glycerine Soap

    Science.gov (United States)

    Herlina; Asnani, A.; Diastuti, H.

    2017-02-01

    Glycerin soap has been colored with red pigment from Streptomyces K-4 B and Dayak onion (Eleutherine palmifolia (L.) Merr). Both red pigments from Streptomyces K-4B and Dayak onion were extracted with ethanol by maceration method, followed with soxhlet extraction. The concentration of red pigment added was varied (0, 200, 300, 400 μL) to evaluate the best product. The resulted glycerine soaps were characterized and analyzed based on SNI 06-3532-1994. The research results indicated that the glycerine soap has water content ranged from 0.36% to 12.56%; the amount of fatty acid ranged from 14% to 36.75%; the amount of free fatty acids ranged from 0% to 0.37%; the non-saponifiable fat ranged from 0.001 to 0.019%; the pH ranged from 10.33 to 11.06; the foam stability ranged from 0.61% to 89.09%. The results of analysis of variance showed that the effect between treatments significantly different at 95% confidence level (α = 0.05) on the characteristics of glycerine soap. The results of an organoleptic test with parameters observed were color, aroma, texture, foam, rough impression upon usage and rough impression after usage, gave “like to very like soap” with a maximum score of 4.67 (1 to 5 scale). Based on the color assessment, the organoleptic panelists preferred the glycerine soap of SK-4B3 (red pigment from Streptomyces K-4B, 200 μL) with the score of 4.30 (like to very like).

  2. The polymorphism interleukin-8 -251A/T is associated with a significantly increased risk of cancers from a meta-analysis.

    Science.gov (United States)

    Wang, Ziliang; Liu, Yang; Yang, Lina; Yin, Sheng; Zang, Rongyu; Yang, Gong

    2014-07-01

    Emerging evidences show that interleukin-8 (IL-8) has important regulatory functions in tumorigenesis. IL-8 -251A/T is a single nucleotide polymorphism in the promoter region of the IL-8 gene and affects IL-8 production. Analysis of previous studies on the association of -251A/T polymorphism with different cancer types remained to be illustrated. To further assess the effect of -251A/T polymorphism on cancer risks, we performed this meta-analysis, up to November 2013, of 12,917 cases with different cancer types and 17,689 controls from 47 published case-control designed studies. Statistical analyses were performed using STATA 11.0 software. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were used to assess the strength of associations. ORs with 95 % CIs for IL-8 -251A/T polymorphism and cancer were estimated using fixed- and random-effects models when appropriate. Significantly increased risks were found in overall under the models of A allele vs. T allele, AA vs. TT, and AA vs. AT/TT. Significantly elevated risks were observed in breast cancer under the models of A allele vs. T allele, AT vs. TT, AA/AT vs. TT, and AA vs. AT/TT, and in nasopharyngeal carcinoma under the models of AT vs. TT, AA/AT vs. TT, and AA vs. AT/TT. We found that significantly elevated risks were observed in the Asian population and hospital-based studies in all comparison models. Thus, this meta-analysis indicates that IL-8 -251A/T polymorphism is associated with a significantly increased risk of cancers and may provide evidence-based medical certificate to study the cancer susceptibility.

  3. Sunitinib significantly suppresses the proliferation, migration, apoptosis resistance, tumor angiogenesis and growth of triple-negative breast cancers but increases breast cancer stem cells.

    Science.gov (United States)

    Chinchar, Edmund; Makey, Kristina L; Gibson, John; Chen, Fang; Cole, Shelby A; Megason, Gail C; Vijayakumar, Srinivassan; Miele, Lucio; Gu, Jian-Wei

    2014-01-01

    The majority of triple-negative breast cancers (TNBCs) are basal-like breast cancers. However there is no reported study on anti-tumor effects of sunitinib in xenografts of basal-like TNBC (MDA-MB-468) cells. In the present study, MDA-MB-231, MDA-MB-468, MCF-7 cells were cultured using RPMI 1640 media with 10% FBS. Vascular endothelia growth factor (VEGF) protein levels were detected using ELISA (R & D Systams). MDA-MB-468 cells were exposed to sunitinib for 18 hours for measuring proliferation (3H-thymidine incorporation), migration (BD Invasion Chamber), and apoptosis (ApopTag and ApoScreen Anuexin V Kit). The effect of sunitinib on Notch-1 expression was determined by Western blot in cultured MDA-MB-468 cells. 10(6) MDA-MB-468 cells were inoculated into the left fourth mammary gland fat pad in athymic nude-foxn1 mice. When the tumor volume reached 100 mm(3), sunitinib was given by gavage at 80 mg/kg/2 days for 4 weeks. Tumor angiogenesis was determined by CD31 immunohistochemistry. Breast cancer stem cells (CSCs) isolated from the tumors were determined by flow cytometry analysis using CD44(+)/CD24(-) or low. ELISA indicated that VEGF was much more highly expressed in MDA-MB-468 cells than MDA-MB-231 and MCF-7 cells. Sunitinib significantly inhibited the proliferation, invasion, and apoptosis resistance in cultured basal like breast cancer cells. Sunitinib significantly increased the expression of Notch-1 protein in cultured MDA-MB-468 or MDA-MB-231 cells. The xenograft models showed that oral sunitinib significantly reduced the tumor volume of TNBCs in association with the inhibition of tumor angiogeneisis, but increased breast CSCs. These findings support the hypothesis that the possibility should be considered of sunitinib increasing breast CSCs though it inhibits TNBC tumor angiogenesis and growth/progression, and that effects of sunitinib on Notch expression and hypoxia may increase breast cancer stem cells. This work provides the groundwork for an

  4. Addition of a third field significantly increases dose to the brachial plexus for patients undergoing tangential whole-breast therapy after lumpectomy

    Energy Technology Data Exchange (ETDEWEB)

    Stanic, Sinisa; Mathai, Mathew; Mayadev, Jyoti S.; Do, Ly V.; Purdy, James A. [Department of Radiation Oncology, University of California, Davis, Sacramento, CA (United States); Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu [Department of Radiation Oncology, University of California, Davis, Sacramento, CA (United States)

    2012-07-01

    Our goal was to evaluate brachial plexus (BP) dose with and without the use of supraclavicular (SCL) irradiation in patients undergoing breast-conserving therapy with whole-breast radiation therapy (RT) after lumpectomy. Using the standardized Radiation Therapy Oncology Group (RTOG)-endorsed guidelines delineation, we contoured the BP for 10 postlumpectomy breast cancer patients. The radiation dose to the whole breast was 50.4 Gy using tangential fields in 1.8-Gy fractions, followed by a conedown to the operative bed using electrons (10 Gy). The prescription dose to the SCL field was 50.4 Gy, delivered to 3-cm depth. The mean BP volume was 14.5 {+-} 1.5 cm{sup 3}. With tangential fields alone, the median mean dose to the BP was 0.57 Gy, the median maximum dose was 1.93 Gy, and the irradiated volume of the BP receiving 40, 45, and 50 Gy was 0%. When the third (SCL field) was added, the dose to the BP was significantly increased (P = .01): the median mean dose to the BP was 40.60 Gy, and the median maximum dose was 52.22 Gy. With 3-field RT, the median irradiated volume of the BP receiving 40, 45, and 50 Gy was 83.5%, 68.5%, and 24.6%, respectively. The addition of the SCL field significantly increases dose to the BP. The possibility of increasing the risk of BP morbidity should be considered in the context of clinical decision making.

  5. Addition of a third field significantly increases dose to the brachial plexus for patients undergoing tangential whole-breast therapy after lumpectomy.

    Science.gov (United States)

    Stanic, Sinisa; Mathai, Mathew; Mayadev, Jyoti S; Do, Ly V; Purdy, James A; Chen, Allen M

    2012-01-01

    Our goal was to evaluate brachial plexus (BP) dose with and without the use of supraclavicular (SCL) irradiation in patients undergoing breast-conserving therapy with whole-breast radiation therapy (RT) after lumpectomy. Using the standardized Radiation Therapy Oncology Group (RTOG)-endorsed guidelines delineation, we contoured the BP for 10 postlumpectomy breast cancer patients. The radiation dose to the whole breast was 50.4 Gy using tangential fields in 1.8-Gy fractions, followed by a conedown to the operative bed using electrons (10 Gy). The prescription dose to the SCL field was 50.4 Gy, delivered to 3-cm depth. The mean BP volume was 14.5 ± 1.5 cm(3). With tangential fields alone, the median mean dose to the BP was 0.57 Gy, the median maximum dose was 1.93 Gy, and the irradiated volume of the BP receiving 40, 45, and 50 Gy was 0%. When the third (SCL field) was added, the dose to the BP was significantly increased (P = .01): the median mean dose to the BP was 40.60 Gy, and the median maximum dose was 52.22 Gy. With 3-field RT, the median irradiated volume of the BP receiving 40, 45, and 50 Gy was 83.5%, 68.5%, and 24.6%, respectively. The addition of the SCL field significantly increases dose to the BP. The possibility of increasing the risk of BP morbidity should be considered in the context of clinical decision making.

  6. Clinical significance of increased cerebellar default-mode network connectivity in resting-state patients with drug-naive somatization disorder

    Science.gov (United States)

    Wang, Houliang; Guo, Wenbin; Liu, Feng; Chen, Jindong; Wu, Renrong; Zhang, Zhikun; Yu, Miaoyu; Li, Lehua; Zhao, Jingping

    2016-01-01

    Abstract The cerebellum has been proven to be connected to the brain network, as in the default-mode network (DMN), among healthy subjects and patients with psychiatric disorders. However, whether or not abnormal cerebellar DMN connectivity exists and what its clinical significance is among drug-naive patients with somatization disorder (SD) at rest remain unclear. A total of 25 drug-naive patients with SD and 28 healthy controls were enrolled for a resting-state scan. The imaging data were analyzed using the seed-based functional connectivity (FC) method. Compared with the controls, patients with SD showed increased left/right Crus I-left/right angular gyrus (AG) connectivity and Lobule IX-left superior medial prefrontal cortex (MPFC) connectivity. The FC values of the left/right Crus I-right AG connectivity of the patients were positively correlated with their scores in the somatization subscale of the symptom checklist-90 (Scl-90). A trend level of correlations was observed between the FC values of the left Crus I-left AG connectivity of the patients and their scores for the somatization subscale of Scl-90, as well as between the FC values of their Lobule IX-left superior MPFC connectivity and their scores for the Eysenck personality questionnaire (EPQ) extraversion. Our findings show the increased cerebellar DMN connectivity in patients with SD and therefore highlight the importance of the DMN in the neurobiology of SD. Increased cerebellar DMN connectivities are also correlated with their somatization severity and personality, both of which bear clinical significance. PMID:27428190

  7. The In Vitro Mass-Produced Model Mycorrhizal Fungus, Rhizophagus irregularis, Significantly Increases Yields of the Globally Important Food Security Crop Cassava

    Science.gov (United States)

    Ceballos, Isabel; Ruiz, Michael; Fernández, Cristhian; Peña, Ricardo

    2013-01-01

    The arbuscular mycorrhizal symbiosis is formed between arbuscular mycorrhizal fungi (AMF) and plant roots. The fungi provide the plant with inorganic phosphate (P). The symbiosis can result in increased plant growth. Although most global food crops naturally form this symbiosis, very few studies have shown that their practical application can lead to large-scale increases in food production. Application of AMF to crops in the tropics is potentially effective for improving yields. However, a main problem of using AMF on a large-scale is producing cheap inoculum in a clean sterile carrier and sufficiently concentrated to cheaply transport. Recently, mass-produced in vitro inoculum of the model mycorrhizal fungus Rhizophagus irregularis became available, potentially making its use viable in tropical agriculture. One of the most globally important food plants in the tropics is cassava. We evaluated the effect of in vitro mass-produced R. irregularis inoculum on the yield of cassava crops at two locations in Colombia. A significant effect of R. irregularis inoculation on yield occurred at both sites. At one site, yield increases were observed irrespective of P fertilization. At the other site, inoculation with AMF and 50% of the normally applied P gave the highest yield. Despite that AMF inoculation resulted in greater food production, economic analyses revealed that AMF inoculation did not give greater return on investment than with conventional cultivation. However, the amount of AMF inoculum used was double the recommended dose and was calculated with European, not Colombian, inoculum prices. R. irregularis can also be manipulated genetically in vitro, leading to improved plant growth. We conclude that application of in vitro R. irregularis is currently a way of increasing cassava yields, that there is a strong potential for it to be economically profitable and that there is enormous potential to improve this efficiency further in the future. PMID:23950975

  8. KdmB, a Jumonji Histone H3 Demethylase, Regulates Genome-Wide H3K4 Trimethylation and Is Required for Normal Induction of Secondary Metabolism in Aspergillus nidulans.

    Directory of Open Access Journals (Sweden)

    Agnieszka Gacek-Matthews

    2016-08-01

    Full Text Available Histone posttranslational modifications (HPTMs are involved in chromatin-based regulation of fungal secondary metabolite biosynthesis (SMB in which the corresponding genes-usually physically linked in co-regulated clusters-are silenced under optimal physiological conditions (nutrient-rich but are activated when nutrients are limiting. The exact molecular mechanisms by which HPTMs influence silencing and activation, however, are still to be better understood. Here we show by a combined approach of quantitative mass spectrometry (LC-MS/MS, genome-wide chromatin immunoprecipitation (ChIP-seq and transcriptional network analysis (RNA-seq that the core regions of silent A. nidulans SM clusters generally carry low levels of all tested chromatin modifications and that heterochromatic marks flank most of these SM clusters. During secondary metabolism, histone marks typically associated with transcriptional activity such as H3 trimethylated at lysine-4 (H3K4me3 are established in some, but not all gene clusters even upon full activation. KdmB, a Jarid1-family histone H3 lysine demethylase predicted to comprise a BRIGHT domain, a zinc-finger and two PHD domains in addition to the catalytic Jumonji domain, targets and demethylates H3K4me3 in vivo and mediates transcriptional downregulation. Deletion of kdmB leads to increased transcription of about ~1750 genes across nutrient-rich (primary metabolism and nutrient-limiting (secondary metabolism conditions. Unexpectedly, an equally high number of genes exhibited reduced expression in the kdmB deletion strain and notably, this group was significantly enriched for genes with known or predicted functions in secondary metabolite biosynthesis. Taken together, this study extends our general knowledge about multi-domain KDM5 histone demethylases and provides new details on the chromatin-level regulation of fungal secondary metabolite production.

  9. Unusual prostate carcinoma characterized by extensive metastasis, significantly increased serum level of prostatic-specific antigen, and neuroendocrine differentiation: a case report

    Institute of Scientific and Technical Information of China (English)

    HU Yuxin; YE Juan; JIANG Ying; ZHANG Qin-fang; WU Yue-long; CHEN Yue-yu

    2005-01-01

    @@ Some rare variants of prostate carcinoma have been described in recent years.1-3 In this article we report a man with uncommon prostate carcinoma with the following three pathological characteristics: (a) extensive metastasis to bone and lymph nodes of the abdomen, pelvis, and supraclavicular area; (b) significantly increased serum level of prostatic-specific antigen (PSA) as high as 1800 ng/ml; and (c) partial neuroendocrine differentiation in cancer tissue. The patient died 7 months after pathological diagnosis or 22 months after appearance of initial signs. This case has drawn our attention to the fact that pathological diversity of prostate neoplasm might easily lead to misdiagnosis or to delayed diagnosis, and moreover, reasonable therapy for such a case should be based on a thorough investigation. On the other hand, early initiation of appropriate treatment of advanced neuroendocrine carcinoma may improve the prognosis.

  10. Immunization of teenagers with a fifth dose of reduced DTaP-IPV induces high levels of pertussis antibodies with a significant increase in opsonophagocytic activity.

    Science.gov (United States)

    Aase, Audun; Herstad, Tove Karin; Merino, Samuel; Bolstad, Merete; Sandbu, Synne; Bakke, Hilde; Aaberge, Ingeborg S

    2011-08-01

    Waning vaccine-induced immunity against Bordetella pertussis is observed among adolescents and adults. A high incidence of pertussis has been reported in this population, which serves as a reservoir for B. pertussis. A fifth dose of reduced antigen of diphtheria-tetanus-acellular-pertussis and inactivated polio vaccine was given as a booster dose to healthy teenagers. The antibody activity against B. pertussis antigens was measured prior to and 4 to 8 weeks after the booster by different assays: enzyme-linked immunosorbent assays (ELISAs) of IgG and IgA against pertussis toxin (PT) and filamentous hemagglutinin (FHA), IgG against pertactin (PRN), opsonophagocytic activity (OPA), and IgG binding to live B. pertussis. There was a significant increase in the IgG activity against PT, FHA, and PRN following the booster immunization (P antibodies against FHA and PRN contribute the most to the OPA and IgG binding.

  11. Histone H3R2 Symmetric Dimethylation and Histone H3K4 Trimethylation Are Tightly Correlated in Eukaryotic Genomes

    OpenAIRE

    Chih-Chi Yuan; Adam G.W. Matthews; Yi Jin; Chang Feng Chen; Brad A. Chapman; Toshiro K. Ohsumi; Karen C. Glass; Tatiana G. Kutateladze; Mark L. Borowsky; Kevin Struhl; Marjorie A. Oettinger

    2012-01-01

    The preferential in vitro interaction of the PHD finger of RAG2, a subunit of the V(D)J recombinase, with histone H3 tails simultaneously trimethylated at lysine 4 and symmetrically dimethylated at arginine 2 (H3R2me2sK4me3) predicted the existence of the previously unknown histone modification H3R2me2s. Here, we report the in vivo identification of H3R2me2s . Consistent with the binding specificity of the RAG2 PHD finger, high levels of H3R2me2sK4me3 are found at antigen receptor gene segmen...

  12. A Three-Lesson Teaching Unit Significantly Increases High School Students’ Knowledge about Epilepsy and Positively Influences Their Attitude towards This Disease

    Science.gov (United States)

    Simon, Uwe K.; Gesslbauer, Lisa; Fink, Andreas

    2016-01-01

    Epilepsy is not a regular topic in many countries’ schools. Thus many people harbor misconceptions about people suffering from this disease. It was our aim to a) examine what grade ten students know and believe about epilepsy, and b) to develop and test a teaching unit to improve their knowledge and attitude. The test group comprised eight grade ten classes from six different Austrian high schools (54 girls and 51 boys aged 14–17), the control group (no intervention) five grade ten classes from the same schools (26 girls and 37 boys aged 14–17). The teaching unit consisted of three 45-min lessons using different methods and material. Changes in knowledge about and attitude towards epilepsy as a result of the intervention were psychometrically assessed in a pre-test intervention post-test design (along with a follow-up assessment two months after the intervention) by means of a questionnaire capturing different facets of epilepsy-related knowledge and attitude. Across all knowledge/attitude domains, students of the test group had a significantly improved knowledge about and a more positive attitude towards epilepsy and people suffering from it after the teaching unit. However, starting levels were different between the five knowledge/attitude domains tested. Medical background knowledge was lowest and consequently associated with the highest increase after the intervention. This study shows that epilepsy-related knowledge of many grade ten high school students is fragmentary and that some harbor beliefs and attitudes which require improvement. Our comprehensive but concise teaching unit significantly increased knowledge about epilepsy and positively influenced attitude towards individuals with epilepsy. Thus we recommend implementing this unit into regular school curricula. PMID:26919557

  13. A Three-Lesson Teaching Unit Significantly Increases High School Students' Knowledge about Epilepsy and Positively Influences Their Attitude towards This Disease.

    Science.gov (United States)

    Simon, Uwe K; Gesslbauer, Lisa; Fink, Andreas

    2016-01-01

    Epilepsy is not a regular topic in many countries' schools. Thus many people harbor misconceptions about people suffering from this disease. It was our aim to a) examine what grade ten students know and believe about epilepsy, and b) to develop and test a teaching unit to improve their knowledge and attitude. The test group comprised eight grade ten classes from six different Austrian high schools (54 girls and 51 boys aged 14-17), the control group (no intervention) five grade ten classes from the same schools (26 girls and 37 boys aged 14-17). The teaching unit consisted of three 45-min lessons using different methods and material. Changes in knowledge about and attitude towards epilepsy as a result of the intervention were psychometrically assessed in a pre-test intervention post-test design (along with a follow-up assessment two months after the intervention) by means of a questionnaire capturing different facets of epilepsy-related knowledge and attitude. Across all knowledge/attitude domains, students of the test group had a significantly improved knowledge about and a more positive attitude towards epilepsy and people suffering from it after the teaching unit. However, starting levels were different between the five knowledge/attitude domains tested. Medical background knowledge was lowest and consequently associated with the highest increase after the intervention. This study shows that epilepsy-related knowledge of many grade ten high school students is fragmentary and that some harbor beliefs and attitudes which require improvement. Our comprehensive but concise teaching unit significantly increased knowledge about epilepsy and positively influenced attitude towards individuals with epilepsy. Thus we recommend implementing this unit into regular school curricula.

  14. Long-term use of amiodarone before heart transplantation significantly reduces early post-transplant atrial fibrillation and is not associated with increased mortality after heart transplantation

    Directory of Open Access Journals (Sweden)

    Rivinius R

    2016-02-01

    group (P=0.0123. There was no statistically significant difference between patients with and without long-term use of amiodarone prior to HTX in 1-year (P=0.8596, 2-year (P=0.8620, 5-year (P=0.2737, or overall follow-up mortality after HTX (P=0.1049. Moreover, Kaplan–Meier survival analysis showed no statistically significant difference in overall survival (P=0.1786.Conclusion: Long-term use of amiodarone in patients before HTX significantly reduces early post-transplant AF and is not associated with increased mortality after HTX. Keywords: amiodarone, atrial fibrillation, heart failure, heart transplantation, mortality

  15. The inflammatory kinase MAP4K4 promotes reactivation of Kaposi's sarcoma herpesvirus and enhances the invasiveness of infected endothelial cells.

    Directory of Open Access Journals (Sweden)

    Darya A Haas

    Full Text Available Kaposi's sarcoma (KS is a mesenchymal tumour, which is caused by Kaposi's sarcoma herpesvirus (KSHV and develops under inflammatory conditions. KSHV-infected endothelial spindle cells, the neoplastic cells in KS, show increased invasiveness, attributed to the elevated expression of metalloproteinases (MMPs and cyclooxygenase-2 (COX-2. The majority of these spindle cells harbour latent KSHV genomes, while a minority undergoes lytic reactivation with subsequent production of new virions and viral or cellular chemo- and cytokines, which may promote tumour invasion and dissemination. In order to better understand KSHV pathogenesis, we investigated cellular mechanisms underlying the lytic reactivation of KSHV. Using a combination of small molecule library screening and siRNA silencing we found a STE20 kinase family member, MAP4K4, to be involved in KSHV reactivation from latency and to contribute to the invasive phenotype of KSHV-infected endothelial cells by regulating COX-2, MMP-7, and MMP-13 expression. This kinase is also highly expressed in KS spindle cells in vivo. These findings suggest that MAP4K4, a known mediator of inflammation, is involved in KS aetiology by regulating KSHV lytic reactivation, expression of MMPs and COX-2, and, thereby modulating invasiveness of KSHV-infected endothelial cells.

  16. Signalling couples hair follicle stem cell quiescence with reduced histone H3 K4/K9/K27me3 for proper tissue homeostasis.

    Science.gov (United States)

    Lee, Jayhun; Kang, Sangjo; Lilja, Karin C; Colletier, Keegan J; Scheitz, Cornelia Johanna Franziska; Zhang, Ying V; Tumbar, Tudorita

    2016-04-15

    Mechanisms of plasticity to acquire different cell fates are critical for adult stem cell (SC) potential, yet are poorly understood. Reduced global histone methylation is an epigenetic state known to mediate plasticity in cultured embryonic SCs and T-cell progenitors. Here we find histone H3 K4/K9/K27me3 levels actively reduced in adult mouse skin and hair follicle stem cells (HFSCs) during G0 quiescence. The level of marks over specific gene promoters did not correlate to mRNA level changes in quiescent HFSCs. Skin hypomethylation during quiescence was necessary for subsequent progression of hair homeostasis (cycle). Inhibiting BMP signal, a known HFSC anti-proliferative factor, elevated HFSC methylation in vivo during quiescence prior to proliferation onset. Furthermore, removal of proliferation factors and addition of BMP4 reduced histone methylases and increased demethylases mRNAs in cultured skin epithelial cells. We conclude that signalling couples hair follicle stem cell quiescence with reduced H3 K4/K9/K27me3 levels for proper tissue homeostasis.

  17. Potent and Selective KDM5 Inhibitor Stops Cellular Demethylation of H3K4me3 at Transcription Start Sites and Proliferation of MM1S Myeloma Cells.

    Science.gov (United States)

    Tumber, Anthony; Nuzzi, Andrea; Hookway, Edward S; Hatch, Stephanie B; Velupillai, Srikannathasan; Johansson, Catrine; Kawamura, Akane; Savitsky, Pavel; Yapp, Clarence; Szykowska, Aleksandra; Wu, Na; Bountra, Chas; Strain-Damerell, Claire; Burgess-Brown, Nicola A; Ruda, Gian Filippo; Fedorov, Oleg; Munro, Shonagh; England, Katherine S; Nowak, Radoslaw P; Schofield, Christopher J; La Thangue, Nicholas B; Pawlyn, Charlotte; Davies, Faith; Morgan, Gareth; Athanasou, Nick; Müller, Susanne; Oppermann, Udo; Brennan, Paul E

    2017-03-16

    Methylation of lysine residues on histone tail is a dynamic epigenetic modification that plays a key role in chromatin structure and gene regulation. Members of the KDM5 (also known as JARID1) sub-family are 2-oxoglutarate (2-OG) and Fe(2+)-dependent oxygenases acting as histone 3 lysine 4 trimethyl (H3K4me3) demethylases, regulating proliferation, stem cell self-renewal, and differentiation. Here we present the characterization of KDOAM-25, an inhibitor of KDM5 enzymes. KDOAM-25 shows biochemical half maximal inhibitory concentration values of <100 nM for KDM5A-D in vitro, high selectivity toward other 2-OG oxygenases sub-families, and no off-target activity on a panel of 55 receptors and enzymes. In human cell assay systems, KDOAM-25 has a half maximal effective concentration of ∼50 μM and good selectivity toward other demethylases. KDM5B is overexpressed in multiple myeloma and negatively correlated with the overall survival. Multiple myeloma MM1S cells treated with KDOAM-25 show increased global H3K4 methylation at transcriptional start sites and impaired proliferation. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. An expedient Pd/DBU mediated cyanation of aryl/heteroaryl bromides with K4[Fe(CN)6].

    Science.gov (United States)

    Zhang, Dengyou; Sun, Haifeng; Zhang, Lei; Zhou, Yu; Li, Chunpu; Jiang, Hualiang; Chen, Kaixian; Liu, Hong

    2012-03-18

    A practical Pd(PPh(3))(4)/DBU catalytic system for the synthesis of pharmaceutically relevant aminopyridine nitrile intermediates, as well as a variety of other aryl nitriles using non-toxic K(4)[Fe(CN)(6)] has been developed. The key features of our new protocol for cyanation lie in that the reaction can be carried out with readily available Pd(PPh(3))(4) under mild and green conditions, even without the assistance of other ligands.

  19. Aspectos estruturais relacionados ao processo de troca iônica no niobato lamelar K4Nb6O17

    Directory of Open Access Journals (Sweden)

    Marcos A. Bizeto

    2006-12-01

    Full Text Available The niobate with formula K4Nb6O17 has a layered structure formed by stacked negative sheets and exchangeable cations in the interlayer region. In this study we discuss some structural aspects related to the ion exchange in layered hexaniobate based on X-ray diffractometry and vibrational Raman spectroscopy data. Hexaniobate has two distinct interlayer regions and the potassium ions of one interlayer in particular are preferably exchanged by other cations, leading to an interstratified material.

  20. Methylated H3K4, a transcription-associated histone modification, is involved in the DNA damage response pathway.

    Science.gov (United States)

    Faucher, David; Wellinger, Raymund J

    2010-08-26

    Eukaryotic genomes are associated with a number of proteins such as histones that constitute chromatin. Post-translational histone modifications are associated with regulatory aspects executed by chromatin and all transactions on genomic DNA are dependent on them. Thus, it will be relevant to understand how histone modifications affect genome functions. Here we show that the mono ubiquitylation of histone H2B and the tri-methylation of histone H3 on lysine 4 (H3K4me3), both known for their involvement in transcription, are also important for a proper response of budding yeast cells to DNA damaging agents and the passage through S-phase. Cells that cannot methylate H3K4 display a defect in double-strand break (DSB) repair by non-homologous end joining. Furthermore, if such cells incur DNA damage or encounter a stress during replication, they very rapidly lose viability, underscoring the functional importance of the modification. Remarkably, the Set1p methyltransferase as well as the H3K4me3 mark become detectable on a newly created DSB. This recruitment of Set1p to the DSB is dependent on the presence of the RSC complex, arguing for a contribution in the ensuing DNA damage repair process. Taken together, our results demonstrate that Set1p and its substrate H3K4me3, which has been reported to be important for the transcription of active genes, also plays an important role in genome stability of yeast cells. Given the high degree of conservation for the methyltransferase and the histone mark in a broad variety of organisms, these results could have similar implications for genome stability mechanisms in vertebrate and mammalian cells.

  1. [The influence of Acinetobacter calcoaceticus K-4 surface-active substances on the efficiency of microbial destruction of oil pollutants].

    Science.gov (United States)

    Pyroh, T P; Antoniuk, S I; Sorokina, A I

    2009-01-01

    The possibility of the use of Acinetobacter calcoaceticus K-4 surface-active substances (SAS) for water purification from oil was shown. The efficiency of oil degradation (2.6 g/l) in the presence of SAS preparations (5-15 %) in the form of postfermentation of cultural liquid or its supernatant was established to be 81-95 %. Intensification of oil destruction was determined by SAS affecting the activity of oil-oxidizing microbial population.

  2. Synthesis and Structural Determination of Binuclear Nine-Coordinate K4[Y2(Httha)2]·14H2O

    Institute of Scientific and Technical Information of China (English)

    2002-01-01

    A Y3+ complex with triethylenetetraaminehexaacetic acid was prepared and its composition and structure were determined as K4[Y2(Httha)2]*14H2O by elemental analysis and single-crystal X-ray four circle diffraction analysis. In the binuclear complex, the two YN3O6 parts all form nine-coordinate monocapped square anti prismatic structures. There are a lot of water molecules in the unit cell which form hydrogen bonds.

  3. Methylated H3K4, a transcription-associated histone modification, is involved in the DNA damage response pathway.

    Directory of Open Access Journals (Sweden)

    David Faucher

    2010-08-01

    Full Text Available Eukaryotic genomes are associated with a number of proteins such as histones that constitute chromatin. Post-translational histone modifications are associated with regulatory aspects executed by chromatin and all transactions on genomic DNA are dependent on them. Thus, it will be relevant to understand how histone modifications affect genome functions. Here we show that the mono ubiquitylation of histone H2B and the tri-methylation of histone H3 on lysine 4 (H3K4me3, both known for their involvement in transcription, are also important for a proper response of budding yeast cells to DNA damaging agents and the passage through S-phase. Cells that cannot methylate H3K4 display a defect in double-strand break (DSB repair by non-homologous end joining. Furthermore, if such cells incur DNA damage or encounter a stress during replication, they very rapidly lose viability, underscoring the functional importance of the modification. Remarkably, the Set1p methyltransferase as well as the H3K4me3 mark become detectable on a newly created DSB. This recruitment of Set1p to the DSB is dependent on the presence of the RSC complex, arguing for a contribution in the ensuing DNA damage repair process. Taken together, our results demonstrate that Set1p and its substrate H3K4me3, which has been reported to be important for the transcription of active genes, also plays an important role in genome stability of yeast cells. Given the high degree of conservation for the methyltransferase and the histone mark in a broad variety of organisms, these results could have similar implications for genome stability mechanisms in vertebrate and mammalian cells.

  4. Putative floral brood-site mimicry, loss of autonomous selfing, and reduced vegetative growth are significantly correlated with increased diversification in Asarum (Aristolochiaceae).

    Science.gov (United States)

    Sinn, Brandon T; Kelly, Lawrence M; Freudenstein, John V

    2015-08-01

    The drivers of angiosperm diversity have long been sought and the flower-arthropod association has often been invoked as the most powerful driver of the angiosperm radiation. We now know that features that influence arthropod interactions cannot only affect the diversification of lineages, but also expedite or constrain their rate of extinction, which can equally influence the observed asymmetric richness of extant angiosperm lineages. The genus Asarum (Aristolochiaceae; ∼100 species) is widely distributed in north temperate forests, with substantial vegetative and floral divergence between its three major clades, Euasarum, Geotaenium, and Heterotropa. We used Binary-State Speciation and Extinction Model (BiSSE) Net Diversification tests of character state distributions on a Maximum Likelihood phylogram and a Coalescent Bayesian species tree, inferred from seven chloroplast markers and nuclear rDNA, to test for signal of asymmetric diversification, character state transition, and extinction rates of floral and vegetative characters. We found that reduction in vegetative growth, loss of autonomous self-pollination, and the presence of putative fungal-mimicking floral structures are significantly correlated with increased diversification in Asarum. No significant difference in model likelihood was identified between symmetric and asymmetric rates of character state transitions or extinction. We conclude that the flowers of the Heterotropa clade may have converged on some aspects of basidiomycete sporocarp morphology and that brood-site mimicry, coupled with a reduction in vegetative growth and the loss of autonomous self-pollination, may have driven diversification within Asarum. Copyright © 2015 Elsevier Inc. All rights reserved.

  5. Incorporating biologic measurements (SF(2), CFE) into a tumor control probability model increases their prognostic significance: a study in cervical carcinoma treated with radiation therapy.

    Science.gov (United States)

    Buffa, F M; Davidson, S E; Hunter, R D; Nahum, A E; West, C M

    2001-08-01

    To assess whether incorporation of measurements of surviving fraction at 2 Gy (SF(2)) and colony-forming efficiency (CFE) into a tumor control probability (tcp) model increases their prognostic significance. Measurements of SF(2) and CFE were available from a study on carcinoma of the cervix treated with radiation alone. These measurements, as well as tumor volume, dose, and treatment time, were incorporated into a Poisson tcp model (tcp(alpha,rho)). Regression analysis was performed to assess the prognostic power of tcp(alpha,rho) vs. the use of either tcp models with biologic parameters fixed to best-fit estimates (but incorporating individual dose, volume, and treatment time) or the use of SF(2) and CFE measurements alone. In a univariate regression analysis of 44 patients, tcp(alpha,rho) was a better prognostic factor for both local control and survival (p CFE alone (p = 0.015 for local control, p = 0.38 for survival). In multivariate analysis, tcp(alpha,rho) emerged as the most important prognostic factor for local control (p CFE was still a significant independent prognostic factor for local control, whereas SF(2) was not. The sensitivities of tcp(alpha,rho) and SF(2) as predictive tests for local control were 87% and 65%, respectively. Specificities were 70% and 77%, respectively. A Poisson tcp model incorporating individual SF(2), CFE, dose, tumor volume, and treatment time was found to be the best independent prognostic factor for local control and survival in cervical carcinoma patients.

  6. Loading of the knee during 3.0 T MRI is associated with significantly increased medial meniscus extrusion in mild and moderate osteoarthritis

    Energy Technology Data Exchange (ETDEWEB)

    Stehling, Christoph, E-mail: christoph.stehling@radiology.ucsf.edu [Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA (United States); Department of Clinical Radiology, University of Muenster, Muenster (Germany); Souza, Richard B. [Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA (United States); Graverand, Marie-Pierre Hellio Le; Wyman, Bradley T. [Pfizer Inc. New London, CT (United States); Li, Xiaojuan; Majumdar, Sharmila; Link, Thomas M. [Musculoskeletal and Quantitative Imaging Group (MQIR), Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA (United States)

    2012-08-15

    Purpose: Standard knee MRI is performed under unloading (ULC) conditions and not much is known about changes of the meniscus, ligaments or cartilage under loading conditions (LC). The aim is to study the influence of loading of different knee structures at 3 Tesla (T) in subjects with osteoarthritis (OA) and normal controls. Materials and methods: 30 subjects, 10 healthy and 20 with radiographic evidence of OA (10 mild and 10 moderate) underwent 3 T MRI under ULC and LC at 50% body weight. All images were analyzed by two musculoskeletal radiologists identifying and grading cartilage, meniscal, ligamentous abnormalities. The changes between ULC and LC were assessed. For meniscus, cartilage and ligaments the changes of lesions, signal and shape were evaluated. In addition, for the meniscus changes in extrusion were examined. A multivariate regression model was used for correlations to correct the data for the impact of age, gender, BMI. A paired T-Test was performed to calculate the differences in meniscus extrusion. Results: Subjects with degenerative knee abnormalities demonstrated significantly increased meniscus extrusion under LC when compared to normal subjects (p = 0.0008-0.0027). Subjects with knee abnormalities and higher KL scores showed significantly more changes in lesion, signal and shape of the meniscus (80% (16/20) vs. 20% (2/10); p = 0.0025), ligaments and cartilage during LC. Conclusion: The study demonstrates that axial loading has an effect on articular cartilage, ligament, and meniscus morphology, which is more significant in subjects with degenerative disease and may serve as an additional diagnostic tool for disease diagnosis and assessing progression in subjects with knee OA.

  7. Significant increase of salivary testosterone levels after single therapeutic transdermal administration of testosterone: suitability as a potential screening parameter in doping control.

    Science.gov (United States)

    Thieme, Detlef; Rautenberg, Claudia; Grosse, Joachim; Schoenfelder, Martin

    2013-01-01

    The legally defensible proof of the abuse of endogenous steroids in sports is currently based on carbon isotope ratio mass spectrometry (IRMS), i.e. a comparison between (13)C/(12)C ratios of diagnostic precursors and metabolites of testosterone. The application of this technique requires a chromatographic baseline separation of respective steroids prior to IRMS detection and hence laborious sample pre-processing of the urinary steroid extracts including clean up by solid-phase extraction and/or liquid chromatography. Consequently, an efficient pre-selection of suspicious control urine samples is essential for appropriate follow up confirmation by IRMS and effective doping control. Two single transdermal administration studies of testosterone (50 mg Testogel® and Testopatch® at 3.8 mg in 16 h, respectively) were conducted and resulting profiles of salivary testosterone and urinary steroid profiles and corresponding carbon isotope ratios were determined. Conventional doping control markers (testosterone/epitestosterone ratio, threshold concentrations of androsterone, etiocholanolone, or androstanediols) did not approach or exceed critical thresholds. In contrast to these moderate variations, the testosterone concentration in oral fluid increased from basal values (30-142 pg/mg) to peak concentrations above 1000 pg/mg. It is likely that this significant increase in oral fluid is due to a pulsatile elevation of free (protein unbound) circulating testosterone after transdermal administration and may be assumed to represent a more diagnostic marker for transdermal testosterone administration.

  8. Changes in epidemiologic features of testicular germ cell cancer: age at diagnosis and relative frequency of seminoma are constantly and significantly increasing.

    Science.gov (United States)

    Ruf, Christian G; Isbarn, Hendrik; Wagner, Walter; Fisch, Margit; Matthies, Cord; Dieckmann, Klaus-Peter

    2014-01-01

    Testicular germ cell tumors (GCTs) have their incidence peak in the third and fourth decades of life. Histologically, GCTs comprise of seminoma and nonseminoma at almost equal proportions with a slight preponderance of nonseminoma in most of the major series. Since decades, there is a shift toward decreasing age at presentation. Recently, there are suggestions of a reversal of the age trend, and also, the histologic subtype ratio appears to shift toward seminoma. We retrospectively looked to our patient populations to verify these recent trends. A total of 2,482 patients with histologically proven GCT diagnosed between 1976 and 2010 were retrospectively evaluated regarding the year of diagnosis, histology of primary tumor, and age at presentation. Patients were categorized according to the following time periods of treatment: before 1990, 1990 to 1994, 1995 to 1999, 2000 to 2004, and 2005 to 2010. Mean age and relative proportion of seminoma were compared among patient categories by employing the chi-square test and analysis of variance, respectively. The mean age significantly increased from 28 to 36 years. The age difference between the 2 histologic subtypes remained constant between 6 and 8 years during the entire observation period. The relative proportion of seminoma continuously increased from 30.9% to 56% (P seminoma is constantly increasing at the expense of nonseminoma. The reasons for these developments are obscure. However, 2 old theories regarding the pathogenesis of GCT may receive support from our results: first, the theory of divergent pathogenetic pathways of seminoma and nonseminoma and second, the involvement of postnatal environmental factors in the pathogenesis of GCTs. Copyright © 2014 Elsevier Inc. All rights reserved.

  9. PHF20 Readers Link Methylation of Histone H3K4 and p53 with H4K16 Acetylation

    Directory of Open Access Journals (Sweden)

    Brianna J. Klein

    2016-10-01

    Full Text Available PHF20 is a core component of the lysine acetyltransferase complex MOF (male absent on the first-NSL (non-specific lethal that generates the major epigenetic mark H4K16ac and is necessary for transcriptional regulation and DNA repair. The role of PHF20 in the complex remains elusive. Here, we report on functional coupling between methylation readers in PHF20. We show that the plant homeodomain (PHD finger of PHF20 recognizes dimethylated lysine 4 of histone H3 (H3K4me2 and represents an example of a native reader that selects for this modification. Biochemical and structural analyses help to explain this selectivity and the preference of Tudor2, another reader in PHF20, for dimethylated p53. Binding of the PHD finger to H3K4me2 is required for histone acetylation, accumulation of PHF20 at target genes, and transcriptional activation. Together, our findings establish a unique PHF20-mediated link between MOF histone acetyltransferase (HAT, p53, and H3K4me2, and suggest a model for rapid spreading of H4K16ac-enriched open chromatin.

  10. PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3.

    Science.gov (United States)

    Chung, Ho-Ryun; Xu, Chao; Fuchs, Alisa; Mund, Andreas; Lange, Martin; Staege, Hannah; Schubert, Tobias; Bian, Chuanbing; Dunkel, Ilona; Eberharter, Anton; Regnard, Catherine; Klinker, Henrike; Meierhofer, David; Cozzuto, Luca; Winterpacht, Andreas; Di Croce, Luciano; Min, Jinrong; Will, Hans; Kinkley, Sarah

    2016-05-25

    PHF13 is a chromatin affiliated protein with a functional role in differentiation, cell division, DNA damage response and higher chromatin order. To gain insight into PHF13's ability to modulate these processes, we elucidate the mechanisms targeting PHF13 to chromatin, its genome wide localization and its molecular chromatin context. Size exclusion chromatography, mass spectrometry, X-ray crystallography and ChIP sequencing demonstrate that PHF13 binds chromatin in a multivalent fashion via direct interactions with H3K4me2/3 and DNA, and indirectly via interactions with PRC2 and RNA PolII. Furthermore, PHF13 depletion disrupted the interactions between PRC2, RNA PolII S5P, H3K4me3 and H3K27me3 and resulted in the up and down regulation of genes functionally enriched in transcriptional regulation, DNA binding, cell cycle, differentiation and chromatin organization. Together our findings argue that PHF13 is an H3K4me2/3 molecular reader and transcriptional co-regulator, affording it the ability to impact different chromatin processes.

  11. Emerged HA and NA mutants of the pandemic influenza H1N1 viruses with increasing epidemiological significance in Taipei and Kaohsiung, Taiwan, 2009-10.

    Directory of Open Access Journals (Sweden)

    Chuan-Liang Kao

    Full Text Available The 2009 influenza pandemic provided an opportunity to observe dynamic changes of the hemagglutinin (HA and neuraminidase (NA of pH1N1 strains that spread in two metropolitan areas--Taipei and Kaohsiung. We observed cumulative increases of amino acid substitutions of both HA and NA that were higher in the post-peak than in the pre-peak period of the epidemic. About 14.94% and 3.44% of 174 isolates had one and two amino acids changes, respective, in the four antigenic sites. One unique adaptive mutation of HA2 (E374K was first detected three weeks before the epidemic peak. This mutation evolved through the epidemic, and finally emerged as the major circulated strain, with significantly higher frequency in the post-peak period than in the pre-peak (64.65% vs 9.28%, p<0.0001. E374K persisted until ten months post-nationwide vaccination without further antigenic changes (e.g. prior to the highest selective pressure. In public health measures, the epidemic peaked at seven weeks after oseltamivir treatment was initiated. The emerging E374K mutants spread before the first peak of school class suspension, extended their survival in high-density population areas before vaccination, dominated in the second wave of class suspension, and were fixed as herd immunity developed. The tempo-spatial spreading of E374K mutants was more concentrated during the post-peak (p = 0.000004 in seven districts with higher spatial clusters (p<0.001. This is the first study examining viral changes during the naïve phase of a pandemic of influenza through integrated virological/serological/clinical surveillance, tempo-spatial analysis, and intervention policies. The vaccination increased the percentage of E374K mutants (22.86% vs 72.34%, p<0.001 and significantly elevated the frequency of mutations in Sa antigenic site (2.36% vs 23.40%, p<0.001. Future pre-vaccination public health efforts should monitor amino acids of HA and NA of pandemic influenza viruses isolated at

  12. Enhancer-associated H3K4 monomethylation by trithorax-related, the drosophila homolog of mammalian MLL3/MLL4

    NARCIS (Netherlands)

    H.-M. Herz (Hans-Martin); M. Mohan (Man); A.S. Garruss (Alexander); K. Liang (Kaiwei); Y.-H. Takahashi (Yoh-hei); K. Mickey (Kristen); O. Voets (Olaf); C.P. Verrijzer (Peter); A. Shilatifard (Ali)

    2012-01-01

    textabstractMonomethylation of histone H3 on Lys 4 (H3K4me1) and acetylation of histone H3 on Lys 27 (H3K27ac) are histone modifications that are highly enriched over the body of actively transcribed genes and on enhancers. Although in yeast all H3K4 methylation patterns, including H3K4me1, are impl

  13. Hydroxyl radical generation caused by the reaction of singlet oxygen with a spin trap, DMPO, increases significantly in the presence of biological reductants.

    Science.gov (United States)

    Nishizawa, Chiho; Takeshita, Keizo; Ueda, Jun-ichi; Mizuno, Michiko; Suzuki, Kazuo T; Ozawa, Toshihiko

    2004-04-01

    Photosensitizers newly developed for photodynamic therapy of cancer need to be assessed using accurate methods of measuring reactive oxygen species (ROS). Little is known about the characteristics of the reaction of singlet oxygen (1O2) with spin traps, although this knowledge is necessary in electron spin resonance (ESR)/spin trapping. In the present study, we examined the effect of various reductants usually present in biological samples on the reaction of 1O2 with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). The ESR signal of the hydroxyl radical (*OH) adduct of DMPO (DMPO-OH) resulting from 1O2-dependent generation of *OH strengthened remarkably in the presence of reduced glutathione (GSH), 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox), ascorbic acid, NADPH, etc. A similar increase was observed in the photosensitization of uroporphyrin (UP), rose bengal (RB) or methylene blue (MB). Use of 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline-N-oxide (DEPMPO) as a spin trap significantly lessened the production of its *OH adduct (DEPMPO-OH) in the presence of the reductants. The addition of DMPO to the DEPMPO-spin trapping system remarkably increased the signal intensity of DEPMPO-OH. DMPO-mediated generation of *OH was also confirmed utilizing the hydroxylation of salicylic acid (SA). These results suggest that biological reductants enhance the ESR signal of DMPO-OH produced by DMPO-mediated generation of *OH from 1O2, and that spin trap-mediated *OH generation hardly occurs with DEPMPO.

  14. Dephytinisation with intrinsic wheat phytase and iron fortification significantly increase iron absorption from fonio (Digitaria exilis) meals in West African women.

    Science.gov (United States)

    Koréissi-Dembélé, Yara; Fanou-Fogny, Nadia; Moretti, Diego; Schuth, Stephan; Dossa, Romain A M; Egli, Ines; Zimmermann, Michael B; Brouwer, Inge D

    2013-01-01

    Low iron and high phytic acid content make fonio based meals a poor source of bioavailable iron. Phytic acid degradation in fonio porridge using whole grain cereals as phytase source and effect on iron bioavailability when added to iron fortified fonio meals were investigated. Grains, nuts and seeds collected in Mali markets were screened for phytic acid and phytase activity. We performed an iron absorption study in Beninese women (n = 16), using non-dephytinised fonio porridge (FFP) and dephytinised fonio porridge (FWFP; 75% fonio-25% wheat), each fortified with (57)Fe or (58)Fe labeled FeSO4. Iron absorption was quantified by measuring the erythrocyte incorporation of stable iron isotopes. Phytic acid varied from 0.39 (bambara nut) to 4.26 g/100 g DM (pumpkin seed), with oilseeds values higher than grains and nuts. Phytase activity ranged from 0.17±1.61 (fonio) to 2.9±1.3 phytase unit (PU) per g (whole wheat). Phytic acid was almost completely degraded in FWFP after 60 min of incubation (pH≈5.0, 50°C). Phytate∶iron molar ratios decreased from 23.7∶1 in FFP to 2.7∶1 in FWFP. Iron fortification further reduced phytate∶iron molar ratio to 1.9∶1 in FFP and 0.3∶1 in FWFP, respectively. Geometric mean (95% CI) iron absorption significantly increased from 2.6% (0.8-7.8) in FFP to 8.3% (3.8-17.9) in FWFP (Pporridge with intrinsic wheat phytase increased fractional iron absorption 3.2 times, suggesting it could be a possible strategy to decrease PA in cereal-based porridges.

  15. Dephytinisation with intrinsic wheat phytase and iron fortification significantly increase iron absorption from fonio (Digitaria exilis meals in West African women.

    Directory of Open Access Journals (Sweden)

    Yara Koréissi-Dembélé

    Full Text Available Low iron and high phytic acid content make fonio based meals a poor source of bioavailable iron. Phytic acid degradation in fonio porridge using whole grain cereals as phytase source and effect on iron bioavailability when added to iron fortified fonio meals were investigated. Grains, nuts and seeds collected in Mali markets were screened for phytic acid and phytase activity. We performed an iron absorption study in Beninese women (n = 16, using non-dephytinised fonio porridge (FFP and dephytinised fonio porridge (FWFP; 75% fonio-25% wheat, each fortified with (57Fe or (58Fe labeled FeSO4. Iron absorption was quantified by measuring the erythrocyte incorporation of stable iron isotopes. Phytic acid varied from 0.39 (bambara nut to 4.26 g/100 g DM (pumpkin seed, with oilseeds values higher than grains and nuts. Phytase activity ranged from 0.17±1.61 (fonio to 2.9±1.3 phytase unit (PU per g (whole wheat. Phytic acid was almost completely degraded in FWFP after 60 min of incubation (pH≈5.0, 50°C. Phytate∶iron molar ratios decreased from 23.7∶1 in FFP to 2.7∶1 in FWFP. Iron fortification further reduced phytate∶iron molar ratio to 1.9∶1 in FFP and 0.3∶1 in FWFP, respectively. Geometric mean (95% CI iron absorption significantly increased from 2.6% (0.8-7.8 in FFP to 8.3% (3.8-17.9 in FWFP (P<0.0001. Dephytinisation of fonio porridge with intrinsic wheat phytase increased fractional iron absorption 3.2 times, suggesting it could be a possible strategy to decrease PA in cereal-based porridges.

  16. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

    Science.gov (United States)

    Gómez-Reino, Juan J; Carmona, Loreto; Valverde, Vicente Rodríguez; Mola, Emilio Martín; Montero, Maria Dolores

    2003-08-01

    The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

  17. Precision intrauterine contraception may significantly increase continuation of use: a review of long-term clinical experience with frameless copper-releasing intrauterine contraception devices

    Directory of Open Access Journals (Sweden)

    Wildemeersch D

    2013-04-01

    Full Text Available Dirk Wildemeersch,1 Ansgar Pett,2 Sohela Jandi,2 Thomas Hasskamp,3 Patrick Rowe,4 Marc Vrijens5 1Gynecological Outpatient Clinic and IUD Training Center, Ghent, Belgium; 2Gynecological Outpatient Clinic, Berlin, Germany; 3Gynecological Outpatient Clinic, Münster, Germany; 4Formely IUD Research Group at the UNDP/UNFPA/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction, World Health Organization, Geneva, Switzerland; 5Gynecological Outpatient Clinic, Ghent, Belgium Objective: The purpose of this paper is to review the experience with the frameless, anchored, GyneFix copper-releasing intrauterine contraceptive devices (IUCDs/IUDs (Contrel Europe, Belgium, and to demonstrate their high acceptability and low rate of discontinuation of use, which could contribute to current efforts that aim to reduce radically the high number of unintended pregnancies and induced abortions, particularly in young women. Materials and methods: This paper is based on studies that examined the differences in uterine volume and cavity size, related to age and parity, and on original clinical research data and practical experience with frameless copper IUDs, as well as on literature data on the IUD–endometrial cavity relationship of conventional IUDs, with special reference to side effects and user discontinuation. Results: The mean transverse diameter in nulliparous and parous women is significantly less than the length of the transverse arm of the TCu380A IUD (ParaGard, Duramed, NY, USA or the levonorgestrel intrauterine system (Mirena, Bayer, Germany. Small, frameless, flexible, and unidimensional copper IUDs appear to be well tolerated, with less impact on menstrual bleeding, resulting in low discontinuation rates when compared with standard-size conventional IUDs, which often result in increased expulsion rates, complaints of pain and erratic or increased menstrual bleeding, and subsequent high rates of

  18. The Clinical Significance of Increased Serum Proinflammatory Cytokines, C-Reactive Protein, and Erythrocyte Sedimentation Rate in Patients with Hidradenitis Suppurativa

    Directory of Open Access Journals (Sweden)

    D. Jiménez-Gallo

    2017-01-01

    Full Text Available Objectives. To assess inflammatory serum markers including serum proinflammatory cytokines, C-reactive protein (CRP, and erythrocyte sedimentation rate (ESR according to the clinical inflammatory activity of patients with hidradenitis suppurativa (HS. Patients and Methods. Seventy-four patients with HS were studied based on the Hidradenitis Suppurativa-Physician Global Assessment (HS-PGA score and Hurley staging system. Proinflammatory cytokines were measured using a multiplex cytokine assay. Twenty-two healthy volunteers were recruited. Results. Serum interleukin- (IL- 6, IL-23, soluble tumour necrosis factor alpha (TNF-α receptor I (sTNF-RI, CRP, and ESR were different in the patients with HS compared with those in the healthy controls (P0.25, P<0.05. The levels of IL-6 (r=0.53, P<0.001, CRP (r=0.54, P<0.001, and ESR (r=0.60, P<0.001 were especially well correlated with clinical inflammatory activity based on HS-PGA scores. The levels of IL-6, IL-8, sTNF-RI, sTNF-RII, CRP, and ESR were significantly elevated according to Hurley staging system. Conclusions. Serum proinflammatory cytokines, CRP, and ESR are increased in relation to the clinical inflammatory activity of patients with HS compared with healthy controls. Serum IL-6, CRP, and ESR are effective biomarkers for evaluating the severity of HS.

  19. High-dose cholecalciferol supplementation significantly increases peripheral CD4⁺ Tregs in healthy adults without negatively affecting the frequency of other immune cells.

    Science.gov (United States)

    Prietl, Barbara; Treiber, Gerlies; Mader, Julia K; Hoeller, Evelyne; Wolf, Michael; Pilz, Stefan; Graninger, Winfried B; Obermayer-Pietsch, Barbara M; Pieber, Thomas R

    2014-04-01

    Regulatory T cells (Tregs) play a central role in the maintenance of self-tolerance. Animal and in vitro studies suggest that vitamin D is involved in reducing the risk of autoimmunity by modulating Tregs. In a double-blind, placebo controlled study in 60 healthy volunteers, we assessed the effect of a 12-week high-dose oral cholecalciferol supplementation (140,000 IU/month) on the number and function of CD4(pos)CD25(high)FoxP3(pos)CD127(dim) Tregs. We also assessed the clinical safety of the supplementation and the effect on the frequency of other immune cells such as monocytes, dendritic cells, natural killer cells, natural killer T cells, B cells and subgroups of T cells. We also tested the in vitro effect of cholecalciferol on Tregs in human cell cultures. By using FACS analysis, ex vivo suppressive co-cultures and apoptosis assays, we were able to show that a cholecalciferol supplementation leads to significantly increased numbers of peripheral Tregs in vivo. Tregs function and the frequency of other immune cells remained unchanged, and no clinically relevant safety concerns were found. The in vitro exposure of human peripheral blood mononuclear cells to cholecalciferol also supported our in vivo findings. Our results indicate a substantial effect of a supplementation with inactive vitamin D on the immune system of healthy humans in vivo and provide a rationale for future studies to investigate the immunomodulatory effects of vitamin D in autoimmune diseases.

  20. In vitro exposure to the herbicide atrazine inhibits T cell activation, proliferation, and cytokine production and significantly increases the frequency of Foxp3+ regulatory T cells.

    Science.gov (United States)

    Thueson, Lindsay E; Emmons, Tiffany R; Browning, Dianna L; Kreitinger, Joanna M; Shepherd, David M; Wetzel, Scott A

    2015-02-01

    The herbicide atrazine (2-chloro-4-[ethylamino]-6-[isopropylamino]-s-triazine) is the most common water contaminant in the United States. Atrazine is a phosphodiesterase inhibitor and is classified as an estrogen disrupting compound because it elevates estrogen levels via induction of the enzyme aromatase. Previous studies have shown that atrazine exposure alters the function of innate immune cells such as NK cells, DC, mast cells, and macrophages. In this study we have examined the impact of in vitro atrazine exposure on the activation, proliferation, and effector cytokine production by primary murine CD4(+) T lymphocytes. We found that atrazine exposure significantly inhibited CD4(+) T cell proliferation and accumulation as well as the expression of the activation markers CD25 and CD69 in a dose-dependent manner. Interestingly, the effects were more pronounced in cells from male animals. These effects were partially mimicked by pharmacological reagents that elevate intracellular cAMP levels and addition of exogenous rmIL-2 further inhibited proliferation and CD25 expression. Consistent with these findings, atrazine exposure during T cell activation resulted in a 2- to 5-fold increase in the frequency of Foxp3(+) CD4(+) T cells. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Pathological concentration of zinc dramatically accelerates abnormal aggregation of full-length human Tau and thereby significantly increases Tau toxicity in neuronal cells.

    Science.gov (United States)

    Hu, Ji-Ying; Zhang, De-Lin; Liu, Xiao-Ling; Li, Xue-Shou; Cheng, Xiao-Qing; Chen, Jie; Du, Hai-Ning; Liang, Yi

    2017-02-01

    A pathological hallmark of Alzheimer disease and other tauopathies is the formation of neurofibrillary tangles mainly composed of bundles of fibrils formed by microtubule-associated protein Tau. Here we study the effects of Zn(2+) on abnormal aggregation and cytotoxicity of a pathological mutant ΔK280 of full-length human Tau. As revealed by Congo red binding assays, transmission electron microscopy, immunofluorescence, Western blot, and immunogold electron microscopy, pathological concentration of Zn(2+) dramatically accelerates the fibrillization of ΔK280 both in vitro and in SH-SY5Y neuroblastoma cells. As evidenced by annexin V-FITC apoptosis detection assay and MTT reduction assay, pathological concentration of Zn(2+) remarkably enhances ΔK280 fibrillization-induced apoptosis and toxicity in SH-SY5Y cells. Substitution of Cys-291 and Cys-322 with Ala, however, essentially eliminates such enhancing effects of Zn(2+) on the fibrillization and the consequent cytotoxicity of ΔK280. Furthermore, Zn(2+) is co-localized with and highly enriched in amyloid fibrils formed by ΔK280 in SH-SY5Y cells. The results from isothermal titration calorimetry show that Zn(2+) binds to full-length human Tau by interacting with Cys-291 and Cys-322, forming a 1:1 Zn(2+)-Tau complex. Our data demonstrate that zinc dramatically accelerates abnormal aggregation of human Tau and significantly increases Tau toxicity in neuronal cells mainly via bridging Cys-291 and Cys-322. Our findings could explain how pathological zinc regulates Tau aggregation and toxicity associated with Alzheimer disease. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. The Oryza sativa Regulator HDR1 Associates with the Kinase OsK4 to Control Photoperiodic Flowering.

    Directory of Open Access Journals (Sweden)

    Xuehui Sun

    2016-03-01

    Full Text Available Rice is a facultative short-day plant (SDP, and the regulatory pathways for flowering time are conserved, but functionally modified, in Arabidopsis and rice. Heading date 1 (Hd1, an ortholog of Arabidopsis CONSTANS (CO, is a key regulator that suppresses flowering under long-day conditions (LDs, but promotes flowering under short-day conditions (SDs by influencing the expression of the florigen gene Heading date 3a (Hd3a. Another key regulator, Early heading date 1 (Ehd1, is an evolutionarily unique gene with no orthologs in Arabidopsis, which acts as a flowering activator under both SD and LD by promoting the rice florigen genes Hd3a and RICE FLOWERING LOCUST 1 (RFT1. Here, we report the isolation and characterization of the flowering regulator Heading Date Repressor1 (HDR1 in rice. The hdr1 mutant exhibits an early flowering phenotype under natural LD in a paddy field in Beijing, China (39°54'N, 116°23'E, as well as under LD but not SD in a growth chamber, indicating that HDR1 may functionally regulate flowering time via the photoperiod-dependent pathway. HDR1 encodes a nuclear protein that is most active in leaves and floral organs and exhibits a typical diurnal expression pattern. We determined that HDR1 is a novel suppressor of flowering that upregulates Hd1 and downregulates Ehd1, leading to the downregulation of Hd3a and RFT1 under LDs. We have further identified an HDR1-interacting kinase, OsK4, another suppressor of rice flowering under LDs. OsK4 acts similarly to HDR1, suppressing flowering by upregulating Hd1 and downregulating Ehd1 under LDs, and OsK4 can phosphorylate HD1 with HDR1 presents. These results collectively reveal the transcriptional regulators of Hd1 for the day-length-dependent control of flowering time in rice.

  3. The Oryza sativa Regulator HDR1 Associates with the Kinase OsK4 to Control Photoperiodic Flowering.

    Science.gov (United States)

    Sun, Xuehui; Zhang, Zhiguo; Wu, Jinxia; Cui, Xuean; Feng, Dan; Wang, Kai; Xu, Ming; Zhou, Li; Han, Xiao; Gu, Xiaofeng; Lu, Tiegang

    2016-03-01

    Rice is a facultative short-day plant (SDP), and the regulatory pathways for flowering time are conserved, but functionally modified, in Arabidopsis and rice. Heading date 1 (Hd1), an ortholog of Arabidopsis CONSTANS (CO), is a key regulator that suppresses flowering under long-day conditions (LDs), but promotes flowering under short-day conditions (SDs) by influencing the expression of the florigen gene Heading date 3a (Hd3a). Another key regulator, Early heading date 1 (Ehd1), is an evolutionarily unique gene with no orthologs in Arabidopsis, which acts as a flowering activator under both SD and LD by promoting the rice florigen genes Hd3a and RICE FLOWERING LOCUST 1 (RFT1). Here, we report the isolation and characterization of the flowering regulator Heading Date Repressor1 (HDR1) in rice. The hdr1 mutant exhibits an early flowering phenotype under natural LD in a paddy field in Beijing, China (39°54'N, 116°23'E), as well as under LD but not SD in a growth chamber, indicating that HDR1 may functionally regulate flowering time via the photoperiod-dependent pathway. HDR1 encodes a nuclear protein that is most active in leaves and floral organs and exhibits a typical diurnal expression pattern. We determined that HDR1 is a novel suppressor of flowering that upregulates Hd1 and downregulates Ehd1, leading to the downregulation of Hd3a and RFT1 under LDs. We have further identified an HDR1-interacting kinase, OsK4, another suppressor of rice flowering under LDs. OsK4 acts similarly to HDR1, suppressing flowering by upregulating Hd1 and downregulating Ehd1 under LDs, and OsK4 can phosphorylate HD1 with HDR1 presents. These results collectively reveal the transcriptional regulators of Hd1 for the day-length-dependent control of flowering time in rice.

  4. Activity measurements of the radionuclides 18F and 99mTc for the NMISA, South Africa in the ongoing comparisons BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Tc-99m

    Science.gov (United States)

    Michotte, C.; Nonis, M.; Van Rooy, M. W.; Van Staden, M. J.; Lubbe, J.

    2017-01-01

    In 2015, comparisons of activity measurements of 18F and 99mTc using the Transfer Instrument of the International Reference System (SIRTI) took place at the National Metrology Institute of South Africa (NMISA, South Africa). Ampoules containing about 25 kBq of 18F and 99mTc solutions were measured in the SIRTI for more than two half-lives. The NMISA standardized the activity in the ampoules by ionization chamber measurements traceable to 4π(LS)β-γ coincidence measurements. The comparisons, identifiers BIPM.RI(II)-K4.F-18 and BIPM.RI(II)-K4.Tc-99m, are linked to the corresponding BIPM.RI(II)-K1.F-18 and BIPM.RI(II)-K1.Tc-99m comparisons and degrees of equivalence with the respective key comparison reference values have been evaluated. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  5. 乳腺癌细胞Twist和Trkb的表达及其意义%Increased Expression of Twist and Trkb in Breast Cancer and Their Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    欧武陵; 胡胜; 余伟江; 吴月兵

    2011-01-01

    Objective: To study the expression of Twist and Trkb in human breast cancers, and to investigate the role of Twist and Trkb in breast cancer progression, metastasis, and prognosis.Methods: The MCF-7 human breast cancer cell line was cultured under mammosphere forming conditions and implanted into nude mice. RT-PCR technique was used to measure the expression of Twist and Trkb mRNA in the tissue samples from 14 nude mice and 86 human human breast tumors. Results: In the nude mice implanted with breast cancer cells, the level of the Twist and Trkb mRNA in the samples from metastasis tissues was higher than that of primary tissues (the relative OD value of Twist and Trkb mRNA was 2. 1±0.2 vs 1.4±0.2,2.3±0. 4 vs 1.5±0.3;t =2.4, 2.8;P=0.03, 0. 02 respectively). In human tumor samples, the level of the Twist and Trkb mRNA of lymph node metastasis was higher than that of breast tissues (1.67±0. 32 vs 0.83±0.23, 1.58±0.41 vs 0.65±0.24 respectively;t=2.6,P=0.02; t=3.01, P=0.01). The level of the Twist and Trkb mRNA of breast cancers was higher than that of primary tissues (2.38±0.22 vs 1.84±0. 43, 2. 17±0. 41 vs 1.62±0. 32 respectively;t=3. 23, P=0. 01; t= 2.84, P=0.03). The expression of Twist and Trkb was significantly correlated with clinical stages, tumor lymph node metastasis and loss of differentiation (all P<0.05). However, there was no correlation between Twist or Trkb mRNA levels and age or tumor size (all P>0. 05). Increased expression of Twist correlated with shorter overall survival ([28.4 ± 2.2] vs [32.7 ± 2.4] months, LogRank= 3.88, P = 0. 037), while no significant correlations were observed between increased expression of Trkb and shorter overall survival([29.9±2.6] vs [31.5±2. 5] months, LogRank= 2.46, P=0. 08). Conclusion: Expression of Twist and Trkb associate with breast cancer infiltration and metastasis, and increased expression of Twist may implicate in breast cancer prognosis.%目的:探讨乳腺癌细胞Twist和Trkb的表达及

  6. Meiotic behavior and H3K4m distribution in B chromosomes of Characidium gomesi (Characiformes, Crenuchidae)

    Science.gov (United States)

    Serrano, Érica Alves; Araya-Jaime, Cristian; Suárez-Villota, Elkin Y.; Oliveira, Claudio; Foresti, Fausto

    2016-01-01

    Abstract Characidium gomesi Travasso, 1956 specimens from the Pardo River have up to four heterochromatic supernumerary chromosomes, derived from the sex chromosomes. To access the meiotic behavior and distribution of an active chromatin marker, males and females of Characidium gomesi with two or three B chromosomes were analyzed. Mitotic chromosomes were characterized using C-banding and FISH with B chromosome probes. Meiocytes were subjected to immunofluorescence-FISH assay using anti-SYCP3, anti-H3K4m, and B chromosomes probes. Molecular homology of supernumeraries was confirmed by FISH and by its bivalent conformation in individuals with two of these chromosomes. In individuals with three Bs, these elements formed a bivalent and a univalent. Supernumerary and sex chromosomes exhibited H3K4m signals during pachytene contrasting with their heterochromatic and asynaptic nature, which suggest a more structural role than functional of this histone modification. The implications of this result are discussed in light of the homology, meiotic nuclear organization, and meiotic silencing of unsynapsed chomatin. PMID:27551347

  7. Trithorax monomethylates histone H3K4 and interacts directly with CBP to promote H3K27 acetylation and antagonize Polycomb silencing.

    Science.gov (United States)

    Tie, Feng; Banerjee, Rakhee; Saiakhova, Alina R; Howard, Benny; Monteith, Kelsey E; Scacheri, Peter C; Cosgrove, Michael S; Harte, Peter J

    2014-03-01

    Trithorax (TRX) antagonizes epigenetic silencing by Polycomb group (PcG) proteins, stimulates enhancer-dependent transcription, and establishes a 'cellular memory' of active transcription of PcG-regulated genes. The mechanisms underlying these TRX functions remain largely unknown, but are presumed to involve its histone H3K4 methyltransferase activity. We report that the SET domains of TRX and TRX-related (TRR) have robust histone H3K4 monomethyltransferase activity in vitro and that Tyr3701 of TRX and Tyr2404 of TRR prevent them from being trimethyltransferases. The trx(Z11) missense mutation (G3601S), which abolishes H3K4 methyltransferase activity in vitro, reduces the H3K4me1 but not the H3K4me3 level in vivo. trx(Z11) also suppresses the impaired silencing phenotypes of the Pc(3) mutant, suggesting that H3K4me1 is involved in antagonizing Polycomb silencing. Polycomb silencing is also antagonized by TRX-dependent H3K27 acetylation by CREB-binding protein (CBP). We show that perturbation of Polycomb silencing by TRX overexpression requires CBP. We also show that TRX and TRR are each physically associated with CBP in vivo, that TRX binds directly to the CBP KIX domain, and that the chromatin binding patterns of TRX and TRR are highly correlated with CBP and H3K4me1 genome-wide. In vitro acetylation of H3K27 by CBP is enhanced on K4me1-containing H3 substrates, and independently altering the H3K4me1 level in vivo, via the H3K4 demethylase LSD1, produces concordant changes in H3K27ac. These data indicate that the catalytic activities of TRX and CBP are physically coupled and suggest that both activities play roles in antagonizing Polycomb silencing, stimulating enhancer activity and cellular memory.

  8. K4MY METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  9. K4BM METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  10. K4BL METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  11. Chromosomal distribution of H3K4me2, H3K9me2 and 5-methylcytosine: variations associated with polyploidy and hybridization in Brachiaria (Poaceae).

    Science.gov (United States)

    de Paula, Cristina Maria Pinto; Souza Sobrinho, Fausto; Techio, Vânia Helena

    2016-06-01

    Assessment of chromosomal distribution of modified histones and 5-methylcytosine shown that there are diversification of chromosomal types among species of Brachiaria and its interspecific hybrids. Histone post-translational modifications and DNA methylation are epigenetic processes that are involved in structural and functional organization of the genome. This study compared the chromosomal distribution of modified histones and 5-methylcytosine (5-mCyt) in species and interspecific hybrids of Brachiaria with different ploidy levels and reproduction modes. The relation between H3K9me2 and 5-mCyt was observed in the nucleolus organizer region, centromeric central domain and pericentromeric region. H3K4me2 was detected in euchromatic domains, mainly in the terminal chromosomal regions. Comparison of chromosomal distribution among species and hybrids showed greater variation of chromosomal types for the H3K9me2 in B. decumbens (tetraploid and apomictic species) and the 963 hybrid, while, for the H3K4me2, the variation was higher in B. brizantha and B. decumbens (tetraploid and apomictic species) and 963 hybrid. The chromosome distribution of 5-mCyt was similar between B. brizantha and B. decumbens, which differ from the distribution observed in B. ruziziensis (diploid and sexual species). Significant alterations in DNA methylation were observed in the artificially tetraploidized B. ruziziensis and in the interspecific hybrids, possibly as result of hybridization and polyploidization processes. The monitoring of histone modifications and DNA methylation allowed categorizing nuclear and chromosomal distribution of these epigenetic marks, thus contributing to the knowledge of composition and structure of the genome/epigenome of Brachiaria species and hybrids. These data can be useful for speciation and genome evolution studies in genus Brachiaria, and represent important markers to explore relationships between genomes.

  12. Community reinforcement training for family and significant others of drug abusers: a unilateral intervention to increase treatment entry of drug users.

    Science.gov (United States)

    Kirby, K C; Marlowe, D B; Festinger, D S; Garvey, K A; La Monaca, V

    1999-08-02

    We randomly assigned 32 concerned family members and significant others (FSOs) of drug users (DUs) to a community reinforcement training intervention or a popular 12-step self-help group. We measured problems arising from the DU's behavior, social functioning of the DU and FSO, and mood of the FSO at baseline and 10 weeks later. We also monitored the FSOs' treatment attendance and treatment entry of the DUs. The treatment groups showed equal reductions from baseline to follow-up in problems and improvements in social functioning and mood of the FSO. However the community reinforcement intervention was significantly better at retaining FSOs in treatment and inducing treatment entry of the DUs.

  13. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ruy M [Los Alamos National Laboratory

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

  14. Co-downregulation of the hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyl transferase and coumarate 3-hydroxylase significantly increases cellulose content in transgenic alfalfa (Medicago sativa L.).

    Science.gov (United States)

    Tong, Zongyong; Li, Heng; Zhang, Rongxue; Ma, Lei; Dong, Jiangli; Wang, Tao

    2015-10-01

    Lignin is a component of the cell wall that is essential for growth, development, structure and pathogen resistance in plants, but high lignin is an obstacle to the conversion of cellulose to ethanol for biofuel. Genetically modifying lignin and cellulose contents can be a good approach to overcoming that obstacle. Alfalfa (Medicago sativa L.) is rich in lignocellulose biomass and used as a model plant for the genetic modification of lignin in this study. Two key enzymes in the lignin biosynthesis pathway-hydroxycinnamoyl -CoA:shikimate hydroxycinnamoyl transferase (HCT) and coumarate 3-hydroxylase (C3H)-were co-downregulated. Compared to wild-type plants, the lignin content in the modified strain was reduced by 38%, cellulose was increased by 86.1%, enzyme saccharification efficiency was increased by 10.9%, and cell wall digestibility was increased by 13.0%. The modified alfalfa exhibited a dwarf phenotype, but normal above ground biomass. This approach provides a new strategy for reducing lignin and increasing cellulose contents and creates a new genetically modified crop with enhanced value for biofuel. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  15. The significance of the European beaver (Castor fibre activity for the process of renaturalization of river valleys in the era of increasing

    Directory of Open Access Journals (Sweden)

    Kusztal Piotr

    2017-03-01

    Full Text Available Changes in the environment that are caused by the activity of beavers bring numerous advantages. They affect the increase in biodiversity, contribute to improving the condition of cleanliness of watercourses, improve local water relations and restore the natural landscape of river valleys.

  16. Sgf29 binds histone H3K4me2/3 and is required for SAGA complex recruitment and histone H3 acetylation

    Energy Technology Data Exchange (ETDEWEB)

    Bian, Chuanbing; Xu, Chao; Ruan, Jianbin; Lee, Kenneth K.; Burke, Tara L.; Tempel, Wolfram; Barsyte, Dalia; Li, Jing; Wu, Minhao; Zhou, Bo O.; Fleharty, Brian E.; Paulson, Ariel; Allali-Hassani, Abdellah; Zhou, Jin-Qiu; Mer, Georges; Grant, Patrick A.; Workman, Jerry L.; Zang, Jianye; Min, Jinrong (Toronto); (Stowers); (UST - China); (UV); (Chinese Aca. Sci.); (MCCM)

    2011-09-28

    The SAGA (Spt-Ada-Gcn5 acetyltransferase) complex is an important chromatin modifying complex that can both acetylate and deubiquitinate histones. Sgf29 is a novel component of the SAGA complex. Here, we report the crystal structures of the tandem Tudor domains of Saccharomyces cerevisiae and human Sgf29 and their complexes with H3K4me2 and H3K4me3 peptides, respectively, and show that Sgf29 selectively binds H3K4me2/3 marks. Our crystal structures reveal that Sgf29 harbours unique tandem Tudor domains in its C-terminus. The tandem Tudor domains in Sgf29 tightly pack against each other face-to-face with each Tudor domain harbouring a negatively charged pocket accommodating the first residue alanine and methylated K4 residue of histone H3, respectively. The H3A1 and K4me3 binding pockets and the limited binding cleft length between these two binding pockets are the structural determinants in conferring the ability of Sgf29 to selectively recognize H3K4me2/3. Our in vitro and in vivo functional assays show that Sgf29 recognizes methylated H3K4 to recruit the SAGA complex to its targets sites and mediates histone H3 acetylation, underscoring the importance of Sgf29 in gene regulation.

  17. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia — significance for activation of the kynurenine pathway

    Science.gov (United States)

    Schwieler, Lilly; Larsson, Markus K.; Skogh, Elisabeth; Kegel, Magdalena E.; Orhan, Funda; Abdelmoaty, Sally; Finn, Anja; Bhat, Maria; Samuelsson, Martin; Lundberg, Kristina; Dahl, Marja-Liisa; Sellgren, Carl; Schuppe-Koistinen, Ina; Svensson, Camilla I.; Erhardt, Sophie; Engberg, Göran

    2015-01-01

    Background Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway. Methods We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry. Results We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA. Limitations The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age. Conclusion We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-d-aspartate receptor antagonist KYNA in patients with schizophrenia. PMID:25455350

  18. Seed-Specific Expression of a Lysine-Rich Protein Gene, GhLRP, from Cotton Significantly Increases the Lysine Content in Maize Seeds

    Directory of Open Access Journals (Sweden)

    Jing Yue

    2014-03-01

    Full Text Available Maize seed storage proteins are a major source of human and livestock consumption. However, these proteins have poor nutritional value, because they are deficient in lysine and tryptophan. Much research has been done to elevate the lysine content by reducing zein content or regulating the activities of key enzymes in lysine metabolism. Using the naturally lysine-rich protein genes, sb401 and SBgLR, from potato, we previously increased the lysine and protein contents of maize seeds. Here, we examined another natural lysine-rich protein gene, GhLRP, from cotton, which increased the lysine content of transgenic maize seeds at levels varying from 16.2% to 65.0% relative to the wild-type. The total protein content was not distinctly different, except in the six transgenic lines. The lipid and starch levels did not differ substantially in Gossypium hirsutum L. lysine-rich protein (GhLRP transgenic kernels when compared to wild-type. The agronomic characteristics of all the transgenic maize were also normal. GhLRP is a high-lysine protein candidate gene for increasing the lysine content of maize. This study provided a valuable model system for improving maize lysine content.

  19. Partial depletion of CD4(+)CD25(+)Foxp3(+) T regulatory cells significantly increases morbidity during acute phase Toxoplasma gondii infection in resistant BALB/c mice.

    Science.gov (United States)

    Morampudi, Vijay; De Craeye, Stephane; Le Moine, Alain; Detienne, Sophie; Braun, M Y; D'Souza, Sushila

    2011-04-01

    CD4(+)CD25(+)Foxp3(+) T regulatory (Treg) cells, are known to regulate responses to infectious agents. Here we compared disease progression in BALB/c and C57BL/6(B6) mice infected perorally with Toxoplasma gondii for 7 days and examined the affect of partial depletion of Treg cells in these mice. BALB/c mice were seen to be resistant to peroral infection whereas B6 mice were susceptible in terms of mortality. Although the depletion of Treg cells before infection had no effect on the survival of B6 or BALB/c mice, it resulted in increased parasite burdens in BALB/c mice, especially in the lamina propria, but not in B6 mice. Pro-inflammatory cytokines were also increased in Treg cells depleted BALB/c mice as compared to B6 mice. In addition Treg cell depleted BALB/c mice displayed increased ileal histopathology compared to their non-treated counterparts. These findings provide evidence for the contribution of Treg cells, in the resistance of BALB/c mice against peroral T. gondii infection.

  20. Seed-specific expression of a lysine-rich protein gene, GhLRP, from cotton significantly increases the lysine content in maize seeds.

    Science.gov (United States)

    Yue, Jing; Li, Cong; Zhao, Qian; Zhu, Dengyun; Yu, Jingjuan

    2014-03-27

    Maize seed storage proteins are a major source of human and livestock consumption. However, these proteins have poor nutritional value, because they are deficient in lysine and tryptophan. Much research has been done to elevate the lysine content by reducing zein content or regulating the activities of key enzymes in lysine metabolism. Using the naturally lysine-rich protein genes, sb401 and SBgLR, from potato, we previously increased the lysine and protein contents of maize seeds. Here, we examined another natural lysine-rich protein gene, GhLRP, from cotton, which increased the lysine content of transgenic maize seeds at levels varying from 16.2% to 65.0% relative to the wild-type. The total protein content was not distinctly different, except in the six transgenic lines. The lipid and starch levels did not differ substantially in Gossypium hirsutum L. lysine-rich protein (GhLRP) transgenic kernels when compared to wild-type. The agronomic characteristics of all the transgenic maize were also normal. GhLRP is a high-lysine protein candidate gene for increasing the lysine content of maize. This study provided a valuable model system for improving maize lysine content.

  1. Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2

    DEFF Research Database (Denmark)

    Pasini, Diego; Hansen, Klaus H; Christensen, Jesper;

    2008-01-01

    Polycomb group (PcG) proteins regulate important cellular processes such as embryogenesis, cell proliferation, and stem cell self-renewal through the transcriptional repression of genes determining cell fate decisions. The Polycomb-Repressive Complex 2 (PRC2) is highly conserved during evolution......, and its intrinsic histone H3 Lys 27 (K27) trimethylation (me3) activity is essential for PcG-mediated transcriptional repression. Here, we show a functional interplay between the PRC2 complex and the H3K4me3 demethylase Rbp2 (Jarid1a) in mouse embryonic stem (ES) cells. By genome-wide location analysis we...... found that Rbp2 is associated with a large number of PcG target genes in mouse ES cells. We show that the PRC2 complex recruits Rbp2 to its target genes, and that this interaction is required for PRC2-mediated repressive activity during ES cell differentiation. Taken together, these results demonstrate...

  2. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation

    Energy Technology Data Exchange (ETDEWEB)

    Korzeneva, Inna B., E-mail: inna.korzeneva@molgen.vniief.ru [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Kostuyk, Svetlana V.; Ershova, Liza S. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation); Osipov, Andrian N. [Federal Medial and Biological Center named after Burnazyan of the Federal Medical and Biological Agency (FMBTz named after Burnazyan of FMBA), Moscow (Russian Federation); State Research Center - Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Zhivopisnaya, 46, Moscow, 123098 (Russian Federation); Zhuravleva, Veronika F.; Pankratova, Galina V. [Russian Federal Nuclear Center – All-Russian Research Institute of Experimental Physics (RFNC-VNIIEF) 607190, Sarov, 37 Mira ave., Nizhniy Novgorod Region (Russian Federation); Porokhovnik, Lev N.; Veiko, Natalia N. [Research Centre for Medical Genetics, Russian Academy of Medical Sciences, 115478 Moscow, 1 Moskvorechye str. (Russian Federation)

    2015-09-15

    Highlights: • The chronic exposure to low-dose IR induces DSBs in human lymphocytes (TM index). • Exposure to IR decreases the level of human circulating DNA (cfDNA index). • IR induces an increase of DNase1 activity (DNase1 index) in plasma. • IR induces an increase of the level of antibodies to DNA (Ab DNA index) in plasma. • The ratio cfDNA/(DNase 1 × Ab DNA × TM) is a potential marker of human exposure to IR. - Abstract: The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism’s cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1 × Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab

  3. The influence of agitation sequence and ionic strength on in vitro drug release from hypromellose (E4M and K4M) ER matrices--the use of the USP III apparatus.

    Science.gov (United States)

    Asare-Addo, Kofi; Kaialy, Waseem; Levina, Marina; Rajabi-Siahboomi, Ali; Ghori, Mohammed U; Supuk, Enes; Laity, Peter R; Conway, Barbara R; Nokhodchi, Ali

    2013-04-01

    Theophylline extended release (ER) matrices containing hypromellose (hydroxypropyl methylcellulose (HPMC) E4M and K4M were evaluated in media with a pH range of 1.2-7.5, using an automated USP type III, Bio-Dis dissolution apparatus. The objectives of this study were to evaluate the effects of systematic agitation, ionic strength and pH on the release of theophylline from the gel forming hydrophilic polymeric matrices with different methoxyl substitution levels. Tribo-electric charging of hypromellose, theophylline and their formulated blends containing E4M and K4M grades has been characterised, along with quantitative observations of flow, compression behaviour and particle morphology. Agitations were studied at 5, 10, 15, 20, 25, 30 dips per minute (dpm) and also in the ascending and descending order in the dissolution vials. The ionic concentration strength of the media was also varied over a range of 0-0.4M to simulate the gastrointestinal fed and fasted states and various physiological pH conditions. To study the effect of ionic strength on the hydrophilic matrices, agitation was set at 20 dpm. The charge results on individual components imply that the positively charged particles have coupled with the negatively charged particles to form a stable ordered mixture which is believed to result in a more homogeneous and stable system. The particle shape analysis showed the HPMC K4M polymer to have a more irregular morphology and a rougher surface texture in comparison to the HPMC E4M polymer, possibly a contributory factor to the gelation process. The results showed gelation occurred quicker for the K4M tablet matrices. Drug release increased with increased agitation. This was more pronounced for the E4M tablet matrices. The ionic strength also had more of an effect on the drug release from the E4M matrices. The experiments highlighted the resilience of the K4M matrices in comparison with the E4M matrices. The results thus show that despite similar viscosities of

  4. Nontraditional approaches to first-in-human studies to increase efficiency of drug development: will microdose studies make a significant impact?

    Science.gov (United States)

    Boyd, R A; Lalonde, R L

    2007-01-01

    Much has been written recently about low productivity in the pharmaceutical industry and the high cost of drug development. Over a 10-year period ending in 2000, only approximately 11% of compounds tested in humans across 10 large pharmaceutical companies were eventually approved for marketing in the United States and/or Europe. Attrition was highest during phase II (62%) but still significant in phase III (45%) and at the time of registration (23%). Clearly, given the high cost and time required for clinical development, these late-stage failures are unsustainable.

  5. Increased numbers of Australian Indigenous nurses would make a significant contribution to 'closing the gap' in Indigenous health: what is getting in the way?

    Science.gov (United States)

    West, Roianne; Usher, Kim; Foster, Kim

    2010-01-01

    The provision of a well trained and culturally safe health workforce is critical to the alleviation of health inequities for Australian Indigenous peoples. Educating and graduating significant numbers of Indigenous registered nurses is one way the 'Close the Gap' initiative succeeds. Indigenous nurses bring a set of unique skills, knowledge and understanding to health service delivery. Their contribution has the potential to enhance future outcomes for Indigenous people by improving access to health services, ensure services are culturally appropriate and respectful, and assist non-Indigenous nurses to deliver culturally appropriate care. This paper discusses the background to the current numbers of Indigenous undergraduate nursing students enrolled in and completing tertiary nursing courses, with a focus on Queensland nursing programs. A range of identified barriers impede Indigenous nursing students' successful completion of their studies. We propose recommendations for education, research and employment to help overcome these problems, and ensure greater Indigenous participation in the nursing workforce.

  6. iNKT/CD1d-antitumor immunotherapy significantly increases the efficacy of therapeutic CpG/peptide-based cancer vaccine.

    Science.gov (United States)

    Corgnac, Stéphanie; Perret, Rachel; Zhang, Lianjun; Mach, Jean-Pierre; Romero, Pedro; Donda, Alena

    2014-01-01

    Therapeutic cancer vaccines aim to boost the natural immunity against transformed cancer cells, and a series of adjuvants and co-stimulatory molecules have been proposed to enhance the immune response against weak self-antigens expressed on cancer cells. For instance, a peptide/CpG-based cancer vaccine has been evaluated in several clinical trials and was shown in pre-clinical studies to favor the expansion of effector T versus Tregs cells, resulting in a potent antitumor activity, as compared to other TLR ligands. Alternatively, the adjuvant activity of CD1d-restricted invariant NKT cells (iNKT) on the innate and adaptive immunity is well demonstrated, and several CD1d glycolipid ligands are under pre-clinical and clinical evaluation. Importantly, additive or even synergistic effects have been shown upon combined CD1d/NKT agonists and TLR ligands. The aim of the present study is to combine the activation and tumor targeting of activated iNKT, NK and T cells. Activation and tumor targeting of iNKT cells via recombinant α-galactosylceramide (αGC)-loaded CD1d-anti-HER2 fusion protein (CD1d-antitumor) is combined or not with OVA peptide/CpG vaccine. Circulating and intratumoral NK and H-2Kb/OVA-specific CD8 responses are monitored, as well as the state of activation of dendritic cells (DC) with regard to activation markers and IL-12 secretion. The resulting antitumor therapy is tested against established tumor grafts of B16 melanoma cells expressing human HER2 and ovalbumin. The combined CD1d/iNKT antitumor therapy and CpG/peptide-based immunization leads to optimized expansion of NK and OVA-specific CD8 T cells (CTLs), likely resulting from the maturation of highly pro-inflammatory DCs as seen by a synergistic increase in serum IL-12. The enhanced innate and adaptive immune responses result in higher tumor inhibition that correlates with increased numbers of OVA-specific CTLs at the tumor site. Antibody-mediated depletion experiments further demonstrate that in

  7. Human circulating plasma DNA significantly decreases while lymphocyte DNA damage increases under chronic occupational exposure to low-dose gamma-neutron and tritium β-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Liza S; Osipov, Andrian N; Zhuravleva, Veronika F; Pankratova, Galina V; Porokhovnik, Lev N; Veiko, Natalia N

    2015-09-01

    The blood plasma of healthy people contains cell-fee (circulating) DNA (cfDNA). Apoptotic cells are the main source of the cfDNA. The cfDNA concentration increases in case of the organism's cell death rate increase, for example in case of exposure to high-dose ionizing radiation (IR). The objects of the present research are the blood plasma and blood lymphocytes of people, who contacted occupationally with the sources of external gamma/neutron radiation or internal β-radiation of tritium N = 176). As the controls (references), blood samples of people, who had never been occupationally subjected to the IR sources, were used (N = 109). With respect to the plasma samples of each donor there were defined: the cfDNA concentration (the cfDNA index), DNase1 activity (the DNase1 index) and titre of antibodies to DNA (the Ab DNA index). The general DNA damage in the cells was defined (using the Comet assay, the tail moment (TM) index). A chronic effect of the low-dose ionizing radiation on a human being is accompanied by the enhancement of the DNA damage in lymphocytes along with a considerable cfDNA content reduction, while the DNase1 content and concentration of antibodies to DNA (Ab DNA) increase. All the aforementioned changes were also observed in people, who had not worked with the IR sources for more than a year. The ratio cfDNA/(DNase1×Ab DNA × TM) is proposed to be used as a marker of the chronic exposure of a person to the external low-dose IR. It was formulated the assumption that the joint analysis of the cfDNA, DNase1, Ab DNA and TM values may provide the information about the human organism's cell resistivity to chronic exposure to the low-dose IR and about the development of the adaptive response in the organism that is aimed, firstly, at the effective cfDNA elimination from the blood circulation, and, secondly - at survival of the cells, including the cells with the damaged DNA. Copyright © 2015. Published by Elsevier B.V.

  8. Yearly variation of spontaneous somatic mutation frequency in the stamen hairs of Tradescantia clone KU 9 grown outdoors, which showed a significant increase after the Chernobyl accident.

    Science.gov (United States)

    Ichikawa, S; Nakano, A; Kenmochi, M; Yamamoto, I; Murai, M; Takahashi, E; Yamaguchi, A; Watanabe, K; Tomiyama, M; Sugiyama, K; Yogo, A; Yazaki, T; Okumura, M; Shima, N; Satoh, M; Yoshimoto, M; Xiao, L Z

    1996-02-01

    Scoring of spontaneous somatic pink mutation frequency in the stamen hairs of Tradescantia clone KU 9, a heterozygote for flower color (blue/pink; the blue color being dominant), was carried out for 11 years on plants grown outdoors, during the period of May 11-31 (for 3 weeks) in every year from 1982 to 1992. Weekly and yearly variations of the spontaneous mutation frequency were observed, and such variations could mostly be correlated to the difference in temperature. That is, the mutation frequency was generally higher in the weeks and years when the temperature was relatively low, showing the strongest negative correlation with the average minimum temperature. The variations were also correlated to the diurnal temperature difference, the mutation frequency being higher with larger diurnal temperature difference in general. However, the mutation frequency observed in 1986 was exceptionally higher than that expected from the temperature for this year, and was very significantly higher than for other years. The scoring of mutation frequency was thus continued in 1986 for an additional 4 weeks (June 1-28), and it was confirmed that such higher mutation frequencies lasted for 6 weeks in total. The exceptionally high mutation frequency seemed to be related to the radioactive fallout which occurred in early to mid May of 1986, even in Japan, after the serious nuclear reactor accident at Chernobyl, and also to the biological concentrations of radioactive nuclides which subsequently occurred, although it was difficult to conclude this definitely. The mutation frequency in 1987 was second highest, and was also significantly higher than the lowest mutation frequency observed in 1990.

  9. Knockout of the DNA ligase IV homolog gene in the sphingoid base producing yeast Pichia ciferrii significantly increases gene targeting efficiency.

    Science.gov (United States)

    Schorsch, Christoph; Köhler, Tim; Boles, Eckhard

    2009-08-01

    The yeast Pichia ciferrii produces large quantities of the sphingoid base tetraacetyl phytosphingosine (TAPS) and is an interesting platform organism for the biotechnological production of sphingolipids and ceramides. Ceramides have attracted great attention as a specialty ingredient for moisture retention and protection of the skin in the cosmetics industry. First attempts have been started to metabolically engineer P. ciferrii for improved production of TAPS and other sphingoid bases. However, rational metabolic engineering of P. ciferrii is difficult due to a low gene targeting efficiency. In eukaryotes, two major pathways coexist, which are responsible for genomic DNA integration, homologous recombination (HR) and non-homologous end joining (NHEJ). Integration via HR is targeted, while NHEJ involves ectopic (non-targeted) integration depending on a ligation step mediated by DNA ligase IV (Lig4). Here, we demonstrate a dramatical increase in gene targeting efficiency in a P. ciferrii lig4 knockout strain, deficient in NHEJ. Furthermore, a quick and easy to use freeze-thaw method was developed to transform P. ciferrii with high efficiency. Owing to the ability of targeting genomic DNA integration our results pave the way for further genetic and metabolic engineering approaches with P. ciferrii by means of knocking out or overexpressing predestinated genes.

  10. Heterozygous carriers of the I171V mutation of the NBS1 gene have a significantly increased risk of solid malignant tumours.

    Science.gov (United States)

    Nowak, Jerzy; Mosor, Maria; Ziółkowska, Iwona; Wierzbicka, Malgorzta; Pernak-Schwarz, Monika; Przyborska, Marta; Roznowski, Krzysztof; Pławski, Andrzej; Słomski, Ryszard; Januszkiewicz, Danuta

    2008-03-01

    Homozygous mutation 657del5 within the NBS1 gene is responsible for the majority of Nijmegen breakage syndrome (NBS) cases. NBS patients are characterised by increased susceptibility to malignancies mainly of lymphoid origin. Recently it has been postulated that heterozygous carriers of 657del5 NBS1 mutation are at higher risk of cancer development. The aim of the study was to analyse the frequency of I171V mutation in NBS1 gene in 270 women with breast cancer, 176 patients with larynx cancer, 81 with second primary tumours of head and neck, 131 with colorectal carcinoma and 600 healthy individuals. I171V mutation was present in 17 cancer patients compared with only one in healthy individuals. This constitutes 2.58% in studied patients with malignancies and 0.17% in the control group (P=0.0002; relative risk 1.827; odds ratio 15.886; 95% confidence interval 2.107-119.8). Since DNA was isolated from non malignant cells, all mutations found in cancer patients appeared to be of germinal origin. It can be concluded that NBS1 allele I171V may be a general susceptibility gene in solid tumours.

  11. Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy of Inhibiting HER2 via HER2-dependent and -independent Mechanisms

    Science.gov (United States)

    Singh, Jagdeep K.; Farnie, Gillian; Bundred, Nigel J.; Simões, Bruno M; Shergill, Amrita; Landberg, Göran; Howell, Sacha; Clarke, Robert B.

    2012-01-01

    Purpose Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are predicted to be responsible for tumour initiation, maintenance and metastases. Interleukin-8 (IL-8) is upregulated in breast cancer and associated with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. We investigated the role of IL-8 in the regulation of CSC activity using patient-derived breast cancers and determined the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy. Experimental design CSC activity of metastatic and invasive human breast cancers (n=19) was assessed ex vivo using the mammosphere colony forming assay. Results Metastatic fluid IL-8 level correlated directly with mammosphere formation (r=0.652; P<0.05; n=10). Recombinant IL-8 directly increased mammosphere formation/self-renewal in metastatic and invasive breast cancers (n=17). IL-8 induced activation of EGFR/HER2 and downstream signalling pathways and effects were abrogated by inhibition of SRC, EGFR/HER2, PI3K or MEK. Furthermore, lapatinib inhibited the mammosphere-promoting effect of IL-8 in both HER2-positive and negative patient-derived cancers. CXCR1/2 inhibition also blocked the effect of IL-8 on mammosphere formation and added to the efficacy of lapatinib in HER2-positive cancers. Conclusions These studies establish a role for IL-8 in the regulation of patient-derived breast CSC activity and demonstrate that IL-8/CXCR1/2 signalling is partly mediated via a novel SRC and EGFR/HER2-dependent pathway. Combining CXCR1/2 inhibitors with current HER2-targeted therapies has potential as an effective therapeutic strategy to reduce CSC activity in breast cancer and improve the survival of HER2-positive patients. PMID:23149820

  12. Yeast-Derived β-1,3-Glucan Substrate Significantly Increased the Diversity of Methanogens DuringIn vitro Fermentation of Porcine Colonic Digesta

    Institute of Scientific and Technical Information of China (English)

    LUO Yu-heng; LI Hua; LUO Jun-qiu; ZHANG Ke-ying

    2013-01-01

    Theβ-1,3-glucan from yeast has been extensively examined for its immuno-enhancing effects in animals. However, investigation on the relationship amongβ-glucan, gut microbiota and immune-modulating effects remains limited particularly in pigs. Considering the critical roles of gut methanogens in the microbial fermentation, energy metabolism and disease resistance, we investigated the phylogenetic diversity of methanogens from fermented cultures of porcine colonic digesta with (G) or without (N) yeastβ-glucan based on sequences of the archaeal 16S rRNA gene. A total of 145 sequences in the G library were assigned into 8 operational taxonomic units (OTUs) with the majority of sequences (114/145) related to strainsMethanobrevibactermillerae orMethanobrevibactergottschalkii with high identities ranging from 97.9 to 98.6%, followed by 23 sequences toMethanobrevibacter ruminantium, 2 sequences toMethanobrevibactersmithii and one sequence toMethanobrevibacter wolinii. The 142 sequences in the N library were assigned to 2 OTUs with most sequences (127/142) related to strainsM.millerae orM.gottschalkii with sequence identities ranging from 97.9 to 98.5%, and 15 sequences related toM.gottschalkiiwith 97.9% identity. Shannon diversity index showed that the G library exhibited signiifcantly higher archaeal diversity (P<0.05) and Libshuff analysis indicated the differences in the community structure between the two libraries were signiifcant (P<0.0001). In conclusion, the current study provides evidence that addition of yeast β-glucan signiifcantly increased the diversity of methanogens inin vitro fermented porcine colonic digesta.

  13. High fasting blood glucose and obesity significantly and independently increase risk of breast cancer death in hormone receptor-positive disease.

    Science.gov (United States)

    Minicozzi, Pamela; Berrino, Franco; Sebastiani, Federica; Falcini, Fabio; Vattiato, Rosa; Cioccoloni, Francesca; Calagreti, Gioia; Fusco, Mario; Vitale, Maria Francesca; Tumino, Rosario; Sigona, Aurora; Budroni, Mario; Cesaraccio, Rosaria; Candela, Giuseppa; Scuderi, Tiziana; Zarcone, Maurizio; Campisi, Ildegarda; Sant, Milena

    2013-12-01

    We investigated the effect of fasting blood glucose and body mass index (BMI) at diagnosis on risk of breast cancer death for cases diagnosed in five Italian cancer registries in 2003-2005 and followed up to the end of 2008. For 1607 Italian women (≥15 years) with information on BMI or blood glucose or diabetes, we analysed the risk of breast cancer death in relation to glucose tertiles (≤84.0, 84.1-94.0, >94.0 mg/dl) plus diabetic and unspecified categories; BMI tertiles (≤23.4, 23.5-27.3, >27.3 kg/m(2), unspecified), stage (T1-3N0M0, T1-3N+M0 plus T4anyNM0, M1, unspecified), oestrogen (ER) and progesterone (PR) status (ER+PR+, ER-PR-, ER and PR unspecified, other), age, chemotherapy and endocrine therapy, using multiple regression models. Separate models for ER+PR+ and ER-PR- cases were also run. Patients often had T1-3N0M0, ER+PR+ cancers and received chemotherapy or endocrine therapy; only 6% were M1 and 17% ER-PR-. Diabetic patients were older and had more often high BMI (>27 kg/m(2)), ER-PR-, M1 cancers than other patients. For ER+PR+ cases, with adjustment for other variables, breast cancer mortality was higher in women with high BMI than those with BMI 23.5-27.3 kg/m(2) (hazard ratio (HR)=2.9, 95% confidence interval (CI) 1.2-6.9). Breast cancer mortality was also higher in women with high (>94 mg/dl) blood glucose compared to those with glucose 84.1-94.0mg/dl (HR=2.6, 95% CI 1.2-5.7). Our results provide evidence that in ER+PR+ patients, high blood glucose and high BMI are independently associated with increased risk of breast cancer death. Detection and correction of these factors in such patients may improve prognosis. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Site-directed immobilization of a genetically engineered anti-methotrexate antibody via an enzymatically introduced biotin label significantly increases the binding capacity of immunoaffinity columns.

    Science.gov (United States)

    Davenport, Kaitlynn R; Smith, Christopher A; Hofstetter, Heike; Horn, James R; Hofstetter, Oliver

    2016-05-15

    In this study, the effect of random vs. site-directed immobilization techniques on the performance of antibody-based HPLC columns was investigated using a single-domain camelid antibody (VHH) directed against methotrexate (MTX) as a model system. First, the high flow-through support material POROS-OH was activated with disuccinimidyl carbonate (DSC), and the VHH was bound in a random manner via amines located on the protein's surface. The resulting column was characterized by Frontal Affinity Chromatography (FAC). Then, two site-directed techniques were explored to increase column efficiency by immobilizing the antibody via its C-terminus, i.e., away from the antigen-binding site. In one approach, a tetra-lysine tail was added, and the antibody was immobilized onto DSC-activated POROS. In the second site-directed approach, the VHH was modified with the AviTag peptide, and a biotin-residue was enzymatically incorporated at the C-terminus using the biotin ligase BirA. The biotinylated antibody was subsequently immobilized onto NeutrAvidin-derivatized POROS. A comparison of the FAC analyses, which for all three columns showed excellent linearity (R(2)>0.999), revealed that both site-directed approaches yield better results than the random immobilization; the by far highest efficiency, however, was determined for the immunoaffinity column based on AviTag-biotinylated antibody. As proof of concept, all three columns were evaluated for quantification of MTX dissolved in phosphate buffered saline (PBS). Validation using UV-detection showed excellent linearity in the range of 0.04-12μM (R(2)>0.993). The lower limit of detection (LOD) and lower limit of quantification (LLOQ) were found to be independent of the immobilization strategy and were 40nM and 132nM, respectively. The intra- and inter-day precision was below 11.6%, and accuracy was between 90.7% and 112%. To the best of our knowledge, this is the first report of the AviTag-system in chromatography, and the first

  15. High cell density cultivation of Escherichia coli K4 in a microfiltration bioreactor: a step towards improvement of chondroitin precursor production

    OpenAIRE

    Catapano Angela; De Rosa Mario; Cimini Donatella; Restaino Odile; Schiraldi Chiara

    2011-01-01

    Abstract Background The bacteria Escherichia coli K4 produces a capsular polysaccharide (K4 CPS) whose backbone is similar to the non sulphated chondroitin chain. The chondroitin sulphate is one of the major components of the extra-cellular matrix of the vertebrate connective tissues and a high value molecule, widely employed as active principle in the treatment of osteoarthritis. It is usually obtained by extraction from animal tissues, but the risk of virus contaminations, as well as the sc...

  16. FOXP3 Orchestrates H4K16 Acetylation and H3K4 Tri-Methylation for Activation of Multiple Genes through Recruiting MOF and Causing Displacement of PLU-1

    Science.gov (United States)

    Katoh, Hiroto; Qin, Zhaohui S.; Liu, Runhua; Wang, Lizhong; Li, Weiquan; Li, Xiangzhi; Wu, Lipeng; Du, Zhanwen; Lyons, Robert; Liu, Chang-Gong; Liu, Xiuping; Dou, Yali; Zheng, Pan; Liu, Yang

    2011-01-01

    SUMMARY Both H4K16 acetylation and H3K4 tri-methylation are required for gene activation. However, it is still largely unclear how these modifications are orchestrated by transcriptional factors. Here we analyzed the mechanism of the transcriptional activation by FOXP3, an X-linked suppressor of autoimmune diseases and cancers. FOXP3 binds near transcriptional start sites of its target genes. By recruiting MOF and displacing histone H3K4 demethylase PLU-1, FOXP3 increases both H4K16 acetylation and H3K4 tri-methylation at the FOXP3-associated chromatins of multiple FOXP3-activated genes. RNAi-mediated silencing of MOF reduced both gene activation and tumor suppression by FOXP3, while both somatic mutations in clinical cancer samples and targeted mutation of FOXP3 in mouse prostate epithelial disrupted nuclear localization of MOF. Our data demonstrate a pull-push model in which a single transcription factor orchestrates two epigenetic alterations necessary for gene activation and provide a mechanism for somatic inactivation of the FOXP3 protein function in cancer cells. PMID:22152480

  17. Remarks on Vertex-Distinguishing IE-Total Coloring of Complete Bipartite Graphs K4,n and Kn,n

    Institute of Scientific and Technical Information of China (English)

    Xiang'en CHEN; Xiaoqing XIN; Wenyu HE

    2012-01-01

    Let G be a simple graph.An IE-total coloring f of G refers to a coloring of the vertices and edges of G so that no two adjacent vertices receive the same color.Let C(u) be the set of colors of vertex u and edges incident to u under f.For an IE-total coloring f of G using k colors,if C(u) ≠ C(v) for any two different vertices u and v of V(G),then f is called a k-vertex-distinguishing IE-total-coloring of G,or a k-VDIET coloring of G for short.The minimum number of colors required for a VDIET coloring of G is denoted by xievt(G),and it is called the VDIET chromatic number of G.We will give VDIET chromatic numbers for complete bipartite graph K4,n (n ≥ 4),Kn,n (5 ≤ n ≤ 21) in this article.

  18. Decreased H3K27 and H3K4 trimethylation on mortal chromosomes in distributed stem cells.

    Science.gov (United States)

    Huh, Y H; Sherley, J L

    2014-12-04

    The role of immortal DNA strands that co-segregate during mitosis of asymmetrically self-renewing distributed stem cells (DSCs) is unknown. Previously, investigation of immortal DNA strand function and molecular mechanisms responsible for their nonrandom co-segregation was precluded by difficulty in identifying DSCs and immortal DNA strands. Here, we report the use of two technological innovations, selective DSC expansion and establishment of H2A.Z chromosomal asymmetry as a specific marker of 'immortal chromosomes,' to investigate molecular properties of immortal chromosomes and opposing 'mortal chromosomes' in cultured mouse hair follicle DSCs. Although detection of the respective suppressive and activating H3K27me3 and H3K4me3 epigenetic marks on immortal chromosomes was similar to randomly segregated chromosomes, detection of both was lower on mortal chromosomes destined for lineage-committed sister cells. This global epigenomic feature of nonrandom co-segregation may reveal a mechanism that maintains an epigenome-wide 'poised' transcription state, which preserves DSC identity, while simultaneously activating sister chromosomes for differentiation.

  19. Sal k 4, a new allergen of Salsola kali, is profilin: a predictive value of conserved conformational regions in cross-reactivity with other plant-derived profilins.

    Science.gov (United States)

    Assarehzadegan, Mohammad Ali; Amini, Akram; Sankian, Mojtaba; Tehrani, Mohsen; Jabbari, Farahzad; Varasteh, Abdolreza

    2010-01-01

    The aim of this study was to investigate a new allergen of Salsola kali, Sal k 4, and to investigate the predictive value of the conserved conformational regions in cross-reactivity with other plant-derived profilins. The Sal k 4-coding sequence was cloned, expressed, and purified by one-step Ni2+ affinity chromatography to recover high-purity target protein. We assessed cross-reactivity and predicted conserved conformational regions among rSal k 4 and other plant-derived profilins. Immunodetection and inhibition assays using 30 individual sera from S. kali allergic patients indicated that purified rSal k 4 might be the same as that in the crude extract. The results of inhibition assays among rSal k 4 and other plant-derived profilins were in accordance with the homology of the predicted conserved conformational regions. Amino acid sequence homology analysis showed that a high degree of IgE cross-reactivity among plant-derived profilins might depend on the predicted conserved conformational regions.

  20. AMPA, NMDA and kainate glutamate receptor subunits are expressed in human peripheral blood mononuclear cells (PBMCs) where the expression of GluK4 is altered by pregnancy and GluN2D by depression in pregnant women.

    Science.gov (United States)

    Bhandage, Amol K; Jin, Zhe; Hellgren, Charlotte; Korol, Sergiy V; Nowak, Krzysztof; Williamsson, Louise; Sundström-Poromaa, Inger; Birnir, Bryndis

    2017-04-15

    The amino acid glutamate opens cation permeable ion channels, the iGlu receptors. These ion channels are abundantly expressed in the mammalian brain where glutamate is the main excitatory neurotransmitter. The neurotransmitters and their receptors are being increasingly detected in the cells of immune system. Here we examined the expression of the 18 known subunits of the iGlu receptors families; α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainate, N-methyl-d-aspartate (NMDA) and delta in human peripheral blood mononuclear cells (PBMCs). We compared the expression of the subunits between four groups: men, non-pregnant women, healthy pregnant women and depressed pregnant women. Out of 18 subunits of the iGlu receptors, mRNAs for 11 subunits were detected in PBMCs from men and non-pregnant women; AMPA: GluA3, GluA4, kainate: GluK2, GluK4, GluK5, NMDA: GluN1, GluN2C, GluN2D, GluN3A, GluN3B, and delta: GluD1. In the healthy and the depressed pregnant women, in addition, the delta GluD2 subunit was identified. The mRNAs for GluK4, GluK5, GluN2C and GluN2D were expressed at a higher level than other subunits. Gender, pregnancy or depression during pregnancy altered the expression of GluA3, GluK4, GluN2D, GluN3B and GluD1 iGlu subunit mRNAs. The greatest changes recorded were the lower GluA3 and GluK4 mRNA levels in pregnant women and the higher GluN2D mRNA level in healthy but not in depressed pregnant women as compared to non-pregnant individuals. Using subunit specific antibodies, the GluK4, GluK5, GluN1, GluN2C and GluN2D subunit proteins were identified in the PBMCs. The results show expression of specific iGlu receptor subunit in the PBMCs and support the idea of physiology-driven changes of iGlu receptors subtypes in the immune cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. FAKTOR-FAKTOR YANG BERHUBUNGAN DENGAN KUNJUNGAN K4 DALAM PELAYANAN ANTENATAL DI KELURAHAN RAWANG BARAT PADANG

    Directory of Open Access Journals (Sweden)

    Hasni Mastian

    2009-09-01

    Full Text Available Aternal, mortality rate in Indonesia was 470 per 100.000 life birth in 2004. Public Health Centre (PHC Rawang Barat is the only one of all PHC in Padang City that has under target reached of the fourth examination of pregnancy with 77,2%. One intervention to decrease the maternal mortality is to have antenatal care at least once in first and second trimester and twice in third trimester during of any pregnancy's period. This research is to get some factors related to the fourth antenatal care of pregnancy. The research design is across sectional study, done at Rawang Barat in September 2008 up to April 2009. Population in this research are all mothers with 0-6 months of baby with amount 67 babies: The research has univariate and bivariate analysis with chi-square test. The research results are 20,9% mothers with non-complete fourth antenatal care, 29,9% mothers with highly pregnant risk, 38,8% mothers with afar residence from integrated health services unit (Posyandu, and 44,8% mother with lower education. Bivariate analysis get no significant correlation between age, distance to Posyandu and the fourth antenatal care, meanwhile it get significant correlation between knowledge and the fourth antenatal care. Intensive Health Education is needed to increase amount of antenatal care, especially the fourth antenatal care.

  2. An HST COS 'SNAPSHOT' spectrum of the K supergiant λ Vel (K4Ib-II)

    Energy Technology Data Exchange (ETDEWEB)

    Carpenter, Kenneth G. [NASA/GSFC Code 667, Greenbelt, MD 20771 (United States); Ayres, Thomas R. [University of Colorado, CASA, 389-UCB, Boulder, CO 80309 (United States); Harper, Graham M. [School of Physics, Trinity College, Dublin 2 (Ireland); Kober, Gladys; Nielsen, Krister E.; Wahlgren, Glenn M., E-mail: Kenneth.G.Carpenter@nasa.gov [Deptartment of Physics, Catholic University of America, Washington, DC 20064 (United States)

    2014-10-10

    We present a far-ultraviolet spectrum of the K4 Ib-II supergiant λ Vel obtained with the Hubble Space Telescope's Cosmic Origins Spectrograph (COS) as a part of the SNAPshot program 'SNAPing coronal iron' (GO 11687). The observation covers a wavelength region (1326-1467 Å) not previously recorded for λ Vel at a spectral resolving power of R ∼ 20,000 and displays strong emission and absorption features, superposed on a bright chromospheric continuum. Fluorescent excitation is responsible for much of the observed emission, mainly powered by strong H I Lyα and the O I (UV 2) triplet emission near λ1304. The molecular CO and H{sub 2} fluorescences are weaker than in the early-K giant α Boo while the Fe II and Cr II lines, also pumped by H I Lyα, are stronger in λ Vel. This pattern of relative line strengths between the two stars is explained by the lower iron-group element abundance in α Boo, which weakens that star's Fe II and Cr II emission without reducing the molecular fluorescences. The λ Vel spectrum shows fluorescent Fe II, Cr II, and H{sub 2} emission similar to that observed in the M supergiant α Ori, but more numerous well-defined narrow emissions from CO. The additional CO emissions are visible in the spectrum of λ Vel since that star does not have the cool, opaque circumstellar shells that surround α Ori and produce broad circumstellar CO (A-X) band absorptions that hide those emissions in the cooler star. The presence of Si IV emission in λ Vel indicates a ∼8 × 10{sup 4} K plasma that is mixed into the cooler chromosphere. Evidence of the stellar wind is seen in the C II λλ1334,1335 lines and in the blueshifted Fe II and Ni II wind absorption lines. Line modeling using Sobolev with Exact Integration for the C II lines indicates a larger terminal velocity (∼45 versus ∼30 km s{sup –1}) and turbulence (∼27 versus <21 km s{sup –1}) with a more quickly accelerating wind (β = 0.35 versus 0.7) at the time of

  3. Significant Reduction in Mitral Regurgitation Volume Is the Main Contributor for Increase in Systolic Forward Flow in Patients with Functional Mitral Regurgitation after Transcatheter Aortic Valve Replacement: Hemodynamic Analysis Using Echocardiography.

    Science.gov (United States)

    Itabashi, Yuji; Shibayama, Kentaro; Mihara, Hirotsugu; Utsunomiya, Hiroto; Berdejo, Javier; Arsanjani, Reza; Siegel, Robert; Chakravarty, Tarun; Jilaihawi, Hasan; Makkar, Raj R; Shiota, Takahiro

    2015-11-01

    Reduction in mitral regurgitation (MR) after transcatheter aortic valve replacement (TAVR) has previously been reported. However, the hemodynamic effects of TAVR in patients with MR have not been previously evaluated. We analyzed 571 patients who underwent TAVR from December 2010 to December 2013. We studied 20 patients with moderate or severe preprocedural functional mitral regurgitation (FMR) who also had a follow-up transthoracic echocardiography (TTE) examination between 90 and 360 days (median 213 days) after TAVR (Significant FMR Group). We also studied age- and gender-matched 20 patients with mild or lesser MR (Nonsignificant MR Group). Left ventricular functional measurements were assessed using echocardiography before and after TAVR. Left ventricular outflow tract stroke volume measurements using pulsed-wave Doppler (SVLVOT ) were calculated as a representative of systolic forward flow, and stroke volume by the Simpson's method (SVSimpson ) was calculated as a parameter of degree of LV contraction. MR grade improved in 22 of 40 patients after TAVR. In both groups, BNP level decreased, left ventricular ejection fraction increased, and SVLVOT increased after TAVR. SVSimpson increased in the Nonsignificant MR Group and remained unchanged in the Significant FMR Group. Vena contracta width of MR (MRVC) decreased in the Significant FMR Group. Using multivariable analysis in the Significant FMR Group, the increase in SVLVOT significantly correlated with the decrease in MRVC (P FMR. In these patients, increase in SVLVOT after TAVR was associated with decrease in severity of MR. © 2015, Wiley Periodicals, Inc.

  4. The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9

    Science.gov (United States)

    Dhayalan, Arunkumar; Tamas, Raluca; Bock, Ina; Tattermusch, Anna; Dimitrova, Emilia; Kudithipudi, Srikanth; Ragozin, Sergey; Jeltsch, Albert

    2011-01-01

    Mutations in the ATRX protein are associated with the alpha-thalassemia and mental retardation X-linked syndrome (ATR-X). Almost half of the disease-causing mutations occur in its ATRX-Dnmt3-Dnmt3L (ADD) domain. By employing peptide arrays, chromatin pull-down and peptide binding assays, we show specific binding of the ADD domain to H3 histone tail peptides containing H3K9me3. Peptide binding was disrupted by the presence of the H3K4me3 and H3K4me2 modification marks indicating that the ATRX-ADD domain has a combined readout of these two important marks (absence of H3K4me2 and H3K4me3 and presence of H3K9me3). Disease-causing mutations reduced ATRX-ADD binding to H3 tail peptides. ATRX variants, which fail in the H3K9me3 interaction, show a loss of heterochromatic localization in cells, which indicates the chromatin targeting function of the ADD domain of ATRX. Disruption of H3K9me3 binding may be a general pathogenicity pathway of ATRX mutations in the ADD domain which may explain the clustering of disease mutations in this part of the ATRX protein. PMID:21421568

  5. The ATRX-ADD domain binds to H3 tail peptides and reads the combined methylation state of K4 and K9.

    Science.gov (United States)

    Dhayalan, Arunkumar; Tamas, Raluca; Bock, Ina; Tattermusch, Anna; Dimitrova, Emilia; Kudithipudi, Srikanth; Ragozin, Sergey; Jeltsch, Albert

    2011-06-01

    Mutations in the ATRX protein are associated with the alpha-thalassemia and mental retardation X-linked syndrome (ATR-X). Almost half of the disease-causing mutations occur in its ATRX-Dnmt3-Dnmt3L (ADD) domain. By employing peptide arrays, chromatin pull-down and peptide binding assays, we show specific binding of the ADD domain to H3 histone tail peptides containing H3K9me3. Peptide binding was disrupted by the presence of the H3K4me3 and H3K4me2 modification marks indicating that the ATRX-ADD domain has a combined readout of these two important marks (absence of H3K4me2 and H3K4me3 and presence of H3K9me3). Disease-causing mutations reduced ATRX-ADD binding to H3 tail peptides. ATRX variants, which fail in the H3K9me3 interaction, show a loss of heterochromatic localization in cells, which indicates the chromatin targeting function of the ADD domain of ATRX. Disruption of H3K9me3 binding may be a general pathogenicity pathway of ATRX mutations in the ADD domain which may explain the clustering of disease mutations in this part of the ATRX protein.

  6. The Meiotic Recombination Activator PRDM9 Trimethylates Both H3K36 and H3K4 at Recombination Hotspots In Vivo.

    Science.gov (United States)

    Powers, Natalie R; Parvanov, Emil D; Baker, Christopher L; Walker, Michael; Petkov, Petko M; Paigen, Kenneth

    2016-06-01

    In many mammals, including humans and mice, the zinc finger histone methyltransferase PRDM9 performs the first step in meiotic recombination by specifying the locations of hotspots, the sites of genetic recombination. PRDM9 binds to DNA at hotspots through its zinc finger domain and activates recombination by trimethylating histone H3K4 on adjacent nucleosomes through its PR/SET domain. Recently, the isolated PR/SET domain of PRDM9 was shown capable of also trimethylating H3K36 in vitro, raising the question of whether this reaction occurs in vivo during meiosis, and if so, what its function might be. Here, we show that full-length PRDM9 does trimethylate H3K36 in vivo in mouse spermatocytes. Levels of H3K4me3 and H3K36me3 are highly correlated at hotspots, but mutually exclusive elsewhere. In vitro, we find that although PRDM9 trimethylates H3K36 much more slowly than it does H3K4, PRDM9 is capable of placing both marks on the same histone molecules. In accord with these results, we also show that PRDM9 can trimethylate both K4 and K36 on the same nucleosomes in vivo, but the ratio of K4me3/K36me3 is much higher for the pair of nucleosomes adjacent to the PRDM9 binding site compared to the next pair further away. Importantly, H3K4me3/H3K36me3-double-positive nucleosomes occur only in regions of recombination: hotspots and the pseudoautosomal (PAR) region of the sex chromosomes. These double-positive nucleosomes are dramatically reduced when PRDM9 is absent, showing that this signature is PRDM9-dependent at hotspots; the residual double-positive nucleosomes most likely come from the PRDM9-independent PAR. These results, together with the fact that PRDM9 is the only known mammalian histone methyltransferase with both H3K4 and H3K36 trimethylation activity, suggest that trimethylation of H3K36 plays an important role in the recombination process. Given the known requirement of H3K36me3 for double strand break repair by homologous recombination in somatic cells, we

  7. Synthesis of PbS Intercalated K4Nb6O17 Composite and Its Photocatalytic Activity for Hydrogen Production%PbS插层K4Nb6O17复合物的制备及其光催化制氢活性

    Institute of Scientific and Technical Information of China (English)

    崔文权; 刘艳飞; 胡金山; 刘利; 梁英华

    2012-01-01

    采用固相法合成层状半导体K4Nb6O17,通过层间离子交换反应、胺插入反应以及硫化反应制备了纳米PbS插层的K4Nb6O17复合光催化剂(记作K4Nb6O17/PbS).利用X射线衍射(XRD),场发射扫描电镜(SEM),X射线荧光光谱仪(XRF),紫外-可见漫反射(UV-Vis)和分子荧光光谱(PL)等技术对其进行表征.考察了催化剂在Na2SO3和Na2S为牺牲剂的光催化制氢活性.结果表明,PbS的插层拓展了K4Nb6O17对可见光的响应,催化制氢活性也有明显提高.在紫外光和可见光下3h产氢量分别达到123.94和0.66 mmol/(g cat).最后讨论了插层复合催化剂光生电荷转移的机理.%The layered compound K4Nb6O17 was prepared via high temperature solid reaction, and PbS intercalated K4Nb6O17 (designated as K4Nb6O17/PbS) photocatalyst was synthesized via direct ion exchange, alkylamines intercalation and sulfurization procedures. The as-prepared samples were characterized by X-ray diffraction (XRD), scanning electron microscope (SEM), ultraviolet-visible diffuse reflection spectra (UV-Vis) and photoluminescence measurement (PL), energy dispersive X-ray detector (EDS) and X-ray fluorescence spectrometer (XRF). The photocatalytic performance of these catalysts for hydrogen production was also investigated in the presence of Na2S and Na2SO3 sacrificial reagents. The absorption edge of K4Nb6O17 shifted to visible light region after the intercalation of PbS. K4Nb6O17/PbS photocatalysts exhibit higher activities for photocatalytic hydrogen production under both UV light and visible light irradiation, and the amounts of hydrogen produced are 123.94 mmol/(g cat) and 0.66 mmol/(g cat) after 3 h irradiation, respectively. The mechanism of charge separation is also discussed.

  8. Enhanced photoelectrocatalytic decomposition of copper cyanide complexes and simultaneous recovery of copper with a Bi2MoO6 electrode under visible light by EDTA/K4P2O7.

    Science.gov (United States)

    Zhao, Xu; Zhang, Juanjuan; Qiao, Meng; Liu, Huijuan; Qu, Jiuhui

    2015-04-07

    Simultaneous photoelectrocatalytic (PEC) oxidation of cyanides and recovery of copper in a PEC reactor with a Bi(2)MoO(6) photoanode was investigated at alkaline conditions under visible light irradiation. The surface variation of the Bi(2)MoO(6) photoanode and titanium cathode was characterized. The Cu mass distribution onto the anode, in the solution, and onto the cathode was fully investigated. In the individual PEC oxidation of copper cyanides, the formation of a black copper oxide on the anode occurred. By keeping the initial cyanide concentration at 0.01 mM, the effect of EDTA/K(4)P(2)O(7) was examined at different molar ratios of EDTA/K(4)P(2)O(7) to cyanide. It was indicated that the oxidation of cyanides increased and simultaneous copper electrodeposition with zero value onto the cathode was feasible at pH 11. Under the optimal conditions, the total cyanide concentration was lowered from 250 to 5.0 mg/L, and the Cu recovery efficiency deposited onto the cathode was higher than 90%. Cyanate was the only product. The role of the photogenerated hole in the oxidation of cyanide ions was confirmed.

  9. Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer

    Directory of Open Access Journals (Sweden)

    Susanne Beyer

    2017-02-01

    Full Text Available Chromatin remodeling alters gene expression in carcinoma tissue. Although cervical cancer is the fourth most common cancer in women worldwide, a systematic study about the prognostic value of specific changes in the chromatin structure, such as histone acetylation or histone methylation, is missing. In this study, the expression of histone H3 acetyl K9, which is known to denote active regions at enhancers and promoters, and histone H3 tri methyl K4, which preferentially identifies active gene promoters, were examined as both show high metastatic potential. A panel of patients with cervical cancer was selected and the importance of the histone modifications concerning survival-time (overall survival and relapse-free survival was analyzed in 250 cases. Histone H3 acetyl K9 staining was correlated with low grading, low FIGO (TNM classification and the International Federation of Gynecology and Obstetrics status, negative N-status and low T-status in cervical cancer, showing a higher expression in adenocarcinoma than in squamous cell carcinoma. Cytoplasmic expression of histone H3 tri methyl K4 in a cervical cancer specimen was correlated with advanced T-status and poor prognosis. While cytoplasmic H3K4me3 expression seemed to be a marker of relapse-free survival, nuclear expression showed a correlation to poor prognosis in overall survival. Within this study, we analyzed the chemical modification of two histone proteins that are connected to active gene expression. Histone H3 acetyl K9 was found to be an independent marker of overall survival. Histone H3 tri methyl K4 was correlated with poor prognosis and it was found to be an independent marker of relapse-free survival. Therefore, we could show that chromatin remodeling plays an important role in cervical cancer biology.

  10. Histone H3 Acetyl K9 and Histone H3 Tri Methyl K4 as Prognostic Markers for Patients with Cervical Cancer.

    Science.gov (United States)

    Beyer, Susanne; Zhu, Junyan; Mayr, Doris; Kuhn, Christina; Schulze, Sandra; Hofmann, Simone; Dannecker, Christian; Jeschke, Udo; Kost, Bernd P

    2017-02-23

    Chromatin remodeling alters gene expression in carcinoma tissue. Although cervical cancer is the fourth most common cancer in women worldwide, a systematic study about the prognostic value of specific changes in the chromatin structure, such as histone acetylation or histone methylation, is missing. In this study, the expression of histone H3 acetyl K9, which is known to denote active regions at enhancers and promoters, and histone H3 tri methyl K4, which preferentially identifies active gene promoters, were examined as both show high metastatic potential. A panel of patients with cervical cancer was selected and the importance of the histone modifications concerning survival-time (overall survival and relapse-free survival) was analyzed in 250 cases. Histone H3 acetyl K9 staining was correlated with low grading, low FIGO (TNM classification and the International Federation of Gynecology and Obstetrics) status, negative N-status and low T-status in cervical cancer, showing a higher expression in adenocarcinoma than in squamous cell carcinoma. Cytoplasmic expression of histone H3 tri methyl K4 in a cervical cancer specimen was correlated with advanced T-status and poor prognosis. While cytoplasmic H3K4me3 expression seemed to be a marker of relapse-free survival, nuclear expression showed a correlation to poor prognosis in overall survival. Within this study, we analyzed the chemical modification of two histone proteins that are connected to active gene expression. Histone H3 acetyl K9 was found to be an independent marker of overall survival. Histone H3 tri methyl K4 was correlated with poor prognosis and it was found to be an independent marker of relapse-free survival. Therefore, we could show that chromatin remodeling plays an important role in cervical cancer biology.

  11. Novel Cell-Ess ® supplement used as a feed or as an initial boost to CHO serum free media results in a significant increase in protein yield and production

    Directory of Open Access Journals (Sweden)

    Adam Elhofy

    2016-01-01

    Full Text Available Many metrics, including metabolic profiles, have been used to analyze cell health and optimize productivity. In this study, we investigated the ability of a lipid supplement to increase protein yield. At a concentration of 1% (v/v the lipid supplement caused a significant increase in protein titer (1118 ± 65.4 ng 105 cells−1 days−1 when compared to cultures grown in the absence of supplementation (819.3 ± 38.1 ng 105 cells−1 days−1; p < 0.05. This equated to a 37% increase in productivity. Furthermore, metabolic profiles of ammonia, glutamate, lactate, and glucose were not significantly altered by the polar lipid supplement. In a separate set of experiments, using the supplement as a feed resulted in 2 notable effects. The first was a 25% increase in protein titer. The second was an extension of peak protein production from 1 day to 2 days. These results suggest that lipid supplementation is a promising avenue for enhancing protein production. In addition, our results also suggest that an increase in protein production may not necessarily require a change in the metabolic state of the cells.

  12. Pro Isomerization in MLL1 PHD3-Bromo Cassette Connects H3K4me Readout to CyP33 and HDAC-Mediated Repression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Zhanxin; Song, Jikui; Milne, Thomas A.; Wang, Gang G.; Li, Haitao; Allis, C. David; Patel, Dinshaw J. (MSKCC); (Rockefeller)

    2010-09-13

    The MLL1 gene is a frequent target for recurrent chromosomal translocations, resulting in transformation of hematopoietic precursors into leukemia stem cells. Here, we report on structure-function studies that elucidate molecular events in MLL1 binding of histone H3K4me3/2 marks and recruitment of the cyclophilin CyP33. CyP33 contains a PPIase and a RRM domain and regulates MLL1 function through HDAC recruitment. We find that the PPIase domain of CyP33 regulates the conformation of MLL1 through proline isomerization within the PHD3-Bromo linker, thereby disrupting the PHD3-Bromo interface and facilitating binding of the MLL1-PHD3 domain to the CyP33-RRM domain. H3K4me3/2 and CyP33-RRM target different surfaces of MLL1-PHD3 and can bind simultaneously to form a ternary complex. Furthermore, the MLL1-CyP33 interaction is required for repression of HOXA9 and HOXC8 genes in vivo. Our results highlight the role of PHD3-Bromo cassette as a regulatory platform, orchestrating MLL1 binding of H3K4me3/2 marks and cyclophilin-mediated repression through HDAC recruitment.

  13. The Demethylase JMJD2C Localizes to H3K4me3 Positive Transcription Start Sites and Is Dispensable for Embryonic Development

    DEFF Research Database (Denmark)

    Pedersen, Marianne Terndrup; Agger, Karl; Laugesen, Anne

    2014-01-01

    cell (ESC) self-renewal and embryonic development. Moreover, we report that JMJD2C localizes to H3K4me3 positive transcription start sites in both primary cells and in the human carcinoma KYSE150 cell line, containing an amplification of the JMJD2C locus. Binding is dependent on the double Tudor domain...... of JMJD2C, which recognizes H3K4me3, but not H4K20me2/me3 in vitro, thus showing a different binding specificity than the double Tudor domains of JMJD2A and JMJD2B. Depletion of JMJD2C in KYSE150 cells has modest impact on H3K9me3 and H3K36me3 levels, but impairs proliferation and leads to deregulated...... expression of a subset of target genes involved in cell cycle progression. Taken together, we show that JMJD2C is targeted to H3K4me3 positive transcription start sites, where it can contribute to transcriptional regulation, and report that the putative oncogene, JMJD2C, is not generally required...

  14. Spp1, a member of the Set1 Complex, promotes meiotic DSB formation in promoters by tethering histone H3K4 methylation sites to chromosome axes.

    Science.gov (United States)

    Sommermeyer, Vérane; Béneut, Claire; Chaplais, Emmanuel; Serrentino, Maria Elisabetta; Borde, Valérie

    2013-01-10

    Meiotic chromosomes are organized into arrays of loops that are anchored to the chromosome axis structure. Programmed DNA double-strand breaks (DSBs) that initiate meiotic recombination, catalyzed by Spo11 and accessory DSB proteins, form in loop sequences in promoters, whereas the DSB proteins are located on chromosome axes. Mechanisms bridging these two chromosomal regions for DSB formation have remained elusive. Here we show that Spp1, a conserved member of the histone H3K4 methyltransferase Set1 complex, is required for normal levels of DSB formation and is associated with chromosome axes during meiosis, where it physically interacts with the Mer2 DSB protein. The PHD finger module of Spp1, which reads H3K4 methylation close to promoters, promotes DSB formation by tethering these regions to chromosome axes and activating cleavage by the DSB proteins. This paper provides the molecular mechanism linking DSB sequences to chromosome axes and explains why H3K4 methylation is important for meiotic recombination.

  15. The histone-H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD fingers.

    Science.gov (United States)

    Klein, Brianna J; Piao, Lianhua; Xi, Yuanxin; Rincon-Arano, Hector; Rothbart, Scott B; Peng, Danni; Wen, Hong; Larson, Connie; Zhang, Xi; Zheng, Xia; Cortazar, Michael A; Peña, Pedro V; Mangan, Anthony; Bentley, David L; Strahl, Brian D; Groudine, Mark; Li, Wei; Shi, Xiaobing; Kutateladze, Tatiana G

    2014-01-30

    The histone lysine demethylase KDM5B regulates gene transcription and cell differentiation and is implicated in carcinogenesis. It contains multiple conserved chromatin-associated domains, including three PHD fingers of unknown function. Here, we show that the first and third, but not the second, PHD fingers of KDM5B possess histone binding activities. The PHD1 finger is highly specific for unmodified histone H3 (H3K4me0), whereas the PHD3 finger shows preference for the trimethylated histone mark H3K4me3. RNA-seq analysis indicates that KDM5B functions as a transcriptional repressor for genes involved in inflammatory responses, cell proliferation, adhesion, and migration. Biochemical analysis reveals that KDM5B associates with components of the nucleosome remodeling and deacetylase (NuRD) complex and may cooperate with the histone deacetylase 1 (HDAC1) in gene repression. KDM5B is downregulated in triple-negative breast cancer relative to estrogen-receptor-positive breast cancer. Overexpression of KDM5B in the MDA-MB 231 breast cancer cells suppresses cell migration and invasion, and the PHD1-H3K4me0 interaction is essential for inhibiting migration. These findings highlight tumor-suppressive functions of KDM5B in triple-negative breast cancer cells and suggest a multivalent mechanism for KDM5B-mediated transcriptional regulation. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  16. The Histone-H3K4-Specific Demethylase KDM5B Binds to Its Substrate and Product through Distinct PHD Fingers

    Directory of Open Access Journals (Sweden)

    Brianna J. Klein

    2014-01-01

    Full Text Available The histone lysine demethylase KDM5B regulates gene transcription and cell differentiation and is implicated in carcinogenesis. It contains multiple conserved chromatin-associated domains, including three PHD fingers of unknown function. Here, we show that the first and third, but not the second, PHD fingers of KDM5B possess histone binding activities. The PHD1 finger is highly specific for unmodified histone H3 (H3K4me0, whereas the PHD3 finger shows preference for the trimethylated histone mark H3K4me3. RNA-seq analysis indicates that KDM5B functions as a transcriptional repressor for genes involved in inflammatory responses, cell proliferation, adhesion, and migration. Biochemical analysis reveals that KDM5B associates with components of the nucleosome remodeling and deacetylase (NuRD complex and may cooperate with the histone deacetylase 1 (HDAC1 in gene repression. KDM5B is downregulated in triple-negative breast cancer relative to estrogen-receptor-positive breast cancer. Overexpression of KDM5B in the MDA-MB 231 breast cancer cells suppresses cell migration and invasion, and the PHD1-H3K4me0 interaction is essential for inhibiting migration. These findings highlight tumor-suppressive functions of KDM5B in triple-negative breast cancer cells and suggest a multivalent mechanism for KDM5B-mediated transcriptional regulation.

  17. 油水自组装制备Ag@AgCl/K4Nb6 O17及其光催化降解有机污染物的研究∗%Oil-water self-assembly synthesis of Ag@AgCl/K4 Nb6 O17 and enhanced photocatalytic degradation of organic pollutants

    Institute of Scientific and Technical Information of China (English)

    赵俊秀; 刘利; 胡金山; 梁英华; 崔文权

    2015-01-01

    在高温固相法制备K4 Nb6 O17的基础上,采用油水自组装合成复合光催化剂 Ag @ AgCl/K4 Nb6 O17,利用 XRD、SEM、TEM、EDX、UV-Vis、PL、BET等多种手段对复合光催化剂的微观结构、形貌和性能进行了表征,并研究了可见光下降解亚甲基蓝(MB)的催化性能.研究表明,Ag@AgCl 的粒径约为20 nm,均匀分散在二维层状结构K4 Nb6 O17的表面上;贵金属Ag纳米粒子的表面等离子体效应显著,对可见光的吸收范围从400 nm 拓展到800 nm;Ag@AgCl(25%(质量分数))/K4Nb6O17在可见光照射60 min对亚甲基蓝的降解率为88.2%,远远高于单体Ag@AgCl和K4 Nb6 O17的活性.循环实验证明催化剂具有较好的稳定性,同时对苯酚和罗丹明 B(RhB)也具有一定的催化降解活性.淬灭实验表明自由基和空穴均为活性物种,并在此基础上提出降解机理.%The composite photocatalyst of Ag@AgCl/K4 Nb6 O17 was composed of by the oil-water self-assembly method,on the basis that K4 Nb6 O17 was prepared in the high-temperature solid-state method.The microstruc-ture,morphology and properties of Ag@AgCl/K4 Nb6 O17 composite photocatalyst were characterized by means of XRD,SEM,TEM,EDX,UV-vis,PL,BET;and the photocatalytic performance was valued by the degra-dation of methylene blue (MB),phenol,and Rhodamine B (RhB)under visible light irradiation.The results shows that Ag@AgCl particles with the size of about 20 nm were dispersed in two-dimensional layer structure on the surface of K4 Nb6 O17 and the absorption of visible light of the composite photocatalyst ranged from 400 to 800 nm due to the surface plasmon resonance of Ag.The degradation rate of MB solution over Ag@AgCl (25wt%)/K4 Nb6 O17 under the visible light irradiation reaches 88.2% in an hour,which is more than two times compared with the sum of the Ag@AgCl and K4 Nb6 O17 degradation rate.The composite photocatalyst still ex-hibited high catalytic activity after recycled five times

  18. 严重糖尿病酮症酸中毒引发 BNP 明显升高1例%Severe diabetic ketoacidosis triggered the BNP increased significantly:A case report

    Institute of Scientific and Technical Information of China (English)

    吕树泉; 刘爱茹; 张淑芳; 苏秀海; 郭瑞卿

    2015-01-01

    ABSTRACT:A male patient at age of 35 years was admitted to the hospital,because of nausea, vomiting 3 days, increased with upper abdominal pain 10 hours of admission. A healthy. Physical examination, blood pressure is low, the skin is dry, the deep breathing, slow reaction, increased heart rate, cold limbs. Laboratory examination of metabolic acidosis, blood glucose increased significantly, urine ketone body positive, abnormal cardiac enzyme, BNP increased significantly. A diagnosis of type 1 diabetes mellitus, diabetic ketoacidosis.%患者男,35岁,因恶心、呕吐3天,加重伴上腹疼痛10小时入院。既往体健。入院查体,血压低,皮肤干燥,呼吸深大,反应迟钝,心率增快,四肢冰冷。实验室检查代谢性酸中毒,血糖明显升高,尿酮体阳性,心肌酶异常, BNP 明显升高。诊断为1型糖尿病、糖尿病酮症酸中毒。

  19. Long-term omeprazole and esomeprazole treatment does not significantly increase gastric epithelial cell proliferation and epithelial growth factor receptor expression and has no effect on apoptosis and p53 expression

    Institute of Scientific and Technical Information of China (English)

    Istvan Hritz; Laszlo Herszenyi; Bela Molnar; Zsolt Tulassay; Laszlo Pronai

    2005-01-01

    AIM: To study the effect of proton pump inhibitor (PPI)treatment on patients with reflux esophagitis and its in vivo effect on apoptosis, p53- and epidermal growth factor receptor (EGFR) expression.METHODS: After informed consent was obtained, gastric biopsies of the antrum were taken from patients with reflux oesophagitis prior to and after 6 mo of 20 mg omeprazole (n = 14) or 40 mg esomeprazole (n = 12) therapy.Patients did not take any other medications known to affect the gastric mucosa. All patients were Helicobacter pylori negative as confirmed by rapid urease test and histology,respectively. Cell proliferation, apoptosis, EGFR, and p53expression were measured by immunohistochemical techniques. At least 600 glandular epithelial cells were encountered and results were expressed as percentage of total cells counted. Was considered statistically significant.RESULTS: Although there was a trend towards increase of cell proliferation and EGFR expression both in omeprazole and esomeprazole treated group, the difference was not statistically significant. Neither apoptosis nor p53 expression was affected.CONCLUSION: Long-term PPI treatment does not significantly increase gastric epithelial cell proliferation and EGFR expression and has no effect on apoptosis and p53 expression.

  20. Age-related increase in food spilling by laboratory mice may lead to significant overestimation of actual food consumption: implications for studies on dietary restriction, metabolism, and dose calculations.

    Science.gov (United States)

    Starr, Marlene E; Saito, Hiroshi

    2012-10-01

    It is widely accepted that food consumption in humans declines with advanced age; however, data from mice remain controversial. Based on our previous observation that mice spill a considerable amount of food while eating, we hypothesized that increased food spillage in old mice masks actual food intake. To investigate whether mice exhibit age-associated declines in food consumption, we evaluated the actual food consumption of C57BL/6 mice at various ages by measuring both the amount of food in the food receptacle and the amount dropped to the cage bottom during feeding. We found that old mice dropped significantly more food (36% ± 8%) than young mice (18% ± 5%), which led to overestimations of food consumption, particularly in old mice. Although actual food consumption decreased in very old mice, food intake per body weight did not significantly change. These findings suggest that caution should be taken to accurately quantify food consumption by aged animals.

  1. The highly selective 5-hydroxytryptamine (5-HT)2A receptor antagonist, EMD 281014, significantly increases swimming and decreases immobility in male congenital learned helpless rats in the forced swim test.

    Science.gov (United States)

    Patel, Jignesh G; Bartoszyk, Gerd D; Edwards, Emmeline; Ashby, Charles R

    2004-04-01

    We examined the effect of the highly selective 5-hydroxytryptamine (5-HT)(2A) receptor antagonist 7-[4-[2-(4-fluoro-phenyl)-ethyl]-piperazine-1-carbonyl]-1H-indole-3-carbonitrile HCl (EMD 281014) in congenital learned helpless male rats in the forced swim test. The administration of EMD-281014 (0.3-30 mg/kg i.p.) to congenital learned helpless rats dose-dependently and significantly (at 10 and 30 mg/kg) decreased immobility and increased swimming compared to vehicle-treated animals. Thus, EMD 281014 produces effects in the forced swim test resembling those of antidepressants.

  2. Solitary Inhibition of the Breast Cancer Resistance Protein Efflux Transporter Results in a Clinically Significant Drug-Drug Interaction with Rosuvastatin by Causing up to a 2-Fold Increase in Statin Exposure.

    Science.gov (United States)

    Elsby, Robert; Martin, Paul; Surry, Dominic; Sharma, Pradeep; Fenner, Katherine

    2016-03-01

    The intestinal efflux transporter breast cancer resistance protein (BCRP) restricts the absorption of rosuvastatin. Of the transporters important to rosuvastatin disposition, fostamatinib inhibited BCRP (IC50 = 50 nM) and organic anion-transporting polypeptide 1B1 (OATP1B1; IC50 > 10 μM), but not organic anion transporter 3, in vitro, predicting a drug-drug interaction (DDI) in vivo through inhibition of BCRP only. Consequently, a clinical interaction study between fostamatinib and rosuvastatin was performed (and reported elsewhere). This confirmed the critical role BCRP plays in statin absorption, as inhibition by fostamatinib resulted in a significant 1.96-fold and 1.88-fold increase in rosuvastatin area under the plasma concentration-time curve (AUC) and Cmax, respectively. An in vitro BCRP inhibition assay, using polarized Caco-2 cells and rosuvastatin as probe substrate, was subsequently validated with literature inhibitors and used to determine BCRP inhibitory potencies (IC50) of the perpetrator drugs eltrombopag, darunavir, lopinavir, clopidogrel, ezetimibe, fenofibrate, and fluconazole. OATP1B1 inhibition was also determined using human embryonic kidney 293-OATP1B1 cells versus estradiol 17β-glucuronide. Calculated parameters of maximum enterocyte concentration [Igut max], maximum unbound hepatic inlet concentration, transporter fraction excreted value, and determined IC50 value were incorporated into mechanistic static equations to compute theoretical increases in rosuvastatin AUC due to inhibition of BCRP and/or OATP1B1. Calculated theoretical increases in exposure correctly predicted the clinically observed changes in rosuvastatin exposure and suggested intestinal BCRP inhibition (not OATP1B1) to be the mechanism underlying the DDIs with these drugs. In conclusion, solitary inhibition of the intestinal BCRP transporter can result in clinically significant DDIs with rosuvastatin, causing up to a maximum 2-fold increase in exposure, which may warrant

  3. Electrochemical studies on Li+/K+ ion exchange behaviour in K4Fe(CN)6 cathode material for Li, K-ion battery

    Indian Academy of Sciences (India)

    Bikash Mandal; I Basumallick; Susanta Ghosha

    2015-01-01

    The electrochemical studies of anhydrous K4Fe(CN)6 is reported. Anhydrous material was produced after dehydrating K4Fe(CN)6.3H2O crystal at 200°C in an open atmosphere. The material, as obtained, was characterized by various spectroscopic techniques, such as UV-Visible, FTIR, powder X-ray diffraction and FESEM-EDX. Electrochemical and Li+/K+ ion exchange behaviour of the synthesized material were studied by cyclic voltametry (CV), chronoamperometry (CA) and galvanostatic charge-discharge method after preparing a laboratory model cell against lithium anode instead of potassium. During anodic scan in the 1st cycle, peak maximum was observed at 3.93 V vs. Li+/Li due to removal of K+ ions from the ferrocyanide matrix, whereas, in the reverse scan (cathodic sweep) as well as in consequent cycles, peak maxima due to Li+ ion insertion and extraction were observed at 2.46 V and 3.23 V vs. Li+/Li, respectively. Cell, assembled using ferrocyanide cathode and lithium anode, shows an open circuit potential of 3.08 V and delivers a maximum capacity of 61 mAh g-1 (theoretical capacity 72 mAh g-1) at a rate of 0.2 C at room temperature.

  4. H3K4me3 demethylation by the histone demethylase KDM5C/JARID1C promotes DNA replication origin firing.

    Science.gov (United States)

    Rondinelli, Beatrice; Schwerer, Hélène; Antonini, Elena; Gaviraghi, Marco; Lupi, Alessio; Frenquelli, Michela; Cittaro, Davide; Segalla, Simona; Lemaitre, Jean-Marc; Tonon, Giovanni

    2015-03-11

    DNA replication is a tightly regulated process that initiates from multiple replication origins and leads to the faithful transmission of the genetic material. For proper DNA replication, the chromatin surrounding origins needs to be remodeled. However, remarkably little is known on which epigenetic changes are required to allow the firing of replication origins. Here, we show that the histone demethylase KDM5C/JARID1C is required for proper DNA replication at early origins. JARID1C dictates the assembly of the pre-initiation complex, driving the binding to chromatin of the pre-initiation proteins CDC45 and PCNA, through the demethylation of the histone mark H3K4me3. Fork activation and histone H4 acetylation, additional early events involved in DNA replication, are not affected by JARID1C downregulation. All together, these data point to a prominent role for JARID1C in a specific phase of DNA replication in mammalian cells, through its demethylase activity on H3K4me3.

  5. Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome

    Science.gov (United States)

    Liang, Gangning; Lin, Joy C. Y.; Wei, Vivian; Yoo, Christine; Cheng, Jonathan C.; Nguyen, Carvell T.; Weisenberger, Daniel J.; Egger, Gerda; Takai, Daiya; Gonzales, Felicidad A.; Jones, Peter A.

    2004-01-01

    Almost 1-2% of the human genome is located within 500 bp of either side of a transcription initiation site, whereas a far larger proportion (≈25%) is potentially transcribable by elongating RNA polymerases. This observation raises the question of how the genome is packaged into chromatin to allow start sites to be recognized by the regulatory machinery at the same time as transcription initiation, but not elongation, is blocked in the 25% of intragenic DNA. We developed a chromatin scanning technique called ChAP, coupling the chromatin immunoprecipitation assay with arbitrarily primed PCR, which allows for the rapid and unbiased comparison of histone modification patterns within the eukaryotic nucleus. Methylated lysine 4 (K4) and acetylated K9/14 of histone H3 were both highly localized to the 5′ regions of transcriptionally active human genes but were greatly decreased downstream of the start sites. Our results suggest that the large transcribed regions of human genes are maintained in a deacetylated conformation in regions read by elongating polymerase. Common models depicting widespread histone acetylation and K4 methylation throughout the transcribed unit do not therefore apply to the majority of human genes. PMID:15123803

  6. The histone H3K4-specific demethylase KDM5B binds to its substrate and product through distinct PHD fingers

    Science.gov (United States)

    Klein, Brianna J.; Piao, Lianhua; Xi, Yuanxin; Rincon-Arano, Hector; Rothbart, Scott B.; Peng, Danni; Wen, Hong; Larson, Connie; Zhang, Xi; Zheng, Xia; Cortazar, Michael A.; Peña, Pedro V.; Mangan, Anthony; Bentley, David L.; Strahl, Brian D.; Groudine, Mark; Li, Wei; Shi, Xiaobing; Kutateladze, Tatiana G.

    2014-01-01

    SUMMARY The histone lysine demethylase KDM5B regulates gene transcription and cell differentiation. It contains three PHD fingers, the biological roles of which remain elusive. Here, we show that the first PHD1 finger of KDM5B binds unmodified histone H3, whereas the third PHD3 finger prefers the trimethylated mark, H3K4me3. RNA-seq analysis indicates that KDM5B functions as a transcriptional repressor for a set of genes. Biochemical analysis reveals that KDM5B associates with components of the nucleosome remodeling and deacetylase (NuRD) complex and may cooperate with HDAC1 in gene repression. Compared with the estrogen receptor positive breast cancers, KDM5B is downregulated in the triple-negative breast cancer. Overexpression of KDM5B in the MDA-MB 231 breast cancer cells suppresses cell migration and invasion ability, and the PHD1-H3K4me0 interaction is important for inhibition of migration. These findings highlight tumor-suppressive functions of KDM5B in triple-negative breast cancer cells and suggest a novel multivalent mechanism for KDM5B-mediated transcriptional regulation. PMID:24412361

  7. K4I3 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  8. K4C0 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  9. K4V0 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  10. K4M9 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  11. K4A9 METAR

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — METAR is a routine scheduled observation and is the primary observation code used in the United States to satisfy requirements for reporting surface meteorological...

  12. Significant increase in HBV, HCV, HIV and syphilis infections among blood donors in West Bengal, Eastern India 2004-2005: Exploratory screening reveals high frequency of occult HBV infection

    Institute of Scientific and Technical Information of China (English)

    Prasun Bhattacharya; Partha Kumar Chandra; Sibnarayan Datta; Arup Banerjee; Subhashish Chakraborty; Krishnan Rajendran; Subir Kumar Basu; Sujit Kumar Bhattacharya; Runu Chakravarty

    2007-01-01

    AIM: To evaluate the prevalence of markers of hepatitis B virus (HBV) and hepatitis C virus (HCV) and human immunodeficiency virus (HIV) among blood donors in Kolkata, Eastern India for two consecutive years and to conduct a pilot study to explore the presence of HBV DNA among hepatitis B surface antigen (HBsAg) negative but anti-HBc positive blood donors.METHODS: Seroprevalence of HBsAg, anti-HCV and anti-HIV was studied among 113051 and 106695 voluntary blood donors screened in 2004 and 2005,respectively. Moreover, a pilot study on 1027 HBsAg negative donors was carried out for evaluating the presence of HBV DNA by PCR on HBsAg negative/antiHBc positive donors.RESJLTS: A statistically significant increase in the prevalence of HBV (1448 vs 1768, P < 0.001), HIV (262vs 374, P < 0.001), HCV (314 vs 372, P = 0.003) and syphilis (772 vs 853, P = 0.001) infections was noted among blood donors of Kolkata West Bengal in 2005 as compared to 2004. Moreover, the exploratory study on 1027 HBsAg negative donors revealed that 188 (18.3%) of them were anti-HBc positive out of which 21% were positive for HBV DNA.CONCLUSION: The findings of this study underscore the significantly increasing endemicity of hepatitis viruses, syphilis and HIV among the voluntary blood donors of our community. The pilot study indicates a high rate of prevalence of HBV DNA among HBsAg negative/anti-HBc positive donors and thus emphasizes the need for a more sensitive and stringent screening algorithm for blood donations.

  13. Effects of histone acetylation and H3K4 methylation on PRA/PRB in human uterine smooth muscle cells during pregnancy%组蛋白H3、H4乙酰化及H3K4甲基化对人妊娠子宫平滑肌细胞PRA/PRB的影响

    Institute of Scientific and Technical Information of China (English)

    罗慧; 陈诚; 梁志清

    2014-01-01

    目的 通过组蛋白去乙酰化酶抑制剂(trichostatin A,TSA)、H3 K4甲基化酶抑制剂(5’-deoxy-5’-methylthioadenosine,MTA)处理人妊娠子宫平滑肌细胞,干预组蛋白H3、H4乙酰化及H3K4甲基化水平,探讨组蛋白H3、H4乙酰化及H3K4甲基化对人妊娠子宫平滑肌细胞PRA/PRB的影响.方法 分离纯化人妊娠子宫平滑肌细胞(n=16),免疫组化定位孕激素受体(progesterone receptor,PR)及孕激素受体B(progesterone receptor B,PRB)在子宫平滑肌细胞核的表达.分别利用不同浓度TSA、MTA对其进行处理,Real-time PCR检测PR、PRA、PRB mRNA的表达;染色质免疫共沉淀技术(Chromatin immunoprecipitation,ChIP)比较处理前后PRA、PRB启动子区H3、H4乙酰化及H3K4三甲基化水平.结果 TSA可使PRA/PRB明显增高(P<0.05),使PRA启动子区H3、H4乙酰化水平明显上升(P<0.05).MTA可使PRA/PRB明显下降(P<0.05),PRA启动子区H3K4乙酰化水平明显下降(P<0.05).两种药物的干预主要通过对PRA的调控来调节PRA/PRB比值.结论 组蛋白H3、H4乙酰化和H3K4甲基化均可使人妊娠子宫平滑肌细胞PRA/PRB比值发生改变,可能参与“功能性孕激素撤退”机制的调节.

  14. MicroRNA-25通过调控MAP2 K4抑制糖尿病肾病纤维化的研究%Study of Inhibition Fibrosis of MicroRNA-25 on Diabetic Nephropathy by Regulating Expression of MAP2 K4

    Institute of Scientific and Technical Information of China (English)

    王晓莉; 刘洁婷; 张春雷; 王超男; 冯彪; 初彦辉; 张涛

    2015-01-01

    Objective To determine the expression level of microRNA-25 in animal models of diabetic nephropathy and human renal tubular epithelial cells (HK-2) cultured in different conditions, and to explore its regulating effect on the fibrosis in diabetic nephropathy. Methods The expression of microRNA-25 was detected by real-time PCR. The downstream target protein of microRNA-25 was verified by bioinformatic prediction, transient transfection of cells and Western blotting. Results MicroRNA-25 was down-regulated in animal models of diabetic nephropathy and HK-2 cells which were cultured in high-glucose medium (P<0. 01). MAP2K4 might be the downstream target protein of microRNA-25. Overexpression of microRNA-25 reduced the protein expression of MAP2K4 and α-SMA (P<0. 01). Conclusion MicroRNA-25 inhibits the fibrosis in diabetic nephropathy by regulating the expression of MAP2K4.%目的:检测microRNA-25在糖尿病肾病动物模型及不同条件培养下的人肾小管上皮细胞( HK-2)中的表达,探讨其对糖尿病肾病纤维化的调节作用。方法实时荧光定量聚合酶链反应检测microRNA-25的表达。生物信息学预测、细胞瞬时转染和Western blot验证microRNA-25的下游靶蛋白。结果 microRNA-25在糖尿病肾病动物模型及高糖培养下的HK-2中表达降低(P<0.01)。 MAP2K4可能是microRNA-25的下游靶蛋白。过表达microRNA-25可以从蛋白水平上抑制MAP2K4、α-SMA的表达(P<0.01)。结论 microRNA-25可以通过调控MAP2K4从而抑制糖尿病肾病纤维化的进展。

  15. Choosing Outcomes of Significance.

    Science.gov (United States)

    Spady, William G.

    1994-01-01

    Outcomes are high-quality, culminating demonstrations of significant learning in context. The High Success Network uses the "Demonstration Mountain" to differentiate among three major "learning zones" and six different forms of learning demonstrations that increase in complexity, generalizability, and significance, along with…

  16. Neither moderate hypoxia nor mild hypoglycaemia alone causes any significant increase in cerebral [Ca2+]i: only a combination of the two insults has this effect. A 31P and 19F NMR study.

    Science.gov (United States)

    Badar-Goffer, R S; Thatcher, N M; Morris, P G; Bachelard, H S

    1993-12-01

    (1) The energy state and free intracellular calcium concentration ([Ca2+]i) of superfused cortical slices were measured in moderate hypoxia (approximately 65 microM O2), in mild hypoglycaemia (0.5 mM glucose), and in combinations of the two insults using 19F and 31P NMR spectroscopy. (2) Neither hypoxia nor hypoglycaemia alone caused any significant change in [Ca2+]i. Hypoxia caused a 40% fall in phosphocreatine (PCr) content but not in ATP level, and hypoglycaemia produced a slight fall in both (as expected from previous studies). These changes in the energy state recovered on return to control conditions. (3) A combined sequential insult (hypoxia, followed by hypoxia plus hypoglycaemia) produced a 100% increase in [Ca2+]i and a decrease in PCr level to approximately 25% of control. The reverse combined sequential insult (hypoglycaemia, followed by hypoglycaemia plus hypoxia) had the same effect. On return to control conditions there was some decrease in [Ca2+]i and a small increase in PCr content, but neither recovered to control levels. (4) Exposure of the tissue to the combined simultaneous insult (hypoxia plus hypoglycaemia) immediately after the control spectra had been recorded resulted in a fivefold increase in [Ca2+]i and a similar decrease in PCr level to 20-25% of control. There was little if any change of [Ca2+]i or PCr level on return to control conditions. (5) These results are discussed in terms of metabolic adaptation of some but not all of the cortical cells to the single type of insult, which renders the tissues less vulnerable to the combined insult.

  17. Serum hCG-β levels of postovulatory day 12 and 14 with the sequential application of hCG-β fold change significantly increased predictability of pregnancy outcome after IVF-ET cycle.

    Science.gov (United States)

    Sung, Nayoung; Kwak-Kim, Joanne; Koo, H S; Yang, K M

    2016-09-01

    To investigate hCG-β level on postovulatory day (POD) 12 and its fold increase as predictors for pregnancy outcome after in vitro fertilization (IVF) cycles. A retrospective cohort study was performed in total 1408 fresh and 598 frozen cycles between November 2008 and October 2011, which resulted in biochemical pregnancy, early pregnancy loss, or live birth of singleton pregnancy. The serum hCG-β levels of POD 12 and 14 were compared among biochemical pregnancy, early pregnancy loss, and live birth groups. The cutoff values of POD 12 and 14 hCG-β levels and the degree of hCG-β increase from POD 12 to 14 were determined for each pregnancy outcome. POD 12 and 14 hCG-β levels stratified based on pregnancy outcomes were significantly different among the biochemical pregnancy, early pregnancy loss, and live birth in both fresh and frozen cycles. Serum hCG-β levels of POD 12 and 14 and the fold increase of hCG-β levels from POD 12 to 14 significantly predict pregnancy outcomes after fresh and frozen cycles. Among these, the cutoff value of POD 14 hCG-β had the highest sensitivity and positive predictive value (PPV). In fresh cycles, the cutoff values of POD 12 and 14 serum hCG-β levels for clinical pregnancies were 30.2 mIU/mL (sensitivity 81.3 %, specificity 79.6 %, and PPV 92.3 %) and 70.5 mIU/mL (sensitivity 88.4 %, specificity 85.2 %, and PPV 94.7 %). In pregnancies with POD 12 serum hCG-β levels ≥30.2 mIU/mL, the cutoff level of increase of hCG-β for clinical pregnancy was 2.56 (sensitivity 73.6 %, specificity 72.4 %, and PPV 97.8 %). Sequential application of cutoff values such as POD 12 hCG-β and fold increase of hCG-β improved predictability of pregnancy outcome as compared with that of POD 12 hCG-β alone. The cutoff values of POD 12 and 14 serum hCG-β levels for live birth were 40.5 mIU/mL (sensitivity 75.2 %, specificity 72.6 %, PPV 78.9 %) and 104.5 mIU/mL (sensitivity 80.3 %, specificity 74.1 %, PPV 80.8 %). In the frozen

  18. K4Sn3Se8的固相合成、晶体结构和反射光谱研究%Solid state synthesis,crystal structure and diffuse reflectance spectra of K4Sn3Se8

    Institute of Scientific and Technical Information of China (English)

    王志霞; 郭洪猷

    2003-01-01

    采用反应性熔盐法,通过中温固相反应在500 ℃下合成晶体K4Sn3Se8.该晶体属正交晶系,空间群Ccca,晶胞参数:a=0.821 15(6) nm,b=2.779 0(2) nm,c=0.818 65(6) nm,V=1.868 2(2) nm3,Z=4.K4Sn3Se8由[Sn3Se8]4-三聚体负离子和K+正离子组成.漫反射光谱研究表明该材料能隙(Eg)为2.6 eV,属于半导体,对太阳能具有选择吸收的特性.

  19. H3K4 dimethylation in hepatocellular carcinoma is rare compared with other hepatobiliary and gastrointestinal carcinomas and correlates with expression of the methylase Ash2 and the demethylase LSD1.

    Science.gov (United States)

    Magerl, Christian; Ellinger, Jörg; Braunschweig, Till; Kremmer, Elisabeth; Koch, Lin Kristin; Höller, Tobias; Büttner, Reinhard; Lüscher, Bernhard; Gütgemann, Ines

    2010-02-01

    Methylation of core histones regulates chromatin structure and gene expression. Recent studies have demonstrated that these methylation patterns have prognostic value for some tumors. Therefore, we investigated dimethylation of histone H3 at lysine 4 (H3K4diMe) and H3K4 methylating (Ash2 complex) and demethylating enzymes (LSD1) in carcinomas of the hepatic and gastrointestinal tract. High levels of H3K4diMe were rarely observed in 15.7% of hepatocellular carcinoma (8/51) unlike other carcinomas including, in ascending order, cholangiocellular carcinoma/adenocarcinoma of the extrahepatic biliary tract, gastric carcinoma, pancreatic ductal adenocarcinoma, and neuroendocrine carcinoma (P carcinomas (38/45) and correlated directly with H3K4diMe modification (correlation coefficient r = 0.53) and LSD1 expression (r = 0.35). In contrast to other carcinomas, 65.9% (29/44) of hepatocellular carcinomas analyzed showed no LSD1 expression (P carcinomas without LSD1 expression appeared to be frequently Ash2 and H3K4diMe weak or negative (P = .004). In summary, high H3K4diMe expression is rare in hepatocellular carcinoma compared with other carcinomas (negative predictive value 92.3%), which may aid in the differential diagnosis. Lack of H3K4diMe is possibly due to complex epigenetic regulation involving Ash2 and LSD1.

  20. In Vivo Imaging Reveals Significant Tumor Vascular Dysfunction and Increased Tumor Hypoxia-Inducible Factor-1α Expression Induced by High Single-Dose Irradiation in a Pancreatic Tumor Model.

    Science.gov (United States)

    Maeda, Azusa; Chen, Yonghong; Bu, Jiachuan; Mujcic, Hilda; Wouters, Bradly G; DaCosta, Ralph S

    2017-01-01

    To investigate the effect of high-dose irradiation on pancreatic tumor vasculature and microenvironment using in vivo imaging techniques. A BxPC3 pancreatic tumor xenograft was established in a dorsal skinfold window chamber model and a subcutaneous hind leg model. Tumors were irradiated with a single dose of 4, 12, or 24 Gy. The dorsal skinfold window chamber model was used to assess tumor response, vascular function and permeability, platelet and leukocyte adhesion to the vascular endothelium, and tumor hypoxia for up to 14 days after 24-Gy irradiation. The hind leg model was used to monitor tumor size, hypoxia, and vascularity for up to 65 days after 24-Gy irradiation. Tumors were assessed histologically to validate in vivo observations. In vivo fluorescence imaging revealed temporary vascular dysfunction in tumors irradiated with a single dose of 4 to 24 Gy, but most significantly with a single dose of 24 Gy. Vascular functional recovery was observed by 14 days after irradiation in a dose-dependent manner. Furthermore, irradiation with 24 Gy caused platelet and leukocyte adhesion to the vascular endothelium within hours to days after irradiation. Vascular permeability was significantly higher in irradiated tumors compared with nonirradiated controls 14 days after irradiation. This observation corresponded with increased expression of hypoxia-inducible factor-1α in irradiated tumors. In the hind leg model, irradiation with a single dose of 24 Gy led to tumor growth delay, followed by tumor regrowth. Irradiation of the BxPC3 tumors with a single dose of 24 Gy caused transient vascular dysfunction and increased expression of hypoxia-inducible factor-1α. Such biological changes may impact tumor response to high single-dose and hypofractionated irradiation, and further investigations are needed to better understand the clinical outcomes of stereotactic body radiation therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Final Report on the Key Comparison CCM.P-K4.2012 in Absolute Pressure from 1 Pa to 10 kPa.

    Science.gov (United States)

    Ricker, Jacob; Hendricks, Jay; Bock, Thomas; Dominik, Pražák; Kobata, Tokihiko; Torres, Jorge; Sadkovskaya, Irina

    2017-01-01

    The report summarizes the Consultative Committee for Mass (CCM) key comparison CCM.P-K4.2012 for absolute pressure spanning the range of 1 Pa to 10 000 Pa. The comparison was carried out at six National Metrology Institutes (NMIs), including National Institute of Standards and Technology (NIST), Physikalisch-Technische Bundesanstalt (PTB), Czech Metrology Institute (CMI), National Metrology Institute of Japan (NMIJ), Centro Nacional de Metrología (CENAM), and DI Mendeleyev Institute for Metrology (VNIIM). The comparison was made via a calibrated transfer standard measured at each of the NMIs facilities using their laboratory standard during the period May 2012 to September 2013. The transfer package constructed for this comparison preformed as designed and provided a stable artifact to compare laboratory standards. Overall the participants were found to be statistically equivalent to the key comparison reference value.

  2. Effect of sleep deprivation on H3K9 and H3K4 methylation in the different brain region of rats%REM期睡眠剥夺对大鼠不同脑区组蛋白H3K9和H3K4甲基化水平的影响

    Institute of Scientific and Technical Information of China (English)

    马安东; 马妮; 史明; 田丰仓; 吴中亮

    2016-01-01

    目的:研究REM期睡眠剥夺对成年大鼠不同脑区包括海马、腹内侧前额叶皮质、下丘脑和中缝核群的组蛋白H3K9和H3K4三甲基化水平的影响.方法:将成年SD大鼠随机分为正常对照组(con)、睡眠剥夺1d组(SD1 d)、睡眠剥夺3d组(SD3 d)、睡眠剥夺6d组(SD6 d).采用改良式多平台水环境法建立REM期睡眠剥夺模型,分别于睡眠剥夺后1、3、6d断头取脑,用免疫荧光染色与Western Blot检测大鼠海马、腹内侧前额叶皮质、下丘脑和中缝核群H3K9和H3K4三甲基化水平的变化,最终结果进行统计学分析.结果:Western Blot结果显示:(1)海马、腹内侧前额叶皮质三个SD组H3K9三甲基化水平均低于control组(P<0.05),H3K4三甲基化水平均高于control组(P<0.05);(2)下丘脑三个SD组H3K9三甲基化水平均低于control组(P<0.01),但SD1 d组H3K4三甲基化水平高于control组(P<0.05),SD3 d、SD6 d组H3K4三甲基化水平低于control组(P<0.05);(3)中缝核群三个SD组H3K9和H3K4三甲基化水平均高于control组(P<0.05).对海马与下丘脑免疫荧光验证H3K9三甲基化结果与Western Blot结果趋势一致,且说明细胞无减少.结论:睡眠剥夺可能与海马、腹内侧前额叶皮质、下丘脑和中缝核群的组蛋白H3K9和H3K4三甲基化水平密切相关.

  3. K_4CuNb_8O_(23)掺杂对K_(0.44)Na_(0.52)Li_(0.04)Nb_(0.86)Ta_(0.10)Sb_(0.04)O_3压电陶瓷性能的影响%Effect of K_4CuNb_8O_(23) Doped on the Properties of K_(0.44)Na_(0.52)Li_(0.04)Nb_(0.86)Ta_(0.10)Sb_(0.04)O_3 Piezoelectric Ceramics

    Institute of Scientific and Technical Information of China (English)

    陈燕; 江向平; 涂娜; 冯子义; 陈超; 李月明

    2009-01-01

    采用固相反应法制备了K_(0.44)Na_(0.52)Li_(0.04)Nb_(0.86)Ta_(0.10)Sb_(0.04)O_3+x mol %K_4CuNb_8O_(23)(0≤x≤2)(简称LF4-KCN)无铅压电陶瓷,使用XRD、SEM、 Agilent 4294A精密阻抗分析仪等对该体系的相组成、显微结构、压电及介电等性能进行表征.XRD分析表明,随着KCN含量的增加,室温时样品由四方相向正交相转变,且当x≥1时,出现K_6Li_4Nb_(10)O_(30)杂相.SEM分析表明,掺入KCN后,样品晶粒尺寸减小,晶粒轮廓清晰.随着KCN含量的增加,在100 ℃附近的介电常数温度曲线上出现第二介电常数极大值,即正交→四方铁电相变温度T_(O-T),同时居里温度TC向低温方向移动.KCN掺杂量对LF4的电性能有很大影响,表现为"硬性"掺杂,其压电常数d_(33),平面机电耦合系数k_p,1kHz频率下的介电损耗tanδ和介电常数ε_r均随着 KCN含量的增加而降低,而机械品质因素Q_m整体提高,样品的密度也显著增大.%The K_(0.44)Na_(0.52)Li_(0.04)Nb_(0.86)Ta_(0.10)Sb_(0.04)O_3+x mol%K_4CuNb_8O_(23)(0≤x≤2)(abbreviated as LF4-KCN) lead-free piezoelectric ceramics were fabricated by solid state reaction. The phase, microstructure, electric properties of the samples were characterized by XRD, SEM and Agilent 4294A impedance analyzer. XRD result shows that the phase of the sample transforms from tetragonal into orthorhombic with the increasing of KCN content. When x≥1, the trace amount of second phase K_6Li_4Nb_(10)O_(30) can be detected. SEM shows that the grain size of those materials decreases as the KCN content increasing, and the figure of the grain becomes clearly. There is another dielectric constant maximum value around 100 ℃, which is the phase transition from orthorhombic to tetragonal (T_(O-T)), while the curie temperature (TC) shifts to higher temperature. The KCN-doping has great influence on the electrical properties, the ceramic becomes "hardened", the piezoelectric constant (d_(33)), electromechanical planar

  4. Dot1-dependent histone H3K79 methylation promotes the formation of meiotic double-strand breaks in the absence of histone H3K4 methylation in budding yeast.

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    Mohammad Bani Ismail

    Full Text Available Epigenetic marks such as histone modifications play roles in various chromosome dynamics in mitosis and meiosis. Methylation of histones H3 at positions K4 and K79 is involved in the initiation of recombination and the recombination checkpoint, respectively, during meiosis in the budding yeast. Set1 promotes H3K4 methylation while Dot1 promotes H3K79 methylation. In this study, we carried out detailed analyses of meiosis in mutants of the SET1 and DOT1 genes as well as methylation-defective mutants of histone H3. We confirmed the role of Set1-dependent H3K4 methylation in the formation of double-strand breaks (DSBs in meiosis for the initiation of meiotic recombination, and we showed the involvement of Dot1 (H3K79 methylation in DSB formation in the absence of Set1-dependent H3K4 methylation. In addition, we showed that the histone H3K4 methylation-defective mutants are defective in SC elongation, although they seem to have moderate reduction of DSBs. This suggests that high levels of DSBs mediated by histone H3K4 methylation promote SC elongation.

  5. [Diagnostic significance of multiparametric MRI combined with US-fusion guided biopsy of the prostate in patients with increased PSA levels and negative standard biopsy results to detect significant prostate cancer - Correlation with the Gleason score. Korrelation mit dem Gleason Score].

    Science.gov (United States)

    Hoffmann, Manuela; Hoffmann, Manuela A; Wieler, Helmut J; Jakobs, Frank M; Taymoorian, Kasra; Gerhards, Arnd; Miederer, Matthias; Schreckenberger, Mathias

    2017-08-14

    To increase diagnostic precision and to reduce overtreatment of low-risk malignant disease, multiparametric MRI (mpMRI) combined with ultrasound (US) fusion guided biopsy of the prostate were performed. In 99 male patients with increased PSA plasma levels and previous negative standard biopsy procedures, mpMRI was carried out followed by US fusion guided perineal biopsy. PI-RADS-Data (PS) of mpMRI and histopathological Gleason score (GS) were categorized and statistically compared. Lesions in 72/99 (73 %) of patients were determined to be suspect of malignancy, based on a PS 4 or 5. In 33/99 (33 %) of patients, malignancy could not be confirmed by histopathology. With regard to the remaining 66 patients with previous negative biopsy results, 42 (64 %) were diagnosed with a low-grade carcinoma (GS 6, 7a) and 24 (36 %) with a high-grade carcinoma (GS ≥ 7b). The proportion of corresponding results in mpMRI (PS 4-5) when a high-grade carcinoma had been detected, was 21/24 (88 %), which related to a sensitivity of 88 % and a negative predictive value (NPV) of 85 % (p = 0,002). In addition, 35 of 42 patients (83%), graded PS 4-5 in mpMRI, were diagnosed with low-grade carcinoma-positive (p < 0,001). Sensitivity to differentiation between low- and high-grade carcinomas (GS ≤ 7a vs. ≥ 7b) by means of PS was 88 % with a NPV of 70 % (p = 0,74). Our results suggest that mpMRI combined with US-fusion guided biopsy is able to detect considerably higher rates of clinically relevant prostate malignancies compared to conventional diagnostic procedures. However, no statistical significance could be shown regarding the differentiation between high- and low-grade carcinomas. It is hoped that the hybrid methods PSMA-PET/CT or PSMA-PET/MRI will lead to the next optimization step in the differentiation between high- and low-grade carcinomas which so far has been unsatisfactory.

  6. Final report on the key comparison CCM.P-K4.2012 in absolute pressure from 1 Pa to 10 kPa

    Science.gov (United States)

    Ricker, Jacob; Hendricks, Jay; Bock, Thomas; Dominik, Pražák; Kobata, Tokihiko; Torres, Jorge; Sadkovskaya, Irina

    2017-01-01

    The report summarizes the Consultative Committee for Mass (CCM) key comparison CCM.P-K4.2012 for absolute pressure spanning the range of 1 Pa to 10 000 Pa. The comparison was carried out at six National Metrology Institutes (NMIs), including National Institute of Standards and Technology (NIST), Physikalisch-Technische Bundesanstalt (PTB), Czech Metrology Institute (CMI), National Metrology Institute of Japan (NMIJ), Centro Nacional de Metrología (CENAM), and DI Mendeleyev Institute for Metrology (VNIIM). The comparison was made via a calibrated transfer standard measured at each of the NMIs facilities using their laboratory standard during the period May 2012 to September 2013. The transfer package constructed for this comparison preformed as designed and provided a stable artifact to compare laboratory standards. Overall the participants were found to be statistically equivalent to the key comparison reference value. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  7. Magnetic transition in K4Cu4OCl10: A model system of three-dimensional spin-(1)/(2) tetrahedra

    Science.gov (United States)

    Fujihala, Masayoshi; Zheng, Xu-Guang; Morodomi, Hiroki; Kawae, Tatsuya; Watanabe, Isao

    2013-04-01

    Isolated spin tetrahedral systems with weak intertetrahedral couplings, as have been reported for Cu2Te2O5X2 (X = Cl, Br) and the related compound Cu4Te5O12Cl4, have received much attention recently because they represent an interesting class of magnets that consist of weakly coupled magnetic clusters and, in particular, they can directly demonstrate the interplay of intertetrahedral couplings with built-in tetrahedral frustration. However, there is much debate about the structural low dimensionality of the Cu-Te-O-Cl(Br) compounds and its effect on the magnetism of the material. Here, we present a model spin tetrahedral system K4Cu4OCl10, with almost isotropic magnetic coupling within the tetrahedron and three-dimensional connection of the tetrahedra. The system enters a spin-singlet state with a susceptibility maximum at Tmax = 11 K, and then enters an antiferromagnetic order at TN = 4.4 K. The ratio TN/Tmax = 0.40 is close to the TN/Tmax = 0.38 for Cu2Te2O5Br2, which is viewed as an indicator of closeness to quantum criticality. Evidence in muon-spin rotation or relaxation suggests an incommensurate ordering. This work shows that the previously revealed ground state in anisotropically structured Cu2Te2O5X2 compounds also exists in an isotropic spin tetrahedral system.

  8. 儿童真菌性肠炎患者血清IL-27增高及其意义%Clinical significance of increased serum IL-27 in children with mycosis intestinalis

    Institute of Scientific and Technical Information of China (English)

    程娟娟; 潘敏; 韩志君; 葛小丽

    2012-01-01

    Objective To evaluate the diagnostic value of serum IL-27 on children with mycosis intestinalis. Methods The serum level of IL-27 and PCT of 89 children with mycosis intestinalis, 61 viralgastroenteritis and 41 healthy volunteers were detected by ELJSA. The association between IL-27 and white blood cell count and PCT was analysed. The diagnostic value of IL-27 on children with mycosis intestinalis was evaluated by receiver operating characteristics (ROC) curve analysis. Results The level of serum IL-27 was significantly increased in children with mycosis intestinalis than that of viral intestinalis group and healthy control group ( P <0.01). The level of serum IL-27 positive correlated with PCT, was observed in children with mycosis intestinalis. Area under cure (AUC) confirmed by ROC analysis was 0.82 (95% Confidence interval (CI): 0.63-0. 89) for IL-27. At the best cut-off value of 0. 82 pg/ml, the diagnostic sensitivity and specificity of IL-27 are 0.75 and 0.79 respectively. Conclusions Serum IL-27 has high diagnostic performance for children with mycosis intestinalis, which should be an early biomarker for children with mycosis intestinalis.%目的 评价血清IL-27对儿童真菌性肠炎的诊断价值.方法 收集89例儿童真菌性肠炎,61例儿童病毒性肠炎和41例健康对照者的临床资料及血清.酶联免疫吸附试验(ELISA)检测血清中IL-27和降钙素原(Procalcitionin,PCT)的水平,全自动血球分析仪检测各项白细胞参数,分析IL-27与白细胞计数和PCT的相关性,采用受试者工作曲线(ROC)法评价血清IL-27对儿童真菌性肠炎患者的诊断价值.结果 儿童真菌性肠炎患者血清IL-27水平较儿童病毒性肠炎组和健康对照组显著增高(P<0.01),儿童真菌性肠炎患者IL-27的水平与白细胞计数无显著相关性(R=-0.198,P>0.05),与PCT水平呈显著正相关(R=0.419,P<0.01).IL-27诊断儿童真菌性肠炎的ROC曲线下面积为0.82(95%可信区间:0.63~0.89,P<0

  9. Final report on the EURAMET.M.FF-K4.2.2014 volume comparison at 100 μL—calibration of micropipettes

    Science.gov (United States)

    Batista, Elsa; Matus, Michael; Metaxiotou, Zoe; Tudor, Maria; Lenard, Elzbieta; Buker, Oliver; Wennergren, Per; Piluri, Erinda; Miteva, Mariana; Vicarova, Martina; Vospĕlová, Alena; Turnsek, Urska; Micic, Ljiljana; Grue, Lise-Lote; Mihailovic, Mirjana; Sarevska, Anastazija

    2017-01-01

    During the EURAMET TC-F meeting of 2014 and following the finalization of CCM.FF-K4.2.2011 comparison, it was agreed to start a Regional Key Comparison (KC) on volume measurements using two 100 μL micropipettes (piston pipettes) allowing the participating laboratories to assess the agreement of their results and uncertainties. Two 100 μL micropipettes were tested by 15 participants. One participant was not a member or associate member of the BIPM and was be removed from this report. The comparison started in July 2015 and ended in March 2016. The Volume and Flow Laboratory of the Portuguese Institute for Quality (IPQ) was the pilot laboratory and performed the initial and final measurements of the micropipettes. The micropipettes showed a stable volume during the whole comparison, which was confirmed by the results from the pilot laboratory. The original results of all participant NMIs were corrected to the standard atmospheric pressure in order to compare results under the same calibration conditions, and the contribution of the 'process-related handling contribution' was added to the uncertainty budget of each participant. In general the declared CMCs are in accordance with the KCDB. For the micropipette 354828Z, two laboratories had inconsistent results. For micropipette 354853Z, three laboratories had inconsistent results. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  10. Significant increase of Curie temperature and large piezoelectric coefficient in Ba(Ti0.80Zr0.20)O3-0.5(Ba0.70Ca0.30)TiO3 nanofibers

    Science.gov (United States)

    Fu, Bi; Yang, Yaodong; Gao, Kun; Wang, Yaping

    2015-07-01

    Ba(Ti0.80Zr0.20)O3-0.5(Ba0.7Ca0.3)TiO3 (abbreviated as BTZ-0.5BCT) is a piezoelectric ceramic with a high piezoelectric coefficient d33 (˜620 pC N-1) and has been regarded as one of the most promising candidates to replace PZT-based materials (200-710 pC N-1). However, its Curie temperature TC is relatively low (93 °C) limiting its application. In this letter, we found a temperature dependent Raman spectrum in BTZ-0.5BCT nanofibers (NFs), demonstrating a diffused tetragonal-to-cubic phase transition at 300 °C. This means that the TC of the NFs is nearly 207 °C higher than that of the normal bulk material. The increased TC is considered to be associated with the size effect of BTZ-0.5BCT nanoceramic subunits and the nanoporous nature of the fiber, resulting in discontinuous physical properties. The variation of the ferro/piezoelectricity over the fiber surface is attributed to the polycrystalline structure. The d33 (173.32 pm V-1) is improved in terms of the decreased Q factor result in an increase in d33 of 236.54 pm V-1 after polarization. With a high TC and a very large d33, BTZ-0.5BCT NFs are capable of providing electromechanical behavior used in moderate temperatures.

  11. Human circulating ribosomal DNA content significantly increases while circulating satellite III (1q12) content decreases under chronic occupational exposure to low-dose gamma- neutron and tritium beta-radiation.

    Science.gov (United States)

    Korzeneva, Inna B; Kostuyk, Svetlana V; Ershova, Elizaveta S; Skorodumova, Elena N; Zhuravleva, Veronika F; Pankratova, Galina V; Volkova, Irina V; Stepanova, Elena V; Porokhovnik, Lev N; Veiko, Natalia N

    A single exposure to ionizing radiation (IR) results in an elevated cell-free DNA (cfDNA) content in the blood plasma. In this case, the cfDNA concentration can be a marker of the cell death in the organism. However, a chronic exposure to a low-dose IR enhances both the endonuclease activity and titer of antibodies to DNA in blood plasma, resulting in a decrease of the total concentration of circulating cfDNA in exposed people. In this case, the total cfDNA concentration should not be considered as a marker of the cell death in an exposed body. We assumed that a pool of the cfDNA circulating in the exposed people contains DNA fragments, which are resistant to a double-strand break formation in the environment of the elevated plasma endonuclease activity, and can be accumulated in the blood plasma. In order to test this hypothesis, we studied the content of GC-rich sequences (69%GC) of the transcribed region of human ribosomal repeat (rDNA), as well as the content of AT-rich repeat (63%AT) of satellite III (1q12) in the cfDNA samples obtained from 285 individuals. We have found that a chronic exposure to gamma-neutron radiation (N=88) and tritium β-radiation (N=88) evokes an increase of the rDNA content (RrDNA index) and a decrease of the satellite III content (RsatIII index) in the circulating cfDNA as compared with the cfDNA of non-exposed people (N=109). Such index that simultaneously displays both the increase of rDNA content and decrease of satellite III content in the cfDNA (RrDNA/RsatIII) can be recommended as a marker of chronic processes in the body that involve the elevated cell death rate and/or increased blood plasma endonuclease activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. Increased frequency of dicentric chromosomes in therapy-related MDS and AML compared to de novo disease is significantly related to previous treatment with alkylating agents and suggests a specific susceptibility to chromosome breakage at the centromere.

    Science.gov (United States)

    Andersen, M K; Pedersen-Bjergaard, J

    2000-01-01

    Dicentric chromosomes are observed in many malignant diseases including myelodysplasia (MDS) and acute myeloid leukemia (AML) and have often been observed in a subset of these diseases, namely therapy-related MDS (t-MDS) and AML (t-AML). Using fluorescence in situ hybridization (FISH) with centromere-specific probes, we investigated the frequency and type of dicentric chromosomes in 180 consecutive patients with t-MDS and t-AML and in 231 consecutive patients with de novo MDS and AML, whose karyotypes had been studied previously by conventional G-banding. Twenty-seven out of 180 patients with t-MDS or t-AML presented dicentric chromosomes compared to only seven out of 231 patients with de novo disease (P = 0.00003). A dic(1q;7p) was observed in 10 cases, a dic(5p;17q) was observed in six cases, whereas various isodicentric chromosomes were observed in six cases. Excluding these six cases with isodicentrics, all 25 patients with dicentric chromosomes had involvement of at least one of the chromosome arms 1q, 5p, or 7p resulting in monosomy for 5q or 7q, and/or trisomy for 1q. Patients with dicentric chromosomes presented significantly more often as t-MDS compared to patients without dicentrics (P = 0.046), and the presence of a dicentric chromosome was significantly related to previous therapy with alkylating agents (P = 0.026). Thus, only one out of 27 patients with a dicentric chromosome had not previously received an alkylating agent. A specific susceptibility to breakage at the centromere after exposure to alkylating agents is suggested and may explain the frequent loss of whole chromosomes, in particular chromosomes 5 and 7 in t-MDS and t-AML, if the breaks are not followed by rejoining. Leukemia (2000) 14, 105-111.

  13. Preimplantation genetic screening for all 24 chromosomes by microarray comparative genomic hybridization significantly increases implantation rates and clinical pregnancy rates in patients undergoing in vitro fertilization with poor prognosis

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    Gaurav Majumdar

    2016-01-01

    Full Text Available CONTEXT: A majority of human embryos produced in vitro are aneuploid, especially in couples undergoing in vitro fertilization (IVF with poor prognosis. Preimplantation genetic screening (PGS for all 24 chromosomes has the potential to select the most euploid embryos for transfer in such cases. AIM: To study the efficacy of PGS for all 24 chromosomes by microarray comparative genomic hybridization (array CGH in Indian couples undergoing IVF cycles with poor prognosis. SETTINGS AND DESIGN: A retrospective, case–control study was undertaken in an institution-based tertiary care IVF center to compare the clinical outcomes of twenty patients, who underwent 21 PGS cycles with poor prognosis, with 128 non-PGS patients in the control group, with the same inclusion criterion as for the PGS group. MATERIALS AND METHODS: Single cells were obtained by laser-assisted embryo biopsy from day 3 embryos and subsequently analyzed by array CGH for all 24 chromosomes. Once the array CGH results were available on the morning of day 5, only chromosomally normal embryos that had progressed to blastocyst stage were transferred. RESULTS: The implantation rate and clinical pregnancy rate (PR per transfer were found to be significantly higher in the PGS group than in the control group (63.2% vs. 26.2%, P = 0.001 and 73.3% vs. 36.7%, P = 0.006, respectively, while the multiple PRs sharply declined from 31.9% to 9.1% in the PGS group. CONCLUSIONS: In this pilot study, we have shown that PGS by array CGH can improve the clinical outcome in patients undergoing IVF with poor prognosis.

  14. k482ar.m77t - MGD77 data file for Geophysical data from field activity K-4-82-AR in Arctic from 09/13/1982 to 10/10/1982

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Single-beam bathymetry data along with DGPS navigation data was collected as part of field activity K-4-82-AR in Arctic from 09/13/1982 to 10/10/1982,...

  15. Software Tool for Significantly Increasing Airport Throughput Project

    Data.gov (United States)

    National Aeronautics and Space Administration — NASA's Next Generation Air Transportation System (NextGen) Airportal effort seeks to optimize aircraft surface movements through approaches that could double or...

  16. Measurement of the Energy Expenditures in Daily Physical Activities with K4b2%应用K4b2心肺功能测定仪对日常体力活动能量消耗的测定

    Institute of Scientific and Technical Information of China (English)

    刘健敏; 李颜; 杨晓光

    2010-01-01

    应用K4b2心肺功能测定仪对日常体力活动的能量消耗进行现场测定,以期为我国体力活动指南的制定提供基础资料.选取23名北医青年学生作为受试者,其中男11名,女12名,应用K4b2心肺功能测定仪对受试者在静息、慢走(3 km/h)、快走(6 km/h)、慢跑(8 km/h)、骑自行车(12 km/h)状态下的能量消耗进行测定.各项体力活动的能量消耗及代谢当量由大到小排列,依次为幔跑((6.26±1.22)kcal·kg-1~·h-1,6.0 MET)、骑自行车((4.30±0.67)kcal·kg-1·h-1,4.2 MET)、快走((3.75±0.73)kcal·ks-1·h-1,3.6 MET)、慢走((1.24±0.26)kcal·kg-1·h-1,1.2 MET)、静息((1.08±0.24)kcal·kg-1·h-1,1.0 MET),按照体力活动强度分级,属于中低强度体力活动.慢走、快走、慢跑、骑自行车等日常体力活动适于在中国人群中推广.

  17. Otters Increasing - Threats Increasing

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    Andreas Kranz

    1994-10-01

    Full Text Available In some parts of Central Europe populations of otters are apparently increasing. Until recently, no research was being conducted on the ecology of otters in mainly artificial habitats like fish farms. Otters are not only a new source of conflict requiring species management, but appear once again threatened by illegal hunting. Austria is dealing with this problem using compensation for otter damage, electric fencing and translocation of problem otters. Despite a rise in illegal killing, Austria does not formally recognise this as a threat.

  18. Meaning and significance of

    Directory of Open Access Journals (Sweden)

    Ph D Student Roman Mihaela

    2011-05-01

    Full Text Available The concept of "public accountability" is a challenge for political science as a new concept in this area in full debate and developement ,both in theory and practice. This paper is a theoretical approach of displaying some definitions, relevant meanings and significance odf the concept in political science. The importance of this concept is that although originally it was used as a tool to improve effectiveness and eficiency of public governance, it has gradually become a purpose it itself. "Accountability" has become an image of good governance first in the United States of America then in the European Union.Nevertheless,the concept is vaguely defined and provides ambiguous images of good governance.This paper begins with the presentation of some general meanings of the concept as they emerge from specialized dictionaries and ancyclopaedies and continues with the meanings developed in political science. The concept of "public accontability" is rooted in economics and management literature,becoming increasingly relevant in today's political science both in theory and discourse as well as in practice in formulating and evaluating public policies. A first conclusin that emerges from, the analysis of the evolution of this term is that it requires a conceptual clarification in political science. A clear definition will then enable an appropriate model of proving the system of public accountability in formulating and assessing public policies, in order to implement a system of assessment and monitoring thereof.

  19. GmPHD5 acts as an important regulator for crosstalk between histone H3K4 di-methylation and H3K14 acetylation in response to salinity stress in soybean

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    Wu Tao

    2011-12-01

    Full Text Available Abstract Background Accumulated evidence suggest that specific patterns of histone posttranslational modifications (PTMs and their crosstalks may determine transcriptional outcomes. However, the regulatory mechanisms of these "histone codes" in plants remain largely unknown. Results In this study, we demonstrate for the first time that a salinity stress inducible PHD (plant homeodomain finger domain containing protein GmPHD5 can read the "histone code" underlying the methylated H3K4. GmPHD5 interacts with other DNA binding proteins, including GmGNAT1 (an acetyl transferase, GmElongin A (a transcription elongation factor and GmISWI (a chromatin remodeling protein. Our results suggest that GmPHD5 can recognize specific histone methylated H3K4, with preference to di-methylated H3K4. Here, we illustrate that the interaction between GmPHD5 and GmGNAT1 is regulated by the self-acetylation of GmGNAT1, which can also acetylate histone H3. GmGNAT1 exhibits a preference toward acetylated histone H3K14. These results suggest a histone crosstalk between methylated H3K4 and acetylated H3K14. Consistent to its putative roles in gene regulation under salinity stress, we showed that GmPHD5 can bind to the promoters of some confirmed salinity inducible genes in soybean. Conclusion Here, we propose a model suggesting that the nuclear protein GmPHD5 is capable of regulating the crosstalk between histone methylation and histone acetylation of different lysine residues. Nevertheless, GmPHD5 could also recruit chromatin remodeling factors and transcription factors of salt stress inducible genes to regulate their expression in response to salinity stress.

  20. Significant NRC Enforcement Actions

    Data.gov (United States)

    Nuclear Regulatory Commission — This dataset provides a list of Nuclear Regulartory Commission (NRC) issued significant enforcement actions. These actions, referred to as "escalated", are issued by...

  1. Arabidopsis AL PHD-PRC1 complexes promote seed germination through H3K4me3-to-H3K27me3 chromatin state switch in repression of seed developmental genes.

    Science.gov (United States)

    Molitor, Anne Marie; Bu, Zhongyuan; Yu, Yu; Shen, Wen-Hui

    2014-01-01

    Seed germination and subsequent seedling growth define crucial steps for entry into the plant life cycle. For those events to take place properly, seed developmental genes need to be silenced whereas vegetative growth genes are activated. Chromatin structure is generally known to play crucial roles in gene transcription control. However, the transition between active and repressive chromatin states during seed germination is still poorly characterized and the underlying molecular mechanisms remain largely unknown. Here we identified the Arabidopsis PHD-domain H3K4me3-binding ALFIN1-like proteins (ALs) as novel interactors of the Polycomb Repressive Complex 1 (PRC1) core components AtBMI1b and AtRING1a. The interactions were confirmed by diverse in vitro and in vivo assays and were shown to require the AL6 N-terminus containing PAL domain conserved in the AL family proteins and the AtRING1a C-terminus containing RAWUL domain conserved in animal and plant PRC1 ring-finger proteins (including AtRNIG1a/b and AtBMI1a/b). By T-DNA insertion mutant analysis, we found that simultaneous loss of AL6 and AL7 as well as loss of AtBMI1a and AtBMI1b retards seed germination and causes transcriptional derepression and a delayed chromatin state switch from H3K4me3 to H3K27me3 enrichment of several seed developmental genes (e.g. ABI3, DOG1, CRU3, CHO1). We found that AL6 and the PRC1 H3K27me3-reader component LHP1 directly bind at ABI3 and DOG1 loci. In light of these data, we propose that AL PHD-PRC1 complexes, built around H3K4me3, lead to a switch from the H3K4me3-associated active to the H3K27me3-associated repressive transcription state of seed developmental genes during seed germination. Our finding of physical interactions between PHD-domain proteins and PRC1 is striking and has important implications for understanding the connection between the two functionally opposite chromatin marks: H3K4me3 in activation and H3K27me3 in repression of gene transcription.

  2. Arabidopsis AL PHD-PRC1 complexes promote seed germination through H3K4me3-to-H3K27me3 chromatin state switch in repression of seed developmental genes.

    Directory of Open Access Journals (Sweden)

    Anne Marie Molitor

    2014-01-01

    Full Text Available Seed germination and subsequent seedling growth define crucial steps for entry into the plant life cycle. For those events to take place properly, seed developmental genes need to be silenced whereas vegetative growth genes are activated. Chromatin structure is generally known to play crucial roles in gene transcription control. However, the transition between active and repressive chromatin states during seed germination is still poorly characterized and the underlying molecular mechanisms remain largely unknown. Here we identified the Arabidopsis PHD-domain H3K4me3-binding ALFIN1-like proteins (ALs as novel interactors of the Polycomb Repressive Complex 1 (PRC1 core components AtBMI1b and AtRING1a. The interactions were confirmed by diverse in vitro and in vivo assays and were shown to require the AL6 N-terminus containing PAL domain conserved in the AL family proteins and the AtRING1a C-terminus containing RAWUL domain conserved in animal and plant PRC1 ring-finger proteins (including AtRNIG1a/b and AtBMI1a/b. By T-DNA insertion mutant analysis, we found that simultaneous loss of AL6 and AL7 as well as loss of AtBMI1a and AtBMI1b retards seed germination and causes transcriptional derepression and a delayed chromatin state switch from H3K4me3 to H3K27me3 enrichment of several seed developmental genes (e.g. ABI3, DOG1, CRU3, CHO1. We found that AL6 and the PRC1 H3K27me3-reader component LHP1 directly bind at ABI3 and DOG1 loci. In light of these data, we propose that AL PHD-PRC1 complexes, built around H3K4me3, lead to a switch from the H3K4me3-associated active to the H3K27me3-associated repressive transcription state of seed developmental genes during seed germination. Our finding of physical interactions between PHD-domain proteins and PRC1 is striking and has important implications for understanding the connection between the two functionally opposite chromatin marks: H3K4me3 in activation and H3K27me3 in repression of gene transcription.

  3. Significance Testing Without Truth

    Science.gov (United States)

    2012-07-27

    ICES REPORT 12-34 August 2012 Significance testing without truth by William Perkins, Mark Tygert, and Rachel Ward The Institute for Computational...testing without truth , ICES REPORT 12-34, The Institute for Computational Engineering and Sciences, The University of Texas at Austin, August 2012...2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Significance testing without truth 5a. CONTRACT NUMBER 5b

  4. A Significant Play

    Institute of Scientific and Technical Information of China (English)

    梁海光; 陈明

    2002-01-01

    Yesterday evening, I went to see a play. It was really significant. It was about Zheng Xiaoyue, a very clever and diligent middle school student. Unfortunately, her mother died when she and her brother were very young. Her father was out of work and,

  5. Quantitative analysis of ChIP-seq data uncovers dynamic and sustained H3K4me3 and H3K27me3 modulation in cancer cells under hypoxia.

    Science.gov (United States)

    Adriaens, Michiel E; Prickaerts, Peggy; Chan-Seng-Yue, Michelle; van den Beucken, Twan; Dahlmans, Vivian E H; Eijssen, Lars M; Beck, Timothy; Wouters, Bradly G; Voncken, Jan Willem; Evelo, Chris T A

    2016-01-01

    A comprehensive assessment of the epigenetic dynamics in cancer cells is the key to understanding the molecular mechanisms underlying cancer and to improving cancer diagnostics, prognostics and treatment. By combining genome-wide ChIP-seq epigenomics and microarray transcriptomics, we studied the effects of oxygen deprivation and subsequent reoxygenation on histone 3 trimethylation of lysine 4 (H3K4me3) and lysine 27 (H3K27me3) in a breast cancer cell line, serving as a model for abnormal oxygenation in solid tumors. A priori, epigenetic markings and gene expression levels not only are expected to vary greatly between hypoxic and normoxic conditions, but also display a large degree of heterogeneity across the cell population. Where traditionally ChIP-seq data are often treated as dichotomous data, the model and experiment here necessitate a quantitative, data-driven analysis of both datasets. We first identified genomic regions with sustained epigenetic markings, which provided a sample-specific reference enabling quantitative ChIP-seq data analysis. Sustained H3K27me3 marking was located around centromeres and intergenic regions, while sustained H3K4me3 marking is associated with genes involved in RNA binding, translation and protein transport and localization. Dynamic marking with both H3K4me3 and H3K27me3 (hypoxia-induced bivalency) was found in CpG-rich regions at loci encoding factors that control developmental processes, congruent with observations in embryonic stem cells. In silico-identified epigenetically sustained and dynamic genomic regions were confirmed through ChIP-PCR in vitro, and obtained results are corroborated by published data and current insights regarding epigenetic regulation.

  6. Significant Tsunami Events

    Science.gov (United States)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  7. Significant Scales in Community Structure

    CERN Document Server

    Traag, V A; Van Dooren, P

    2013-01-01

    Many complex networks show signs of modular structure, uncovered by community detection. Although many methods succeed in revealing various partitions, it remains difficult to detect at what scale some partition is significant. This problem shows foremost in multi-resolution methods. We here introduce an efficient method for scanning for resolutions in one such method. Additionally, we introduce the notion of "significance" of a partition, based on subgraph probabilities. Significance is independent of the exact method used, so could also be applied in other methods, and can be interpreted as the gain in encoding a graph by making use of a partition. Using significance, we can determine "good" resolution parameters, which we demonstrate on benchmark networks. Moreover, optimizing significance itself also shows excellent performance. We demonstrate our method on voting data from the European Parliament. Our analysis suggests the European Parliament has become increasingly ideologically divided and that nationa...

  8. A Significant Step Forward

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Australia officially ratified the Kyoto Protocol on December 3,the first act of its new government under Prime Minister Kevin Rudd.Rudd signed the instrument of ratification the very day he was sworn in by Australia’s Governor General Michael Jeffery. This is a significant step in Australia’s efforts to fight climate change domestically and with the international community,Rudd said in a statement.The Australian Government will do everything in its power to help Australia meet its Kyoto obligations,he added.

  9. The Significance of Science

    Science.gov (United States)

    Pielke, R.

    2002-05-01

    Whether global warming, terrestrial carbon sinks, ecosystem functioning, genetically modified organisms, cloning, vaccination or chemicals in the environment, science is increasingly the battlefield on which political advocates, not least lawyers and commercial interests, manipulate `facts' to their preferred direction, which fosters the politicization of science. Debate putatively over science increasingly relies on tactics such as ad hominem attacks and criticism of process (for example, peer review or sources of funding), through paid advertisements, press releases and other publicity campaigns. As political battles are waged through `science', many scientists are willing to adopt tactics of demagoguery and character assassination as well as, or even instead of, reasoned argument, as in aspects of debate over genetically modified crops or global warming. Science is becoming yet another playing field for power politics, complete with the trappings of media spin and a win-at-all-costs attitude. Sadly, much of what science can offer policymakers, and hence society, is lost. This talk will use cases from the atmospheric sciences as points of departure to explore the politicization of science from several perspectives and address questions such as: Is it a problem? For whom and what outcomes? What are the alternatives to business-as-usual?

  10. Predicting significant torso trauma.

    Science.gov (United States)

    Nirula, Ram; Talmor, Daniel; Brasel, Karen

    2005-07-01

    Identification of motor vehicle crash (MVC) characteristics associated with thoracoabdominal injury would advance the development of automatic crash notification systems (ACNS) by improving triage and response times. Our objective was to determine the relationships between MVC characteristics and thoracoabdominal trauma to develop a torso injury probability model. Drivers involved in crashes from 1993 to 2001 within the National Automotive Sampling System were reviewed. Relationships between torso injury and MVC characteristics were assessed using multivariate logistic regression. Receiver operating characteristic curves were used to compare the model to current ACNS models. There were a total of 56,466 drivers. Age, ejection, braking, avoidance, velocity, restraints, passenger-side impact, rollover, and vehicle weight and type were associated with injury (p < 0.05). The area under the receiver operating characteristic curve (83.9) was significantly greater than current ACNS models. We have developed a thoracoabdominal injury probability model that may improve patient triage when used with ACNS.

  11. Anthropological significance of phenylketonuria.

    Science.gov (United States)

    Saugstad, L F

    1975-01-01

    The highest incidence rates of phenylketonuria (PKU) have been observed in Ireland and Scotlant. Parents heterozygous for PKU in Norway differ significantly from the general population in the Rhesus, Kell and PGM systems. The parents investigated showed an excess of Rh negative, Kell plus and PGM type 1 individuals, which makes them similar to the present populations in Ireland and Scotlant. It is postulated that the heterozygotes for PKU in Norway are descended from a completely assimilated sub-population of Celtic origin, who came or were brought here, 1ooo years ago. Bronze objects of Western European (Scottish, Irish) origin, found in Viking graves widely distributed in Norway, have been taken as evidence of Vikings returning with loot (including a number of Celts) from Western Viking settlements. The continuity of residence since the Viking age in most habitable parts of Norway, and what seems to be a nearly complete regional relationship between the sites where Viking graves contain western imported objects and the birthplaces of grandparents of PKUs identified in Norway, lend further support to the hypothesis that the heterozygotes for PKU in Norway are descended from a completely assimilated subpopulation. The remarkable resemblance between Iceland and Ireland, in respect of several genetic markers (including the Rhesus, PGM and Kell systems), is considered to be an expression of a similar proportion of people of Celtic origin in each of the two countries. Their identical, high incidence rates of PKU are regarded as further evidence of this. The significant decline in the incidence of PKU when one passes from Ireland, Scotland and Iceland, to Denmark and on to Norway and Sweden, is therefore explained as being related to a reduction in the proportion of inhabitants of Celtic extraction in the respective populations.

  12. A significant resource

    Energy Technology Data Exchange (ETDEWEB)

    Umana, E.; Suarez, J.A.; Santon, D.G.

    2002-03-01

    The paper discusses Colombia's aims to enhance coal export levels in order to increase its world market share. The objectives set by the Colombian mining authorities include: achieving and sustaining a share of 10% in the world's thermal coal market commercialised by sea; attaining a 20% share of Colombia's energy basket by 2010; modernising small and medium-sized coal mines located in regions other than northern Colombia (Guajira-Cesar complex), in order to make them sustainable at technical, economic and environmental levels; maintaining and enhancing the transport and shipping infrastructure; and encouraging private, national and foreign capital involvement in the country's coal projects. 1 fig., 3 tabs., 3 photos.

  13. K4W2OCl10

    Science.gov (United States)

    Villars, P.; Cenzual, K.; Daams, J.; Gladyshevskii, R.; Shcherban, O.; Dubenskyy, V.; Kuprysyuk, V.; Savysyuk, I.; Zaremba, R.

    This document is part of Subvolume A10 'Structure Types. Part 10: Space Groups (140) I4/mcm - (136) P42/mnm' of Volume 43 'Crystal Structures of Inorganic Compounds' of Landolt-Börnstein - Group III 'Condensed Matter'.

  14. Final report on EURAMET.M.P-K4.2010: Key and supplementary comparison of national pressure standards in the range 1 Pa to 15 kPa of absolute and gauge pressure

    Science.gov (United States)

    Krajíček, Zdeněk; Bergoglio, Mercede; Jousten, Karl; Otal, Pierre; Sabuga, Wladimir; Saxholm, Sari; Pražák, Dominik; Vičar, Martin

    2014-01-01

    This report describes a EURAMET comparison of five European National Metrology Institutes in low gauge and absolute pressure in gas (nitrogen), denoted as EURAMET.M.P-K4.2010. Its main intention is to state equivalence of the pressure standards, in particular those based on the technology of force-balanced piston gauges such as e.g. FRS by Furness Controls, UK and FPG8601 by DHI-Fluke, USA. It covers the range from 1 Pa to 15 kPa, both gauge and absolute. The comparison in absolute mode serves as a EURAMET Key Comparison which can be linked to CCM.P-K4 and CCM.P-K2 via PTB. The comparison in gauge mode is a supplementary comparison. The comparison was carried out from September 2008 till October 2012. The participating laboratories were the following: CMI, INRIM, LNE, MIKES, PTB-Berlin (absolute pressure 1 kPa and below) and PTB-Braunschweig (absolute pressure 1 kPa and above and gauge pressure). CMI was the pilot laboratory and provided a transfer standard for the comparison. This transfer standard was also the laboratory standard of CMI at the same time, which resulted in a unique and logistically difficult star comparison. Both in gauge and absolute pressures all the participating institutes successfully proved their equivalence with respect to the reference value and all also proved mutual bilateral equivalences in all the points. All the participating laboratories are also equivalent with the reference values of CCM.P-K4 and CCM.P-K2 in the relevant points. The comparison also proved the ability of FPG8601 to serve as a transfer standard. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  15. Regulation of Transcription of Nucleotide-Binding Leucine-Rich Repeat-Encoding Genes SNC1 and RPP4 via H3K4 Trimethylation1[C][W][OA

    Science.gov (United States)

    Xia, Shitou; Cheng, Yu Ti; Huang, Shuai; Win, Joe; Soards, Avril; Jinn, Tsung-Luo; Jones, Jonathan D.G.; Kamoun, Sophien; Chen, She; Zhang, Yuelin; Li, Xin

    2013-01-01

    Plant nucleotide-binding leucine-rich repeat (NB-LRR) proteins serve as intracellular sensors to detect pathogen effectors and trigger immune responses. Transcription of the NB-LRR-encoding Resistance (R) genes needs to be tightly controlled to avoid inappropriate defense activation. How the expression of the NB-LRR R genes is regulated is poorly understood. The Arabidopsis (Arabidopsis thaliana) suppressor of npr1-1, constitutive 1 (snc1) mutant carries a gain-of-function mutation in a Toll/Interleukin1 receptor-like (TIR)-NB-LRR-encoding gene, resulting in the constitutive activation of plant defense responses. A snc1 suppressor screen identified modifier of snc1,9 (mos9), which partially suppresses the autoimmune phenotypes of snc1. Positional cloning revealed that MOS9 encodes a plant-specific protein of unknown function. Expression analysis showed that MOS9 is required for the full expression of TIR-NB-LRR protein-encoding RECOGNITION OF PERONOSPORA PARASITICA 4 (RPP4) and SNC1, both of which reside in the RPP4 cluster. Coimmunoprecipitation and mass spectrometry analyses revealed that MOS9 associates with the Set1 class lysine 4 of histone 3 (H3K4) methyltransferase Arabidopsis Trithorax-Related7 (ATXR7). Like MOS9, ATXR7 is also required for the full expression of SNC1 and the autoimmune phenotypes in the snc1 mutant. In atxr7 mutant plants, the expression of RPP4 is similarly reduced, and resistance against Hyaloperonospora arabidopsidis Emwa1 is compromised. Consistent with the attenuated expression of SNC1 and RPP4, trimethylated H3K4 marks are reduced around the promoters of SNC1 and RPP4 in mos9 plants. Our data suggest that MOS9 functions together with ATXR7 to regulate the expression of SNC1 and RPP4 through H3K4 methylation, which plays an important role in fine-tuning their transcription levels and functions in plant defense. PMID:23690534

  16. H2A.Z demarcates intergenic regions of the plasmodium falciparum epigenome that are dynamically marked by H3K9ac and H3K4me3.

    Directory of Open Access Journals (Sweden)

    Richárd Bártfai

    Full Text Available Epigenetic regulatory mechanisms and their enzymes are promising targets for malaria therapeutic intervention; however, the epigenetic component of gene expression in P. falciparum is poorly understood. Dynamic or stable association of epigenetic marks with genomic features provides important clues about their function and helps to understand how histone variants/modifications are used for indexing the Plasmodium epigenome. We describe a novel, linear amplification method for next-generation sequencing (NGS that allows unbiased analysis of the extremely AT-rich Plasmodium genome. We used this method for high resolution, genome-wide analysis of a histone H2A variant, H2A.Z and two histone H3 marks throughout parasite intraerythrocytic development. Unlike in other organisms, H2A.Z is a constant, ubiquitous feature of euchromatic intergenic regions throughout the intraerythrocytic cycle. The almost perfect colocalisation of H2A.Z with H3K9ac and H3K4me3 suggests that these marks are preferentially deposited on H2A.Z-containing nucleosomes. By performing RNA-seq on 8 time-points, we show that acetylation of H3K9 at promoter regions correlates very well with the transcriptional status whereas H3K4me3 appears to have stage-specific regulation, being low at early stages, peaking at trophozoite stage, but does not closely follow changes in gene expression. Our improved NGS library preparation procedure provides a foundation to exploit the malaria epigenome in detail. Furthermore, our findings place H2A.Z at the cradle of P. falciparum epigenetic regulation by stably defining intergenic regions and providing a platform for dynamic assembly of epigenetic and other transcription related complexes.

  17. [Hypertriglyceridemia: concept and clinical significance].

    Science.gov (United States)

    Hirano, Tsutomu

    2013-09-01

    Hypertriglyceridemia is a common lipid disorder as well as hypercholesterolemia. However clinical significance of hypertriglyceridemia is not fully understood because of its heterogeneous lipoprotein phenotypes and complex etiology. Severe hypertriglyceridemia increases the risk for pancreatitis, whereas mild or moderate hypertriglyceridemia may be a risk factor for cardiovascular disease. Patients with hypertriglyceridemia are usually accompanied by other cardiovascular related disorders, such as central obesity, type 2 diabetes, and liver steatosis. Ectopic fat accumulation is often seen in hypertriglyceridemic subjects and various organ injuries are developed by the lipotoxicity. Hypertriglyceridemia is strongly associated with remnant lipoprotein accumulation, increased small dense LDL, and low HDL-cholesterol. All these lipid abnormalities are recognized as cardiovascular risk factors. The pathophysiology of lipoprotein metabolism related to the hypertriglyceridemia is summarized in this brief review.

  18. Price increase

    CERN Multimedia

    2006-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced, as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  19. Price increase

    CERN Multimedia

    2005-01-01

    Please take note that after five years of stable prices at Restaurant No 1 a price increase will come into force on 1st January 2006. This increase has been agreed after discussions between the CSR (Comité de Surveillance des Restaurants) and the catering company Novae and will reflect the inflation rate of the last few years. In addition, a new children's menu will be introduced as well as 'Max Havelaar' fair-trade coffee at a price of 1.70 CHF.

  20. Significance of biofilms in dentistry.

    Science.gov (United States)

    Wróblewska, Marta; Strużycka, Izabela; Mierzwińska-Nastalska, Elżbieta

    2015-01-01

    In the past decades significant scientific progress has taken place in the knowledge about biofilms. They constitute multilayer conglomerates of bacteria and fungi, surrounded by carbohydrates which they produce, as well as substances derived from saliva and gingival fluid. Modern techniques showed significant diversity of the biofilm environment and a system of microbial communication (quorum sensing), enhancing their survival. At present it is believed that the majority of infections, particularly chronic with exacerbations, are a result of biofilm formation, particularly in the presence of biomaterials. It should be emphasised that penetration of antibiotics and other antimicrobial agents into deeper layers of a biofilm is poor, causing therapeutic problems and necessitating sometimes removal of the implant or prosthesis. Biofilms play an increasing role in dentistry as a result of more and more broad use in dental practice of plastic and implantable materials. Biofilms are produced on the surfaces of teeth as dental plaque, in the para-nasal sinuses, on prostheses, dental implants, as well as in waterlines of a dental unit, constituting a particular risk for severely immunocompromised patients. New methods of therapy and prevention of infections linked to biofilms are under development.

  1. Report on EUROMET.RI(I)-K1 and EUROMET.RI(I)-K4 (EUROMET project no. 813): Comparison of air kerma and absorbed dose to water measurements of {sup 60}Co radiation beams for radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Csete, I. [National Office of Measures (OMH) - pilot laboratory and corresponding author (Hungary); Leiton, A.G. [Research Centre for Energy, Environment and Technology (CMRI-CIEMAT) (Spain); Sochor, V. [Czech Metrology Institute (CMI) (Czech Republic); Lapenas, A. [Latvian National Metrology Center (LNMC-RMTC) (Latvia); Grindborg, J.E. [Swedish Radiation Protection Authority (SSI) (Sweden); Jokelainen, I. [Radiation and Nuclear Safety Authority (STUK) (Finland); Bjerke, H. [Norwegian Radiation Protection Authority (NRPA) (Norway); Dobrovodsky, J. [Slovak Institute of Metrology (SMU) (Slovakia); Megzifene, A. [International Atomic Energy Agency, IAEA, Vienna (Austria); Hourdakis, C.J. [Hellenic Atomic Energy Committee (HAEC-HIRCL) (Greece); Ivanov, R. [National Centre of Metrology (NCM) (Bulgaria); Vekic, B. [Rudjer Boskovic Institute (IRB) (Croatia); Kokocinski, J. [Central Office of Measures (GUM) (Poland); Cardoso, J. [Institute for Nuclear Technology (ITN-LMRIR) (Portugal); Buermann, L. [Physikalisch Technische Bundesanstalt (PTB) (Germany); Tiefenboeck, W. [Bundesamt fur Eich und Vermesungswesen (BEV) (Austria); Stucki, G. [17 Bundesamt fur Metrologie (METAS) (Switzerland); Van Dijk, E. [NMi Van Swinden Laboratorium (NMi) (Netherlands); Toni, M.P. [ENEA-CR Istituto Nazionale di Metrologia delle Radiazioni Ionizzanti (ENEA) (Italy); Minniti, R. [20 National Institute of Standards and Technology (NIST) (United States); McCaffrey, J.P. [National Research Council Canada (NRC) (Canada); Silva, C.N.M. [National Metrology Laboratory of Ionizing Radiation (LNMRI-IRD) (Brazil); Kharitonov, I. [D I Mendeleyev Institute for Metrology (VNIIM) (RU); Webb, D. [Australian Radiation Protection and Nuclear Safety Agency (ARPANSA) (Australia); Saravi, M. [National Atomic Energy Commission (CNEA-CAE) (Argentina); Delaunay, F. [Laboratoire National Henri Becquerel (LNE-LNHB) (France)

    2010-06-15

    The results of an unprecedented international effort involving 26 countries are reported. The EUROMET.RI(I)-K1 and EUROMET.RI(I)-K4 key comparisons were conducted with the goal of supporting the relevant calibration and measurement capabilities (CMC) planned for publication by the participant laboratories. The measured quantities were the air kerma (K{sub air}) and the absorbed dose to water (Dw) in {sup 60}Co radiotherapy beams. The comparison was conducted by the pilot laboratory MKEH (Hungary), in a star-shaped arrangement from January 2005 to December 2008. The calibration coefficients of four transfer ionization chambers were measured using two electrometers. The largest deviation between any two calibration coefficients for the four chambers in terms of air kerma and absorbed dose to water was 2.7% and 3.3% respectively. An analysis of the participant uncertainty budgets enabled the calculation of degrees of equivalence (DoE), in terms of the deviations of the results and their associated uncertainties. As a result of this EUROMET project 813 comparison, the BIPM key comparison database (KCDB) will include eleven new Kair and fourteen new D{sub w} DoE values of European secondary standard dosimetry laboratories (SSDLs), and the KCDB will be updated with the new DoE values of the other participant laboratories. The pair-wise degrees of equivalence of participants were also calculated. In addition to assessing calibration techniques and uncertainty calculations of the participants, these comparisons enabled the experimental determinations of N{sub Dw}/N{sub Kair} ratios in the {sup 60}Co gamma radiation beam for the four radiotherapy transfer chambers. (authors)

  2. THE VOLATILE COMPOSITION OF COMET C/2003 K4 (LINEAR) AT NEAR-IR WAVELENGTHS—COMPARISONS WITH RESULTS FROM THE NANÇAY RADIO TELESCOPE AND FROM THE ODIN, SPITZER, AND SOHO SPACE OBSERVATORIES

    Energy Technology Data Exchange (ETDEWEB)

    Paganini, L.; Mumma, M. J.; Villanueva, G. L.; DiSanti, M. A.; Bonev, B. P., E-mail: lucas.paganini@nasa.gov [Goddard Center for Astrobiology, NASA GSFC, MS 690, Greenbelt, MD 20771 (United States)

    2015-07-20

    We observed comet C/2003 K4 (LINEAR) using NIRSPEC at the Keck Observatory on UT 2004 November 28, when the comet was at 1.28 AU from the Sun (post-perihelion) and 1.38 AU from Earth. We detected six gaseous species (H{sub 2}O, OH*, C{sub 2}H{sub 6}, CH{sub 3}OH, CH{sub 4}, and HCN) and obtained upper limits for three others (H{sub 2}CO, C{sub 2}H{sub 2}, and NH{sub 3}). Our results indicate a water production rate of (1.72 ± 0.18) × 10{sup 29} molecules s{sup −1}, in reasonable agreement with production rates from SOHO (on the same day), Odin (one day earlier), and Nançay (about two weeks earlier). We also report abundances (relative to water) for seven trace species: CH{sub 3}OH (∼1.8%), CH{sub 4} (∼0.9%), and C{sub 2}H{sub 6} (∼0.4%) that were consistent with mean values among Oort cloud (OC) comets, while NH{sub 3} (<0.55%), HCN (∼0.07%), H{sub 2}CO (<0.07%), and C{sub 2}H{sub 2} (<0.04%) were “lower” than the mean values in other OC comets. We extracted inner-coma rotational temperatures for four species (H{sub 2}O, C{sub 2}H{sub 6}, CH{sub 3}OH, and CH{sub 4}), all of which are consistent with 70 K (within 1σ). The extracted ortho-para ratio for water was 3.0 ± 0.15, corresponding to spin temperatures larger than 39 K (at the 1σ level) and agreeing with those obtained with the Spitzer Space Telescope at the 2σ level.

  3. Micro–Positron Emission Tomography/Contrast-Enhanced Computed Tomography Imaging of Orthotopic Pancreatic Tumor–Bearing Mice Using the αvβ3 Integrin Tracer 64Cu-Labeled Cyclam-RAFT-c(-RGDfK-4

    Directory of Open Access Journals (Sweden)

    Winn Aung

    2013-09-01

    Full Text Available The purpose of this study was to develop a clinically relevant orthotopic xenotransplantation model of pancreatic cancer and to perform a preclinical evaluation of a new positron emission tomography (PET imaging probe, 64Cu-labeled cyclam-RAFT-c(-RGDfK-4 peptide (64Cu-RAFT-RGD, using this model. Varying degrees of αvβ3 integrin expression in several human pancreatic cancer cell lines were examined by flow cytometry and Western blotting. The cell line BxPC-3, which is stably transfected with a red fluorescence protein (RFP, was used for surgical orthotopic implantation. Orthotopic xenograft was established in the pancreas of recipient nude mice. An in vivo probe biodistribution and receptor blocking study, preclinical PET imaging coregistered with contrast-enhanced computed tomography (CECT comparing 64Cu-RAFT-RGD and 18F-fluoro-2-deoxy-D-glucose (18F-FDG accumulation in tumor, postimaging autoradiography, and histologic and immunohistochemical examinations were done. Biodistribution evaluation with a blocking study confirmed that efficient binding of probe to tumor is highly αvβ3 integrin specific. 64Cu-RAFT-RGD PET combined with CECT provided for precise and easy detection of cancer lesions. Autoradiography, histologic, and immunohistochemical examinations confirmed the accumulation of 64Cu-RAFT-RGD in tumor versus nontumor tissues. In comparative PET studies, 64Cu-RAFT-RGD accumulation provided better tumor contrast to background than 18F-FDG. Our results suggest that 64Cu-RAFT-RGD PET imaging is potentially applicable for the diagnosis of αvβ3 integrin–expressing pancreatic tumors.

  4. Monoclonal gammopathy of undetermined significance

    National Research Council Canada - National Science Library

    Kyle, Robert A; Vincent Rajkumar, S

    2006-01-01

    Summary Significant advances have been made in our understanding of the natural history, pathogenesis, mechanisms of progression and prognosis of monoclonal gammopathy of undetermined significance (MGUS...

  5. Chromatin alterations in response to forced swimming underlie increased prodynorphin transcription.

    Science.gov (United States)

    Reed, B; Fang, N; Mayer-Blackwell, B; Chen, S; Yuferov, V; Zhou, Y; Kreek, M J

    2012-09-18

    Antagonism of the kappa opioid receptor (KOR) has been reported to have anti-depressant-like properties. The dynorphin/KOR system is a crucial neurochemical substrate underlying the pathologies of addictive diseases, affective disorders and other disease states. However, the molecular underpinnings and neuroanatomical localization of the dysregulation of this system have not yet been fully elucidated. Utilizing the Porsolt Forced Swim Test (FST), an acute stressor commonly used as in rodent models measuring antidepressant efficacy, male Sprague-Dawley rats were subject to forced swimming for 15 min, treated 1h with vehicle or norbinaltorphimine (nor-BNI) (5 or 10mg/kg), and then 1 day later subject to FST for 5 min. In accordance with previous findings, nor-BNI dose dependently increased climbing time and reduced immobility. In comparison to control animals not exposed to FST, we observed a significant elevation in prodynorphin (pDyn) mRNA levels following FST using real-time optical polymerase chain reaction (PCR) in the caudate putamen but not in the nucleus accumbens, hypothalamus, amygdala, frontal cortex, or hippocampus. nor-BNI treatment did not affect pDyn mRNA levels in comparison to animals that received vehicle. The corresponding brain regions from the opposite hemisphere were analyzed for underlying chromatin modifications of the prodynorphin gene promoter region using chromatin immunoprecipitation with antibodies against specifically methylated histones H3K27Me2, H3K27Me3, H3K4Me2, and H3K4Me3, as well as CREB-1 and MeCP2. Significant alterations in proteins bound to DNA in the Cre-3, Cre-4, and Sp1 regions of the prodynorphin promoter were found in the caudate putamen of the FST saline-treated animals compared to control animals, with no changes observed in the hippocampus. Epigenetic changes resulting in elevated dynorphin levels specifically in the caudate putamen may in part underlie the enduring effects of stress.

  6. Chromatin Alterations in Response to Forced Swimming Underlie Increased Prodynorphin Transcription

    Science.gov (United States)

    Reed, Brian; Fang, Nancy; Blackwell-Mayer, Brandan; Chen, Shasha; Yuferov, Vadim; Zhou, Yan; Kreek, Mary Jeanne

    2012-01-01

    Antagonism of the kappa opioid receptor (KOR) has been reported to have anti-depressant-like properties. The dynorphin/KOR system is a crucial neurochemical substrate underlying the pathologies of addictive diseases, affective disorders and other disease states. However, the molecular underpinnings and neuroanatomical localization of the dysregulation of this system have not yet been fully elucidated. Utilizing the Porsolt Forced Swim Test (FST), an acute stressor commonly used as in rodent models measuring antidepressant efficacy, male Sprague-Dawley rats were subject to forced swimming for 15 minutes, treated 1 hour with vehicle or nor-BNI (5 or 10 mg/kg), and then 1 day later subject to FST for five minutes. In accordance with previous findings, nor-BNI dose dependently increased climbing time and reduced immobility. In comparison to control animals not exposed to FST, we observed a significant elevation in prodynorphin (pDyn) mRNA levels following FST using real-time optical PCR in the caudate putamen but not in the nucleus accumbens, hypothalamus, amygdala, frontal cortex, or hippocampus. Nor-BNI treatment did not affect pDyn mRNA levels in comparison to animals that received vehicle. The corresponding brain regions from the opposite hemisphere were analyzed for underlying chromatin modifications of the prodynorphin gene promoter region using chromatin immunoprecipitation with antibodies against specifically methylated histones H3K27Me2, H3K27Me3, H3K4Me2, and H3K4Me3, as well as CREB-1 and MeCP2. Significant alterations in proteins bound to DNA in the Cre-3, Cre-4, and Sp1 regions of the prodynorphin promoter were found in the caudate putamen of the FST saline-treated animals compared to control animals, with no changes observed in the hippocampus. Epigenetic changes resulting in elevated dynorphin levels specifically in the caudate putamen may in part underlie the enduring effects of stress. PMID:22698692

  7. DNA methylation and not H3K4 trimethylation dictates the expression status of miR-152 gene which inhibits migration of breast cancer cells via DNMT1/CDH1 loop.

    Science.gov (United States)

    Sengupta, Dipta; Deb, Moonmoon; Rath, Sandip Kumar; Kar, Swayamsiddha; Parbin, Sabnam; Pradhan, Nibedita; Patra, Samir Kumar

    2016-08-15

    MicroRNAs (miRNA) are small non-coding RNAs which targets most protein-coding transcripts (mRNA) and destroy them. Thus miRNA controls the abundance of those specific proteins and impact on developmental, physiological and pathological processes. Dysregulation of miRNA function thus may lead to various clinicopathological complications, including breast cancer. Silencing of miR-152 gene due to promoter DNA methylation alter the expression pattern of several other genes. E-cadherin (CDH1) forms the core of adherent junctions between surrounding epithelial cells, link with actin cytoskeleton and affects cell signaling. CDH1 gene is down regulated by promoter DNA methylation during cancer progression. In this investigation, we attempt to elucidate the correlation of miR-152 and CDH1 function, as it is well known that the loss of CDH1 function is one of the major reasons for cancer metastasis and aggressiveness of spreading. For the first time we have shown that loss of CDH1 expression is directly proportional to the loss of miR-152 function in breast cancer cells. mRNA and protein expression profile of DNMT1 implicate that miR-152 targets DNMT1 mRNA and inhibits its protein expression. Tracing the molecular marks on DNA and histone 3 for understanding the mechanism of gene regulation by ChIP analyses leads to a paradoxical result that shows DNA methylation adjacent to active histone marking (enrichment of H3K4me3) silence miR-152 gene. Further experiments revealed that DNMT1 plays crucial role for regulation of miR-152 gene. When DNMT1 protein function is blocked miR-152 expression prevails and destroys the mRNA of DNMT1; this molecular regulatory mechanism is creating a cyclic feedback loop, which is now focused as DNMT1/miR-152 switch for on/off of DNMT1 target genes. We discovered modulation of CDH1 gene expression by DNMT1/miR-152 switches. We have demonstrated further that DNMT1 down regulation mediated upregulation of CDH1 (hereafter, DNMT1/CDH1 loop) in

  8. Factors significantly increasing or inhibiting early stages of malignant melanoma (M.M.) and non-invasive evaluation of new treatment by ingestion and external application of optimal doses of the most effective anti-M.M. substances: haritaki, cilantro, vitamin D3, nori, EPA with DHA, & application of special (+) solar energy stored paper, which reduced the M.M. active area & asbestos rapidly.

    Science.gov (United States)

    Omura, Yoshiaki; Jones, Marilyn; Duvvi, Harsha; Paluch, Kamila; Shimotsuura, Yasuhiro; Ohki, Motomu

    2013-01-01

    Sterilizing the pre-cancer skin of malignant melanoma (M.M.) with 70% Isopropyl alcohol intensified malignancy & the malignant response extended to surrounding normal looking skin, while sterilizing with 80% (vodka) or 12% (plum wine) ethyl alcohol completely inhibited M.M. in the area (both effects lasted for about 90 minutes initially). Burnt food (bread, vegetables, meat, and fish), a variety of smoked & non-smoked fish-skin, many animal's skin, pepper, Vitamin C over 75 mg, mango, pineapple, coconut, almond, sugars, Saccharine & Aspartame, garlic, onion, etc & Electromagnetic field from cellular phones worsened M.M. & induced abnormal M.M. response of surrounding skin. We found the following factors inhibit early stage of M.M. significantly: 1) Increasing normal cell telomere, by taking 500 mg Haritaki, often reached between 400-1150 ng& gradually diminished, but the M.M. response was completely inhibited until normal cell telomeres are reduced to 150 ng, which takes 6-8 hours. More than 70 mg Vitamin C, Orange Juice, & other high Vitamin C containing substances shouldn't be taken because they completely inhibit the effects of Haritaki. 2) We found Chrysotile asbestos & Tremolite asbestos (% of the Chrysotile amount) coexist. A special Cilantro tablet was used to remove asbestos & some toxic metals. 3) Vitamin D3 400 I.U. has a maximum inhibiting effect on M.M. but 800 I.U. or higher promotes malignancy. 4) Noricontaining Iodine, etc., was used. 5) EPA 180 mm with DHA 120 mg was most effectively used after metastasis to the surrounding skin was eliminated. When we combined 1 Cilantro tablet & Vitamin D3 400 I.U. withsmall Nori pieces & EPA with DHA, the effect of complete inhibition of M.M. lasted 9-11 hours. When these anti-M.M.substances (Haritaki, Vitamin D3, Cilantro, Nori, EPA. with DHA) were taken together, the effect lasted 12-14 hoursand M.M. involvement in surrounding normal-looking skin disappeared rapidly & original dark brown or black are as

  9. Significance Tests for Periodogram Peaks

    CERN Document Server

    Frescura, F A M; Frank, B S

    2007-01-01

    We discuss methods currently in use for determining the significance of peaks in the periodograms of time series. We discuss some general methods for constructing significance tests, false alarm probability functions, and the role played in these by independent random variables and by empirical and theoretical cumulative distribution functions. We also discuss the concept of "independent frequencies" in periodogram analysis. We propose a practical method for estimating the significance of periodogram peaks, applicable to all time series irrespective of the spacing of the data. This method, based on Monte Carlo simulations, produces significance tests that are tailor-made for any given astronomical time series.

  10. The significance of task significance: Job performance effects, relational mechanisms, and boundary conditions.

    Science.gov (United States)

    Grant, Adam M

    2008-01-01

    Does task significance increase job performance? Correlational designs and confounded manipulations have prevented researchers from assessing the causal impact of task significance on job performance. To address this gap, 3 field experiments examined the performance effects, relational mechanisms, and boundary conditions of task significance. In Experiment 1, fundraising callers who received a task significance intervention increased their levels of job performance relative to callers in 2 other conditions and to their own prior performance. In Experiment 2, task significance increased the job dedication and helping behavior of lifeguards, and these effects were mediated by increases in perceptions of social impact and social worth. In Experiment 3, conscientiousness and prosocial values moderated the effects of task significance on the performance of new fundraising callers. The results provide fresh insights into the effects, relational mechanisms, and boundary conditions of task significance, offering noteworthy implications for theory, research, and practice on job design, social information processing, and work motivation and performance.

  11. Studies of H3K4me3 demethylation by KDM5B/Jarid1B/PLU1 reveals strong substrate recognition in vitro and identifies 2,4-pyridine-dicarboxylic acid as an in vitro and in cell inhibitor

    DEFF Research Database (Denmark)

    Kristensen, Line Hyltoft; Nielsen, Anders Laerke; Helgstrand, Charlotte

    2012-01-01

    Dynamic methylations and demethylations of histone lysine residues are important for gene regulation and are facilitated by histone methyltransferases and histone demethylases (HDMs). KDM5B/Jarid1B/PLU1 is an H3K4me3/me2 specific lysine demethylase belonging to the family of JmjC domain containin...

  12. Increased Expression and Clinical Significance of Th22 Cells and Th17 Cells in the Peripheral Blood of Patients with Ankylosing Spondylitis and Rheumatoid Arthritis%强直性脊椎炎和类风湿性关节炎患者外周血中Th22和Th17细胞含量上升及临床意义

    Institute of Scientific and Technical Information of China (English)

    郭勇; 朱海波

    2014-01-01

    目的:研究强直性脊椎炎(AS)和类风湿性关节炎(RA)患者外周血中Th1细胞、Th17细胞和Th22细胞的表达,为进一步探讨AS和RA的发病机制提供新的理论依据。方法采用流式细胞术测定38例AS患者、40例RA患者及30名健康体检者外周血中Th1细胞、Th17细胞及Th22细胞的含量。结果AS患者Th17和Th22细胞的含量分别为(3.78±1.93)%、(1.63±0.53)%,RA患者Th17和Th22的含量分别为(3.66±1.84)%、(1.58±0.65)%。结果显示,与健康对照相比, AS和RA患者的Th17和Th22细胞的含量差异都有统计学意义(P<0.05)。结论AS和RA患者外周血中Th22细胞和Th17细胞含量上升,提示Th22细胞和Th17细胞与AS和RA的发病机制有关。%Objective To investigate the expression of Th1 cells, Th17 cells and Th22 cells in peripheral blood from patients with ankylosing spondylitis (AS) and rheumatoid arthritis (RA), and provide the reference for the further research of AS and RA pathological mechanism. Methods A total of 38 AS, 40 RA and 30 healthy subjects were enrolled in the research. The expression percentages of Th1, Th22 and Th17 cells were determined by flow cytometry. Results The expression of Th17 and Th22 cells in AS patients were (3.78±1.93)%, (1.63±0.53)%respectively, while in RA patients, they were (3.66±1.84)%and (1.58±0.65)%, respectively. The results showed that the expressions of Th17 and Th22 cells in AS patients were significantly higher than those of healthy controls (P<0.05), as well as RA patients. Conclusion The expression of Th17 and Th22 cells were increased in peripheral blood from patients with AS and patients with RA. These findings suggest that Th17 cells and Th22 cells may be implicated in the pathogenesis of AS and RA.

  13. Astronomical Significance of Ancient Monuments

    Science.gov (United States)

    Simonia, I.

    2011-06-01

    Astronomical significance of Gokhnari megalithic monument (eastern Georgia) is considered. Possible connection of Amirani ancient legend with Gokhnari monument is discussed. Concepts of starry practicality and solar stations are proposed.

  14. Historical Significant Volcanic Eruption Locations

    Data.gov (United States)

    Department of Homeland Security — A significant eruption is classified as one that meets at least one of the following criteriacaused fatalities, caused moderate damage (approximately $1 million or...

  15. Significance analysis of prognostic signatures.

    Directory of Open Access Journals (Sweden)

    Andrew H Beck

    Full Text Available A major goal in translational cancer research is to identify biological signatures driving cancer progression and metastasis. A common technique applied in genomics research is to cluster patients using gene expression data from a candidate prognostic gene set, and if the resulting clusters show statistically significant outcome stratification, to associate the gene set with prognosis, suggesting its biological and clinical importance. Recent work has questioned the validity of this approach by showing in several breast cancer data sets that "random" gene sets tend to cluster patients into prognostically variable subgroups. This work suggests that new rigorous statistical methods are needed to identify biologically informative prognostic gene sets. To address this problem, we developed Significance Analysis of Prognostic Signatures (SAPS which integrates standard prognostic tests with a new prognostic significance test based on stratifying patients into prognostic subtypes with random gene sets. SAPS ensures that a significant gene set is not only able to stratify patients into prognostically variable groups, but is also enriched for genes showing strong univariate associations with patient prognosis, and performs significantly better than random gene sets. We use SAPS to perform a large meta-analysis (the largest completed to date of prognostic pathways in breast and ovarian cancer and their molecular subtypes. Our analyses show that only a small subset of the gene sets found statistically significant using standard measures achieve significance by SAPS. We identify new prognostic signatures in breast and ovarian cancer and their corresponding molecular subtypes, and we show that prognostic signatures in ER negative breast cancer are more similar to prognostic signatures in ovarian cancer than to prognostic signatures in ER positive breast cancer. SAPS is a powerful new method for deriving robust prognostic biological signatures from clinically

  16. Significant advancement in algebraic geometry

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    @@ Supported by a grant for Distinguished Young Scholars of the National Natural Science Foundation of China,Prof.SUN Xiaotao with the CAS Academy of Mathematics and Systems Science has recently achieved a research breakthrough in revealing the deep relationship between stability of vector bundles and Frobenius morphism.It is considered as significant work with important theoretical value.

  17. Mining significant semantic locations from GPS data

    DEFF Research Database (Denmark)

    Cao, Xin; Cong, Gao; Jensen, Christian S.

    2010-01-01

    With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

  18. Mining significant semantic locations from GPS data

    DEFF Research Database (Denmark)

    Cao, Xin; Cong, Gao; Jensen, Christian S.

    2010-01-01

    With the increasing deployment and use of GPS-enabled devices, massive amounts of GPS data are becoming available. We propose a general framework for the mining of semantically meaningful, significant locations, e.g., shopping malls and restaurants, from such data. We present techniques capable...... of extracting semantic locations from GPS data. We capture the relationships between locations and between locations and users with a graph. Significance is then assigned to locations using random walks over the graph that propagates significance among the locations. In doing so, mutual reinforcement between...

  19. Significance and Progress of Bionics

    Institute of Scientific and Technical Information of China (English)

    Yongxiang Lu

    2004-01-01

    The four topics are described including the driving force and source of the scientific and technological creation, the definition and history of the bionics, the important significance of bionics in the development of the human beings, and the leading edge and progress of bionics. The appetency of human for the creation is the essential motivity of the innovation in science and technology. Nature and society are the objects for us to cognize and serve, meanwhile, the best teachers for us to learn from them. It is only 5 million years for human's development, but evolution of life has over 3.5 billion years history. Although, copying the creation from the human being is important, however, it has much more potential and opportunity in imitating the nature, and more possibility to promote the ability of original innovation. The significance and progress of bionics are summarized, in this paper, and the leading edges of bionics, in the near future, are forecasted.

  20. Significance evaluation in factor graphs

    DEFF Research Database (Denmark)

    Madsen, Tobias; Hobolth, Asger; Jensen, Jens Ledet

    2017-01-01

    Background Factor graphs provide a flexible and general framework for specifying probability distributions. They can capture a range of popular and recent models for analysis of both genomics data as well as data from other scientific fields. Owing to the ever larger data sets encountered...... in genomics and the multiple-testing issues accompanying them, accurate significance evaluation is of great importance. We here address the problem of evaluating statistical significance of observations from factor graph models. Results Two novel numerical approximations for evaluation of statistical....... Conclusions The applicability of saddlepoint approximation and importance sampling is demonstrated on known models in the factor graph framework. Using the two methods we can substantially improve computational cost without compromising accuracy. This contribution allows analyses of large datasets...

  1. Which Reconstruction Results are Significant?

    Science.gov (United States)

    1980-05-01

    other significant result is due to Tutte [17]. Tutte’s Theorem: The characteristic polynomial of a graph can be reconstructed. Equivalently, two...hypomorphic graphs must have the same characteristic polynomial . Several points should be noted concerning this theorem: 1. The derivative of the...characteristic polynomial is the sum of the char- acteristic polynomials of the vertex-deleted subgraphs. Thus the characteristic polynomials of hypomorphic

  2. Significant Workplace Change: Perspectives of Survivors

    Science.gov (United States)

    Kohut, Ann Marie

    2010-01-01

    The ever-increasing pace of workplace change is well documented in the literature, yet little is known about how an individual adapts to significant change in the workplace. Continuous learning is key to successful adaptation; however, are employees' adaptation to change influenced by their approaches to learning? The purpose of this study was to…

  3. Scope and Significance of Eating Disorders.

    Science.gov (United States)

    Mitchell, James E.; Eckert, Elke D.

    1987-01-01

    Describes the increasing prevalence of anorexia nervosa and bulimia in many industrialized societies, and their association with significant morbidity and mortality. Discusses the genetic risks for the development of anorexia nervosa, and treatment strategies. Of these, pharmacotherapy and psychotherapy, particularly those incorporating…

  4. Health significance of metal exposures

    DEFF Research Database (Denmark)

    Grandjean, Philippe

    2007-01-01

    focus on existing web-based resources for further reading New information on community-based participatory research Timely new chapter on bioterrorism and preparedness Additional insights on the amelioration of disease-producing lifestyles Research-enhancing lists and catalogs based on federal and other......, and policy issues, including critical lessons learned from the SARS epidemic, the most recent perspectives on monkey pox, plus an increased emphasis on West Nile Virus Restructured infectious and communicable disease section that reflects the emergence of many emerging and recrudescent conditions Greater...

  5. Robust Simulations and Significant Separations

    CERN Document Server

    Fortnow, Lance

    2010-01-01

    We define and study a new notion of "robust simulations" between complexity classes which is intermediate between the traditional notions of infinitely-often and almost-everywhere, as well as a corresponding notion of "significant separations". A language L has a robust simulation in a complexity class C if there is a language in C which agrees with L on arbitrarily large polynomial stretches of input lengths. There is a significant separation of L from C if there is no robust simulation of L in C. The new notion of simulation is a cleaner and more natural notion of simulation than the infinitely-often notion. We show that various implications in complexity theory such as the collapse of PH if NP = P and the Karp-Lipton theorem have analogues for robust simulations. We then use these results to prove that most known separations in complexity theory, such as hierarchy theorems, fixed polynomial circuit lower bounds, time-space tradeoffs, and the theorems of Allender and Williams, can be strengthened to signifi...

  6. Engineering Significant of Swelling Soils

    Directory of Open Access Journals (Sweden)

    Behzad Kalantari

    2012-08-01

    Full Text Available This study describes some of the most important swelling characters of expansive soils when used as foundation materials to support various types of civil engineering structures. Expansive soils are considered among difficult foundation materials and expand upon wetting and shrink upon losing moisture. They are considered problematic soils for architectural and civil engineers. These types of soils may cause minor to major structural damages to pavements as well as buildings. It is therefore essential to detect swelling soils from non-problematic foundation soils before any civil engineering projects are constructed over or adjacent to them. The study begins with definition of expansive soils and shows its distributions in the world as well as the basic causes for swelling potential that these type of soils poses. It is also shown that, the most probable depth of expansion to check for possible swelling potential for swelling soils is soil’s active zone. This zone is the most upper depth of expansive soil and it may extend up to 20 ft. (6 m below ground level. The moisture content of soil through active zone varies during different seasons while in lower part of expansive soil the moisture content stays constant during hot and cold season. Among various methods to check for swelling potential, plastic index and liquid limits are two most crucial factors, as these factors tend to increase, the swelling potential increase as well.

  7. The significance of constitutional values

    Directory of Open Access Journals (Sweden)

    HN Nisihara

    2001-12-01

    Full Text Available This article addresses the question of the meaning and legal significance of constitutional values in contemporary times. The article attends also to related questions namely, what constitute “constitutional values” and what are the limitations of the meaning afforded to this notion. Attention is paid in the particular, to freedom, equality and democracy as value-neutral criteria of fairness and government neutrality with reference to the South African and German contexts as well as to value-neutrality as a culturally conditioned value. The author concludes with a cosmopolitan view of freedom and the right to peace with reference to the constitutional texts of Japan and the United States.

  8. The significance of small streams

    Science.gov (United States)

    Wohl, Ellen

    2017-09-01

    Headwaters, defined here as first- and secondorder streams, make up 70%‒80% of the total channel length of river networks. These small streams exert a critical influence on downstream portions of the river network by: retaining or transmitting sediment and nutrients; providing habitat and refuge for diverse aquatic and riparian organisms; creating migration corridors; and governing connectivity at the watershed-scale. The upstream-most extent of the channel network and the longitudinal continuity and lateral extent of headwaters can be difficult to delineate, however, and people are less likely to recognize the importance of headwaters relative to other portions of a river network. Consequently, headwaters commonly lack the legal protections accorded to other portions of a river network and are more likely to be significantly altered or completely obliterated by land use.

  9. Quassinoids and Their Chemotaxonomic Significance

    Directory of Open Access Journals (Sweden)

    Anakshi Khare

    2013-06-01

    Full Text Available The quassinoids are a group of complex, highly oxygenated, degraded triterpene mostly found in Simaroubaceae family. Two quassinoids (degraded triterpenes, 1 and 2 were isolated first time from the stem bark of Ailanthus excelsa. Compound 1 is C19 quassinoid. C19 quassinoid derived biogenetically from a C20 quassinoid, via a 1,2 –dioxo derivative. The structural elucidation is based on the analysis of spectroscopic data. Interest in these quassinoids has increased enormously in recent years due in part to the finding of the American National Cancer Institute that these compounds display marked antileukamic activity. The ways in which plants interact with other organisms in an environment are complex. Ailanthus also produces toxins in its root, bark and leaves. These toxins inhibit the growth of other plants. The isolated quassinoids are currently being studied as a possible source of a natural herbicide. Extracts of this plant have anti-insect activity and anti-tuberculosis activity.

  10. Calculation of the total electron excitation cross section in the Born approximation using Slater wave functions for the Li (2s yields 2p), Li (2s yields 3p), Na (3s yields 4p), Mg (3p yields 4s), Ca (4s yields 4p) and K (4s yields 4p) excitations. M.S. Thesis

    Science.gov (United States)

    Simsic, P. L.

    1974-01-01

    Excitation of neutral atoms by inelastic scattering of incident electrons in gaseous nebulae were investigated using Slater Wave functions to describe the initial and final states of the atom. Total cross sections using the Born Approximation are calculated for: Li(2s yields 2p), Na(3s yields 4p), k(4s yields 4p). The intensity of emitted radiation from gaseous nebulae is also calculated, and Maxwell distribution is employed to average the kinetic energy of electrons.

  11. Activity measurements of the radionuclide 99mTc for the VNIIM, Russian Federation and ENEA-INMRI, Italy, in the ongoing comparison BIPM.RI(II)-K4.Tc-99m and KCRV update in the BIPM.RI(II)-K1.Tc-99m comparison

    Science.gov (United States)

    Michottea, C.; Nonisa, M.; Alekseevb, I. V.; Kharitonovb, I. A.; Tereshchenkob, E. E.; Zanevskiyb, A. V.; Capognic, M.; De Felicec, P.; Fazioc, A.; Carconic, P.

    2016-01-01

    In 2014, comparisons of activity measurements of 99mTc using the Transfer Instrument of the International Reference System (SIRTI) took place at the VNIIM (Russian Federation) and at the ENEA-INMRI (Italy), with comparison identifier BIPM.RI(II)-K4.Tc-99m. Ampoules containing about 32 kBq of 99mTc solutions were measured in the SIRTI for three half-lives. There are now nine results in the BIPM.RI(II)-K4.Tc-99m comparison. This comparison is linked to the BIPM.RI(II)-K1.Tc-99m comparison and the key comparison reference value (KCRV) of the BIPM.RI(II)-K1.Tc-99m has been updated to include eligible results from BIPM.RI(II)-K4.Tc-99m. The degrees of equivalence between each equivalent activity measured in the SIR or the SIRTI and the KCRV have been calculated and the results are given in the form of a table. A graphical presentation is also given. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  12. Significance of oxygen transport through aquaporins

    Science.gov (United States)

    Zwiazek, Janusz J.; Xu, Hao; Tan, Xiangfeng; Navarro-Ródenas, Alfonso; Morte, Asunción

    2017-01-01

    Aquaporins are membrane integral proteins responsible for the transmembrane transport of water and other small neutral molecules. Despite their well-acknowledged importance in water transport, their significance in gas transport processes remains unclear. Growing evidence points to the involvement of plant aquaporins in CO2 delivery for photosynthesis. The role of these channel proteins in the transport of O2 and other gases may also be more important than previously envisioned. In this study, we examined O2 permeability of various human, plant, and fungal aquaporins by co-expressing heterologous aquaporin and myoglobin in yeast. Two of the most promising O2-transporters (Homo sapiens AQP1 and Nicotiana tabacum PIP1;3) were confirmed to facilitate O2 transport in the spectrophotometric assay using yeast protoplasts. The over-expression of NtPIP1;3 in yeasts significantly increased their O2 uptake rates in suspension culture. In N. tabacum roots subjected to hypoxic hydroponic conditions, the transcript levels of the O2-transporting aquaporin NtPIP1;3 significantly increased after the seven-day hypoxia treatment, which was accompanied by the increase of ATP levels in the apical root segments. Our results suggest that the functional significance of aquaporin-mediated O2 transport and the possibility of controlling the rate of transmembrane O2 transport should be further explored. PMID:28079178

  13. Statistically significant relational data mining :

    Energy Technology Data Exchange (ETDEWEB)

    Berry, Jonathan W.; Leung, Vitus Joseph; Phillips, Cynthia Ann; Pinar, Ali; Robinson, David Gerald; Berger-Wolf, Tanya; Bhowmick, Sanjukta; Casleton, Emily; Kaiser, Mark; Nordman, Daniel J.; Wilson, Alyson G.

    2014-02-01

    This report summarizes the work performed under the project (3z(BStatitically significant relational data mining.(3y (BThe goal of the project was to add more statistical rigor to the fairly ad hoc area of data mining on graphs. Our goal was to develop better algorithms and better ways to evaluate algorithm quality. We concetrated on algorithms for community detection, approximate pattern matching, and graph similarity measures. Approximate pattern matching involves finding an instance of a relatively small pattern, expressed with tolerance, in a large graph of data observed with uncertainty. This report gathers the abstracts and references for the eight refereed publications that have appeared as part of this work. We then archive three pieces of research that have not yet been published. The first is theoretical and experimental evidence that a popular statistical measure for comparison of community assignments favors over-resolved communities over approximations to a ground truth. The second are statistically motivated methods for measuring the quality of an approximate match of a small pattern in a large graph. The third is a new probabilistic random graph model. Statisticians favor these models for graph analysis. The new local structure graph model overcomes some of the issues with popular models such as exponential random graph models and latent variable models.

  14. Determining Semantically Related Significant Genes.

    Science.gov (United States)

    Taha, Kamal

    2014-01-01

    GO relation embodies some aspects of existence dependency. If GO term xis existence-dependent on GO term y, the presence of y implies the presence of x. Therefore, the genes annotated with the function of the GO term y are usually functionally and semantically related to the genes annotated with the function of the GO term x. A large number of gene set enrichment analysis methods have been developed in recent years for analyzing gene sets enrichment. However, most of these methods overlook the structural dependencies between GO terms in GO graph by not considering the concept of existence dependency. We propose in this paper a biological search engine called RSGSearch that identifies enriched sets of genes annotated with different functions using the concept of existence dependency. We observe that GO term xcannot be existence-dependent on GO term y, if x- and y- have the same specificity (biological characteristics). After encoding into a numeric format the contributions of GO terms annotating target genes to the semantics of their lowest common ancestors (LCAs), RSGSearch uses microarray experiment to identify the most significant LCA that annotates the result genes. We evaluated RSGSearch experimentally and compared it with five gene set enrichment systems. Results showed marked improvement.

  15. Efectividad de la tecnología Safetac® en la disminución del dolor asociado a las heridas: un factor significativo en la demora de la cicatrización y en el incremento en los costes Effectiveness of Safetac® technology for reducing wound-related pain: a significant factor in delayed healing and increased treatment costs

    Directory of Open Access Journals (Sweden)

    Richard White

    2009-09-01

    Full Text Available El dolor es una experiencia común en las personas con heridas tanto agudas como crónicas. El dolor relacionado con las heridas puede ser intenso, afectar adversamente al funcionamiento físico, prolongar el tiempo de cicatrización, causar aflicción psicológica y reducir la calidad de vida del paciente. Los procedimientos de cambio de apósitos son, a menudo, el aspecto más doloroso del cuidado de las heridas. Se sabe que el cambio de algunos apósitos adhesivos y secos causa traumatismo y dolor. La prevención/minimización de estos efectos debería ser un objetivo clave en la provisión del cuidado de las heridas, si bien no lo es siempre. Muchos clínicos parecen ignorar todavía el dolor relacionado con las heridas, el efecto perjudicial que puede tener en la cicatrización y los remedios disponibles. Además, existen también serias implicaciones en relación con el coste que deben considerarse.Pain is a common experience for people with both acute and chronic wounds. Wound-related pain can be intense, adversely affect physical functioning, prolong the time to healing, cause psychological distress and reduce patient quality of life. Dressing change procedures are often the most painful aspect of wound care. The removal of some adhesive dressings and dry dressings are known to cause trauma and pain. The prevention / minimisation of these unwanted effects should be a key objective in the provision of wound care, but this is not always so. Many clinicians remain unaware of wound-related pain, the detrimental effect that it can have on healing, and the available remedies. There are also significant cost implications to consider.

  16. [Health significance of inhaled particles].

    Science.gov (United States)

    Gillissen, A; Gessner, C; Hammerschmidt, S; Hoheisel, G; Wirtz, H

    2006-03-24

    Particulates refer to particles, dust, dirt, soot and aerosol mists that has suspended in the surrounding air. They may consist of solids of various forms including fibres or liquids. Long term exposure to silicon dioxide containing dusts (crystalline silica: quartz, tridymite, cristobalite, coesite, stishovite) may cause pneumoconiosis in the form of acute or/either chronic silicosis. Asbestos refers to a divers family of crystalline hydrated fibrous siliates typically exhibiting a greater tha 3:1 length ot diameter ratio. It is subdivided into serpentine (Chrysotile) and amphibole (crocidolite, amosite, anthophyllite, tremolite, actinolite). Exposure to asbestos fibres may cause lung fibrosis and promote cancer of the lung or the pleura. Besides the induction of malignant diseases dust exposure may result in obstructive as well as restrictive lung diseases which may be compensate in case of the recognition as a occupational diseases. Other occupational exposures leading to pneumoconiosis are caused be talc, or metals including aluminium containing dusts. Also the group of man-made mineral (MMMFs) or vitreous fibres (MMVFs), including glass wool, rock wool, slag wool, glass filaments, microfibres, refractory ceramic fibres are bioactive under certain experimental conditions. Although it has been shown that MMMFs may cause malignancies when injected intraperitoneally in high quantities in rodents, inhalation trials and human studies could not reproduce these results in the same precision. Fine particles (particulate matter = PM) comprise one of the most widespread and harmful air pollutants in the industrialized world. PM may cause worsening of asthma and other respiratory diseases, reduce lung function development in children, potentially increased the risk of premature death in the elderly and enhance mortality from cardiac diseases. Because of the small size PM2.5 is seen to be even more hazardous than PM10.

  17. [Stress echocardiography: development and significance].

    Science.gov (United States)

    Attenhofer, C; Ritter, M; Jenni, R

    1994-08-27

    Exercise electrocardiography is still the primary method used in the non-invasive assessment of coronary artery disease. Stress echocardiography is now being increasingly used as a more sensitive adjunct technique to assess ischemia. Ischemia provoked by stress can induce reversible wall motion abnormalities which are disclosed by cross-sectional 2-dimensional echocardiography and standard projections. The types of stress used are physical exercise (bicycle, treadmill), atrial pacing or pharmacologic stimulation. In the latter, the catecholamine dobutamine has emerged as preferable to the vasodilators dipyridamole and adenosine. The diagnostic accuracy of dobutamine stress echocardiography is comparable to that of bicycle or treadmill exercise echocardiography, but dobutamine stress echocardiography is technically simpler and can be performed in patients unable to exercise. Its sensitivity in diagnosing ischemic or viable myocardium is comparable to that of nuclear methods, MRI or PET. In contrast to nuclear methods, stress echocardiography is however free of radiation. In the assessment of patients with coronary artery disease, stress echocardiography has been shown to be valuable for diagnosis, preoperative risk stratification and determination of prognosis. Furthermore, low dose dobutamine echocardiography can be used to detect viable myocardium. Despite these very promising aspects of the method, there are recognized disadvantages and limitations: stress echocardiography is very time-consuming and operator-dependent; its sensitivity correlates strongly with the number of studies performed; analysis of wall motion is performed qualitatively on a purely subjective level, and hence lacks the objectivity of a quantitative approach. These factors emphasize the need for intensive research to render stress echocardiographic analysis more objective. Automatic boundary detection of left ventricular endocardium, color-Doppler-based tissue imaging and three

  18. Different instructions during the ten-meter walking test determined significant increases in maximum gait speed in individuals with chronic hemiparesis Diferentes instruções durante teste de velocidade de marcha determinam aumento significativo na velocidade máxima de indivíduos com hemiparesia crônica

    Directory of Open Access Journals (Sweden)

    Lucas R. Nascimento

    2012-04-01

    Full Text Available OBJECTIVE: To evaluate the effects of different instructions for the assessment of maximum walking speed during the ten-meter walking test with chronic stroke subjects. METHODS: Participants were instructed to walk under four experimental conditions: (1 comfortable speed, (2 maximum speed (simple verbal command, (3 maximum speed (modified verbal command-"catch a bus" and (4 maximum speed (verbal command + demonstration. Participants walked three times in each condition and the mean time to cover the intermediate 10 meters of a 14-meter corridor was registered to calculate the gait speed (m/s. Repeated-measures ANOVAs, followed by planned contrasts, were employed to investigate differences between the conditions (α=5%. Means, standard deviations and 95% confidence intervals (CI were calculated. RESULTS: The mean values for the four conditions were: (1 0.74m/s; (2 0.85 m/s; (3 0.93 m/s; (4 0.92 m/s, respectively, with significant differences between the conditions (F=40.9; pOBJETIVO: Avaliar os efeitos de diferentes instruções para avaliação da velocidade de marcha máxima de indivíduos hemiparéticos durante o teste de caminhada de 10 metros. MÉTODOS: Os indivíduos deambularam em quatro condições experimentais: (1 velocidade habitual, (2 velocidade máxima (comando verbal simples, (3 velocidade máxima (comando verbal modificado: pegar ônibus, (4 velocidade máxima (comando verbal + demonstração. Solicitou-se a cada participante que deambulasse três vezes em cada condição, e a média do tempo necessário para percorrer os 10 metros intermediários de um corredor de 14 metros foi utilizada para cálculo da velocidade (m/s. A ANOVA de medidas repetidas, com contrastes pré-planejados, foi utilizada para comparação dos dados (α=5%, sendo apresentados valores de média, desvio-padrão e intervalos de confiança (IC de 95%. RESULTADOS: As médias de velocidade para as quatro condições foram: (1 0,74m/s; (2 0,85m/s; (3 0,93m/s; (4

  19. The feature and significance of increased concentration of SP- A and TNF-α in BALF of early stage pneumoconiosis%早期煤工尘肺支气管肺泡灌洗液中SP-A 及TNF-α含量的变化

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    The increasing concentrations of SP-A and T NF-α in BALF may be effective markers for diagnosing coal dust exposure.

  20. 隐球菌性脑膜炎患者中Th17细胞相关细胞因子的高表达及其临床意义%The increased serum Th17 related cytokine concentration in patients with cryptococcal meningitis and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    黄元兰; 康敏荣; 胡志德; 闫伟; 邓安梅

    2015-01-01

    patients with poor prognosis factors ,including higher cerebrospinal fluid protein level and cryptococcal antigen titer ,lower cerebrospinal fluid glucose concentration and increased cerebrospinal fluid open pressure .Conclusion IL‐17A and IL‐22 were involved in the pathogenesis of cryptococcal meningitis and may be a potential prognosis biomarker for cryptococcal meningitis.

  1. Astrobiological Significance of Microbial Extremophiles

    Science.gov (United States)

    Pikuta, Elena V.; Hoover, Richard B.

    2007-01-01

    The microflora of the cryosphere of planet Earth provides the best analogs for life forms that might be found in the permafrost or polar ice caps of Mars, near the surface of the cometary nuclei, or in the liquid water beneath and the ice crusts of icy moons of Jupiter and Saturn. The importance of study alkaliphilic microorganisms for astrobiology was enhanced by the findings of abundant carbonates and carbonate globules rimmed with possibly biogenic magnetites in association with the putative microfossils in the ALH84001 meteorite. Although the ALH84001 "nanofossils" were to small and simple to be unambiguously recognized as biogenic, they stimulated Astrobiology research and studies of microbial extremophiles and biomarkers in ancient rocks and meteorites. Recent studies of CI and CM carbonaceous meteorites have resulted in the detection of the well-preserved mineralized remains of coccoidal and filamentous microorganisms in cyanobacterial mats. Energy Dispersive X-ray Analysis has shown anomalous biogenic element ratios clearly indicating they are not recent biological contaminants. This paper reviews microbial extremophiles in context of their significance to Astrobiology. The study of halophilic microorganisms was started from work with saline soils and lakes, and one of the record of good growth for Haloferax mediterranei was shown at 30 percent NaC1. Although alkali-tolerant nitrifying bacteria had previously been reported, the first described alkaliphilic microorganism was the bacterium Streptococcus faecalis. Halophilic and alkaliphilic forms are relevant to conditions that might be found in closed impact basins and craters on Mars filled with evaporite deposits. The first obligately acidophilic bacterium described was Acidithiobacillus ferrooxydans (formally Thiobacillus ferrooxidans). Later thermophilic lithotrophic acidophiles were found, and the hyperacidophilic moderately thermophilic species of the genus Picrophilus were found to grow at negative p

  2. Gastric siderosis: patterns and significance.

    Science.gov (United States)

    Marginean, Esmeralda C; Bennick, Michael; Cyczk, Jan; Robert, Marie E; Jain, Dhanpat

    2006-04-01

    Recently, we encountered 2 cases of diffuse iron deposition in gastric antral and fundic glandular epithelium, which in 1 patient eventually led to the diagnosis of hemochromatosis. Gastric mucosal siderosis (GS) has previously been described in hemochromatosis patients, alcoholics, and in association with iron medications. However, the prevalence of various patterns of iron deposition in the gastric mucosa and their clinical significance have not been studied in detail. The 2 index cases mentioned above and 500 additional consecutive gastric biopsies examined over a period of 8 months at our institution were stained for iron by the Prussian blue method. In addition, all patients with genetic hemochromatosis diagnosed by liver biopsy in our department between 1998 and 2003 who also had gastric biopsies were identified from the surgical pathology files and included in the study (n = 3). The location of iron deposition [stromal cells (endothelium, fibroblasts, macrophages), glandular epithelium, or extracellular] was recorded and subjectively graded as 1+ to 3+ according to the severity of deposition within the mucosa. Relevant histologic changes (inflammation, presence of H. pylori, ulceration) and clinical features were reviewed. Three patterns of GS were identified: A) "nonspecific GS" with predominant iron deposition in the stromal cells including macrophages, and focally in epithelium; B) "iron-pill gastritis" with often mild gastritis and reactive gastropathy type changes, and mostly extracellular deposition with focal stromal cells and epithelial deposition; and C) predominant deposition in antral and fundic glandular epithelium. Of the 500 cases studied, a total of 18 (3.6%) cases were found to have GS. Of these 18 cases, 11 (2.2%) showed pattern A, 4 (0.8%) showed pattern B, and 3 (0.6%) showed pattern C. The GS in patterns A and B was always focal or patchy (1+ to 2+), whereas in pattern C it was generally diffuse and strong (2+ to 3+). A history of oral

  3. Innovative trend significance test and applications

    Science.gov (United States)

    Şen, Zekai

    2017-02-01

    Hydro-climatological time series might embed characteristics of past changes concerning climate variability in terms of shifts, cyclic fluctuations, and more significantly in the form of trends. Identification of such features from the available records is one of the prime tasks of hydrologists, climatologists, applied statisticians, or experts in related topics. Although there are different trend identification and significance tests in the literature, they require restrictive assumptions, which may not be existent in the structure of hydro-climatological time series. In this paper, a method is suggested with statistical significance test for trend identification in an innovative manner. This method has non-parametric basis without any restrictive assumption, and its application is rather simple with the concept of sub-series comparisons that are extracted from the main time series. The method provides privilege for selection of sub-temporal half periods for the comparison and, finally, generates trend on objective and quantitative manners. The necessary statistical equations are derived for innovative trend identification and statistical significance test application. The application of the proposed methodology is suggested for three time series from different parts of the world including Southern New Jersey annual temperature, Danube River annual discharge, and Tigris River Diyarbakir meteorology station annual total rainfall records. Each record has significant trend with increasing type in the New Jersey case, whereas in other two cases, decreasing trends exist.

  4. Meaning reconstruction in bereavement: sense and significance.

    Science.gov (United States)

    Hibberd, Rachel

    2013-08-01

    Recently there has been growing empirical and theoretical attention to the role of meaning in grief along with increased recognition of the need for more sophisticated definitions of meaning. The present article highlights philosophical issues inherent in the study of meaning and grief reviews the place of meaning in current theories of grief and provides a brief overview of the ways that meaning has been operationalized by grief researchers, including sense-making, benefit finding, identity change, and purpose in life. It is argued that, in our focus on the ways mourners make sense of loss, we have neglected an important aspect of meaning: life significance. Life significance is the felt perception that some aspect of one's life experience "matters." The construct is explored as a potentially important outcome of bereavement; mourners may lose life significance along with their lost loved one, or they may develop new avenues to life significance as they confront mortality and rebuild shattered worldviews. Related literature, such as appreciation of life as a facet of posttraumatic growth, is surveyed for clues as to the role of life significance in grief. Suggestions for future study are offered.

  5. A Low-Technology Strategy for Increasing Engagement of Students with Autism and Significant Learning Needs

    Science.gov (United States)

    Carnahan, Christi; Basham, James; Musti-Rao, Shobana

    2009-01-01

    Active engagement is critical to promote learning for students with autism. Although evidence-based strategies exist for promoting engagement for individual students with autism, there are few strategies designed for use with small groups. This study used an ABCAC design to assess the effects of a low-technology use strategy, namely interactive…

  6. Doses and risks from uranium are not increased significantly by interactions with natural background photon radiation.

    Science.gov (United States)

    Tanner, R J; Eakins, J S; Jansen, J T M; Harrison, J D

    2012-08-01

    The impact of depleted uranium (DU) on human health has been the subject of much conjecture. Both the chemical and radiological aspects of its behaviour in the human body have previously been investigated in detail, with the radiological impact being assumed to be linked to the alpha decay of uranium. More recently, it has been proposed that the accumulation in tissue of high-Z materials, such as DU, may give rise to enhanced local energy deposition in the presence of natural background photon radiation due to the high photoelectric interaction cross sections of high-Z atoms. It is speculated that, in addition to producing short-range photoelectrons, these events will be followed by intense Auger and Coster-Kronig electron emission, thereby causing levels of cell damage that are unaccounted for in conventional models of radiological risk. In this study, the physical and biological bases of these claims are investigated. The potential magnitudes of any effect are evaluated and discussed, and compared with the risks from other radiological or chemical hazards. Monte Carlo calculations are performed to estimate likely energy depositions due to the presence of uranium in human tissues in photon fields: whole body doses, organ doses in anthropomorphic phantoms and nano-/micro-dosimetric scenarios are each considered. The proposal is shown generally to be based on sound physics, but overall the impact on human health is expected to be negligible.

  7. Creating knowledge structures in the pharmaceutical industry: the increasing significance of virtual organisation.

    Science.gov (United States)

    Salazar, A; Howells, J

    2000-01-01

    This paper explores the specific trend and challenges facing the pharmaceutical industry regarding the exploitation of Internet e-commerce technology and virtual organisation to develop and maintain competitive advantage. There are two important facets of the current trend. One is the rapid development of a complex network of alliances between the established pharmaceutical companies and the specialised biotechnology company start-ups. The other is the rapid growth of internet e-commerce companies dedicated to developing specialised technological platforms for acquiring and selling genetic and biochemical knowledge. The underlying challenge is how big pharmaceutical companies can emulate some of the innovation processes of smaller biotechnology company start-ups, and how they can appropriate and applied new technological knowledge on the development of new drugs. Pharmaceutical companies in order to retain competitive advantage need to continuously monitor all aspects of knowledge management with regard to the R&D and manufacturing process (as well as customer management and marketing). Technological change and organisational restructuring should be aimed at boosting the capacity of large firms to innovate rapidly.

  8. New U.S. SEC rules on oil and gas disclosure may increase reserves significantly

    Energy Technology Data Exchange (ETDEWEB)

    Schollnberger, Wolfgang E.

    2009-06-15

    The US Security Exchange Commission (SEC) released its updated rules and regulations concerning the disclosure and reporting of oil and gas reserves on Dec 29, 2008; they were published in their final form in the US Federal Register on January 14, 2009. The bipartisan Commission voted unanimously in favor of these new rules, which will go into effect on January 1, 2010. The new rules are important, because they directly or indirectly affect oil and gas companies worldwide. Companies that are registered or operating in the US, or whose shares are traded on US stock exchanges fall directly under these rules. However, in today's global economy the valuation of virtually all oil and gas companies and their ability to raise capital is affected by SEC rules. The author was part of an expert group advising the SEC on formulating the new rules. In this article, a short summary of the most important changes is given and own comments are included. The article follows the wording of the SEC very closely to allow the interested reader to easily refer back to the complete SEC document. (orig.)

  9. SIGNIFICANCE OF BUSINESS QUALITY MANAGEMENT FOR INCREASING COMPETITIVENESS OF SERBIAN ECONOMY

    Directory of Open Access Journals (Sweden)

    Marija Andjelković Pešić

    2012-02-01

    Full Text Available This paper points out some challenges Serbian economy is facing at the beginning of the XXIcentury. Based on the fact that the quality, both in theory and practice, has been promoted as the mostimportant dimension of competitiveness, improvement of quality stands out as the primary task ofenterprises in Serbia. In the last part of the paper there are some results of the research, conductedwith purpose of identifying opportunities for improving the quality of business in Serbian economy.The authors have been trying to establish the connection between Serbia’s competitiveness ratingaccording to research results of confidential institutions (World Bank’s Report on Business, GlobalCompetitiveness Report 2010-2011 and presence of quality management concepts and tools inbusiness practice in Serbia. The intention of the authors is to present the research results and toindicate the possibilities for improving competitiveness of Serbian economy, primarily throughimplementation of modern management concepts and models. The one that is suggested in this paperis the Six Sigma concept.

  10. Meeting increased demand.

    Science.gov (United States)

    Blair, Andrew

    2004-07-01

    New Zealand is a little country with a little economy but with a population that's rapidly aging. New Zealand's population is only 4.3 million people. It's GDP is only $US58.6 billion (2002). New Zealand's expenditure on health as a percentage of GDP is not out of line with that of other countries. As a nation we have been increasing expenditure on health over recent years. In 1990 we spent 7% of GDP on health. In 1995 that increased to 7.65% and is now 8.3%. However, in per capita terms our expenditure on health does not compare so well with like countries. The size of New Zealand's economy is restricting what our country spends on health. Health is already the second highest demand on the New Zealand tax dollar. The tolerance of New Zealanders would be challenged if a Government attempted to increase taxes further to meet the growing demands for expenditure on health, but at the same time the population's expectations are increasing. This is the challenging situation we face today. What lies ahead? Like all industrialized countries New Zealand is facing an aging population. The population below age 40 is decreasing, but it is increasing significantly over that age. 16% of the population is currently aged over 60. By 2051 this proportion will almost double to just over 31%. Coupled with the aging population is increased awareness and expectations, as access to options for treatment and technology becomes readily accessible to the population through such media as the internet. The extent of the impact of the aging population can be clearly represented by focusing on one specialty such as orthopaedics. The New Zealand Orthopaecic Association undertook a study in July 2003 which concluded (among other things) that as a result of the projected aging of the population, over the next 50 years: Musculo-skeletal operations will increase by over 30%. The number of hip replacements will nearly double. The incidence of osteoporosis will increase by a massive 201%. The number

  11. Statistical significance of cis-regulatory modules

    Directory of Open Access Journals (Sweden)

    Smith Andrew D

    2007-01-01

    Full Text Available Abstract Background It is becoming increasingly important for researchers to be able to scan through large genomic regions for transcription factor binding sites or clusters of binding sites forming cis-regulatory modules. Correspondingly, there has been a push to develop algorithms for the rapid detection and assessment of cis-regulatory modules. While various algorithms for this purpose have been introduced, most are not well suited for rapid, genome scale scanning. Results We introduce methods designed for the detection and statistical evaluation of cis-regulatory modules, modeled as either clusters of individual binding sites or as combinations of sites with constrained organization. In order to determine the statistical significance of module sites, we first need a method to determine the statistical significance of single transcription factor binding site matches. We introduce a straightforward method of estimating the statistical significance of single site matches using a database of known promoters to produce data structures that can be used to estimate p-values for binding site matches. We next introduce a technique to calculate the statistical significance of the arrangement of binding sites within a module using a max-gap model. If the module scanned for has defined organizational parameters, the probability of the module is corrected to account for organizational constraints. The statistical significance of single site matches and the architecture of sites within the module can be combined to provide an overall estimation of statistical significance of cis-regulatory module sites. Conclusion The methods introduced in this paper allow for the detection and statistical evaluation of single transcription factor binding sites and cis-regulatory modules. The features described are implemented in the Search Tool for Occurrences of Regulatory Motifs (STORM and MODSTORM software.

  12. Boiling significantly promotes photodegradation of perfluorooctane sulfonate.

    Science.gov (United States)

    Lyu, Xian-Jin; Li, Wen-Wei; Lam, Paul K S; Yu, Han-Qing

    2015-11-01

    The application of photochemical processes for perfluorooctane sulfonate (PFOS) degradation has been limited by a low treatment efficiency. This study reports a significant acceleration of PFOS photodegradation under boiling condition compared with the non-boiling control. The PFOS decomposition rate increased with the increasing boiling intensity, but declined at a higher hydronium level or under oxygenation. These results suggest that the boiling state of solution resulted in higher effective concentrations of reactants at the gas-liquid interface and enhanced the interfacial mass transfer, thereby accelerating the PFOS decomposition. This study broadens our knowledge of PFOS photodegradation process and may have implications for development of efficient photodegradation technologies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Obesity increases histone H3 lysine 9 and 18 acetylation at Tnfa and Ccl2 genes in mouse liver.

    Science.gov (United States)

    Mikula, Michal; Majewska, Aneta; Ledwon, Joanna Karolina; Dzwonek, Artur; Ostrowski, Jerzy

    2014-12-01

    Obesity contributes to the development of non-alcoholic fatty liver disease (NAFLD), which is characterized by the upregulated expression of two key inflammatory mediators: tumor necrosis factor (Tnfa) and monocyte chemotactic protein 1 (Mcp1; also known as Ccl2). However, the chromatin make-up at these genes in the liver in obese individuals has not been explored. In this study, to identify obesity-mediated epigenetic changes at Tnfa and Ccl2, we used a murine model of obesity induced by a high-fat diet (HFD) and hyperphagic (ob/ob) mice. Chromatin immunoprecipitation (ChIP) assay was used to determine the abundance of permissive histone marks, namely histone H3 lysine 9 and 18 acetylation (H3K9/K18Ac), H3 lysine 4 trimethylation (H3K4me3) and H3 lysine 36 trimethylation (H3K36me3), in conjunction with polymerase 2 RNA (Pol2) and nuclear factor (Nf)-κB recruitment in the liver. Additionally, to correlate the liver tissue-derived ChIP measurements with a robust in vitro transcriptional response at the Tnfa and Ccl2 genes, we used lipopolysaccharide (LPS) treatment to induce an inflammatory response in Hepa1-6 cells, a cell line derived from murine hepatocytes. ChIP revealed increased H3K9/K18Ac at Tnfa and Ccl2 in the obese mice, although the differences were only statistically significant for Tnfa (pgenes in the obese mice. By contrast, the acute treatment of Hepa1-6 cells with LPS significantly increased the H3K9/K18Ac marks, as well as Pol2 and Nf-κB recruitment at both genes, while the levels of H3K4me3 and H3K36me3 marks remained unaltered. These results demonstrate that increased Tnfa and Ccl2 expression in fatty liver at the chromatin level corresponds to changes in the level of histone H3 acetylation.

  14. Nuosėdų formavimosi sistemose CuSO4 – K4P2O7 – H2O ir CuSO4 – (NH4)4P2O7 – H2O mechanizmo tyrimas

    OpenAIRE

    Timofejeva, Oksana

    2009-01-01

    Disertaciniame darbe naudojant IR-spektrometrijos, rentgenofazinės analizės, atominės absorbcinės spektroskopijos, kolorimetrijos analizės metodus buvo ištirta sistemose CuSO4 – K4P2O7 – H2O ir CuSO4 – (NH4)4P2O7 – H2O susidarančių mažai tirpių junginių sudėtis, jų susidarymo dėsningumai ir vykstančios reakcijos, įvairių veiksnių įtaka nuosėdų sudėčiai ir struktūrai. Nustatyta, kad sistemoje CuSO4 – K4P2O7 – H2O, be jau žinomų mažai tirpių junginių (paprastosios druskos Cu2P2O7 5H2O ir dvigub...

  15. Increasing Childhood Influenza Vaccination

    Science.gov (United States)

    Nowalk, Mary Patricia; Lin, Chyongchiou J.; Hannibal, Kristin; Reis, Evelyn C.; Gallik, Gregory; Moehling, Krissy K.; Huang, Hsin-Hui; Allred, Norma J.; Wolfson, David H.; Zimmerman, Richard K.

    2014-01-01

    Background Since the 2008 inception of universal childhood influenza vaccination, national rates have risen more dramatically among younger children than older children and reported rates across racial/ethnic groups are inconsistent. Interventions may be needed to address age and racial disparities to achieve the recommended childhood influenza vaccination target of 70%. Purpose To evaluate an intervention to increase childhood influenza vaccination across age and racial groups. Methods In 2011–2012, 20 primary care practices treating children were randomly assigned to Intervention and Control arms of a cluster randomized controlled trial to increase childhood influenza vaccination uptake using a toolkit and other strategies including early delivery of donated vaccine, in-service staff meetings, and publicity. Results The average vaccination differences from pre-intervention to the intervention year were significantly larger in the Intervention arm (n=10 practices) than the Control arm (n=10 practices), for children aged 2–8 years (10.2 percentage points (pct pts) Intervention vs 3.6 pct pts Control) and 9–18 years (11.1 pct pts Intervention vs 4.3 pct pts Control, p<0.05), for non-white children (16.7 pct pts Intervention vs 4.6 pct pts Control, p<0.001), and overall (9.9 pct pts Intervention vs 4.2 pct pts Control, p<0.01). In multi-level modeling that accounted for person- and practice-level variables and the interactions among age, race and intervention, the likelihood of vaccination increased with younger age group (6–23 months), white race, commercial insurance, the practice’s pre-intervention vaccination rate, and being in the Intervention arm. Estimates of the interaction terms indicated that the intervention increased the likelihood of vaccination for non-white children in all age groups and white children aged 9–18 years. Conclusions A multi-strategy intervention that includes a practice improvement toolkit can significantly improve influenza

  16. New Math Curriculum Formula for Success: Grades K-4

    Science.gov (United States)

    Curriculum Review, 2007

    2007-01-01

    This article describes Everyday Mathematics, a new math education curriculum targeted to kindergarten, first grade, and second grade students in Holland. It will be introduced to third and fourth grades in 2008. The curriculum helps prepare pupils for standardized tests; allows for students to work at their own rate; involves parents in helping…

  17. History from K-4: What Can We Really Do?

    Science.gov (United States)

    Klee, Mary Beth

    1998-01-01

    Outlines the characteristics of a good history program for kindergarten through grade four, analyzing the Massachusetts History and Social Science Curriculum Framework and the Core Knowledge Sequence as they apply to elementary instruction. Also describes and evaluates principles of teaching history to young children. (Author/SLD)

  18. Yohimbine increases human salivary secretion.

    Science.gov (United States)

    Chatelut, E; Rispail, Y; Berlan, M; Montastruc, J L

    1989-01-01

    The effect of oral yohimbine (14 mg) on salivary secretion was evaluated in healthy volunteers. Yohimbine significantly increased salivary secretion when compared with placebo. This effect was significant from 60 min until 180 min after administration under our experimental conditions. Yohimbine (or alpha 2-adrenoceptor blocking agents) could have a potential interest in the treatment of dry mouths. PMID:2789932

  19. The origins and significance of contemporary terrorism

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, B. [Calgary Univ., AB (Canada)

    2002-07-01

    Terrorism has been the subject of many presidential and prime ministerial statements over the years. Sixteen weeks before the attacks on the World Trade Centre and the Pentagon, the American Secretary of State, referred to a report that indicated an 8 per cent increase in international terrorist attacks during year 2000 and stated that terrorism shows the dark side of globalization. Of the 423 recorded attacks, 200 were directed against the United States. This paper emphasizes three points to understand the significance of terrorism. First, it is necessary to understand the context within which terrorist acts are carried out, namely the modern world in its spiritual and its material dimensions. It is also necessary to understand the direction and trajectory of recent trends in terrorism and what can be done to stop it. 97 refs.

  20. [Pathogenesis and significance of diabetic dyslipidemia].

    Science.gov (United States)

    Zeman, M; Zák, A

    2004-01-01

    Patients with type 2 diabetes mellitus are at the higher risk of development of on arteriosclerosis based cardiovascular diseases. Epidemiological studies have shown that diabetic dislipidemia with hypertriglyceridemia, presence of small dense LDL subfraction, low concentration of HDL-cholesterol and increased postprandial lipemia can represent a serious threat. Several studies have found significant decrease of cardiovascular morbidity and mortality after a treatment of diabetic dislipidemia, namely by statins and fibrates. Contemporary therapeutic algorhithms of European and American professional societies for the hyperlipidemia treatment classify diabetes mellitus as an equivalent of already developed complication of atherosclerosis. Our article presents pathophysiology of the diabetic dislipidemia, recommended target values of pasma lipids in diabetic patients and an overview of present possibilities of pharmacotherapy of the diabetic dislipidemia.

  1. Biotechnological significance of toxic marine dinoflagellates.

    Science.gov (United States)

    Camacho, F Garcia; Rodríguez, J Gallardo; Mirón, A Sánchez; García, M C Cerón; Belarbi, E H; Chisti, Y; Grima, E Molina

    2007-01-01

    Dinoflagellates are microalgae that are associated with the production of many marine toxins. These toxins poison fish, other wildlife and humans. Dinoflagellate-associated human poisonings include paralytic shellfish poisoning, diarrhetic shellfish poisoning, neurotoxic shellfish poisoning, and ciguatera fish poisoning. Dinoflagellate toxins and bioactives are of increasing interest because of their commercial impact, influence on safety of seafood, and potential medical and other applications. This review discusses biotechnological methods of identifying toxic dinoflagellates and detecting their toxins. Potential applications of the toxins are discussed. A lack of sufficient quantities of toxins for investigational purposes remains a significant limitation. Producing quantities of dinoflagellate bioactives requires an ability to mass culture them. Considerations relating to bioreactor culture of generally fragile and slow-growing dinoflagellates are discussed. Production and processing of dinoflagellates to extract bioactives, require attention to biosafety considerations as outlined in this review.

  2. Increasing diversity in radiologic technology.

    Science.gov (United States)

    Carwile, Laura

    2003-01-01

    Diversity is increasingly important in the radiologic technology workplace. For significant changes to occur in work force diversity, educators must first recruit and retain students from a wide variety of backgrounds. This article examines personality, race and gender as factors affecting career choice and how educators can use these factors to increase diversity in their programs. An overview of the ASRT's efforts to improve diversity within the profession is presented, along with suggestions for developing effective recruitment and retention plans to increase diversity.

  3. The public health significance of Trichuris trichiura.

    Science.gov (United States)

    Stephenson, L S; Holland, C V; Cooper, E S

    2000-01-01

    An estimated 1049 million persons harbour T. trichiura, including 114 million preschool-age children and 233 million school-age children. The prevalence of T. trichiura is high and may reach 95% in children in many parts of the world where protein energy malnutrition and anaemias are also prevalent and access to medical care and educational opportunities is often limited. The Trichuris dysentery syndrome (TDS) associated with heavy T. trichiura, which includes chronic dysentery, rectal prolapse, anaemia, poor growth, and clubbing of the fingers constitutes an important public health problem, as do lighter but still heavy infections, even if not strictly TDS, especially in children. The profound growth stunting in TDS can be reversed by repeated treatment for the infection and, initially, oral iron. However findings from Jamaica strongly suggest that the significant developmental and cognitive deficits seen are unlikely to disappear without increasing the positive psychological stimulation in the child's environment. The severe stunting in TDS now appears likely to be a reaction at least in part to a chronic inflammatory response and concomitant decreases in plasma insulin-like growth factor-1 (IGF-1), increases in tumor necrosis factor-alpha (TNF-alpha) in the lamina propria of the colonic mucosa and peripheral blood (which likely decrease appetite and intake of all nutrients) and a decrease in collagen synthesis. Improvements in cognitive performance have been found after treatment for relatively heavy infections (without chronic dysentery) in school-going children; it is unclear precisely how much T. trichiura interferes with children's ability to access educational opportunities, but treatment of infections whenever possible is obviously sensible. The blood loss that can occur in T. trichiura infection is likely to contribute to anaemia, particularly if the child also harbours hookworm, malaria and/or has a low intake of dietary iron. Community control is

  4. Vitronectin significantly influences prognosis in osteosarcoma.

    Science.gov (United States)

    Shi, Kai; Lan, Rui-Long; Tao, Xuan; Wu, Chao-Yang; Hong, Hai-Feng; Lin, Jian-Hua

    2015-01-01

    Vitronectin (Vn), a multifunctional adhesive protein, is found in association with tumor progression, angiogenesis and metastasis in a variety of (human) tumors. But no studies concerning its correlation to osteosarcoma prognosis were found. Hence, we aimed to investigate the prognostic value of Vitronectin (Vn) in osteosarcoma. Here, we studied the expression of VN in the tumor tissues from 67 patients with osteosarcoma and 20 patients with osteochondroma using immunohistochemistry and estimated the effects of VN expression in osteosarcoma on progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier curve and COX proportional hazards regression model. Increased expression of VN in osteosarcoma tissue compared to no VN expression in osteochondroma tissue was shown in immunohistochemical assay. No associations were observed between VN expression and osteosarcoma patients' gender (P = 0.675), age (P = 0.813), tumor size (P = 0.436), histologic subtype (P = 0.0.543) or tumor location (P = 0.456). Univariate survival analysis demonstrated significant correlations of high VN expression with shorter PFS (P = 0.002) and OS (P = 0.001); multivariate survival analysis revealed high VN expression as a significant independent prognostic indicator for shorter PFS (HR 2.788, P = 0.003) and OS (HR2.817, P = 0.003). In conclusion, the high expression of VN in tumor cells independently indicated poor clinical prognosis in patients with osteosarcoma, other than large tumor size and non-neoadjuvant chemoradiotherapy, suggesting that VN may serve as a potential therapeutic target in osteosarcoma.

  5. Increasing Possibilities of Nanosuspension

    Directory of Open Access Journals (Sweden)

    Kumar Bishwajit Sutradhar

    2013-01-01

    Full Text Available Nowadays, a very large proportion of new drug candidates emerging from drug discovery programmes are water insoluble and thus poorly bioavailable. To avoid this problem, nanotechnology for drug delivery has gained much interest as a way to improve the solubility problems. Nano refers to particles size range of 1–1000 nm. The reduction of drug particles into the submicron range leads to a significant increase in the dissolution rate and therefore enhances bioavailability. Nanosuspensions are part of nanotechnology. This interacts with the body at subcellular (i.e., molecular scales with a high degree of specificity and can be potentially translated into targeted cellular and tissue-specific clinical applications designed to achieve maximal therapeutic efficacy with minimal side effects. Production of drugs as nanosuspensions can be developed for drug delivery systems as an oral formulation and nonoral administration. Here, this review describes the methods of pharmaceutical nanosuspension production including advantages and disadvantages, potential benefits, characterization tests, and pharmaceutical applications in drug delivery.

  6. THE SIGNIFICANCE OF STRESS HORMONES IN PSORIASIS

    Directory of Open Access Journals (Sweden)

    F Z Zangeneh

    2008-12-01

    Full Text Available "nPsoriasis is a chronic, non-contagious skin condition characterized by inflamed and scaly lesions of skin. Whilst the pathogenesis of psoriasis is not known, psychological stress has been implicated as a potential trigger in the onset and exacerbation of the condition. Psychiatric and psychological factors play an important role in at least 30% of dermatologic disorder and pathophysiologic link between psychological stress (PS and disease expression remains unclear. Recent studies demonstrated PS-induced alterations in permeability barrier homeostasis, mediated by increased endogenous glucocorticoids. As activation of the hypothalamic pituitary adrenal axis (HPA is critical to a successful stress response, we investigated this in patients with psoriasis. This study was performed on 55 patients (40 females and 15 males visited our clinic for treatment of psoriasis in pharmacology department. We measured the rate of activation of HPA by hormonal changes. These patients displayed higher fasting blood sugar (FBS, epinephrine (Ep, adrenocorticotropin hormone (ACTH, aldosterone, prolactin, growth hormone and estradiol hormones value but diminished cortisol and corticotropin releasing factor (CRF. These results show that HPA and psychoneuroendocrine hormones have a significant role in psoriasis.

  7. Traditional Indian spices and their health significance.

    Science.gov (United States)

    Krishnaswamy, Kamala

    2008-01-01

    India has been recognized all over the world for spices and medicinal plants. Both exhibit a wide range of physiological and pharmacological properties. Current biomedical efforts are focused on their scientific merits, to provide science-based evidence for the traditional uses and to develop either functional foods or nutraceuticals. The Indian traditional medical systems use turmeric for wound healing, rheumatic disorders, gastrointestinal symptoms, deworming, rhinitis and as a cosmetic. Studies in India have explored its anti-inflammatory, cholekinetic and anti-oxidant potentials with the recent investigations focusing on its preventive effect on precarcinogenic, anti-inflammatory and anti atherosclerotic effects in biological systems both under in vitro and in vivo conditions in animals and humans. Both turmeric and curcumin were found to increase detoxifying enzymes, prevent DNA damage, improve DNA repair, decrease mutations and tumour formation and exhibit antioxidative potential in animals. Limited clinical studies suggest that turmeric can significantly impact excretion of mutagens in urine in smokers and regress precancerous palatal lesions. It reduces DNA adducts and micronuclei in oral epithelial cells. It prevents formation of nitroso compounds both in vivo and in vitro. It delays induced cataract in diabetes and reduces hyperlipidemia in obese rats. Recently several molecular targets have been identified for therapeutic / preventive effects of turmeric. Fenugreek seeds, a rich source of soluble fiber used in Indian cuisine reduces blood glucose and lipids and can be used as a food adjuvant in diabetes. Similarly garlic, onions, and ginger have been found to modulate favourably the process of carcinogenesis.

  8. Significance of duon mutations in cancer genomes

    Science.gov (United States)

    Yadav, Vinod Kumar; Smith, Kyle S.; Flinders, Colin; Mumenthaler, Shannon M.; de, Subhajyoti

    2016-06-01

    Functional mutations in coding regions not only affect the structure and function of the protein products, but may also modulate their expression in some cases. This class of mutations, recently dubbed “duon mutations” due to their dual roles, can potentially have major impacts on downstream pathways. However their significance in diseases such as cancer remain unclear. In a survey covering 4606 samples from 19 cancer types, and integrating allelic expression, overall mRNA expression, regulatory motif perturbation, and chromatin signatures in one composite index called REDACT score, we identified potential duon mutations. Several such mutations are detected in known cancer genes in multiple cancer types. For instance a potential duon mutation in TP53 is associated with increased expression of the mutant allelic gene copy, thereby possibly amplifying the functional effects on the downstream pathways. Another potential duon mutation in SF3B1 is associated with abnormal splicing and changes in angiogenesis and matrix degradation related pathways. Our findings emphasize the need to interrogate the mutations in coding regions beyond their obvious effects on protein structures.

  9. Evolutionary significance of ageing in the wild.

    Science.gov (United States)

    Kowald, Axel; Kirkwood, Thomas B L

    2015-11-01

    Human lifespan has risen dramatically over the last 150 years, leading to a significant increase in the fraction of aged people in the population. Until recently it was believed that this contrasted strongly with the situation in wild populations of animals, where the likelihood of encountering demonstrably senescent individuals was believed to be negligible. Over the recent years, however, a series of field studies has appeared that shows ageing can also be observed for many species in the wild. We discuss here the relevance of this finding for the different evolutionary theories of ageing, since it has been claimed that ageing in the wild is incompatible with the so-called non-adaptive (non-programmed) theories, i.e. those in which ageing is presumed not to offer a direct selection benefit. We show that a certain proportion of aged individuals in the population is fully compatible with the antagonistic pleiotropy and the disposable soma theories, while it is difficult to reconcile with the mutation accumulation theory. We also quantify the costs of ageing using life history data from recent field studies and a range of possible metrics. We discuss the merits and problems of the different metrics and also introduce a new metric, yearly death toll, that aims directly at quantifying the deaths caused by the ageing process. Copyright © 2015 Elsevier Inc. All rights reserved.

  10. Phenotypic plasticity: molecular mechanisms and adaptive significance.

    Science.gov (United States)

    Kelly, Scott A; Panhuis, Tami M; Stoehr, Andrew M

    2012-04-01

    Phenotypic plasticity can be broadly defined as the ability of one genotype to produce more than one phenotype when exposed to different environments, as the modification of developmental events by the environment, or as the ability of an individual organism to alter its phenotype in response to changes in environmental conditions. Not surprisingly, the study of phenotypic plasticity is innately interdisciplinary and encompasses aspects of behavior, development, ecology, evolution, genetics, genomics, and multiple physiological systems at various levels of biological organization. From an ecological and evolutionary perspective, phenotypic plasticity may be a powerful means of adaptation and dramatic examples of phenotypic plasticity include predator avoidance, insect wing polymorphisms, the timing of metamorphosis in amphibians, osmoregulation in fishes, and alternative reproductive tactics in male vertebrates. From a human health perspective, documented examples of plasticity most commonly include the results of exercise, training, and/or dieting on human morphology and physiology. Regardless of the discipline, phenotypic plasticity has increasingly become the target of a plethora of investigations with the methodological approaches utilized ranging from the molecular to whole organsimal. In this article, we provide a brief historical outlook on phenotypic plasticity; examine its potential adaptive significance; emphasize recent molecular approaches that provide novel insight into underlying mechanisms, and highlight examples in fishes and insects. Finally, we highlight examples of phenotypic plasticity from a human health perspective and underscore the use of mouse models as a powerful tool in understanding the genetic architecture of phenotypic plasticity.

  11. Effect of increased surface tension and assisted ventilation on /sup 99m/Tc-DTPA clearance

    Energy Technology Data Exchange (ETDEWEB)

    Jefferies, A.L.; Kawano, T.; Mori, S.; Burger, R.

    1988-02-01

    Experiments were performed to determine the effects of conventional mechanical ventilation (CMV) and high-frequency oscillation (HFO) on the clearance of technetium-99m-labeled diethylenetriamine pentaacetate (/sup 99m/Tc-DTPA) from lungs with altered surface tension properties. A submicronic aerosol of /sup 99m/Tc-DTPA was insufflated into the lungs of anesthetized, tracheotomized rabbits before and 1 h after the administration of the aerosolized detergent dioctyl sodium sulfosuccinate (OT). Rabbits were ventilated by one of four methods: 1) spontaneous breathing; 2) CMV at 12 cmH2O mean airway pressure (MAP); 3) HFO at 12 cmH2O MAP; 4) HFO at 16 cmH2O MAP. Administration of OT resulted in decreased arterial PO2 (PaO2), increased lung wet-to-dry weight ratios, and abnormal lung pressure-volume relationships, compatible with increased surface tension. /sup 99m/Tc-DTPA clearance was accelerated after OT in all groups. The post-OT rate of clearance (k) was significantly faster (P less than 0.05) in the CMV at 12 cmH2O MAP (k = 7.57 +/- 0.71%/min (SE)) and HFO at 16 cmH2O MAP (k = 6.92 +/- 0.61%/min) groups than in the spontaneously breathing (k = 4.32 +/- 0.55%/min) and HFO at 12 cmH2O MAP (4.68 +/- 0.63%/min) groups. The clearance curves were biexponential in the former two groups. We conclude that pulmonary clearance of /sup 99m/Tc-DTPA is accelerated in high surface tension pulmonary edema, and this effect is enhanced by both conventional ventilation and HFO at high mean airway pressure.

  12. Assessing statistical significance in causal graphs

    Directory of Open Access Journals (Sweden)

    Chindelevitch Leonid

    2012-02-01

    Full Text Available Abstract Background Causal graphs are an increasingly popular tool for the analysis of biological datasets. In particular, signed causal graphs--directed graphs whose edges additionally have a sign denoting upregulation or downregulation--can be used to model regulatory networks within a cell. Such models allow prediction of downstream effects of regulation of biological entities; conversely, they also enable inference of causative agents behind observed expression changes. However, due to their complex nature, signed causal graph models present special challenges with respect to assessing statistical significance. In this paper we frame and solve two fundamental computational problems that arise in practice when computing appropriate null distributions for hypothesis testing. Results First, we show how to compute a p-value for agreement between observed and model-predicted classifications of gene transcripts as upregulated, downregulated, or neither. Specifically, how likely are the classifications to agree to the same extent under the null distribution of the observed classification being randomized? This problem, which we call "Ternary Dot Product Distribution" owing to its mathematical form, can be viewed as a generalization of Fisher's exact test to ternary variables. We present two computationally efficient algorithms for computing the Ternary Dot Product Distribution and investigate its combinatorial structure analytically and numerically to establish computational complexity bounds. Second, we develop an algorithm for efficiently performing random sampling of causal graphs. This enables p-value computation under a different, equally important null distribution obtained by randomizing the graph topology but keeping fixed its basic structure: connectedness and the positive and negative in- and out-degrees of each vertex. We provide an algorithm for sampling a graph from this distribution uniformly at random. We also highlight theoretical

  13. 儿童期精神分裂症患者的双眼竞争: 意识和潜意识状态下对人际交往信息的认知加工过程%Conclusions: The non-significant increase in the attention children with schizophrenia paid to images depicting interpersonal relationships suggests, but does not prove, that the illness is associated with impairments in the cognitive processing of social

    Institute of Scientific and Technical Information of China (English)

    王美娟; 李春波; 赵金萍; 钱洁; 朱怡康; 杨志; 蒋毅; 王继军; 杜亚松; 翁旭初

    2013-01-01

    Background: Childhood schizophrenia is a severe mental disorder that is believed to affect both conscious and unconscious cognitive functioning, but there have been few studies that have assessed this.Objective: Develop a version of the binocular rivalry test that will assess the conscious and unconscious cognitive processing of interpersonal information and use this test to determine whether or not social cognition is impaired in children with schizophrenia.Methods: Thirty images of three types - with no persons, with 2-3 persons and with 4+ persons - were selected for use in a binocular rivalry test that presented the images both in an interocularly suppressed (unconscious) format and an unsuppressed (conscious) format. Fifteen children under 16 years of age with schizophrenia who had prominent delusional symptoms and 15 healthy children were administered the test. Accuracy rates (in assessing the left or right orientation of a patch presented immediately after the target images) and reaction times were compared between patients and controls.Results: For all types of pictures, the accuracy of patients was less than that of controls, though the differences were only significant in two of the twelve comparisons assessed. Compared to controls, patients showed a non-significant increase in the attention paid to images with people in them compared to images without people in them, both for conscious and unconscious presentations of the images. We did not find any relationship between the severity of psychotic symptoms in the patients and the degree of impairment in the cognitive processing of images. When asked to assess the attributes of the images, patients reported significantly higher levels of happiness depicted in images with 2-3 people than controls.%背景:儿童期精神分裂是一种严重的精神障碍,有理论认为其认知功能无论是意识水平还是潜意识水平都存在异常.但目前尚无针对儿童期精神分裂的潜意识认知功能

  14. Biological significance of soluble IL-2 receptor

    Directory of Open Access Journals (Sweden)

    Calogero Caruso

    1993-01-01

    Full Text Available A NUMBER of receptors for growth factors and differentiation antigens have been found to be secreted or released by cells. Following mononuclear cell (MNC activation and interleukin-2 receptor (IL-2R expression, a soluble form of the Alpha;-chain of IL-2R (sIL-2R is released. The sIL-2R has been shown to be present in the culture supernatants of activated MNCs as well as in normal sera and, in higher amounts, in sera from subjects affected by several diseases including neoplastic, infectious and autoimmune ones, and in sera from transplanted patients suffering allograft rejection. The blood sIL-2R levels depend on the number of producing cells and the number of molecules per cell, so that sIL-2R blood values may represent an index of the number and the functional state of producing cells, both normal and neoplastic. Thus, monitoring of the immune system, mostly T-cells and haematological malignancies might be targets for the measurement of sIL-2R. Since many conditions may influence sIL-2R production, little diagnostic use may result from these measurements. However, since blood sIL-2R levels may correlate with disease progression and/or response to therapy, their measurement may be a useful index of activity and extent of disease. The precise biological role of the soluble form of the IL-2R is still a matter of debate. However, we know that increased sIL-2R levels may be observed in association with several immunological abnormalities and that sIL-2R is able to bind IL-2. It is conceivable then that in these conditions the excess sIL-2R released in vivo by activated lymphoid cells or by neoplastic cells may somehow regulate IL-2-dependent processes. On the other hand, it cannot exclude that sIL-2R is a by-product without biological significance. Finally, it is puzzling that in many conditions in which an increase of blood sIL-2R values has been observed, MNCs display a decreased in vitro capacity to produce sIL-2R. These seemingly contrasting

  15. Effect of increased

    NARCIS (Netherlands)

    Carreira , C.; Heldal, M.; Bratbak, G.

    2013-01-01

    Atmospheric carbon dioxide (CO2) has increased since the pre-industrial period and is predicted to continue to increase throughout the twenty-first century. The ocean is a sink for atmospheric CO2 and increased CO2 concentration will change the carbonate equilibrium of seawater and result in lower c

  16. Increasing Mobility Confidence

    Science.gov (United States)

    ... Español In Your Area NPF Shop Increasing Mobility Confidence To increase your confidence moving, you have to move! Make Text Smaller ... It might seem counterintuitive, but to increase your confidence moving, you have to move! Build physical activity ...

  17. 48 CFR 2110.7003 - Significant events.

    Science.gov (United States)

    2010-10-01

    ... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Significant events. 2110..., AND OTHER PURCHASE DESCRIPTIONS Contract Specifications 2110.7003 Significant events. The contractor is required to inform the contracting officer of all significant events....

  18. Creating Significant Learning Experiences across Disciplines

    Science.gov (United States)

    Levine, Laura E.; Fallahi, Carolyn R.; Nicoll-Senft, Joan M.; Tessier, Jack T.; Watson, Cheryl L.; Wood, Rebecca M.

    2008-01-01

    The purpose of this study was to use Fink's (2003) taxonomy of significant learning to redesign courses and assess student learning. Significant improvements were found across the semester for students in the six courses, but there were differences in which taxa showed improvement in each course. The meta-analysis showed significant, positive…

  19. On combining significances. Some trivial examples

    CERN Document Server

    Krasnikov, N V

    2010-01-01

    For Poisson distribution $Pois(n, \\lambda)$ with $\\lambda \\gg 1$, $n \\gg 1$ we propose to determine significance as $S = \\frac{n_{obs}-\\lambda}{\\sqrt{\\lambda}}$. The significance $S$ coincides up to sign with often used significance. For experiments which measure the same quantities the natural but not unique rule for significance combining is $S_{comb}(S_1, S_2) = \\frac{S_1\\sigma_1+S_2\\sigma_2}{\\sqrt{\\sigma^2_1+\\sigma^2_2}}$, where $\\sigma_1$ and $\\sigma_2$ are variations. We also propose the rule for significances combining for the case with systematic errors.

  20. Development of Quantitative Framework for Event Significance Evaluation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Durk Hun; Kim, Min Chull [Korea Institute of Nuclear Safety, Daejeon (Korea, Republic of); Kim, Inn Seock [ISSA Technology, Maryland (United States)

    2010-10-15

    There is an increasing trend in quantitative evaluation of the safety significance of operational events using Probabilistic Safety Assessment (PSA) technique. An integrated framework for evaluation of event significance has been developed by Korea Institute of Nuclear Safety (KINS), which consists of an assessment hierarchy and a number of matrices. The safety significance of various events, e.g., internal or external initiating events that occurred during at-power or shutdown conditions, can be quantitatively analyzed using this framework, and then, the events rated according to their significance. This paper briefly describes the basic concept of the integrated quantitative framework for evaluation of event significance, focusing on the assessment hierarchy

  1. Increasing Positive Interactive Classroom Behavior.

    Science.gov (United States)

    Kotcher, Elaine; Doremus, Richard R.

    During the spring of 1972 training workshops for 88 elementary and secondary teachers of the Great Neck Public Schools held to examine four hypotheses: 1) workshops in training teachers to observe classroom behavior would significantly increase these same teachers' positive classroom interactive behaviors consisting of teacher, pupil-pupil,…

  2. Studying and Classification of the Most Significant Malicious Software

    CERN Document Server

    Gharibi, Wajeb

    2011-01-01

    As the cost of information processing and Internet accessibility falls, most organizations are becoming increasingly vulnerable to potential cyber threats which its rate has been dramatically increasing every year in recent times. In this paper, we study, discuss and classify the most significant malicious software: viruses, Trojans, worms, adware and pornware which have made step forward in the science of Virology.

  3. Increasingly minimal bias routing

    Energy Technology Data Exchange (ETDEWEB)

    Bataineh, Abdulla; Court, Thomas; Roweth, Duncan

    2017-02-21

    A system and algorithm configured to generate diversity at the traffic source so that packets are uniformly distributed over all of the available paths, but to increase the likelihood of taking a minimal path with each hop the packet takes. This is achieved by configuring routing biases so as to prefer non-minimal paths at the injection point, but increasingly prefer minimal paths as the packet proceeds, referred to herein as Increasing Minimal Bias (IMB).

  4. How do we make sense of significance?

    DEFF Research Database (Denmark)

    Lyhne, Ivar; Kørnøv, Lone

    2013-01-01

    Determination of significance is widely recognised as an important step in environmental assessment (EA) processes. The prescriptive literature and guidance on significance determination is comprehensive within the field of EA, whereas descriptive and explorative studies of how we go about making...... sense, or construct meaning, of actions to determine significance are few. This article makes use of sense-making theory to explore how sense-making among EA researchers and practitioners influence significance determination. Focus is on the situation when persons have their first look at information...... about a strategic choice and as part of this make their initial judgement of significance. An experiment is designed and conducted to investigate how persons make sense of a specific case and determine significance in a screening and scoping context. The experiment indicates patterns in the test persons...

  5. Central Region Regionally Ecological Significant Areas

    Data.gov (United States)

    Minnesota Department of Natural Resources — This is an analysis of regionally significant Terrestrial and Wetland Ecological Areas in the seven county metropolitan area. Individual forest, grassland and...

  6. Regionally Significant Ecological Areas - MLCCS derived 2008

    Data.gov (United States)

    Minnesota Department of Natural Resources — This is an analysis of regionally significant Terrestrial and Wetland Ecological Areas in the seven county metropolitan area. Individual forest, grassland and...

  7. Increasing SLEDed Linac Gradient

    Energy Technology Data Exchange (ETDEWEB)

    Farkas, Zoltan D

    2001-11-08

    This note will show how to increase the SLED [1] gradient by varying Q{sub e}, the external Q of the SLED cavity, by increasing its Q{sub 0} and by increasing the compression ratio. If varying the external Q is to be effective, then the copper losses should be small so that Q{sub 0} >> Q{sub e}. Methods of varying Q{sub e} will be indicated but no experimental data will be presented. If we increase the klystron pulse width from 3.5 to 5 {micro}S and increase Q{sub 0} from the present 100000 to 300000, then the gradient increases by 19% and the beam energy increases from 50 to 60 GeV. This note will also discuss SLED operation at 11424 MHz, the NLC frequency. Without Q{sub e} switching, using SLED at 11424 MHz increases the SLAC gradient from 21 MV/m to 34 MV/m, and at the same repetition rate, uses about 1/5 of rf average power. If we also double the compression ratio, we reach 47 MV/m and over 100 GeV beam energy.

  8. Asymptotic Distributions for Tests of Combined Significance.

    Science.gov (United States)

    Becker, Betsy Jane

    This paper discusses distribution theory and power computations for four common "tests of combined significance." These tests are calculated using one-sided sample probabilities or p values from independent studies (or hypothesis tests), and provide an overall significance level for the series of results. Noncentral asymptotic sampling…

  9. A Differentiated Program: Significant Curriculum Adaptations.

    Science.gov (United States)

    Alonso, Juan A.

    1999-01-01

    This article describes a model for curricular adaptations for gifted students. A distinction is made between non-significant curriculum adaptations that can be easily made by the regular teacher and significant curriculum adaptations that involve deep changes in aims, content, and evaluation criteria. (Contains references.) (DB)

  10. The Vernier Caliper and Significant Figures.

    Science.gov (United States)

    Oberhofer, E. S.

    1985-01-01

    Misconceptions occur because the caliper is often read with the same significant figures as a meter stick; however, the precision of the vernier caliper is greater than the precision of a meter stick. Clarification of scale reading, precision of both tools, and significant figures are discussed. (JN)

  11. Inflammatory stress increases hepatic CD36 translational efficiency via activation of the mTOR signalling pathway.

    Directory of Open Access Journals (Sweden)

    Chuan Wang

    Full Text Available Inflammatory stress is an independent risk factor for the development of non-alcoholic fatty liver disease (NAFLD. Although CD36 is known to facilitate long-chain fatty acid uptake and contributes to NAFLD progression, the mechanisms that link inflammatory stress to hepatic CD36 expression and steatosis remain unclear. As the mammalian target of rapamycin (mTOR signalling pathway is involved in CD36 translational activation, this study was undertaken to investigate whether inflammatory stress enhances hepatic CD36 expression via mTOR signalling pathway and the underlying mechanisms. To induce inflammatory stress, we used tumour necrosis factor alpha (TNF-α and interleukin-6 (IL-6 stimulation of the human hepatoblastoma HepG2 cells in vitro and casein injection in C57BL/6J mice in vivo. The data showed that inflammatory stress increased hepatic CD36 protein levels but had no effect on mRNA expression. A protein degradation assay revealed that CD36 protein stability was not different between HepG2 cells treated with or without TNF-α or IL-6. A polysomal analysis indicated that CD36 translational efficiency was significantly increased by inflammatory stress. Additionally, inflammatory stress enhanced the phosphorylation of mTOR and its downstream translational regulators including p70S6K, 4E-BP1 and eIF4E. Rapamycin, an mTOR-specific inhibitor, reduced the phosphorylation of mTOR signalling pathway and decreased the CD36 translational efficiency and protein level even under inflammatory stress resulting in the alleviation of inflammatory stress-induced hepatic lipid accumulation. This study demonstrates that the activation of the mTOR signalling pathway increases hepatic CD36 translational efficiency, resulting in increased CD36 protein expression under inflammatory stress.

  12. The thresholds for statistical and clinical significance

    DEFF Research Database (Denmark)

    Jakobsen, Janus Christian; Gluud, Christian; Winkel, Per

    2014-01-01

    threshold if the trial is stopped early or if interim analyses have been conducted; (4) adjust the confidence intervals and the P-values for multiplicity due to number of outcome comparisons; and (5) assess clinical significance of the trial results. CONCLUSIONS: If the proposed five-step procedure...... not reflect the probability of getting a result assuming an alternative hypothesis to the null hypothesis is true. Second, a confidence interval or a P-value showing significance may be caused by multiplicity. Third, statistical significance does not necessarily result in clinical significance. Therefore......, assessment of intervention effects in randomised clinical trials deserves more rigour in order to become more valid. METHODS: Several methodologies for assessing the statistical and clinical significance of intervention effects in randomised clinical trials were considered. Balancing simplicity...

  13. SIGNIFICANCE OF SERUM COPPER AND ZINC LEVEL IN GASTROINTESTINAL CANCER

    Directory of Open Access Journals (Sweden)

    Prathibha

    2016-02-01

    Full Text Available The roles of trace elements especially copper and zinc in carcinogenesis in relation to disease activity have shown useful in estimating the extent and prognosis of malignant tumor in the digestive organ. Keeping this in consideration, the study was conducted on 140 subjects either sex out of which 35 normal adults and 105 gastrointestinal (GI cancer patients. The follow up study was further undertaken and values of serum Cu and Zn of the same patients before and after surgery were recorded. The study showed that there was significant elevation (p<0.01 of serum copper levels before surgery and serum copper levels were deceased significantly (p<0.05 after surgery. Serum Zn level was found significantly (p<0.05 lower in GI cancer patients while the Zn level was increased significantly (p<0.01 after surgery. There was significant increase (p<0.01 in Cu/ Zn ratio of GI cancer patients before surgery in contrast to the control. The serum copper level in patients of GI cancer decreased significantly after surgery resulting normalization of metabolic process. A significant increase in serum Zn levels have been observed after treatment of the patients. The Cu/ Zn ratio decreased significantly after the surgery. These observations clearly indicate that serum Cu, Zn and Cu/ Zn ratio are useful in estimating the extent and prognosis of malignant tumors in digestive organs

  14. Clinical significance of Bacillus species isolated from blood cultures.

    Science.gov (United States)

    Weber, D J; Saviteer, S M; Rutala, W A; Thomann, C A

    1989-06-01

    To determine the clinical significance of blood isolates of Bacillus, we reviewed all blood cultures obtained at North Carolina Memorial Hospital between 1981 and 1985. Over the five-year study period the number of patients (incidence per 10,000 hospital admissions) from whom Bacillus was isolated increased from 4.97 in 1981 to 12.5 in 1985. The incidence per 1,000 blood cultures also increased from 1.12 in 1981 to 2.33 in 1985. Review of the medical records of 78 of the 95 patients (82%) with positive cultures allowed retrospective classification of five isolates (6.4%) as clinically significant, 33 isolates (42.3%) as possibly significant, and 40 isolates (51.3%) as nonsignificant. Underlying diseases in patients with clinically significant Bacillus bacteremia included burn trauma in two, leukemia in one, carcinoma in one, and gastrointestinal hemorrhage in one. All isolates judged to be clinically significant and the majority of possibly significant isolates were B cereus. We conclude that the isolation of Bacillus species from blood cultures is clinically significant in 5% to 10% of cases, that the incidence of Bacillus bacteremia is increasing, and that burn trauma should be added to the list of conditions known to predispose to clinically significant Bacillus bacteremia.

  15. Discovering the Significance of Scientific Design Practice

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Baskerville, Richard

    2016-01-01

    This paper discusses and defines the achievement of significance in design science research. We review the values and processes of old-science and how this mode of science attacks the complexity of scientific knowledge production through analysis. We then explain how new-science attacks...... the complexity of scientific knowledge production through synthesis. The work argues that significance of the new-science contribution in design science can be obfuscated when wrapped in old-science. This understanding helps reveal how new-science, such as design science research, constitutes its significance...

  16. Increasing Public Expenditure

    National Research Council Canada - National Science Library

    Ammar Ben Zaed

    2015-01-01

    This article aims to analyze and interpret the phenomenon of increased public expenditures and test explanatory theories as well as to analyze Abstract the relationship between public spending and GDP...

  17. Increasing Public Library Productivity.

    Science.gov (United States)

    Samuelson, Howard

    1981-01-01

    Suggests ways of improving productivity for public libraries faced with increased accountability, dwindling revenues, and continuing inflation. Techniques described include work simplification, work analysis, improved management, and employee motivation. (RAA)

  18. Increased intracranial pressure

    Science.gov (United States)

    ... patient's bedside in an emergency room or hospital. Primary care doctors may sometimes spot early symptoms of increased intracranial pressure such as headache, seizures, or other nervous system problems. An MRI ...

  19. How do we make sense of significance?

    DEFF Research Database (Denmark)

    Lyhne, Ivar; Kørnøv, Lone

    2013-01-01

    sense, or construct meaning, of actions to determine significance are few. This article makes use of sense-making theory to explore how sense-making among EA researchers and practitioners influence significance determination. Focus is on the situation when persons have their first look at information...... about a strategic choice and as part of this make their initial judgement of significance. An experiment is designed and conducted to investigate how persons make sense of a specific case and determine significance in a screening and scoping context. The experiment indicates patterns in the test persons......' sense-making, including important differences in the way individuals screen and scope. These patterns concern what we notice, how fast we frame the choice, and when we are critical about the provided information. The indications provide a basis for reflections on practice and on how to organise EA...

  20. SIGWX Charts - High Level Significant Weather

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — High level significant weather (SIGWX) forecasts are provided for the en-route portion of international flights. NOAA's National Weather Service Aviation Center...

  1. Significant communities in large sparse networks

    CERN Document Server

    Mirshahvalad, Atieh; Derlen, Mattias; Rosvall, Martin

    2011-01-01

    Researchers use community-detection algorithms to reveal large-scale organization in biological and social networks, but community detection is useful only if the communities are significant and not a result of noisy data. To assess the statistical significance of the network communities, or the robustness of the detected structure, one approach is to perturb the network structure by removing links and measure how much the communities change. However, perturbing sparse networks is challenging because they are inherently sensitive; they shatter easily if links are removed. Here we propose a simple method to perturb sparse networks and assess the significance of their communities. We generate resampled networks by adding extra links based on local information, then we aggregate the information from multiple resampled networks to find a coarse-grained description of significant clusters. In addition to testing our method on benchmark networks, we use our method on the sparse network of the European Court of Just...

  2. SRS Process Facility Significance Fire Frequency

    Energy Technology Data Exchange (ETDEWEB)

    Sarrack, A.G. [Westinghouse Savannah River Company, AIKEN, SC (United States)

    1995-10-01

    This report documents the method and assumptions of a study performed to determine a site generic process facility significant fire initiator frequency and explains the proper way this value should be used.

  3. Fostering significant learning in graduate nursing education.

    Science.gov (United States)

    Marrocco, Geraldine F

    2014-03-01

    Faculty who want to energize graduate students with creative classes that lead to long-lasting learning will benefit by designing course objectives, learning activities, and assessment tools using Fink's taxonomy of significant learning and Wiggins's insights on performance-based or educative assessments. Research shows that course designs relying on content-driven lectures and written examinations do not promote significant learning among adult learners. This article reviews six types of significant learning using Fink's taxonomy and examines Wiggins's "backward" approach to designing courses using performance-based assessments that gauge true learning and learning that promotes a lasting change. When designing courses, educators should ask: "What do I really want students to get out of this course?" The answers will direct the design of objectives, learning activities, and assessment tools. Designing graduate courses using Fink's taxonomy and Wiggins's backward approach can lead to significant learning to better prepare nurse practitioners for the future of health care. Copyright 2014, SLACK Incorporated.

  4. Significance of Studies of Stylistics and Rhetoric

    Institute of Scientific and Technical Information of China (English)

    孙越

    2015-01-01

    Stylistics is a scientific study of style. It is a mode of encoding and decoding language and can be associated with various fields. In this paper,we talk about the great significances of stylistic and rhetoric studies. It refers to great help in expressing and understanding languages;in combining the linguistics and literary criticism and linguistics;great help in promoting and developing computer science and information technology;great significance in sharing heritage of human civilizations.

  5. Therapeutic Non Thermal Plasma, Significance and Challenges

    Directory of Open Access Journals (Sweden)

    Wameath Sh. Abdul-Majeed

    2014-06-01

    Full Text Available Plasma is an electrically neutral, highly ionized gas that consists of several species (electrons, ions, reactive species, and UV light and classified into localized thermal equilibrium (LTE plasmas and non-localized thermal equilibrium (n-LTE plasmas. In LTE plasmas, the electron temperature exists in equilibrium with the gas temperature. In contrast, the electron temperature in (n- LTE plasmas can reach temperatures of 1-10 (eV while the gas temperature is kept as low as room temperature, which makes it useful for a wide range of industrial applications (e.g. ozone generation, surface treatment, .., etc. In the past decade, non thermal (cold atmospheric pressure plasmas were developed and emerged as a promising new tool for medical applications as it’s proved to be more selective in its application (e.g. selective killing of microbes. Accordingly, developments of cold atmospheric plasma devices led to the possibility to apply plasma species to heat-sensitive surfaces (e.g. human skin with precise tuning, controllability and without damage of surrounding tissue. On this basis, medical plasma proved effective for skin sterilization, wound healing and tissue regeneration, cancer treatment, malignant cell apoptosis and blood coagulation. Moreover, cold plasma is known to inactivate a wide range of pathogens such as bacteria, viruses, fungi, spores and biofilms. Therefore it has been considered a very efficient alternative to superficially applied antibiotics or disinfectants. It’s worth noting that histological evaluation for the skin treated with atmospheric cold plasma showed that no morphological changes and no significant degree of necrosis or apoptosis were detectable after plasma treatment. Other studies denoted that a limited increase in the number of DNA double-strand breaks was observed in plasma-treated excised human skin. However, varieties of a new generation handheld and battery-operated devices makes it difficult to interpret the

  6. Hypoxia: Exposure Time Until Significant Performance Effects

    Science.gov (United States)

    2016-03-07

    questionnaire which confirmed compliance with pre-established alcohol, caffeine , supplement, and medication usage standards given during consent and...the median reaction times and the third quartile reaction times evokes a relatively recent concept that is primarily associated with sleep ...face of increasing physiological demand, but cannot sustain it. For example, when the need for sleep is high, the level of attention will increase to

  7. Exploding Increase of Population

    Energy Technology Data Exchange (ETDEWEB)

    Kim, J.H. [Sunmoon University, Chonan (Korea)

    2002-03-01

    Until 1650, the population of the world did not increase properly. According to studies of the demography, the annual increase rate of the world population during 2500 years, from 850 B.C. to 1650 A.D., was just 0.07%. Currently, however, the world population, which has exceptionally rapidly increased from 1900, is more than 6 billion as of 2000. After World War II, especially, the increase rate of the population has risen to about 1.8%, so we can use the word, explosion of the population. The explosion of the population accompanies the increase of energy consumption. The energy production of every year cannot sufficiently meet the energy demand, so we can face the grand energy crisis someday. The date might be a someday after 2020. According to the future forecasting of Shell, one of the majors, the peak of oil supply will be between 2015 and 2020. Unless the alternative energy is developed, the whole world will suffer the serious oil crisis.

  8. Increased urinary orosomucoid excretion

    DEFF Research Database (Denmark)

    Christiansen, M S; Iversen, K; Larsen, C T

    2009-01-01

    , impaired left ventricular function and endothelial dysfunction in patients with type 2 diabetes. MATERIAL AND METHODS: We performed a cross-sectional study of 41 patients with type 2 diabetes (17 patients with normal UOER and 24 with increased UOER) with no history of cardiovascular disease and 21 healthy...... controls. Urinary orosomucoid was measured using a particle-enhanced immunoturbidimetric assay. Plasma interleukin-6 (IL-6), tissue plasminogen activator (tPA) and soluble intercellular adhesion molecule-1 (sICAM) were measured using ELISA. Endothelial function measured as vasodilatory capacity...... of the brachial artery and echocardiography were done in all participants. RESULTS: Patients with diabetes and increased UOER had subclinically increased serum orosomucoid (pprotein (CRP) (p

  9. Increasing mobile radiography productivity.

    Science.gov (United States)

    Wong, Edward; Lung, Ngan Tsz; Ng, Kris; Jeor, Patrick

    2013-01-01

    Mobile radiography using computed radiography (CR) cassettes is a common equipment combination with a workflow bottleneck limited by location of CR readers. Advent of direct digital radiography (DDR) mobile x-ray machines removes this limitation by immediate image review and quality control. Through the use of key performance indicators (KPIs), the increase in efficiency can be quantified.

  10. Mycotoxins: significance to global economics and health

    Science.gov (United States)

    Mycotoxins are fungal metabolites produced my micro-fungi (molds and mildews) that have significant impacts on global economics and health. Some of these metabolites are beneficial, but most are harmful and have been associated with well-known epidemics dating back to medieval times. The terms ‘myco...

  11. Social significance of community structure: statistical view.

    Science.gov (United States)

    Li, Hui-Jia; Daniels, Jasmine J

    2015-01-01

    Community structure analysis is a powerful tool for social networks that can simplify their topological and functional analysis considerably. However, since community detection methods have random factors and real social networks obtained from complex systems always contain error edges, evaluating the significance of a partitioned community structure is an urgent and important question. In this paper, integrating the specific characteristics of real society, we present a framework to analyze the significance of a social community. The dynamics of social interactions are modeled by identifying social leaders and corresponding hierarchical structures. Instead of a direct comparison with the average outcome of a random model, we compute the similarity of a given node with the leader by the number of common neighbors. To determine the membership vector, an efficient community detection algorithm is proposed based on the position of the nodes and their corresponding leaders. Then, using a log-likelihood score, the tightness of the community can be derived. Based on the distribution of community tightness, we establish a connection between p-value theory and network analysis, and then we obtain a significance measure of statistical form . Finally, the framework is applied to both benchmark networks and real social networks. Experimental results show that our work can be used in many fields, such as determining the optimal number of communities, analyzing the social significance of a given community, comparing the performance among various algorithms, etc.

  12. The Philosophical Significance of Universal Grammar

    Science.gov (United States)

    Hinzen, Wolfram

    2012-01-01

    Throughout its long history, the project of a science of grammar has always been an inherently philosophical one, in which the study of grammar was taken to have special epistemological significance. I ask why 20th and 21st century inquiry into Universal Grammar (UG) has largely lost this dimension, a fact that I argue is partially responsible for…

  13. Significance tests and sample homogeneity loophole

    CERN Document Server

    Kupczynski, Marian

    2015-01-01

    In their recent comment, published in Nature, Jeffrey T.Leek and Roger D.Peng discuss how P-values are widely abused in null hypothesis significance testing . We agree completely with them and in this short comment we discuss the importance of sample homogeneity tests. No matter with how much scrutiny data are gathered if homogeneity tests are not performed the significance tests suffer from sample homogeneity loophole and the results may not be trusted. For example sample homogeneity loophole was not closed in the experiment testing local realism in which a significant violation of Eberhard inequality was found. We are not surprised that Bell type inequalities are violated since if the contextual character of quantum observables is properly taken into account these inequalities cannot be proven. However in order to trust the significance of the violation sample homogeneity loophole must be closed. Therefore we repeat after Jeffrey T.Leek and Roger D.Peng that sample homogeneity loophole is probably just the ...

  14. Can Educationally Significant Learning Be Assessed?

    Science.gov (United States)

    Stolz, Steven A.

    2017-01-01

    This article argues that assessment is a central feature of teaching, particularly as a means to determine whether what has been taught has been learnt. However, I take issue with the current trend in education which places a significant amount of emphasis upon large-scale public testing, which in turn has exacerbated the…

  15. Social significance of community structure: Statistical view

    Science.gov (United States)

    Li, Hui-Jia; Daniels, Jasmine J.

    2015-01-01

    Community structure analysis is a powerful tool for social networks that can simplify their topological and functional analysis considerably. However, since community detection methods have random factors and real social networks obtained from complex systems always contain error edges, evaluating the significance of a partitioned community structure is an urgent and important question. In this paper, integrating the specific characteristics of real society, we present a framework to analyze the significance of a social community. The dynamics of social interactions are modeled by identifying social leaders and corresponding hierarchical structures. Instead of a direct comparison with the average outcome of a random model, we compute the similarity of a given node with the leader by the number of common neighbors. To determine the membership vector, an efficient community detection algorithm is proposed based on the position of the nodes and their corresponding leaders. Then, using a log-likelihood score, the tightness of the community can be derived. Based on the distribution of community tightness, we establish a connection between p -value theory and network analysis, and then we obtain a significance measure of statistical form . Finally, the framework is applied to both benchmark networks and real social networks. Experimental results show that our work can be used in many fields, such as determining the optimal number of communities, analyzing the social significance of a given community, comparing the performance among various algorithms, etc.

  16. Bullying in Academe: Prevalent, Significant, and Incessant

    Science.gov (United States)

    Cassell, Macgorine A.

    2011-01-01

    This paper examines the top-down perspective of bullying and mobbing of professors by analyzing why it is prevalent, significant, and incessant and then proposes a framework to produce a caring, respectful, and safe environment for professors to engage in their teaching, scholarship, and service. The author suggests that the failure of…

  17. Encounter Probability of Significant Wave Height

    DEFF Research Database (Denmark)

    Liu, Z.; Burcharth, H. F.

    The determination of the design wave height (often given as the significant wave height) is usually based on statistical analysis of long-term extreme wave height measurement or hindcast. The result of such extreme wave height analysis is often given as the design wave height corresponding to a c...

  18. Surface characterization based upon significant topographic features

    Energy Technology Data Exchange (ETDEWEB)

    Blanc, J; Grime, D; Blateyron, F, E-mail: fblateyron@digitalsurf.fr [Digital Surf, 16 rue Lavoisier, F-25000 Besancon (France)

    2011-08-19

    Watershed segmentation and Wolf pruning, as defined in ISO 25178-2, allow the detection of significant features on surfaces and their characterization in terms of dimension, area, volume, curvature, shape or morphology. These new tools provide a robust way to specify functional surfaces.

  19. Discovering the Significance of Scientific Design Practice

    DEFF Research Database (Denmark)

    Pries-Heje, Jan; Baskerville, Richard

    This paper aims at discussing and defining what it is that makes design science research significant. First it reviews the values and processes of old science and how this attacks complexity through analysis. It then shows how new science attacks complexity through synthesis. Then the paper argues...

  20. Significance of Literature in Foreign Language Teaching

    Science.gov (United States)

    Babaee, Ruzbeh; Yahya, Wan Roselezam Bt Wan

    2014-01-01

    This research aims to consider literature as a significant tool for teaching fundamental language skills including speaking, listening, reading and writing. Reasons for the use of literature in language classrooms and major factors for choosing appropriate kinds of literary texts in such classes should be highlighted in order to make readers aware…

  1. Formal conditions for the significance-effect

    DEFF Research Database (Denmark)

    Thellefsen, Torkild Leo; Sørensen, Bent; Thellefsen, Martin

    2006-01-01

    The significance-effect is the right effect of meaning caused upon an interpreting mind. The right effect is understood as the right interpretation of an intended meaning caused by a sign communicated by an utterer. In the article, which is inspired by Charles S. Peirce's doctrine of signs, his...

  2. Sharing data increases citations

    DEFF Research Database (Denmark)

    Drachen, Thea Marie; Ellegaard, Ole; Larsen, Asger Væring

    2016-01-01

    This paper presents some indications to the existence of a citation advantage related to sharing data using astrophysics as a case. Through bibliometric analyses we find a citation advantage for astrophysical papers in core journals. The advantage arises as indexed papers are associated with data...... by bibliographical links, and consists of papers receiving on average significantly more citations per paper per year, than do papers not associated with links to data....

  3. Competitive Intelligence: Significance in Higher Education

    Science.gov (United States)

    Barrett, Susan E.

    2010-01-01

    Historically noncompetitive, the higher education sector is now having to adjust dramatically to new and increasing demands on numerous levels. To remain successfully operational within the higher educational market universities today must consider all relevant forces which can impact present and future planning. Those institutions that were…

  4. Significant Decline in Celebrity Usage in Advertising

    DEFF Research Database (Denmark)

    Schimmelpfennig, Christian; Hollensen, Svend

    2016-01-01

    Over the decades, the use of celebrities in advertising has increased. Research suggests that in western countries between 20% and 30% of all advertising used celebrities in the late 1990s. During the past 10 years, however, the use of celebrities in advertising has plunged. This paper discusses...

  5. Public health significance of elevated homocysteine.

    Science.gov (United States)

    Selhub, Jacob

    2008-06-01

    Homocysteine is a sulfur amino acid whose metabolism stands at the intersection of two pathways: remethylation, which requires folic acid and vitamin B12 coenzymes; and transsulfuration, which requires pyridoxal-5'-phosphate, the vitamin B6 coenzyme. Data from a number of laboratories suggest that mild elevations of homocysteine in plasma are a risk factor for occlusive vascular disease. In the Framingham studies, we have shown that plasma homocysteine concentration is inversely related to the intake and plasma levels of folate and vitamin B6 as well as vitamin B12 plasma levels. Almost two-thirds of the prevalence of high homocysteine is attributable to low vitamin status or intake. Elevated homocysteine concentrations in plasma are a risk factor for prevalence of extracranial carotid-artery stenosis > or = 25% in both men and women. Prospectively elevated plasma homocysteine is associated with increased total and cardiovascular mortality, increased incidence of stroke, increased incidence of dementia and Alzheimer's disease, increased incidence of bone fracture, and higher prevalence of chronic heart failure. It was also shown that elevated plasma homocysteine is a risk factor for preeclampsia and maybe neural tube defects (NTD). This multitude of relationships between elevated plasma homocysteine and diseases that afflict the elderly, pregnant women, and the embryo points to the existence ofa common denominator which may be responsible for these diseases. Whether this denominator is homocysteine itself or homocysteine is merely a marker, remains to be determined.

  6. Increasing income inequality

    DEFF Research Database (Denmark)

    Frederiksen, Anders; Poulsen, Odile

    In recent decades most developed countries have experienced an increase in income inequality. In this paper, we use an equilibrium search framework to shed additional light on what is causing an income distribution to change. The major benefit of the model is that it can accommodate shocks...... to the skill composition in the market, employee bargaining power and productivity. Further, when our model is subjected to skill-upgrading and changes in employee bargaining power, it is capable of predicting the recent changes observed in the Danish income distribution. In addition, the model emphasizes...... that shocks to the employees' relative productivity, i.e., skill-biased technological change, are unlikely to have caused the increase in income inequality....

  7. Pemex increasing offshore activity

    Energy Technology Data Exchange (ETDEWEB)

    Beachy, D.

    1985-05-01

    Although austere by boom-year standards, Mexico's National Energy Program for 1984-1988 calls for forty wildcats and 90 to 144 development wells off the coast, primarily in the prolific Campeche Bay area. Platform additions will include nine drilling platforms, each for twelve wells, and eight eight platforms to drill injection wells. Additionally, 7 production, 6 accomodation, 6 linkage and 8 compression platforms and 13 tetrapods will be installed. The main objectives of the plan are energy self-sufficiency through the turn of the century, and energy diversification, savings and productivity. The most controversial portion of Mexico's energy program is that calling for nuclear energy development. The energy program lists three basic goals in hydrocarbon production: continuing research on better techniques of secondary recovery; increasing capacity for refining primary and secondary crude products and improving production of heavy crudes; and increasing storage capacity and installing pipelines capable of carrying a greater volume of crude.

  8. Market Expects Demand Increase

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In the recent releasing Textile Industry Invigorating Plan,"givingattention to both domestlc and overseas markets"is put into a keyposition.Under a series policies,such as increasing the tax rebaterate for textile and garment exports,and granting loan for SME,thefurther development of this industry is expectative.Otherwise,weshould know that it costs time for demand driving.This need ourpatients.The only questionis how much time we have to wait.