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Sample records for indeksatsiya baz dannykh

  1. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B

    PubMed Central

    2015-01-01

    Bromodomains are acetyl-lysine specific protein interaction domains that have recently emerged as a new target class for the development of inhibitors that modulate gene transcription. The two closely related bromodomain containing proteins BAZ2A and BAZ2B constitute the central scaffolding protein of the nucleolar remodeling complex (NoRC) that regulates the expression of noncoding RNAs. However, BAZ2 bromodomains have low predicted druggability and so far no selective inhibitors have been published. Here we report the development of GSK2801, a potent, selective and cell active acetyl-lysine competitive inhibitor of BAZ2A and BAZ2B bromodomains as well as the inactive control compound GSK8573. GSK2801 binds to BAZ2 bromodomains with dissociation constants (KD) of 136 and 257 nM for BAZ2B and BAZ2A, respectively. Crystal structures demonstrated a canonical acetyl-lysine competitive binding mode. Cellular activity was demonstrated using fluorescent recovery after photobleaching (FRAP) monitoring displacement of GFP-BAZ2A from acetylated chromatin. A pharmacokinetic study in mice showed that GSK2801 had reasonable in vivo exposure after oral dosing, with modest clearance and reasonable plasma stability. Thus, GSK2801 represents a versatile tool compound for cellular and in vivo studies to understand the role of BAZ2 bromodomains in chromatin biology. PMID:25799074

  2. Discovery and Characterization of GSK2801, a Selective Chemical Probe for the Bromodomains BAZ2A and BAZ2B.

    PubMed

    Chen, Peiling; Chaikuad, Apirat; Bamborough, Paul; Bantscheff, Marcus; Bountra, Chas; Chung, Chun-Wa; Fedorov, Oleg; Grandi, Paola; Jung, David; Lesniak, Robert; Lindon, Matthew; Müller, Susanne; Philpott, Martin; Prinjha, Rab; Rogers, Catherine; Selenski, Carolyn; Tallant, Cynthia; Werner, Thilo; Willson, Timothy M; Knapp, Stefan; Drewry, David H

    2016-02-25

    Bromodomains are acetyl-lysine specific protein interaction domains that have recently emerged as a new target class for the development of inhibitors that modulate gene transcription. The two closely related bromodomain containing proteins BAZ2A and BAZ2B constitute the central scaffolding protein of the nucleolar remodeling complex (NoRC) that regulates the expression of noncoding RNAs. However, BAZ2 bromodomains have low predicted druggability and so far no selective inhibitors have been published. Here we report the development of GSK2801, a potent, selective and cell active acetyl-lysine competitive inhibitor of BAZ2A and BAZ2B bromodomains as well as the inactive control compound GSK8573. GSK2801 binds to BAZ2 bromodomains with dissociation constants (KD) of 136 and 257 nM for BAZ2B and BAZ2A, respectively. Crystal structures demonstrated a canonical acetyl-lysine competitive binding mode. Cellular activity was demonstrated using fluorescent recovery after photobleaching (FRAP) monitoring displacement of GFP-BAZ2A from acetylated chromatin. A pharmacokinetic study in mice showed that GSK2801 had reasonable in vivo exposure after oral dosing, with modest clearance and reasonable plasma stability. Thus, GSK2801 represents a versatile tool compound for cellular and in vivo studies to understand the role of BAZ2 bromodomains in chromatin biology. PMID:25799074

  3. Baz, the Bard and Borrowing: "Romeo and Juliet" on Film.

    ERIC Educational Resources Information Center

    Allen, Rhonda; Guest, Peter

    1999-01-01

    Outlines a unit of study of Baz Luhrmann's 1997 film version of "Romeo and Juliet" for Year 10 students in Australia. Includes a series of lessons/questions and activities that include directing students (1) to consider speed and editing and character analysis; (2) to engage in language comparison; and (3) to generate extended responses. (NH)

  4. A Role for the Chromatin-Remodeling Factor BAZ1A in Neurodevelopment.

    PubMed

    Zaghlool, Ammar; Halvardson, Jonatan; Zhao, Jin J; Etemadikhah, Mitra; Kalushkova, Antonia; Konska, Katarzyna; Jernberg-Wiklund, Helena; Thuresson, Ann-Charlotte; Feuk, Lars

    2016-09-01

    Chromatin-remodeling factors are required for a wide range of cellular and biological processes including development and cognition, mainly by regulating gene expression. As these functions would predict, deregulation of chromatin-remodeling factors causes various disease syndromes, including neurodevelopmental disorders. Recent reports have linked mutations in several genes coding for chromatin-remodeling factors to intellectual disability (ID). Here, we used exome sequencing and identified a nonsynonymous de novo mutation in BAZ1A (NM_182648.2:c.4043T > G, p.Phe1348Cys), encoding the ATP-utilizing chromatin assembly and remodeling factor 1 (ACF1), in a patient with unexplained ID. ACF1 has been previously reported to bind to the promoter of the vitamin D receptor (VDR)-regulated genes and suppress their expression. Our results show that the patient displays decreased binding of ACF1 to the promoter of the VDR-regulated gene CYP24A1. Using RNA sequencing, we find that the mutation affects the expression of genes involved in several pathways including vitamin D metabolism, Wnt signaling and synaptic formation. RNA sequencing of BAZ1A knockdown cells and Baz1a knockout mice revealed that BAZ1A carry out distinctive functions in different tissues. We also demonstrate that BAZ1A depletion influence the expression of genes important for nervous system development and function. Our data point to an important role for BAZ1A in neurodevelopment, and highlight a possible link for BAZ1A to ID. PMID:27328812

  5. BAZ1B is dispensable for H2AX phosphorylation on Tyrosine 142 during spermatogenesis

    PubMed Central

    Broering, Tyler J.; Wang, Yuan-Liang; Pandey, Ram Naresh; Hegde, Rashmi S.; Wang, Shao-Chun; Namekawa, Satoshi H.

    2015-01-01

    ABSTRACT Meiosis is precisely regulated by the factors involved in DNA damage response in somatic cells. Among them, phosphorylation of H2AX on Serine 139 (γH2AX) is an essential signal for the silencing of unsynapsed sex chromosomes during male meiosis. However, it remains unknown how adjacent H2AX phosphorylation on Tyrosine 142 (pTyr142) is regulated in meiosis. Here we investigate the meiotic functions of BAZ1B (WSTF), the only known Tyr142 kinase in somatic cells, using mice possessing a conditional deletion of BAZ1B. Although BAZ1B deletion causes ectopic γH2AX signals on synapsed autosomes during the early pachytene stage, BAZ1B is dispensable for fertility and critical events during spermatogenesis. BAZ1B deletion does not alter events on unsynapsed axes and pericentric heterochromatin formation. Furthermore, BAZ1B is dispensable for localization of the ATP-dependent chromatin remodeling protein SMARCA5 (SNF2h) during spermatogenesis despite the complex formation between BAZ1B and SMARCA5, known as the WICH complex, in somatic cells. Notably, pTyr142 is regulated independently of BAZ1B and is dephosphorylated on the sex chromosomes during meiosis in contrast with the presence of adjacent γH2AX. Dephosphorylation of pTyr142 is regulated by MDC1, a binding partner of γH2AX. These results reveal the distinct regulation of two adjacent phosphorylation sites of H2AX during meiosis, and suggest that another kinase mediates Tyr142 phosphorylation. PMID:25979708

  6. Haploinsufficiency of BAZ1B contributes to Williams syndrome through transcriptional dysregulation of neurodevelopmental pathways.

    PubMed

    Lalli, Matthew A; Jang, Jiwon; Park, Joo-Hye C; Wang, Yidi; Guzman, Elmer; Zhou, Hongjun; Audouard, Morgane; Bridges, Daniel; Tovar, Kenneth R; Papuc, Sorina M; Tutulan-Cunita, Andreea C; Huang, Yadong; Budisteanu, Magdalena; Arghir, Aurora; Kosik, Kenneth S

    2016-04-01

    Williams syndrome (WS) is a neurodevelopmental disorder caused by a genomic deletion of ∼28 genes that results in a cognitive and behavioral profile marked by overall intellectual impairment with relative strength in expressive language and hypersocial behavior. Advancements in protocols for neuron differentiation from induced pluripotent stem cells allowed us to elucidate the molecular circuitry underpinning the ontogeny of WS. In patient-derived stem cells and neurons, we determined the expression profile of the Williams-Beuren syndrome critical region-deleted genes and the genome-wide transcriptional consequences of the hemizygous genomic microdeletion at chromosome 7q11.23. Derived neurons displayed disease-relevant hallmarks and indicated novel aberrant pathways in WS neurons including over-activated Wnt signaling accompanying an incomplete neurogenic commitment. We show that haploinsufficiency of the ATP-dependent chromatin remodeler, BAZ1B, which is deleted in WS, significantly contributes to this differentiation defect. Chromatin-immunoprecipitation (ChIP-seq) revealed BAZ1B target gene functions are enriched for neurogenesis, neuron differentiation and disease-relevant phenotypes. BAZ1B haploinsufficiency caused widespread gene expression changes in neural progenitor cells, and together with BAZ1B ChIP-seq target genes, explained 42% of the transcriptional dysregulation in WS neurons. BAZ1B contributes to regulating the balance between neural precursor self-renewal and differentiation and the differentiation defect caused by BAZ1B haploinsufficiency can be rescued by mitigating over-active Wnt signaling in neural stem cells. Altogether, these results reveal a pivotal role for BAZ1B in neurodevelopment and implicate its haploinsufficiency as a likely contributor to the neurological phenotypes in WS. PMID:26755828

  7. High-Throughput Fragment Docking into the BAZ2B Bromodomain: Efficient in Silico Screening for X-Ray Crystallography.

    PubMed

    Lolli, Graziano; Caflisch, Amedeo

    2016-03-18

    Bromodomains are protein modules that bind to acetylated lysine side chains in histones and other proteins. The bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) has been reported to be poorly druggable. Here, we screened an in-house library of 350 fragments by automatic docking to the BAZ2B bromodomain. The top 12 fragments according to the predicted binding energy were selected for experiments of soaking into apo crystals of BAZ2B which yielded the structure of the complex for four of them, which is a hit rate of 33%. Additional crystal structures were solved for BAZ2B and two scaffolds identified by analogy. For three topologically similar fragments, the crystal structures reveal binding modes with different penetration, i.e., with zero, one, and two water molecules, respectively, located between the fragment and the side chain of a conserved tyrosine (Tyr1901) in the bottom of the acetyl lysine pocket of BAZ2B. Furthermore, a remarkable stereoselectivity of the acetyl lysine pocket emerges from the crystal structures of the bromodomains of BAZ2B and SMARCA4 in complex with the chiral diol MPD (2-methyl-2,4-pentanediol). PMID:26942307

  8. Mouse BAZ1A (ACF1) Is Dispensable for Double-Strand Break Repair but Is Essential for Averting Improper Gene Expression during Spermatogenesis

    PubMed Central

    Dowdle, James A.; Mehta, Monika; Kass, Elizabeth M.; Vuong, Bao Q.; Inagaki, Akiko; Egli, Dieter; Jasin, Maria; Keeney, Scott

    2013-01-01

    ATP-dependent chromatin remodelers control DNA access for transcription, recombination, and other processes. Acf1 (also known as BAZ1A in mammals) is a defining subunit of the conserved ISWI-family chromatin remodelers ACF and CHRAC, first purified over 15 years ago from Drosophila melanogaster embryos. Much is known about biochemical properties of ACF and CHRAC, which move nucleosomes in vitro and in vivo to establish ordered chromatin arrays. Genetic studies in yeast, flies and cultured human cells clearly implicate these complexes in transcriptional repression via control of chromatin structures. RNAi experiments in transformed mammalian cells in culture also implicate ACF and CHRAC in DNA damage checkpoints and double-strand break repair. However, their essential in vivo roles in mammals are unknown. Here, we show that Baz1a-knockout mice are viable and able to repair developmentally programmed DNA double-strand breaks in the immune system and germ line, I-SceI endonuclease-induced breaks in primary fibroblasts via homologous recombination, and DNA damage from mitomycin C exposure in vivo. However, Baz1a deficiency causes male-specific sterility in accord with its high expression in male germ cells, where it displays dynamic, stage-specific patterns of chromosomal localization. Sterility is caused by pronounced defects in sperm development, most likely a consequence of massively perturbed gene expression in spermatocytes and round spermatids in the absence of BAZ1A: the normal spermiogenic transcription program is largely intact but more than 900 other genes are mis-regulated, primarily reflecting inappropriate up-regulation. We propose that large-scale changes in chromatin composition that occur during spermatogenesis create a window of vulnerability to promiscuous transcription changes, with an essential function of ACF and/or CHRAC chromatin remodeling activities being to safeguard against these alterations. PMID:24244200

  9. The polarity protein Baz forms a platform for the centrosome orientation during asymmetric stem cell division in the Drosophila male germline

    PubMed Central

    Inaba, Mayu; Venkei, Zsolt G; Yamashita, Yukiko M

    2015-01-01

    Many stem cells divide asymmetrically in order to balance self-renewal with differentiation. The essence of asymmetric cell division (ACD) is the polarization of cells and subsequent division, leading to unequal compartmentalization of cellular/extracellular components that confer distinct cell fates to daughter cells. Because precocious cell division before establishing cell polarity would lead to failure in ACD, these two processes must be tightly coupled; however, the underlying mechanism is poorly understood. In Drosophila male germline stem cells, ACD is prepared by stereotypical centrosome positioning. The centrosome orientation checkpoint (COC) further serves to ensure ACD by preventing mitosis upon centrosome misorientation. In this study, we show that Bazooka (Baz) provides a platform for the correct centrosome orientation and that Baz-centrosome association is the key event that is monitored by the COC. Our work provides a foundation for understanding how the correct cell polarity may be recognized by the cell to ensure productive ACD. DOI: http://dx.doi.org/10.7554/eLife.04960.001 PMID:25793442

  10. A novel RNA binding surface of the TAM domain of TIP5/BAZ2A mediates epigenetic regulation of rRNA genes

    PubMed Central

    Anosova, Irina; Melnik, Svitlana; Tripsianes, Konstantinos; Kateb, Fatiha; Grummt, Ingrid; Sattler, Michael

    2015-01-01

    The chromatin remodeling complex NoRC, comprising the subunits SNF2h and TIP5/BAZ2A, mediates heterochromatin formation at major clusters of repetitive elements, including rRNA genes, centromeres and telomeres. Association with chromatin requires the interaction of the TAM (TIP5/ARBP/MBD) domain of TIP5 with noncoding RNA, which targets NoRC to specific genomic loci. Here, we show that the NMR structure of the TAM domain of TIP5 resembles the fold of the MBD domain, found in methyl-CpG binding proteins. However, the TAM domain exhibits an extended MBD fold with unique C-terminal extensions that constitute a novel surface for RNA binding. Mutation of critical amino acids within this surface abolishes RNA binding in vitro and in vivo. Our results explain the distinct binding specificities of TAM and MBD domains to RNA and methylated DNA, respectively, and reveal structural features for the interaction of NoRC with non-coding RNA. PMID:25916849

  11. The PCP pathway regulates Baz planar distribution in epithelial cells.

    PubMed

    Aigouy, Benoit; Le Bivic, André

    2016-01-01

    The localisation of apico-basal polarity proteins along the Z-axis of epithelial cells is well understood while their distribution in the plane of the epithelium is poorly characterised. Here we provide a systematic description of the planar localisation of apico-basal polarity proteins in the Drosophila ommatidial epithelium. We show that the adherens junction proteins Shotgun and Armadillo, as well as the baso-lateral complexes, are bilateral, i.e. present on both sides of cell interfaces. In contrast, we report that other key adherens junction proteins, Bazooka and the myosin regulatory light chain (Spaghetti squash) are unilateral, i.e. present on one side of cell interfaces. Furthermore, we demonstrate that planar cell polarity (PCP) and not the apical determinants Crumbs and Par-6 control Bazooka unilaterality in cone cells. Altogether, our work unravels an unexpected organisation and combination of apico-basal, cytoskeletal and planar polarity proteins that is different on either side of cell-cell interfaces and unique for the different contacts of the same cell. PMID:27624969

  12. Claire Danes's Star-Body, Teen Female Viewers and the Pluralisation of Authorship in Baz Luhrmann's "William Shakespeare's Romeo + Juliet"

    ERIC Educational Resources Information Center

    Keam, Angela

    2008-01-01

    Teaching William Shakespeare's canonical tragedy "Romeo and Juliet" to teenagers in the context of the English classroom in Australia is not a particularly new pedagogical practice. In the year 2008, when many teachers (particularly those with a feminist bent such as I) are intent on guiding their students to decipher the ideological motivations…

  13. aPKC Phosphorylation of Bazooka Defines the Apical/Lateral Border in Drosophila Epithelial Cells

    PubMed Central

    Morais-de-Sá, Eurico; Mirouse, Vincent; St Johnston, Daniel

    2010-01-01

    Summary Bazooka (PAR-3), PAR-6, and aPKC form a complex that plays a key role in the polarization of many cell types. In epithelial cells, however, Bazooka localizes below PAR-6 and aPKC at the apical/lateral junction. Here, we show that Baz is excluded from the apical aPKC domain in epithelia by aPKC phosphorylation, which disrupts the Baz/aPKC interaction. Removal of Baz from the complex is epithelial-specific because it also requires the Crumbs complex, which prevents the Baz/PAR-6 interaction. In the absence of Crumbs or aPKC phosphorylation of Baz, mislocalized Baz recruits adherens junction components apically, leading to a loss of the apical domain and an expansion of lateral. Thus, apical exclusion of Baz by Crumbs and aPKC defines the apical/lateral border. Although Baz acts as an aPKC targeting and specificity factor in nonepithelial cells, our results reveal that it performs a complementary function in positioning the adherens junction in epithelia. PMID:20434988

  14. The Effect of Breakfast Type on Total Daily Energy Intake and Body Mass Index Among Thai School Children.

    PubMed

    Purttiponthanee, Sasiumphai; Rojroongwasinkul, Nipa; Wimonpeerapattana, Wanphen; Thasanasuwan, Wiyada; Senaprom, Sayamon; Khouw, Ilse; Deurenberg, Paul

    2016-07-01

    The study investigated the association between breakfast types consumed, daily energy intake, and body mass index for age Z-score (BAZ). Cross-sectional data from 1258 children aged 7 to 12.9 years were analyzed for breakfast type, nutrient intakes, BAZ, and proportion of overweight or obesity. Analysis of covariance was used to compare energy and nutrient intakes, BAZ, and proportion of overweight/obese children between breakfast groups. Only 19% of children had adequate energy intake from breakfast. Those consuming snacks had a significantly lower BAZ (Z = -0.73), with 5% of them being overweight/obese. Those consuming beverages and desserts had the lowest total daily energy intake (1314 kcal) and lowest protein intake (8.4 g). The results suggest that breakfast type is associated with daily energy intake and BAZ. Most breakfasts are not adequate. School-based nutrition education programs involving families, teachers, and health professionals can contribute to improve this situation. PMID:27183975

  15. American ASTP prime crew participate in photography mission briefing

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The three American ASTP prime crew astronauts participate in a photography mission briefing in bldg 5 with Dr. Farouk El-Baz (wearing face mask) during Apollo Soyuz Test Project (ASTP) pre-flight activity at JSC. They are, left to right, Thomas P. Stafford, commander; Vance D. Brand, command module pilot; Dr. El-Baz; and Donald K. Slayton, docking module pilot. Dr. El-Baz is with the Center for Earth and Planetary Studies, National Air and Space Museum, Smithsonian Institution. The face mask is to protect the crewmen from possible exposure to disease prior to launch time.

  16. A Par-1-Par-3-Centrosome Cell Polarity Pathway and Its Tuning for Isotropic Cell Adhesion.

    PubMed

    Jiang, Tao; McKinley, R F Andrew; McGill, Melanie A; Angers, Stephane; Harris, Tony J C

    2015-10-19

    To form regulated barriers between body compartments, epithelial cells polarize into apical and basolateral domains and assemble adherens junctions (AJs). Despite close links with polarity networks that generate single polarized domains, AJs distribute isotropically around the cell circumference for adhesion with all neighboring cells [1-3]. How AJs avoid the influence of polarity networks to maintain their isotropy has been unclear. In established epithelia, trans cadherin interactions could maintain AJ isotropy [4], but AJs are dynamic during epithelial development and remodeling [5, 6], and thus specific mechanisms may control their isotropy. In Drosophila, aPKC prevents hyper-polarization of junctions as epithelia develop from cellularization to gastrulation [7]. Here, we show that aPKC does so by inhibiting a positive feedback loop between Bazooka (Baz)/Par-3, a junctional organizer [5, 8-10], and centrosomes. Without aPKC, Baz and centrosomes lose their isotropic distributions and recruit each other to single plasma membrane (PM) domains. Surprisingly, our loss- and gain-of-function analyses show that the Baz-centrosome positive feedback loop is driven by Par-1, a kinase known to phosphorylate Baz and inhibit its basolateral localization [8, 11, 12]. We find that Par-1 promotes the positive feedback loop through both centrosome microtubule effects and Baz phosphorylation. Normally, aPKC attenuates the circuit by expelling Par-1 from the apical domain at gastrulation. The combination of local activation and global inhibition is a common polarization strategy [13-16]. Par-1 seems to couple both effects for a potent Baz polarization mechanism that is regulated for the isotropy of Baz and AJs around the cell circumference. PMID:26455305

  17. aPKC Inhibition by Par3 CR3 Flanking Regions Controls Substrate Access and Underpins Apical-Junctional Polarization.

    PubMed

    Soriano, Erika V; Ivanova, Marina E; Fletcher, Georgina; Riou, Philippe; Knowles, Philip P; Barnouin, Karin; Purkiss, Andrew; Kostelecky, Brenda; Saiu, Peter; Linch, Mark; Elbediwy, Ahmed; Kjær, Svend; O'Reilly, Nicola; Snijders, Ambrosius P; Parker, Peter J; Thompson, Barry J; McDonald, Neil Q

    2016-08-22

    Atypical protein kinase C (aPKC) is a key apical-basal polarity determinant and Par complex component. It is recruited by Par3/Baz (Bazooka in Drosophila) into epithelial apical domains through high-affinity interaction. Paradoxically, aPKC also phosphorylates Par3/Baz, provoking its relocalization to adherens junctions (AJs). We show that Par3 conserved region 3 (CR3) forms a tight inhibitory complex with a primed aPKC kinase domain, blocking substrate access. A CR3 motif flanking its PKC consensus site disrupts the aPKC kinase N lobe, separating P-loop/αB/αC contacts. A second CR3 motif provides a high-affinity anchor. Mutation of either motif switches CR3 to an efficient in vitro substrate by exposing its phospho-acceptor site. In vivo, mutation of either CR3 motif alters Par3/Baz localization from apical to AJs. Our results reveal how Par3/Baz CR3 can antagonize aPKC in stable apical Par complexes and suggests that modulation of CR3 inhibitory arms or opposing aPKC pockets would perturb the interaction, promoting Par3/Baz phosphorylation. PMID:27554858

  18. The "Gatekeeper" Residue Influences the Mode of Binding of Acetyl Indoles to Bromodomains.

    PubMed

    Unzue, Andrea; Zhao, Hongtao; Lolli, Graziano; Dong, Jing; Zhu, Jian; Zechner, Melanie; Dolbois, Aymeric; Caflisch, Amedeo; Nevado, Cristina

    2016-04-14

    Small-molecule hits for the bromodomains of CREBBP and BAZ2B have been identified by scaffold hopping followed by docking of a set of ∼200 compounds containing the acetyl indole scaffold. Chemical synthesis of nearly 30 derivatives has resulted in ligands of representatives of three subfamilies of human bromodomains with favorable ligand efficiency. The X-ray crystal structures of three different bromodomains (CREBBP, BAZ2B, and BRPF1b) in complex with acetyl indole derivatives reveal the influence of the gatekeeper residue on the orientation of small-molecule ligands in the acetyl lysine binding site. PMID:26982797

  19. Drosophila MAGI interacts with RASSF8 to regulate E-Cadherin-based adherens junctions in the developing eye.

    PubMed

    Zaessinger, Sophie; Zhou, Yanxiang; Bray, Sarah J; Tapon, Nicolas; Djiane, Alexandre

    2015-03-15

    Morphogenesis is crucial during development to generate organs and tissues of the correct size and shape. During Drosophila late eye development, interommatidial cells (IOCs) rearrange to generate the highly organized pupal lattice, in which hexagonal ommatidial units pack tightly. This process involves the fine regulation of adherens junctions (AJs) and of adhesive E-Cadherin (E-Cad) complexes. Localized accumulation of Bazooka (Baz), the Drosophila PAR3 homolog, has emerged as a critical step to specify where new E-Cad complexes should be deposited during junction remodeling. However, the mechanisms controlling the correct localization of Baz are still only partly understood. We show here that Drosophila Magi, the sole fly homolog of the mammalian MAGI scaffolds, is an upstream regulator of E-Cad-based AJs during cell rearrangements, and that Magi mutant IOCs fail to reach their correct position. We uncover a direct physical interaction between Magi and the Ras association domain protein RASSF8 through a WW domain-PPxY motif binding, and show that apical Magi recruits the RASSF8-ASPP complex during AJ remodeling in IOCs. We further show that this Magi complex is required for the cortical recruitment of Baz and of the E-Cad-associated proteins α- and β-catenin. We propose that, by controlling the proper localization of Baz to remodeling junctions, Magi and the RASSF8-ASPP complex promote the recruitment or stabilization of E-Cad complexes at junction sites. PMID:25725070

  20. Risk factors during the prenatal period and the first year of life associated with overweight in 7-year-old low-income Chilean children.

    PubMed

    Rios-Castillo, Israel; Cerezo, Sheila; Corvalán, Camila; Martínez, Mario; Kain, Juliana

    2015-10-01

    The objective of this study was to identify in low-income Chilean children with normal birthweight which factors occurring during the prenatal period and the first year are associated with overweight (OW)/obesity at 7 years. The sample included 652 7-year-olds from a larger cohort study. We collected anthropometric data at 0, 12 and 84 months, maternal pre-pregnancy and pregnancy characteristics, early feeding practices, number of siblings, birth order, breastfeeding, and timing of solid introduction information. We determined the residuals for z-scores for body mass index (BMI) (BAZ), weight/age and height/age0-12 months , run univariate analysis (X(2) or t-test) and multivariate logistic analyses (stepwise approach); P < 0.05 was considered significant. We evaluated the goodness of fit of the model using the Hosmer-Lemeshow test and checked for overdispersion using the Pearson's X(2) . The odds of children being OW at 7 years increased if their mothers were OW before pregnancy, if born with a higher BAZ (increase of 18-74% per each additional unit of BAZ) and if their BAZ growth during the first year was higher (62-239% per each unit over the predicted BAZ increase). Higher birth order was protective (6-68% less risk for 2nd birth compared with 1st and 10-73% less for ≥3rd child). All other variables, including gender, were non-significant (P > 0.1). In low-income Chilean children with normal birth, four factors during the prenatal period and the first year were associated with OW at 7 years: pre-pregnancy BMI, BMI at birth, BMI gain between 0 and 12 months, and birth order. PMID:23241511

  1. Analytical approximation to characterize the performance of in situ aquifer bioremediation

    NASA Astrophysics Data System (ADS)

    Keijzer, H.; van Dijke, M. I. J.; van der Zee, S. E. A. T. M.

    The performance of in situ bioremediation to remove organic contaminants from contaminated aquifers depends on the physical and biochemical parameters. We characterize the performance by the contaminant removal rate and the region where biodegradation occurs, the biologically active zone (BAZ). The numerical fronts obtained by one-dimensional in situ bioremediation modeling reveal a traveling wave behavior: fronts of microbial mass, organic contaminant and electron acceptor move with a constant velocity and constant front shape through the domain. Hence, only one front shape and a linear relation between the front position and time is found for each of the three compounds. We derive analytical approximations for the traveling wave front shape and front position that agree perfectly with the traveling wave behavior resulting from the bioremediation model. Using these analytical approximations, we determine the contaminant removal rate and the BAZ. Furthermore, we assess the influence of the physical and biochemical parameters on the performance of the in situ bioremediation technique.

  2. Adaptive capacity of fishing communities at marine protected areas: a case study from the Colombian Pacific.

    PubMed

    Moreno-Sánchez, Rocío del Pilar; Maldonado, Jorge Higinio

    2013-12-01

    Departing from a theoretical methodology, we estimate empirically an index of adaptive capacity (IAC) of a fishing community to the establishment of marine protected areas (MPAs). We carried out household surveys, designed to obtain information for indicators and sub-indicators, and calculated the IAC. Moreover, we performed a sensitivity analysis to check for robustness of the results. Our findings show that, despite being located between two MPAs, the fishing community of Bazán in the Colombian Pacific is highly vulnerable and that the socioeconomic dimension of the IAC constitutes the most binding dimension for building adaptive capacity. Bazán is characterized by extreme poverty, high dependence on resources, and lack of basic public infrastructure. Notwithstanding, social capital and local awareness about ecological conditions may act as enhancers of adaptive capacity. The establishment of MPAs should consider the development of strategies to confer adaptive capacity to local communities highly dependent on resource extraction. PMID:24213997

  3. Seismic detections of the 15 February 2013 Chelyabinsk meteor from the dense ChinArray

    NASA Astrophysics Data System (ADS)

    Li, Lu; Wang, Baoshan; Peng, Zhigang; Wang, Weitao

    2016-07-01

    ChinArray is a dense portable broadband seismic network to cover the entire continental China, and the Phase I is deployed along the north-south seismic belt in southwest China. In this study, we analyze seismic data recorded on the ChinArray following the February 15, 2013 Chelyabinsk (Russia) meteor. This was the largest known object entering the Earth's atmosphere since the 1908 Tunguska meteor. The seismic energy radiated from this event was recorded by seismic stations worldwide including the dense ChinArray that are more than 4000 km away. The weak signal from the meteor event was contaminated by a magnitude 5.8 Tonga earthquake occurred ~20 min earlier. To test the feasibility of detecting the weak seismic signals from the meteor event, we compute vespagram and perform F-K analysis to the surface-wave data. We identify a seismic phase with back azimuth (BAZ) of 329.7° and slowness of 34.73 s/deg, corresponding to the surface wave from the Russian meteor event (BAZ ~325.97°). The surface magnitude (M S) of the meteor event is 3.94 ± 0.18. We also perform similar analysis on the data from the broadband array F-net in Japan, and find the BAZ of the surface waves to be 316.61°. With the different BAZs of ChinArray and F-net, we locate the Russian meteor event at 58.80°N, 58.72°E. The relatively large mislocation (~438 km as compared with 55.15°N, 61.41°E by others) may be a result of the bending propagation path of surface waves, which deviates from the great circle path. Our results suggest that the dense ChinArray and its subarrays could be used to detect weak signals at teleseismic distances.

  4. Magi is associated with the par complex and functions antagonistically with bazooka to regulate the apical polarity complex

    DOE PAGESBeta

    Padash Barmchi, Mojgan; Samarasekera, Gayathri; Gilbert, Mary; Auld, Vanessa J.; Zhang, Bing; Nam, Sang -Chul

    2016-04-13

    The mammalian MAGI proteins play important roles in the maintenance of adherens and tight junctions. The MAGI family of proteins contains modular domains such as WW and PDZ domains necessary for scaffolding of membrane receptors and intracellular signaling components. Loss of MAGI leads to reduced junction stability while overexpression of MAGI can lead to increased adhesion and stabilization of epithelial morphology. However, how Magi regulates junction assembly in epithelia is largely unknown. We investigated the single Drosophila homologue of Magi to study the in vivo role of Magi in epithelial development. Magi is localized at the adherens junction and formsmore » a complex with the polarity proteins, Par3/Bazooka and aPKC. We generated a Magi null mutant and found that Magi null mutants were viable with no detectable morphological defects even though the Magi protein is highly conserved with vertebrate Magi homologues. However, overexpression of Magi resulted in the displacement of Baz/Par3 and aPKC and lead to an increase in the level of PIP3. Interestingly, we found that Magi and Baz functioned in an antagonistic manner to regulate the localization of the apical polarity complex. As a result, maintaining the balance between the level of Magi and Baz is an important determinant of the levels and localization of apical polarity complex.« less

  5. Loss of WSTF results in spontaneous fluctuations of heterochromatin formation and resolution, combined with substantial changes to gene expression

    PubMed Central

    2013-01-01

    Background Williams syndrome transcription factor (WSTF) is a multifaceted protein that is involved in several nuclear processes, including replication, transcription, and the DNA damage response. WSTF participates in a chromatin-remodeling complex with the ISWI ATPase, SNF2H, and is thought to contribute to the maintenance of heterochromatin, including at the human inactive X chromosome (Xi). WSTF is encoded by BAZ1B, and is one of twenty-eight genes that are hemizygously deleted in the genetic disorder Williams-Beuren syndrome (WBS). Results To explore the function of WSTF, we performed zinc finger nuclease-assisted targeting of the BAZ1B gene and isolated several independent knockout clones in human cells. Our results show that, while heterochromatin at the Xi is unaltered, new inappropriate areas of heterochromatin spontaneously form and resolve throughout the nucleus, appearing as large DAPI-dense staining blocks, defined by histone H3 lysine-9 trimethylation and association of the proteins heterochromatin protein 1 and structural maintenance of chromosomes flexible hinge domain containing 1. In three independent mutants, the expression of a large number of genes were impacted, both up and down, by WSTF loss. Conclusions Given the inappropriate appearance of regions of heterochromatin in BAZ1B knockout cells, it is evident that WSTF performs a critical role in maintaining chromatin and transcriptional states, a property that is likely compromised by WSTF haploinsufficiency in WBS patients. PMID:24168170

  6. Magi Is Associated with the Par Complex and Functions Antagonistically with Bazooka to Regulate the Apical Polarity Complex

    PubMed Central

    Padash Barmchi, Mojgan; Samarasekera, Gayathri; Gilbert, Mary; Auld, Vanessa J.; Zhang, Bing

    2016-01-01

    The mammalian MAGI proteins play important roles in the maintenance of adherens and tight junctions. The MAGI family of proteins contains modular domains such as WW and PDZ domains necessary for scaffolding of membrane receptors and intracellular signaling components. Loss of MAGI leads to reduced junction stability while overexpression of MAGI can lead to increased adhesion and stabilization of epithelial morphology. However, how Magi regulates junction assembly in epithelia is largely unknown. We investigated the single Drosophila homologue of Magi to study the in vivo role of Magi in epithelial development. Magi is localized at the adherens junction and forms a complex with the polarity proteins, Par3/Bazooka and aPKC. We generated a Magi null mutant and found that Magi null mutants were viable with no detectable morphological defects even though the Magi protein is highly conserved with vertebrate Magi homologues. However, overexpression of Magi resulted in the displacement of Baz/Par3 and aPKC and lead to an increase in the level of PIP3. Interestingly, we found that Magi and Baz functioned in an antagonistic manner to regulate the localization of the apical polarity complex. Maintaining the balance between the level of Magi and Baz is an important determinant of the levels and localization of apical polarity complex. PMID:27074039

  7. Daily Physical Activity and Screen Time, but Not Other Sedentary Activities, Are Associated with Measures of Obesity during Childhood

    PubMed Central

    Lee, Shoo Thien; Wong, Jyh Eiin; Nik Shanita, Safii; Ismail, Mohd Noor; Deurenberg, Paul; Poh, Bee Koon

    2014-01-01

    Childhood obesity is related to low physical activity level and a sedentary lifestyle. The aim of this study was to assess the physical activity level and sedentary behaviour of Malaysian children aged 7 to 12 years and to examine their association with body mass index (BMI), BMI-for-age Z-score (BAZ), body fatness (%BF) and waist circumference (WC). A total of 1736 children, representing all ethnic groups were recruited from six regions of Malaysia. Anthropometric measurements included body weight, height and waist circumference. Body fat percentage (%BF) was assessed using bioelectrical impedance. Physical activity was assessed by a physical activity questionnaire (PAQ) in all children and by pedometers in a subsample (n = 514). PAQ score and pedometer step counts were negatively associated with BMI, BAZ, %BF and WC after adjusting for covariates. Screen time was positively associated with BAZ and WC. However, other sedentary activities were not significantly related with any anthropometric indicators. Strategies to promote active living among children in Malaysia should focus not only on increasing physical activity but also emphasise reduction in sedentary behaviours. PMID:25546277

  8. Daily physical activity and screen time, but not other sedentary activities, are associated with measures of obesity during childhood.

    PubMed

    Lee, Shoo Thien; Wong, Jyh Eiin; Shanita, Safii Nik; Ismail, Mohd Noor; Deurenberg, Paul; Poh, Bee Koon

    2015-01-01

    Childhood obesity is related to low physical activity level and a sedentary lifestyle. The aim of this study was to assess the physical activity level and sedentary behaviour of Malaysian children aged 7 to 12 years and to examine their association with body mass index (BMI), BMI-for-age Z-score (BAZ), body fatness (%BF) and waist circumference (WC). A total of 1736 children, representing all ethnic groups were recruited from six regions of Malaysia. Anthropometric measurements included body weight, height and waist circumference. Body fat percentage (%BF) was assessed using bioelectrical impedance. Physical activity was assessed by a physical activity questionnaire (PAQ) in all children and by pedometers in a subsample (n = 514). PAQ score and pedometer step counts were negatively associated with BMI, BAZ, %BF and WC after adjusting for covariates. Screen time was positively associated with BAZ and WC. However, other sedentary activities were not significantly related with any anthropometric indicators. Strategies to promote active living among children in Malaysia should focus not only on increasing physical activity but also emphasise reduction in sedentary behaviours. PMID:25546277

  9. Relationship between anthropometric indicators and cognitive performance in Southeast Asian school-aged children.

    PubMed

    Sandjaja; Poh, Bee Koon; Rojroonwasinkul, Nipa; Le Nyugen, Bao Khanh; Budiman, Basuki; Ng, Lai Oon; Soonthorndhada, Kusol; Xuyen, Hoang Thi; Deurenberg, Paul; Parikh, Panam

    2013-09-01

    Nutrition is an important factor in mental development and, as a consequence, in cognitive performance. Malnutrition is reflected in children's weight, height and BMI curves. The present cross-sectional study aimed to evaluate the association between anthropometric indices and cognitive performance in 6746 school-aged children (aged 6-12 years) of four Southeast Asian countries: Indonesia; Malaysia; Thailand; Vietnam. Cognitive performance (non-verbal intelligence quotient (IQ)) was measured using Raven's Progressive Matrices test or Test of Non-Verbal Intelligence, third edition (TONI-3). Height-for-age z-scores (HAZ), weight-for-age z-scores (WAZ) and BMI-for-age z-scores (BAZ) were used as anthropometric nutritional status indices. Data were weighted using age, sex and urban/rural weight factors to resemble the total primary school-aged population per country. Overall, 21% of the children in the four countries were underweight and 19% were stunted. Children with low WAZ were 3·5 times more likely to have a non-verbal IQ < 89 (OR 3·53 and 95% CI 3·52, 3·54). The chance of having a non-verbal IQ < 89 was also doubled with low BAZ and HAZ. In contrast, except for severe obesity, the relationship between high BAZ and IQ was less clear and differed per country. The odds of having non-verbal IQ levels < 89 also increased with severe obesity. In conclusion, undernourishment and non-verbal IQ are significantly associated in 6-12-year-old children. Effective strategies to improve nutrition in preschoolers and school-aged children can have a pronounced effect on cognition and, in the longer term, help in positively contributing to individual and national development. PMID:24016767

  10. Effect of Age at Antiretroviral Therapy Initiation on Catch-Up Growth within the First 24 Months among HIV-Infected Children in the IeDEA West African Pediatric Cohort

    PubMed Central

    Jesson, Julie; Koumakpaï, Sikiratou; Diagne, Ndeye R.; Amorissani-Folquet, Madeleine; Kouéta, Fla; Aka, Addi; Lawson-Evi, Koko; Dicko, Fatoumata; Kouakou, Kouadio; Pety, Touré; Renner, Lorna; Eboua, Tanoh; Coffie, Patrick A.; Desmonde, Sophie; Leroy, Valériane

    2015-01-01

    Background We described malnutrition and the effect of age at antiretroviral therapy (ART) initiation on catch-up growth over 24 months among HIV-infected children enrolled in the IeDEA West African paediatric cohort (pWADA). Methods Malnutrition was defined at ART initiation (baseline) by a Z-score <-2 SD, according to three anthropometric indicators: Weight-for-age (WAZ) for underweight, Height-for-age (HAZ) for stunting, and Weight-for-Height/BMI-for-age (WHZ/BAZ) for wasting. Kaplan-Meier estimates for catch-up growth (Z-score ≥-2 SD) on ART, adjusted for gender, immunodeficiency and malnutrition at ART initiation, ART regimen, time period and country, were compared by age at ART initiation. Cox proportional hazards regression models determined predictors of catch-up growth on ART over 24 months. Results Between 2001 and 2012, 2004 HIV-infected children < 10 years of age were included. At ART initiation, 51% were underweight, 48% were stunted and 33% were wasted. The 24-month adjusted estimates for catch-up growth were 69% (95% confidence interval [CI]: 57;80), 61% (95%CI: 47;70), and 90% (95%CI: 76;95) for WAZ, HAZ, and WHZ/BAZ, respectively. Adjusted catch-up growth was more likely for children <5 years of age at ART initiation compared to children ≥5 years for WAZ, HAZ (P<0.001), and for WHZ/BAZ (P = 0.026). Conclusions Malnutrition among these children is an additional burden that has to be urgently managed. Despite a significant growth improvement after 24 months on ART, especially in children <5 years, a substantial proportion of children still never achieved catch-up growth. Nutritional care should be part of the global healthcare of HIV-infected children in sub-Saharan Africa. PMID:25955835

  11. Alpha-linolenic acid (ALA) is inversely related to development of adiposity in school-age children

    PubMed Central

    Perng, Wei; Villamor, Eduardo; Mora-Plazas, Mercedes; Marin, Constanza; Baylin, Ana

    2015-01-01

    Background/Objectives Studies in adults indicate that dietary polyunsaturated fatty acid (PUFA) composition may play a role in development of adiposity. Because adipocyte quantity is established between late childhood and early adolescence, understanding the impact of PUFAs on weight gain during the school-age years is crucial to developing effective interventions. Subjects/Methods We quantified N-3 and N-6 PUFAs in serum samples of 668 Colombian schoolchildren aged 5–12 years at the time of recruitment into a cohort study, using gas-liquid chromatography. Serum concentrations of N-3 (ALA, EPA, DHA) and N-6 PUFAs (LA, GLA, DGLA, AA) were determined as % total fatty acids. Children’s anthropometry was measured annually for a median of 30 months. We used mixed-effects models with restricted cubic splines to construct population body mass index-for-age z-score (BAZ) growth curves for age-and sex-specific quartiles of each PUFA. Results N-3 ALA was inversely related to BAZ gain after adjustment for sex, baseline age and weight status, and household socioeconomic level. Estimated BAZ change between 6 and 14 years among children in the highest quartile of ALA compared to those in the lowest quartile was 0.45 (95% CI: 0.07, 0.83) lower (P-trend=0.006). Conclusions N-3 ALA may be protective against weight gain in school-age children. Whether improvement in PUFA status reduces adiposity in pediatric populations deserves evaluation in randomized trials. PMID:25271016

  12. Association of Maternal and Child Nutritional Status in Brazil: A Population Based Cross-Sectional Study

    PubMed Central

    Felisbino-Mendes, Mariana Santos; Villamor, Eduardo; Velasquez-Melendez, Gustavo

    2014-01-01

    Background Although child undernutrition and stunting has been decreasing worldwide while obesity rates increase, these extreme conditions might coexist in families from low- and middle-income countries. We examined the association between maternal and child anthropometric indicators using a population representative sample. Methods 4,258 non-pregnant women and their children <60 months who participated in the 2006 Brazilian Demographic Health Survey. We compared the distributions of two nutritional indexes of children, height-for-age (HAZ) and body mass index-for age (BAZ) z-scores, by categories of maternal height, body mass index (BMI), and waist circumference (WC). Adjusted mean differences and 95% confidence intervals (95% CI) were estimated from linear regression, taking into account the complex survey design. We also examined the associations of maternal anthropometry with the prevalence of child stunting (HAZ<−2) and overweight/obesity (BAZ>2). Results HAZ was positively associated with maternal height and WC in a linear fashion. After adjustment, for sociodemographic characteristics, children whose mothers' height was<145 cm had 1.2 lower HAZ than children whose mothers were ≥160 cm tall (p-trend<0.0001). After further adjustment for maternal height and maternal BMI, children of mothers with a waist circumference ≥88 cm had 0.3 higher HAZ than those of mothers with WC<80 cm (p-trend<0.01). Adjusted prevalence ratios and 95% CI for stunting by the categories of maternal height (<145, 145–149, 150–154, 155–159 and ≥160 cm) were, respectively, 2.95 (1.51;5.77), 2.29 (1.33;3.93), 1.09 (0.63;1.87), and 0.89 (0.45;1.77), (p-trend = 0.001). BAZ was positively associated with maternal BMI and WC. Conclusion We observed a strong, positive association of maternal and child nutritional status. Mothers of low stature had children with lower stature, mothers with central obesity had taller children, and mothers with overall or abdominal obesity had

  13. Phase Structures and Piezoelectric Properties of (K,Na,Li)(Nb,Sb)O3-(Bi,Ag)ZrO3 Lead-Free Ceramics

    NASA Astrophysics Data System (ADS)

    Li, ZhiPeng; Zhang, Yang; Li, LingYu; Li, JianKang; Zhai, JiWei

    2016-06-01

    Samples in the pseudoternary lead-free piezoelectric ceramic system 0.94KNN-(0.06 - x)LiSbO3- x(Bi0.5Ag0.5)ZrO3 were prepared using a solid-state reaction technique and their phase transition behavior and electrical properties studied. Results showed that BAZ diffuses into KNN-LS to form a new solid solution, and induces a phase transition from tetragonal to rhombohedral phase with increase of x. At 0.02 ≤ x ≤ 0.03, coexistence of tetragonal and rhombohedral phases is observed, and enhanced piezoelectric properties are achieved in this composition range due to the polymorphic phase transition near room temperature. Doping with (Bi0.5Ag0.5)ZrO3 effectively promotes densification and further enhances the piezoelectric and dielectric properties of of the ceramics. Moreover, the ceramic with x = 0.025 possesses excellent electrical properties of k p = 42.3%, {d_{33}^{*}} = 320 pm/V and d 33 = 235 pC/N, tan δ = 0.039, and T c = 326°C. This result indicates that 0.94KNN-0.035LS-0.025BAZ ceramic is a promising lead-free material for practical applications.

  14. Biobased polyesters with composition-dependent thermomechanical properties: synthesis and characterization of poly(butylene succinate-co-butylene azelate).

    PubMed

    Mincheva, Rosica; Delangre, Adrien; Raquez, Jean-Marie; Narayan, Ramani; Dubois, Philippe

    2013-03-11

    Environmentally friendly poly(butylenesuccinate-co-butyleneazelate) (P(BS-co-BAz)s) aliphatic copolyesters with composition-dependent thermomechanical properties were synthesized from succinic acid (SuA), 1,4-butanediol (BDO), and dimethylazelate (DMAz) through a two-step polycondensation reaction. The molar SuA/AzA ratio was varied from 4:1 to 1:4, and the chemical structure and molecular characteristics of resulting (co)polyesters were characterized by NMR and SEC, whereas thermal properties and crystallinity were studied by differential scanning calorimetry (DSC), dynamic mechanical thermal analyses (DMTA), and X-ray diffraction (XRD). A good agreement between theoretical and experimental SuA/AzA molar ratios in the copolyesters was achieved, together with the recovery of semicrystalline random copolymers of uniform composition along the chains. NMR, DSC, DMTA, and XRD results show that depending on their composition the P(BS-co-BAz) copolyesters might find applications from elastomers to high-impact thermoplastics. PMID:23369072

  15. Predicted reliability of aerospace electronics: Application of two advanced probabilistic concepts

    NASA Astrophysics Data System (ADS)

    Suhir, E.

    Two advanced probabilistic design-for-reliability (PDfR) concepts are addressed and discussed in application to the prediction, quantification and assurance of the aerospace electronics reliability: 1) Boltzmann-Arrhenius-Zhurkov (BAZ) model, which is an extension of the currently widely used Arrhenius model and, in combination with the exponential law of reliability, enables one to obtain a simple, easy-to-use and physically meaningful formula for the evaluation of the probability of failure (PoF) of a material or a device after the given time in operation at the given temperature and under the given stress (not necessarily mechanical), and 2) Extreme Value Distribution (EVD) technique that can be used to assess the number of repetitive loadings that result in the material/device degradation and eventually lead to its failure by closing, in a step-wise fashion, the gap between the bearing capacity (stress-free activation energy) of the material or the device and the demand (loading). It is shown that the material degradation (aging, damage accumulation, flaw propagation, etc.) can be viewed, when BAZ model is considered, as a Markovian process, and that the BAZ model can be obtained as the ultimate steady-state solution to the well-known Fokker-Planck equation in the theory of Markovian processes. It is shown also that the BAZ model addresses the worst, but a reasonably conservative, situation. It is suggested therefore that the transient period preceding the condition addressed by the steady-state BAZ model need not be accounted for in engineering evaluations. However, when there is an interest in understanding the transient degradation process, the obtained solution to the Fokker-Planck equation can be used for this purpose. As to the EVD concept, it attributes the degradation process to the accumulation of damages caused by a train of repetitive high-level loadings, while loadings of levels that are considerably lower than their extreme values do not contribute

  16. Rapid Infancy Weight Gain and 7- to 9-year Childhood Obesity Risk: A Prospective Cohort Study in Rural Western China.

    PubMed

    Zhou, Jing; Dang, Shaonong; Zeng, Lingxia; Gao, Wenlong; Wang, Duolao; Li, Qiang; Jiang, Wenhui; Pei, Leilei; Li, Chao; Yan, Hong

    2016-04-01

    Obesity is increasing in developing countries. This study aimed to identify the association between rapid infancy weight gain and obesity risk among early school-age children.A total of 581 singletons (349 boys, 232 girls) whose mothers participated in an antenatal multiple micronutrient supplement trial in rural western China were followed from birth to between 7 and 9 years of age. Height and weight were measured at birth, 1.5 years, and between 7 and 9 years. At the 7- to 9-year time point, body composition was determined using bioelectrical impedance analysis. Multilevel mixed analysis was used to test the associations between rapid weight gain in infancy (from birth to age 1.5 years) and body size and composition or overweight/obesity among early school-age children.Overall, 31.2% (181 of 581) of the infants showed a weight-for-age Z score gain greater than 0.67 between birth and 1.5 years, indicating rapid weight gain. Approximately 5.7% (33 of 579) of the subjects were overweight (BMI-for-age Z scores [BAZ] >1 and ≤2) or obese (BAZ >2). Rapid infancy weight gain was associated with a higher BAZ (P < 0.001), mid-upper arm circumferences (P < 0.001), percentage body fat (P < 0.001), and fat mass index (P < 0.001) at 7 to 9 years of age after adjusting for biological and social economic factors, genetic factors, and perinatal and postnatal factors. These associations appeared to be independent of gender, economic status at early school age, and maternal nutritional status at enrollment. Rapid growers may have approximately 3 times the risk of being overweight/obese during the early school-age years (odds ratio = 2.94, 95% CI: 1.17-7.43, P = 0.022).Rapid infancy weight gain is a risk factor for being overweight/obesity among early school-age children in rural western China. We propose that social and biological determinants, such as economic status, physical activity, and feeding practice, should be targeted to prevent obesity. PMID

  17. Rapid Infancy Weight Gain and 7- to 9-year Childhood Obesity Risk

    PubMed Central

    Zhou, Jing; Dang, Shaonong; Zeng, Lingxia; Gao, Wenlong; Wang, Duolao; Li, Qiang; Jiang, Wenhui; Pei, Leilei; Li, Chao; Yan, Hong

    2016-01-01

    Abstract Obesity is increasing in developing countries. This study aimed to identify the association between rapid infancy weight gain and obesity risk among early school-age children. A total of 581 singletons (349 boys, 232 girls) whose mothers participated in an antenatal multiple micronutrient supplement trial in rural western China were followed from birth to between 7 and 9 years of age. Height and weight were measured at birth, 1.5 years, and between 7 and 9 years. At the 7- to 9-year time point, body composition was determined using bioelectrical impedance analysis. Multilevel mixed analysis was used to test the associations between rapid weight gain in infancy (from birth to age 1.5 years) and body size and composition or overweight/obesity among early school-age children. Overall, 31.2% (181 of 581) of the infants showed a weight-for-age Z score gain greater than 0.67 between birth and 1.5 years, indicating rapid weight gain. Approximately 5.7% (33 of 579) of the subjects were overweight (BMI-for-age Z scores [BAZ] >1 and ≤2) or obese (BAZ >2). Rapid infancy weight gain was associated with a higher BAZ (P < 0.001), mid-upper arm circumferences (P < 0.001), percentage body fat (P < 0.001), and fat mass index (P < 0.001) at 7 to 9 years of age after adjusting for biological and social economic factors, genetic factors, and perinatal and postnatal factors. These associations appeared to be independent of gender, economic status at early school age, and maternal nutritional status at enrollment. Rapid growers may have approximately 3 times the risk of being overweight/obese during the early school-age years (odds ratio = 2.94, 95% CI: 1.17–7.43, P = 0.022). Rapid infancy weight gain is a risk factor for being overweight/obesity among early school-age children in rural western China. We propose that social and biological determinants, such as economic status, physical activity, and feeding practice, should be targeted to prevent

  18. Disrupting Acetyl-Lysine Recognition: Progress in the Development of Bromodomain Inhibitors.

    PubMed

    Romero, F Anthony; Taylor, Alexander M; Crawford, Terry D; Tsui, Vickie; Côté, Alexandre; Magnuson, Steven

    2016-02-25

    Bromodomains, small protein modules that recognize acetylated lysine on histones, play a significant role in the epigenome, where they function as "readers" that ultimately determine the functional outcome of the post-translational modification. Because the initial discovery of selective BET inhibitors have helped define the role of that protein family in oncology and inflammation, BET bromodomains have continued to garner the most attention of any other bromodomain. More recently, non-BET bromodomain inhibitors that are potent and selective have been disclosed for ATAD2, CBP, BRD7/9, BRPF, BRPF/TRIM24, CECR2, SMARCA4, and BAZ2A/B. Such novel inhibitors can be used to probe the physiological function of these non-BET bromodomains and further understanding of their role in certain disease states. Here, we provide an update to the progress in identifying selective bromodomain inhibitors and their use as biological tools, as well as our perspective on the field. PMID:26572217

  19. Isoxazole-Derived Amino Acids are Bromodomain-Binding Acetyl-Lysine Mimics: Incorporation into Histone H4 Peptides and Histone H3.

    PubMed

    Sekirnik Née Measures, Angelina R; Hewings, David S; Theodoulou, Natalie H; Jursins, Lukass; Lewendon, Katie R; Jennings, Laura E; Rooney, Timothy P C; Heightman, Tom D; Conway, Stuart J

    2016-07-11

    A range of isoxazole-containing amino acids was synthesized that displaced acetyl-lysine-containing peptides from the BAZ2A, BRD4(1), and BRD9 bromodomains. Three of these amino acids were incorporated into a histone H4-mimicking peptide and their affinity for BRD4(1) was assessed. Affinities of the isoxazole-containing peptides are comparable to those of a hyperacetylated histone H4-mimicking cognate peptide, and demonstrated a dependence on the position at which the unnatural residue was incorporated. An isoxazole-based alkylating agent was developed to selectively alkylate cysteine residues in situ. Selective monoalkylation of a histone H4-mimicking peptide, containing a lysine to cysteine residue substitution (K12C), resulted in acetyl-lysine mimic incorporation, with high affinity for the BRD4 bromodomain. The same technology was used to alkylate a K18C mutant of histone H3. PMID:27264992

  20. Control of threshold enhancements in harmonic generation by atoms in a two-color laser field with orthogonal polarizations

    NASA Astrophysics Data System (ADS)

    Frolov, M. V.; Manakov, N. L.; Sarantseva, T. S.; Silaev, A. A.; Vvedenskii, N. V.; Starace, Anthony F.

    2016-02-01

    Threshold phenomena (or channel-closing effects) are analyzed in high-order harmonic generation (HHG) by atoms in a two-color laser field with orthogonal linearly polarized components of a fundamental field and its second harmonic. We show that the threshold behavior of HHG rates for the case of a weak second harmonic component is sensitive to the parity of a closing multiphoton ionization channel and the spatial symmetry of the initial bound state of the target atom, while for the case of comparable intensities of both components, suppression of threshold phenomena is observed as the relative phase between the components of a two-color field varies. A quantum orbit analysis as well as phenomenological considerations in terms of Baz' theory of threshold phenomena [Zh. Eksp. Teor. Fiz. 33, 923 (1957)] are presented in order to describe and explain the major features of threshold phenomena in HHG by a two-color field.

  1. Maternal overweight/obesity characteristics and child anthropometric status in Jos, Nigeria

    PubMed Central

    John, Collins; Ichikawa, Tomo; Abdu, Halima; Ocheke, Isaac; Diala, Udochukwu; Modise-Letsatsi, Virginia; Wada, Takayuki; Okolo, Seline; Yamamoto, Taro

    2015-01-01

    Objective: This study is to determine the pattern of overweight and obesity and its relationship with childhood anthropometric status in Nigeria. Materials and Methods: This cross-sectional study was conducted in Jos, Nigeria. Interviewer administered questionnaire was used in data collection. Maternal and child anthropometric measurements were obtained using standard WHO methods. Child anthropometric Z scores were obtained from WHO Anthroplus while BMI of mothers were also determined. Totally, 262 mother-child pairs were recruited. Results: Mean maternal age and mean child age were 30.8 ± 6.3 yrs (15-47 yrs) and 22.3 ± 18.7 months (3-72 months). Prevalence of maternal underweight, overweight and obesity was 4.2% (11/262), 29.4% (77/262) and 25.9% (68/262), respectively. Child overweight/obesity was 5.4% (14/262), severe under-nutrition 5.7% (15/262). Mean maternal BMI was higher in the older, more educated and higher socioeconomic status (SES). Child mean birth-weight, weight-for-age Z-score and BMI-for-age Z-score (BAZ) were higher among mothers with BMI ≥ 25 kg/m2. All large-for-age babies were in mothers with maternal BMI ≥ 25 kg/m2. Childhood over-nutrition was more common in maternal BMI of ≥25 kg/m2. Overall, BAZ was directly related with maternal BMI, maternal age and birth-weight, although it was inversely related with maternal BM I ≥ 25 kg/m2. Conclusion: Higher BMI is seen in educated and higher SES mothers and this impact on childhood anthropometry. PMID:26759505

  2. Coda Q Attenuation and Source Parameters Analysis in North East India Using Local Earthquakes

    NASA Astrophysics Data System (ADS)

    Mohapatra, A. K.; Mohanty, W. K.; Earthquake Seismology

    2010-12-01

    Alok Kumar Mohapatra1* and William Kumar Mohanty1 *Corresponding author: alokgpiitkgp@gmail.com 1Department of Geology and Geophysics, Indian Institute of Technology, Kharagpur, West Bengal, India. Pin-721302 ABSTRACT In the present study, the quality factor of coda waves (Qc) and the source parameters has been estimated for the Northeastern India, using the digital data of ten local earthquakes from April 2001 to November 2002. Earthquakes with magnitude range from 3.8 to 4.9 have been taken into account. The time domain coda decay method of a single back scattering model is used to calculate frequency dependent values of Coda Q (Qc) where as, the source parameters like seismic moment(Mo), stress drop, source radius(r), radiant energy(Wo),and strain drop are estimated using displacement amplitude spectrum of body wave using Brune's model. The earthquakes with magnitude range 3.8 to 4.9 have been used for estimation Qc at six central frequencies 1.5 Hz, 3.0 Hz, 6.0 Hz, 9.0 Hz, 12.0 Hz, and 18.0 Hz. In the present work, the Qc value of local earthquakes are estimated to understand the attenuation characteristic, source parameters and tectonic activity of the region. Based on a criteria of homogeneity in the geological characteristics and the constrains imposed by the distribution of available events the study region has been classified into three zones such as the Tibetan Plateau Zone (TPZ), Bengal Alluvium and Arakan-Yuma Zone (BAZ), Shillong Plateau Zone (SPZ). It follows the power law Qc= Qo (f/fo)n where, Qo is the quality factor at the reference frequency (1Hz) fo and n is the frequency parameter which varies from region to region. The mean values of Qc reveals a dependence on frequency, varying from 292.9 at 1.5 Hz to 4880.1 at 18 Hz. Average frequency dependent relationship Qc values obtained of the Northeastern India is 198 f 1.035, while this relationship varies from the region to region such as, Tibetan Plateau Zone (TPZ): Qc= 226 f 1.11, Bengal Alluvium

  3. Studies of New Fused Benzazepine as Selective Dopamine D3 Receptor Antagonists Using 3D-QSAR, Molecular Docking and Molecular Dynamics

    PubMed Central

    Liu, Jing; Li, Yan; Zhang, Shuwei; Xiao, Zhengtao; Ai, Chunzhi

    2011-01-01

    In recent years, great interest has been paid to the development of compounds with high selectivity for central dopamine (DA) D3 receptors, an interesting therapeutic target in the treatment of different neurological disorders. In the present work, based on a dataset of 110 collected benzazepine (BAZ) DA D3 antagonists with diverse kinds of structures, a variety of in silico modeling approaches, including comparative molecular field analysis (CoMFA), comparative similarity indices analysis (CoMSIA), homology modeling, molecular docking and molecular dynamics (MD) were carried out to reveal the requisite 3D structural features for activity. Our results show that both the receptor-based (Q2 = 0.603, R2ncv = 0.829, R2pre = 0.690, SEE = 0.316, SEP = 0.406) and ligand-based 3D-QSAR models (Q2 = 0.506, R2ncv =0.838, R2pre = 0.794, SEE = 0.316, SEP = 0.296) are reliable with proper predictive capacity. In addition, a combined analysis between the CoMFA, CoMSIA contour maps and MD results with a homology DA receptor model shows that: (1) ring-A, position-2 and R3 substituent in ring-D are crucial in the design of antagonists with higher activity; (2) more bulky R1 substituents (at position-2 of ring-A) of antagonists may well fit in the binding pocket; (3) hydrophobicity represented by MlogP is important for building satisfactory QSAR models; (4) key amino acids of the binding pocket are CYS101, ILE105, LEU106, VAL151, PHE175, PHE184, PRO254 and ALA251. To our best knowledge, this work is the first report on 3D-QSAR modeling of the new fused BAZs as DA D3 antagonists. These results might provide information for a better understanding of the mechanism of antagonism and thus be helpful in designing new potent DA D3 antagonists. PMID:21541053

  4. Animal Models of Williams Syndrome

    PubMed Central

    OSBORNE, LUCY R.

    2010-01-01

    In recent years, researchers have generated a variety of mouse models in an attempt to dissect the contribution of individual genes to the complex phenotype associated with Williams syndrome (WS). The mouse genome is easily manipulated to produce animals that are copies of humans with genetic conditions, be it with null mutations, hypomorphic mutations, point mutations, or even large deletions encompassing many genes. The existing mouse models certainly seem to implicate hemizygosity for ELN, BAZ1B, CLIP2, and GTF2IRD1 in WS, and new mice with large deletions of the WS region are helping us to understand both the additive and potential combinatorial effects of hemizygosity for specific genes. However, not all genes that are haploinsufficient in humans prove to be so in mice and the effect of genetic background can also have a significant effect on the penetrance of many phenotypes. Thus although mouse models are powerful tools, the information garnered from their study must be carefully interpreted. Nevertheless, mouse models look set to provide a wealth of information about the neuroanatomy, neurophysiology and molecular pathways that underlie WS and in the future will act as essential tools for the development and testing of therapeutics. PMID:20425782

  5. KomTronic® - Aktorische Werkzeugsysteme für die Einsatzerweiterung von Standard-Bearbeitungszentren

    NASA Astrophysics Data System (ADS)

    Fronius, Jürgen

    Die Entwickler spanender Fertigungssysteme stehen seit geraumer Zeit unter erhöhtem Innovationsdruck. Neben dem entscheidenden Aspekt der Stückkosten spielt das gesteigerte Umweltbewusstsein eine zunehmende Rolle. Die aktuelleKrise des Kreditwesens tut ein Übriges um den Forderungen nach geringen Investitionskosten und damit geringem Kreditbedarf oder erhöhter Flexibilität zur Kosteneinsparung bei Serienumstellung, geringem Energiebedarfund ressourcenschonendem Betrieb neuen Nachdruck zu verschaffen. Auf genau diesen Forderungskatalog wurde die KomTronic® - Produktpalette zugeschnitten. Ausgangspunkt war die Flexibilität die besonders bei komplexen, asymmetrischen Bauteilen eine Herausforderung darstellt. Quaderförmige Bauteile wie Hydraulikventilblöcke oder Zylinderköpfe von Verbrennungsmotoren stellen in ihrer Kombination aus Fräs- Drehbearbeitungen die "Königsklasse“ der spanenden Fertigung dar. Die Lösungen, besonders für die Drehkonturen sind im Allgemeinen großserientauglich ausgelegt. Die Konsequenz sind bauteilbezogen ausgelegte Transferstrassen oder Rundtaktmaschinen, eine Kombination dieser Bearbeitungen auf einem flexiblen BAZ waren bislang nicht möglich.

  6. Identification of a Sudden Cardiac Death Susceptibility Locus at 2q24.2 through Genome-Wide Association in European Ancestry Individuals

    PubMed Central

    Reinier, Kyndaron; Teodorescu, Carmen; Uy-Evanado, Audrey; Carter-Monroe, Naima; Kaikkonen, Kari S.; Kortelainen, Marja-Leena; Boucher, Gabrielle; Lagacé, Caroline; Moes, Anna; Zhao, XiaoQing; Kolodgie, Frank; Rivadeneira, Fernando; Hofman, Albert; Witteman, Jacqueline C. M.; Uitterlinden, André G.; Marsman, Roos F.; Pazoki, Raha; Bardai, Abdennasser; Koster, Rudolph W.; Dehghan, Abbas; Hwang, Shih-Jen; Bhatnagar, Pallav; Post, Wendy; Hilton, Gina; Prineas, Ronald J.; Li, Man; Köttgen, Anna; Ehret, Georg; Boerwinkle, Eric; Coresh, Josef; Kao, W. H. Linda; Psaty, Bruce M.; Tomaselli, Gordon F.; Sotoodehnia, Nona; Siscovick, David S.; Burke, Greg L.; Marbán, Eduardo; Spooner, Peter M.; Cupples, L. Adrienne; Jui, Jonathan; Gunson, Karen; Kesäniemi, Y. Antero; Wilde, Arthur A. M.; Tardif, Jean-Claude; O'Donnell, Christopher J.; Bezzina, Connie R.; Virmani, Renu; Stricker, Bruno H. C. h.; Tan, Hanno L.; Albert, Christine M.; Chakravarti, Aravinda; Rioux, John D.; Huikuri, Heikki V.; Chugh, Sumeet S.

    2011-01-01

    Sudden cardiac death (SCD) continues to be one of the leading causes of mortality worldwide, with an annual incidence estimated at 250,000–300,000 in the United States and with the vast majority occurring in the setting of coronary disease. We performed a genome-wide association meta-analysis in 1,283 SCD cases and >20,000 control individuals of European ancestry from 5 studies, with follow-up genotyping in up to 3,119 SCD cases and 11,146 controls from 11 European ancestry studies, and identify the BAZ2B locus as associated with SCD (P = 1.8×10−10). The risk allele, while ancestral, has a frequency of ∼1.4%, suggesting strong negative selection and increases risk for SCD by 1.92–fold per allele (95% CI 1.57–2.34). We also tested the role of 49 SNPs previously implicated in modulating electrocardiographic traits (QRS, QT, and RR intervals). Consistent with epidemiological studies showing increased risk of SCD with prolonged QRS/QT intervals, the interval-prolonging alleles are in aggregate associated with increased risk for SCD (P = 0.006). PMID:21738491

  7. An atypical 7q11.23 deletion in a normal IQ Williams–Beuren syndrome patient

    PubMed Central

    Ferrero, Giovanni Battista; Howald, Cédric; Micale, Lucia; Biamino, Elisa; Augello, Bartolomeo; Fusco, Carmela; Turturo, Maria Giuseppina; Forzano, Serena; Reymond, Alexandre; Merla, Giuseppe

    2010-01-01

    Williams–Beuren syndrome (WBS; OMIM no. 194050) is a multisystemic neurodevelopmental disorder caused by a hemizygous deletion of 1.55 Mb on chromosome 7q11.23 spanning 28 genes. Haploinsufficiency of the ELN gene was shown to be responsible for supravalvular aortic stenosis and generalized arteriopathy, whereas LIMK1, CLIP2, GTF2IRD1 and GTF2I genes were suggested to be linked to the specific cognitive profile and craniofacial features. These insights for genotype–phenotype correlations came from the molecular and clinical analysis of patients with atypical deletions and mice models. Here we report a patient showing mild WBS physical phenotype and normal IQ, who carries a shorter 1 Mb atypical deletion. This rearrangement does not include the GTF2IRD1 and GTF2I genes and only partially the BAZ1B gene. Our results are consistent with the hypothesis that hemizygosity of the GTF2IRD1 and GTF2I genes might be involved in the facial dysmorphisms and in the specific motor and cognitive deficits observed in WBS patients. PMID:19568270

  8. Identification of {sup 162}Gd and a new type of identical bands

    SciTech Connect

    Jones, E. F.; Gore, P. M.; Hamilton, J. H.; Ramayya, A. V.; Dodder, R. S.; Beyer, C. J.; Hwang, J. K.; Zhang, X. Q.; Kormicki, J.; Zhu, S. J.; Lima, A. P. de; Cole, J. D.; Aryaeinejad, R.; Ma, W. C.; Ter-Akopian, G. M.; Daniel, A. V.; Oganessian, Yu. Ts.; Rasmussen, J. O.; Asztalos, S. J.; Lee, I. Y.

    1998-12-21

    From {gamma}-{gamma}-{gamma} coincidence measurements in spontaneous fission of {sup 252}Cf, level energies were established to spins 14{sup +} to 20{sup +} in many neutron-rich nuclei. New isotope {sup 162}Gd was identified. Yrast bands of {sup 152,154,156}Nd, {sup 156,158,160}Sm, and {sup 160,162}Gd exhibit near-identical transition energies and moments of inertia (MOI) shifted by the same constant amounts for every spin state from 2{sup +} to 12{sup +} or 14{sup +} for nuclei differing by 2n, 4n, 2p, 4p, {alpha}, {alpha}+2p, and {alpha}+2n. These shifted identical bands (SIB) are a new phenomenon. Analysis of all known even-even proton- to neutron-rich nuclei from Ba(Z=56) to Os(Z=76) reveal no SIB for proton-rich nuclei and few cases of SIB for the most neutron-rich pairs around N=98-102 separated by 2n and 2p.

  9. Identification of {sup 162}Gd and a new type of identical bands

    SciTech Connect

    Jones, E.F.; Gore, P.M.; Hamilton, J.H.; Ramayya, A.V.; Dodder, R.S.; Beyer, C.J.; Hwang, J.K.; Zhang, X.Q.; Zhu, S.H.; de Lima, A.P.; Ter-Akopian, G.M.; Daniel, A.V. Zhu, S.H.; Ter-Akopian, G.M.; Daniel, A.V. de Lima, A.P.; Aryaeinejad, R. |; Oganessian, Yu. Ts.; Daniel, A.V.; Asztalos, S.J.; Lee, I.Y.; Stoyer, M.A. Prussin, S.G. Donangelo, R.

    1998-12-01

    From {gamma}-{gamma}-{gamma} coincidence measurements in spontaneous fission of {sup 252}Cf, level energies were established to spins 14{sup +} to 20{sup +} in many neutron-rich nuclei. New isotope {sup 162}Gd was identified. Yrast bands of {sup 152,154,156}Nd, {sup 156,158,160}Sm, and {sup 160,162}Gd exhibit near-identical transition energies and moments of inertia (MOI) shifted by the same constant amounts for every spin state from 2{sup +} to 12{sup +} or 14{sup +} for nuclei differing by 2n, 4n, 2p, 4p, {alpha}, {alpha}+2p, and {alpha}+2n. These shifted identical bands (SIB) are a new phenomenon. Analysis of all known even-even proton- to neutron-rich nuclei from Ba(Z=56) to Os(Z=76) reveal no SIB for proton-rich nuclei and few cases of SIB for the most neutron-rich pairs around N=98{endash}102 separated by 2n and 2p. {copyright} {ital 1998 American Institute of Physics.}

  10. Identification of [sup 162]Gd and a new type of identical bands

    SciTech Connect

    Jones, E.F.; Gore, P.M.; Hamilton, J.H.; Ramayya, A.V.; Dodder, R.S.; Beyer, C.J.; Hwang, J.K.; Zhang, X.Q.; Zhu, S.H.; de Lima, A.P.; Ter-Akopian, G.M.; Daniel, A.V. ) Zhu, S.H. ); Ter-Akopian, G.M.; Daniel, A.V. ) de Lima, A.P. ); Aryaeinejad, R. Physics Department, Mississippi State University, Mississippi State, Mississippi 39762 ); Oganessian, Yu. Ts.; Daniel, A.V. ); Asztalos, S.J.; Lee, I.Y. ); Stoyer, M.A. (Lawrence Livermore

    1998-12-01

    From [gamma]-[gamma]-[gamma] coincidence measurements in spontaneous fission of [sup 252]Cf, level energies were established to spins 14[sup +] to 20[sup +] in many neutron-rich nuclei. New isotope [sup 162]Gd was identified. Yrast bands of [sup 152,154,156]Nd, [sup 156,158,160]Sm, and [sup 160,162]Gd exhibit near-identical transition energies and moments of inertia (MOI) shifted by the same constant amounts for every spin state from 2[sup +] to 12[sup +] or 14[sup +] for nuclei differing by 2n, 4n, 2p, 4p, [alpha], [alpha]+2p, and [alpha]+2n. These shifted identical bands (SIB) are a new phenomenon. Analysis of all known even-even proton- to neutron-rich nuclei from Ba(Z=56) to Os(Z=76) reveal no SIB for proton-rich nuclei and few cases of SIB for the most neutron-rich pairs around N=98[endash]102 separated by 2n and 2p. [copyright] [ital 1998 American Institute of Physics.

  11. Molecular Basis of Histone Tail Recognition by Human TIP5 PHD Finger and Bromodomain of the Chromatin Remodeling Complex NoRC

    PubMed Central

    Tallant, Cynthia; Valentini, Erica; Fedorov, Oleg; Overvoorde, Lois; Ferguson, Fleur M.; Filippakopoulos, Panagis; Svergun, Dmitri I.; Knapp, Stefan; Ciulli, Alessio

    2015-01-01

    Summary Binding of the chromatin remodeling complex NoRC to RNA complementary to the rDNA promoter mediates transcriptional repression. TIP5, the largest subunit of NoRC, is involved in recruitment to rDNA by interactions with promoter-bound TTF-I, pRNA, and acetylation of H4K16. TIP5 domains that recognize posttranslational modifications on histones are essential for recruitment of NoRC to chromatin, but how these reader modules recognize site-specific histone tails has remained elusive. Here, we report crystal structures of PHD zinc finger and bromodomains from human TIP5 and BAZ2B in free form and bound to H3 and/or H4 histones. PHD finger functions as an independent structural module in recognizing unmodified H3 histone tails, and the bromodomain prefers H3 and H4 acetylation marks followed by a key basic residue, KacXXR. Further low-resolution analyses of PHD-bromodomain modules provide molecular insights into their trans histone tail recognition, required for nucleosome recruitment and transcriptional repression of the NoRC complex. PMID:25533489

  12. Pins is not required for spindle orientation in the Drosophila wing disc.

    PubMed

    Bergstralh, Dan T; Lovegrove, Holly E; Kujawiak, Izabela; Dawney, Nicole S; Zhu, Jinwei; Cooper, Samantha; Zhang, Rongguang; St Johnston, Daniel

    2016-07-15

    In animal cells, mitotic spindles are oriented by the dynein/dynactin motor complex, which exerts a pulling force on astral microtubules. Dynein/dynactin localization depends on Mud/NUMA, which is typically recruited to the cortex by Pins/LGN. In Drosophila neuroblasts, the Inscuteable/Baz/Par-6/aPKC complex recruits Pins apically to induce vertical spindle orientation, whereas in epithelial cells Dlg recruits Pins laterally to orient the spindle horizontally. Here we investigate division orientation in the Drosophila imaginal wing disc epithelium. Live imaging reveals that spindle angles vary widely during prometaphase and metaphase, and therefore do not reliably predict division orientation. This finding prompted us to re-examine mutants that have been reported to disrupt division orientation in this tissue. Loss of Mud misorients divisions, but Inscuteable expression and aPKC, dlg and pins mutants have no effect. Furthermore, Mud localizes to the apical-lateral cortex of the wing epithelium independently of both Pins and cell cycle stage. Thus, Pins is not required in the wing disc because there are parallel mechanisms for Mud localization and hence spindle orientation, making it a more robust system than in other epithelia. PMID:27287805

  13. Genome-wide association analyses identify 18 new loci associated with serum urate concentrations

    PubMed Central

    Köttgen, Anna; Albrecht, Eva; Teumer, Alexander; Vitart, Veronique; Krumsiek, Jan; Hundertmark, Claudia; Pistis, Giorgio; Ruggiero, Daniela; O’Seaghdha, Conall M; Haller, Toomas; Yang, Qiong; Tanaka, Toshiko; Johnson, Andrew D; Kutalik, Zoltán; Smith, Albert V; Shi, Julia; Struchalin, Maksim; Middelberg, Rita P S; Brown, Morris J; Gaffo, Angelo L; Pirastu, Nicola; Li, Guo; Hayward, Caroline; Zemunik, Tatijana; Huffman, Jennifer; Yengo, Loic; Zhao, Jing Hua; Demirkan, Ayse; Feitosa, Mary F; Liu, Xuan; Malerba, Giovanni; Lopez, Lorna M; van der Harst, Pim; Li, Xinzhong; Kleber, Marcus E; Hicks, Andrew A; Nolte, Ilja M; Johansson, Asa; Murgia, Federico; Wild, Sarah H; Bakker, Stephan J L; Peden, John F; Dehghan, Abbas; Steri, Maristella; Tenesa, Albert; Lagou, Vasiliki; Salo, Perttu; Mangino, Massimo; Rose, Lynda M; Lehtimäki, Terho; Woodward, Owen M; Okada, Yukinori; Tin, Adrienne; Müller, Christian; Oldmeadow, Christopher; Putku, Margus; Czamara, Darina; Kraft, Peter; Frogheri, Laura; Thun, Gian Andri; Grotevendt, Anne; Gislason, Gauti Kjartan; Harris, Tamara B; Launer, Lenore J; McArdle, Patrick; Shuldiner, Alan R; Boerwinkle, Eric; Coresh, Josef; Schmidt, Helena; Schallert, Michael; Martin, Nicholas G; Montgomery, Grant W; Kubo, Michiaki; Nakamura, Yusuke; Tanaka, Toshihiro; Munroe, Patricia B; Samani, Nilesh J; Jacobs, David R; Liu, Kiang; D’Adamo, Pio; Ulivi, Sheila; Rotter, Jerome I; Psaty, Bruce M; Vollenweider, Peter; Waeber, Gerard; Campbell, Susan; Devuyst, Olivier; Navarro, Pau; Kolcic, Ivana; Hastie, Nicholas; Balkau, Beverley; Froguel, Philippe; Esko, Tõnu; Salumets, Andres; Khaw, Kay Tee; Langenberg, Claudia; Wareham, Nicholas J; Isaacs, Aaron; Kraja, Aldi; Zhang, Qunyuan; Wild, Philipp S; Scott, Rodney J; Holliday, Elizabeth G; Org, Elin; Viigimaa, Margus; Bandinelli, Stefania; Metter, Jeffrey E; Lupo, Antonio; Trabetti, Elisabetta; Sorice, Rossella; Döring, Angela; Lattka, Eva; Strauch, Konstantin; Theis, Fabian; Waldenberger, Melanie; Wichmann, H-Erich; Davies, Gail; Gow, Alan J; Bruinenberg, Marcel; Study, LifeLines Cohort; Stolk, Ronald P; Kooner, Jaspal S; Zhang, Weihua; Winkelmann, Bernhard R; Boehm, Bernhard O; Lucae, Susanne; Penninx, Brenda W; Smit, Johannes H; Curhan, Gary; Mudgal, Poorva; Plenge, Robert M; Portas, Laura; Persico, Ivana; Kirin, Mirna; Wilson, James F; Leach, Irene Mateo; van Gilst, Wiek H; Goel, Anuj; Ongen, Halit; Hofman, Albert; Rivadeneira, Fernando; Uitterlinden, Andre G; Imboden, Medea; von Eckardstein, Arnold; Cucca, Francesco; Nagaraja, Ramaiah; Piras, Maria Grazia; Nauck, Matthias; Schurmann, Claudia; Budde, Kathrin; Ernst, Florian; Farrington, Susan M; Theodoratou, Evropi; Prokopenko, Inga; Stumvoll, Michael; Jula, Antti; Perola, Markus; Salomaa, Veikko; Shin, So-Youn; Spector, Tim D; Sala, Cinzia; Ridker, Paul M; Kähönen, Mika; Viikari, Jorma; Hengstenberg, Christian; Nelson, Christopher P; Consortium, CARDIoGRAM; Consortium, DIAGRAM; Consortium, ICBP; Consortium, MAGIC; Meschia, James F; Nalls, Michael A; Sharma, Pankaj; Singleton, Andrew B; Kamatani, Naoyuki; Zeller, Tanja; Burnier, Michel; Attia, John; Laan, Maris; Klopp, Norman; Hillege, Hans L; Kloiber, Stefan; Choi, Hyon; Pirastu, Mario; Tore, Silvia; Probst-Hensch, Nicole M; Völzke, Henry; Gudnason, Vilmundur; Parsa, Afshin; Schmidt, Reinhold; Whitfield, John B; Fornage, Myriam; Gasparini, Paolo; Siscovick, David S; Polašek, Ozren; Campbell, Harry; Rudan, Igor; Bouatia-Naji, Nabila; Metspalu, Andres; Loos, Ruth J F; van Duijn, Cornelia M; Borecki, Ingrid B; Ferrucci, Luigi; Gambaro, Giovanni; Deary, Ian J; Wolffenbuttel, Bruce H R; Chambers, John C; März, Winfried; Pramstaller, Peter P; Snieder, Harold; Gyllensten, Ulf; Wright, Alan F; Navis, Gerjan; Watkins, Hugh; Witteman, Jacqueline C M; Sanna, Serena; Schipf, Sabine; Dunlop, Malcolm G; Tönjes, Anke; Ripatti, Samuli; Soranzo, Nicole; Toniolo, Daniela; Chasman, Daniel I; Raitakari, Olli; Kao, W H Linda; Ciullo, Marina; Fox, Caroline S; Caulfield, Mark; Bochud, Murielle; Gieger, Christian

    2013-01-01

    Elevated serum urate concentrations can cause gout, a prevalent and painful inflammatory arthritis. By combining data from >140,000 individuals of European ancestry within the Global Urate Genetics Consortium (GUGC), we identified and replicated 28 genome-wide significant loci in association with serum urate concentrations (18 new regions in or near TRIM46, INHBB, SFMBT1, TMEM171, VEGFA, BAZ1B, PRKAG2, STC1, HNF4G, A1CF, ATXN2, UBE2Q2, IGF1R, NFAT5, MAF, HLF, ACVR1B-ACVRL1 and B3GNT4). Associations for many of the loci were of similar magnitude in individuals of non-European ancestry. We further characterized these loci for associations with gout, transcript expression and the fractional excretion of urate. Network analyses implicate the inhibins-activins signaling pathways and glucose metabolism in systemic urate control. New candidate genes for serum urate concentration highlight the importance of metabolic control of urate production and excretion, which may have implications for the treatment and prevention of gout. PMID:23263486

  14. Space Age Archaeology

    NASA Technical Reports Server (NTRS)

    1988-01-01

    In 1985, the Egyptian Antiques Organization (EAO) asked Dr. Farouk El-Baz whether it would be possible to examine and sample the second chamber of the subterranean chamber carved in the bedrock near the Great Pyramid of Khufu in Giza, Egypt, without admitting people, air or contaminants. He felt it could by applying space technology to the task. The initial contact led to a two year project which he organized and headed a team, co-sponsored by EAO and the National Geographic Society (NGS), to apply space technology in an effort to examine and photograph the Giza Chamber. The NGS photographic division modified and tested a remotely controlled video system and a 35-millimeter camera, and developed a lighting system that would not elevate the chamber temperature. Still needed was a drill to cut through the limestone cap without using lubricants or cooling fluids that might contaminate the chamber, and an airlock that would admit the drill shaft and photo equipment but not the air. Bob Moores from Black & Decker Corporation tailored a new drill to the Giza exploration. The drill bit broke through into the chamber at a depth of 63 inches, a stainless steel tube was lowered through the airlock to take samples of the chamber air at several levels. The video camera sent images from the chamber revealing that there was a disassembled royal boat that had been there.

  15. Waist circumference as a marker for screening nonalcoholic fatty liver disease in obese adolescents

    PubMed Central

    Clemente, Ana Paula Grotti; Dal Molin, Bárbara; de Carvalho-Ferreira, Joana Pereira; Campos, Raquel Munhoz da Silveira; Ganen, Aline de Piano; Tock, Lian; de Mello, Marco Túlio; Dâmaso, Ana Raimunda

    2016-01-01

    Abstract Objective: To assess the relationship between the degree of waist circumference (WC) and nonalcoholic fatty liver disease (NAFLD) in obese adolescents of both genders, analyzed according to quartiles of WC. Methods: Cross-sectional study that involved 247 obese adolescents aged 12–19 years. Mean values of the nutritional parameters and serum analyses were compared with the groups using the independent t-test. Pearson correlation coefficient was used to determine the relationship of the parameters studied. Chi-square test for trend was used to determine the relationship between the prevalence of the NAFLD and WC quartile by gender. Results: NAFLD were presented in 60% of the study participants. Obese adolescents in the 3rd and 4th quartiles of WC presented higher prevalence of NAFLD when compared with that in the 1st quartile in both genders. The NAFLD patients had significantly higher values for body weight, BMI (body mass index), BAZ-score (BMI-for-age z-scores), total fat (% and kg), WC, visceral fat, insulin, insulin resistance index (HOMA-IR), aspartate aminotransferase and alanine aminotransferase, when compared with non-NAFLD obese adolescents. Conclusions: In conclusion, the results presented here suggest that an increase in WC can reliably predict the risk of NAFLD in obese adolescents. This is a low cost and easy-to-use tool that can help in screening in adolescents. PMID:26830602

  16. Renal Cell Neoplasms Contain Shared Tumor Type–Specific Copy Number Variations

    PubMed Central

    Krill-Burger, John M.; Lyons, Maureen A.; Kelly, Lori A.; Sciulli, Christin M.; Petrosko, Patricia; Chandran, Uma R.; Kubal, Michael D.; Bastacky, Sheldon I.; Parwani, Anil V.; Dhir, Rajiv; LaFramboise, William A.

    2012-01-01

    Copy number variant (CNV) analysis was performed on renal cell carcinoma (RCC) specimens (chromophobe, clear cell, oncocytoma, papillary type 1, and papillary type 2) using high-resolution arrays (1.85 million probes). The RCC samples exhibited diverse genomic changes within and across tumor types, ranging from 106 to 2238 CNV segments in a clear-cell specimen and in a papillary type 2 specimen, respectively. Despite this heterogeneity, distinct CNV segments were common within each tumor classification: chromophobe (seven segments), clear cell (three segments), oncocytoma (nine segments), and papillary type 2 (two segments). Shared segments ranged from a 6.1-kb deletion (oncocytomas) to a 208.3-kb deletion (chromophobes). Among common tumor type–specific variations, chromophobes, clear-cell tumors, and oncocytomas were composed exclusively of noncoding DNA. No CNV regions were common to papillary type 1 specimens, although there were 12 amplifications and 12 deletions in five of six samples. Three microRNAs and 12 mRNA genes had a ≥98% coding region contained within CNV regions, including multiple gene families (chromophobe: amylases 1A, 1B, and 1C; oncocytoma: general transcription factors 2H2, 2B, 2C, and 2D). Gene deletions involved in histone modification and chromatin remodeling affected individual subtypes (clear cell: SFMBT and SETD2; papillary type 2: BAZ1A) and the collective RCC group (KDM4C). The genomic amplifications/deletions identified herein represent potential diagnostic and/or prognostic biomarkers. PMID:22483639

  17. Molecular basis of histone tail recognition by human TIP5 PHD finger and bromodomain of the chromatin remodeling complex NoRC.

    PubMed

    Tallant, Cynthia; Valentini, Erica; Fedorov, Oleg; Overvoorde, Lois; Ferguson, Fleur M; Filippakopoulos, Panagis; Svergun, Dmitri I; Knapp, Stefan; Ciulli, Alessio

    2015-01-01

    Binding of the chromatin remodeling complex NoRC to RNA complementary to the rDNA promoter mediates transcriptional repression. TIP5, the largest subunit of NoRC, is involved in recruitment to rDNA by interactions with promoter-bound TTF-I, pRNA, and acetylation of H4K16. TIP5 domains that recognize posttranslational modifications on histones are essential for recruitment of NoRC to chromatin, but how these reader modules recognize site-specific histone tails has remained elusive. Here, we report crystal structures of PHD zinc finger and bromodomains from human TIP5 and BAZ2B in free form and bound to H3 and/or H4 histones. PHD finger functions as an independent structural module in recognizing unmodified H3 histone tails, and the bromodomain prefers H3 and H4 acetylation marks followed by a key basic residue, KacXXR. Further low-resolution analyses of PHD-bromodomain modules provide molecular insights into their trans histone tail recognition, required for nucleosome recruitment and transcriptional repression of the NoRC complex. PMID:25533489

  18. Pins is not required for spindle orientation in the Drosophila wing disc

    PubMed Central

    Lovegrove, Holly E.; Kujawiak, Izabela; Dawney, Nicole S.; Zhu, Jinwei; Cooper, Samantha; Zhang, Rongguang

    2016-01-01

    In animal cells, mitotic spindles are oriented by the dynein/dynactin motor complex, which exerts a pulling force on astral microtubules. Dynein/dynactin localization depends on Mud/NUMA, which is typically recruited to the cortex by Pins/LGN. In Drosophila neuroblasts, the Inscuteable/Baz/Par-6/aPKC complex recruits Pins apically to induce vertical spindle orientation, whereas in epithelial cells Dlg recruits Pins laterally to orient the spindle horizontally. Here we investigate division orientation in the Drosophila imaginal wing disc epithelium. Live imaging reveals that spindle angles vary widely during prometaphase and metaphase, and therefore do not reliably predict division orientation. This finding prompted us to re-examine mutants that have been reported to disrupt division orientation in this tissue. Loss of Mud misorients divisions, but Inscuteable expression and aPKC, dlg and pins mutants have no effect. Furthermore, Mud localizes to the apical-lateral cortex of the wing epithelium independently of both Pins and cell cycle stage. Thus, Pins is not required in the wing disc because there are parallel mechanisms for Mud localization and hence spindle orientation, making it a more robust system than in other epithelia. PMID:27287805

  19. Evidence of young volcanic vents in the lunar maria

    NASA Astrophysics Data System (ADS)

    Braden, S.; Robinson, M. S.; Stopar, J. D.

    2013-12-01

    from broad areas of mare basalt flows. Changes in extrusion rate and temperature commonly occur at vents, which could explain the IMPs' unique morphology. Furthermore, IMPs are often spatially associated with volcanic features such as mare domes (e.g., Cauchy 5), collapse calderas (e.g., Hyginus crater), and large pyroclastic deposits (e.g., Mare Vaporum). Multispectral analysis on a subset of the largest IMPs using combined Clementine UV-VIS data (950/750 nm ratio) and LROC Wide Angle Camera images (320/415 nm ratio) show that the uneven unit is consistent with a mare basalt composition. The multispectral data also suggest the presence of pyroclastic material in the area directly surrounding some of the IMPs, which is consistent with a vent hypothesis. Thus, the morphology, composition, and distribution of IMPs imply that lunar volcanic activity may be much younger than generally recognized. References: [1] Whitaker E. (1972) NASA SP-289. [2] Schultz P. H. (1976) Moon Morphology, 626 pp., Univ. of Texas. [3] Stooke P. J. (2012) LPSC 43, abst 1011. [4] Braden S. E. et al. (2013) LPSC 44, abst. 2843. [5] El-Baz, F. (1973) NASA SP-330. [6] Strain P. L. and El-Baz F. (1980) PLPSC 11, 2437-2446. [7] Schultz P. H. (2006) Nature, 444, 184-186. [8] Staid M. et al. (2011) LPSC 42, abst. 2499. [9] Garry W. B. et al. (2012) JGR, 117, E00H31. [10] Robinson M. S. et al. (2010) LPSC 41, abst. 2592.

  20. TEMEL ETİK KURAMLAR AÇISINDAN ADALET ve SAĞLIK HAKKI KAVRAMLARININ DEĞERLENDİRMESİ1,2

    PubMed Central

    Ekmekçi, Perihan Elif; Arda, Berna

    2015-01-01

    Sağlık hakkı temel bir insan hakkıdır. Ancak günümüzde sağlık hakkının hayata geçmesi, sağlık sunumunda gereksinim duyulan kaynakların kısıtlı olması nedeniyle engeller ile karşılaşmaktadır. Ayrıca tıp alanındaki hızlı teknolojik ilerlemeler, tanı ve tedavi imkânlarının her geçen gün gelişmesine yol açmaktadır. Bu durum, sağlık hizmetlerinin sunumunu dağıtıcı adaletin bir süjesi haline getirmektedir. Adalet kavramının tanımlanabilmesi için öncelikle, birey ya da toplulukların bir şeye ilişkin hak talebinde bulunmalarının koşullarını tanımlanmalı daha sonra hak edilenin kim tarafından ve nasıl verileceğinin belirlenmelidir. Etik kuramlar, etik açıdan doğru eyleyebilmek için hangi dayanak noktalarından yola çıkarak hangi değerleri önceleyerek karar vermek gerektiği konusunda kendi paradigmalarını oluşturmuşlardır. Adalet ve sağlık hakkı gibi temel kavramlar, temel etik kuramlar tarafından, o kuramın bağlamı içinde değerlendirilmekte ve anlam kazanmaktadır. Sağlık hakkı bazı etik kuramlar tarafından insan varlığının doğal bir bileşeni olarak tanımlanırken, bazı etik kuramlar tarafından bağlamsal olarak kabul edilmekte bazıları tarafından ise reddedilmekte, adalet kavramı ve bağlantılı olarak adaletin materyal ve formal ilkeleri gibi kavramların içerikleri ve taşıdıkları değerler içinden bakılan etik kuramın paradigmasına bağlı olarak farklıklar içermektedir. Etik kuramların paradigmaları sadece kavramların tanımlanmasında değil, aynı zamanda pratik uygulamalarda da farklı yaklaşımları gerektirmektedir. Bu çalışmada, erdem etiği, faydacı etik kuram, ödev etiği, liberal etik kuram ve kommuniteryan etik kuramın adalet ve sağlık hakkını nasıl kavramsallaştırdıklarını ortaya konmaktır. Bu amaçla öncelikle her bir etik kuramın genel çerçevesi tanımlanmış ve bu çerçevenin çizdiği teorik paradigma i

  1. The geovisualisation window of the temporal and spatial variability for Volunteered Geographic Information activities

    NASA Astrophysics Data System (ADS)

    Medynska-Gulij, Beata; Myszczuk, Miłosz

    2012-11-01

    panele jest wyeksponowana graficznie pojedyncza aktywnosc. Przetwarzanie danych odbyło sie w srodowisku open source, a technologia funkcjonowania aplikacji okna geowizualizacji bazowała na zastosowaniu asynchronicznych zapytan do serwera WWW oraz serwera baz danych co zapewnia sprawne "odswiezanie” poszczególnych paneli.

  2. Soil-Transmitted Helminth Infections and Nutritional Status in School-age Children from Rural Communities in Honduras

    PubMed Central

    Sanchez, Ana Lourdes; Gabrie, Jose Antonio; Usuanlele, Mary-Theresa; Rueda, Maria Mercedes; Canales, Maritza; Gyorkos, Theresa W.

    2013-01-01

    Background Soil-transmitted helminth (STH) infections are endemic in Honduras and efforts are underway to decrease their transmission. However, current evidence is lacking in regards to their prevalence, intensity and their impact on children's health. Objectives To evaluate the prevalence and intensity of STH infections and their association with nutritional status in a sample of Honduran children. Methodology A cross-sectional study was done among school-age children residing in rural communities in Honduras, in 2011. Demographic data was obtained, hemoglobin and protein concentrations were determined in blood samples and STH infections investigated in single-stool samples by Kato-Katz. Anthropometric measurements were taken to calculate height-for-age (HAZ), BMI-for-age (BAZ) and weight-for-age (WAZ) to determine stunting, thinness and underweight, respectively. Results Among 320 children studied (48% girls, aged 7–14 years, mean 9.76±1.4) an overall STH prevalence of 72.5% was found. Children >10 years of age were generally more infected than 7–10 year-olds (p = 0.015). Prevalence was 30%, 67% and 16% for Ascaris, Trichuris and hookworms, respectively. Moderate-to-heavy infections as well as polyparasitism were common among the infected children (36% and 44%, respectively). Polyparasitism was four times more likely to occur in children attending schools with absent or annual deworming schedules than in pupils attending schools deworming twice a year (p<0.001). Stunting was observed in 5.6% of children and it was associated with increasing age. Also, 2.2% of studied children were thin, 1.3% underweight and 2.2% had anemia. Moderate-to-heavy infections and polyparasitism were significantly associated with decreased values in WAZ and marginally associated with decreased values in HAZ. Conclusions STH infections remain a public health concern in Honduras and despite current efforts were highly prevalent in the studied community. The role of multiparasite

  3. To Bleed or Not to Bleed. A Prediction Based on Individual Gene Profiling Combined With Dose-Volume Histogram Shapes in Prostate Cancer Patients Undergoing Three-Dimensional Conformal Radiation Therapy

    SciTech Connect

    Valdagni, Riccardo Rancati, Tiziana; Ghilotti, Marco; Cozzarini, Cesare; Vavassori, Vittorio; Fellin, Gianni; Fiorino, Claudio; Girelli, Giuseppe; Barra, Salvina; Zaffaroni, Nadia; Pierotti, Marco Alessandro; Gariboldi, Manuela

    2009-08-01

    Purpose: The main purpose of this work was to try to elucidate why, despite excellent rectal dose-volume histograms (DVHs), some patients treated for prostate cancer exhibit late rectal bleeding (LRB) and others with poor DVHs do not. Thirty-five genes involved in DNA repair/radiation response were analyzed in patients accrued in the AIROPROS 0101 trial, which investigated the correlation between LRB and dosimetric parameters. Methods and Materials: Thirty patients undergoing conformal radiotherapy with prescription doses higher than 70 Gy (minimum follow-up, 48 months) were selected: 10 patients in the low-risk group (rectal DVH with the percent volume of rectum receiving more than 70 Gy [V70Gy] < 20% and the percent volume of rectum receiving more than 50 Gy [V50Gy] < 55%) with Grade 2 or Grade 3 (G2-G3) LRB, 10 patients in the high-risk group (V70Gy > 25% and V50Gy > 60%) with G2-G3 LRB, and 10 patients in the high-risk group with no toxicity. Quantitative reverse-transcriptase polymerase chain reaction was performed on RNA from lymphoblastoid cell lines obtained from Epstein-Barr virus-immortalized peripheral-blood mononucleated cells and on peripheral blood mononucleated cells. Interexpression levels were compared by using the Kruskal-Wallis test. Results: Intergroup comparison showed many constitutive differences: nine genes were significantly down-regulated in the low-risk bleeder group vs. the high-risk bleeder and high-risk nonbleeder groups: AKR1B1 (p = 0.019), BAZ1B (p = 0.042), LSM7 (p = 0.0016), MRPL23 (p = 0.015), NUDT1 (p = 0.0031), PSMB4 (p = 0.079), PSMD1 (p = 0.062), SEC22L1 (p = 0.040), and UBB (p = 0.018). Four genes were significantly upregulated in the high-risk nonbleeder group than in the other groups: DDX17 (p = 0.048), DRAP1 (p = 0.0025), RAD23 (p = 0.015), and SRF (p = 0.024). For most of these genes, it was possible to establish a cut-off value that correctly classified most patients. Conclusions: The predictive value of sensitivity and

  4. Gene-centric Association Signals for Lipids and Apolipoproteins Identified via the HumanCVD BeadChip

    PubMed Central

    Talmud, Philippa J.; Drenos, Fotios; Shah, Sonia; Shah, Tina; Palmen, Jutta; Verzilli, Claudio; Gaunt, Tom R.; Pallas, Jacky; Lovering, Ruth; Li, Kawah; Casas, Juan Pablo; Sofat, Reecha; Kumari, Meena; Rodriguez, Santiago; Johnson, Toby; Newhouse, Stephen J.; Dominiczak, Anna; Samani, Nilesh J.; Caulfield, Mark; Sever, Peter; Stanton, Alice; Shields, Denis C.; Padmanabhan, Sandosh; Melander, Olle; Hastie, Claire; Delles, Christian; Ebrahim, Shah; Marmot, Michael G.; Smith, George Davey; Lawlor, Debbie A.; Munroe, Patricia B.; Day, Ian N.; Kivimaki, Mika; Whittaker, John; Humphries, Steve E.; Hingorani, Aroon D.

    2009-01-01

    Blood lipids are important cardiovascular disease (CVD) risk factors with both genetic and environmental determinants. The Whitehall II study (n = 5592) was genotyped with the gene-centric HumanCVD BeadChip (Illumina). We identified 195 SNPs in 16 genes/regions associated with 3 major lipid fractions and 2 apolipoprotein components at p < 10−5, with the associations being broadly concordant with prior genome-wide analysis. SNPs associated with LDL cholesterol and apolipoprotein B were located in LDLR, PCSK9, APOB, CELSR2, HMGCR, CETP, the TOMM40-APOE-C1-C2-C4 cluster, and the APOA5-A4-C3-A1 cluster; SNPs associated with HDL cholesterol and apolipoprotein AI were in CETP, LPL, LIPC, APOA5-A4-C3-A1, and ABCA1; and SNPs associated with triglycerides in GCKR, BAZ1B, MLXIPL, LPL, and APOA5-A4-C3-A1. For 48 SNPs in previously unreported loci that were significant at p < 10−4 in Whitehall II, in silico analysis including the British Women's Heart and Health Study, BRIGHT, ASCOT, and NORDIL studies (total n > 12,500) revealed previously unreported associations of SH2B3 (p < 2.2 × 10−6), BMPR2 (p < 2.3 × 10−7), BCL3/PVRL2 (flanking APOE; p < 4.4 × 10−8), and SMARCA4 (flanking LDLR; p < 2.5 × 10−7) with LDL cholesterol. Common alleles in these genes explained 6.1%–14.7% of the variance in the five lipid-related traits, and individuals at opposite tails of the additive allele score exhibited substantial differences in trait levels (e.g., >1 mmol/L in LDL cholesterol [∼1 SD of the trait distribution]). These data suggest that multiple common alleles of small effect can make important contributions to individual differences in blood lipids potentially relevant to the assessment of CVD risk. These genes provide further insights into lipid metabolism and the likely effects of modifying the encoded targets therapeutically. PMID:19913121

  5. Pleiotropic genes for metabolic syndrome and inflammation

    PubMed Central

    Kraja, Aldi T.; Chasman, Daniel I.; North, Kari E.; Reiner, Alexander P.; Yanek, Lisa R.; Kilpeläinen, Tuomas O.; Smith, Jennifer A.; Dehghan, Abbas; Dupuis, Josée; Johnson, Andrew D.; Feitosa, Mary F.; Tekola-Ayele, Fasil; Chu, Audrey Y.; Nolte, Ilja M.; Dastani, Zari; Morris, Andrew; Pendergrass, Sarah A.; Sun, Yan V.; Ritchie, Marylyn D.; Vaez, Ahmad; Lin, Honghuang; Ligthart, Symen; Marullo, Letizia; Rohde, Rebecca; Shao, Yaming; Ziegler, Mark A.; Im, Hae Kyung; Schnabel, Renate B.; Jørgensen, Torben; Jørgensen, Marit E.; Hansen, Torben; Pedersen, Oluf; Stolk, Ronald P.; Snieder, Harold; Hofman, Albert; Uitterlinden, Andre G.; Franco, Oscar H.; Ikram, M. Arfan; Richards, J. Brent; Rotimi, Charles; Wilson, James G.; Lange, Leslie; Ganesh, Santhi K.; Nalls, Mike; Rasmussen-Torvik, Laura J.; Pankow, James S.; Coresh, Josef; Tang, Weihong; Kao, W.H. Linda; Boerwinkle, Eric; Morrison, Alanna C.; Ridker, Paul M.; Becker, Diane M.; Rotter, Jerome I.; Kardia, Sharon L.R.; Loos, Ruth J.F.; Larson, Martin G.; Hsu, Yi-Hsiang; Province, Michael A.; Tracy, Russell; Voight, Benjamin F.; Vaidya, Dhananjay; O’Donnell, Christopher; Benjamin, Emelia J.; Alizadeh, Behrooz Z.; Prokopenko, Inga; Meigs, James B.; Borecki, Ingrid B.

    2014-01-01

    Metabolic syndrome (MetS) has become a health and financial burden worldwide. The MetS definition captures clustering of risk factors that predict higher risk for diabetes mellitus and cardiovascular disease. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network. To test this hypothesis a staged approach was undertaken. (a) We analyzed 17 metabolic and inflammatory traits in more than 85,500 participants from 14 large epidemiological studies within the Cross Consortia Pleiotropy Group. Individuals classified with MetS (NCEP definition), versus those without, showed on average significantly different levels for most inflammatory markers studied. (b) Paired average correlations between 8 metabolic traits and 9 inflammatory markers from the same studies as above, estimated with two methods, and factor analyses on large simulated data, helped in identifying 8 combinations of traits for follow-up in meta-analyses, out of 130,305 possible combinations between metabolic traits and inflammatory markers studied. (c) We performed correlated meta-analyses for 8 metabolic traits and 6 inflammatory markers by using existing GWAS published genetic summary results, with about 2.5 million SNPs from twelve predominantly largest GWAS consortia. These analyses yielded 130 unique SNPs/genes with pleiotropic associations (a SNP/gene associating at least one metabolic trait and one inflammatory marker). Of them twenty-five variants (seven loci newly reported) are proposed as MetS candidates. They map to genes MACF1, KIAA0754, GCKR, GRB14, COBLL1, LOC646736-IRS1, SLC39A8, NELFE, SKIV2L, STK19, TFAP2B, BAZ1B, BCL7B, TBL2, MLXIPL, LPL, TRIB1, ATXN2, HECTD4, PTPN11, ZNF664, PDXDC1, FTO, MC4R and TOMM40. Based on large data evidence, we conclude that inflammation is a feature of MetS and several gene variants show pleiotropic genetic

  6. Next generation sequencing of Apis mellifera syriaca identifies genes for Varroa resistance and beneficial bee keeping traits.

    PubMed

    Haddad, Nizar; Mahmud Batainh, Ahmed; Suleiman Migdadi, Osama; Saini, Deepti; Krishnamurthy, Venkatesh; Parameswaran, Sriram; Alhamuri, Zaid

    2016-08-01

    Apis mellifera syriaca exhibits a high degree of tolerance to pests and pathogens including varroa mites. This native honey bee subspecies of Jordan expresses behavioral adaptations to high temperature and dry seasons typical of the region. However, persistent honey bee imports of commercial breeder lines are endangering local honey bee population. This study reports the use of next-generation sequencing (NGS) technology to study the A. m. syriaca genome and to identify genetic factors possibly contributing toward mite resistance and other favorable traits. We obtained a total of 46.2 million raw reads by applying the NGS to sequence A. m. syriaca and used extensive bioinformatics approach to identify several candidate genes for Varroa mite resistance, behavioral and immune responses characteristic for these bees. As a part of characterizing the functional regulation of molecular genetic pathway, we have mapped the pathway genes potentially involved using information from Drosophila melanogaster and present possible functional changes implicated in responses to Varroa destructor mite infestation toward this. We performed in-depth functional annotation methods to identify ∼600 candidates that are relevant, genes involved in pathways such as microbial recognition and phagocytosis, peptidoglycan recognition protein family, Gram negative binding protein family, phagocytosis receptors, serpins, Toll signaling pathway, Imd pathway, Tnf, JAK-STAT and MAPK pathway, heamatopioesis and cellular response pathways, antiviral, RNAi pathway, stress factors, etc. were selected. Finally, we have cataloged function-specific polymorphisms between A. mellifera and A. m. syriaca that could give better understanding of varroa mite resistance mechanisms and assist in breeding. We have identified immune related embryonic development (Cactus, Relish, dorsal, Ank2, baz), Varroa hygiene (NorpA2, Zasp, LanA, gasp, impl3) and Varroa resistance (Pug, pcmt, elk, elf3-s10, Dscam2, Dhc64C, gro

  7. Density Variations in Quartz As a Key for Deciphering Impact-Related Ultrasonic Sounding (Rajlich's Hypothesis)?

    NASA Astrophysics Data System (ADS)

    Mestan, J.; Alvarez Polanco, E. I.

    2014-12-01

    Ultrasound is a form of mechanical energy with a frequency greater than ≈ 20 kHz (upper human hearing limit). It is used in many scientific as well as industrial fields. Most modern applications of ultrasound utilize sources which are either piezoelectric or magnetostrictive (Benwell et Bly 1987). A meteorite impact has been considered to be an ultrasound source during last years (Rajlich 2011). Rajlich (2014) is coming with a hypothesis that white planes made of microcavities in Bohemian quartz have their origin in an impact-related ultrasonic sounding. The Bohemian Massif has been considered to be one of the largest impact craters in whole of the world (Papagiannis et El-Baz 1988, Papagiannis 1989, Rajlich 2014). Rajlich's hypothesis implies a liquid behavior of quartz during the impact event. We state that then there have to exist planes of slightly higher density than their surroundings together with planes of microcavities. They should intersect each other without mutual influencing (as in a case of planes made of microcavities). Because physics of ultrasound during an impact event is a brand new and unknown field, we try to choose a simple way of its cognition. It is possible to take the sine wave and set 3 requirements. (1) There exist some surroundings of points of peak amplitudes. (2) These surroundings are of higher density (compression) or lower density (rarefaction) than the mean density of quartz. (3) The difference between the higher/lower and surrounding density is measurable. There was done an experimental study of Bohemian quartz using QCT bone densitometry at the Radiology Munich. Quartz with a size of ≈ 5 x 8 cm absorbed too much RTG radiation (kV 140, mAs 330), which made a picture of internal structure impossible. We propose another techniques and appeal to other scientists to face this challenge. If Bohemian quartz has a harmonically distributed density, we consider it to be a support for Rajlich's hypothesis. AcknowledgementsWe would like

  8. Association of NOD2 and IL23R with Inflammatory Bowel Disease in Puerto Rico

    PubMed Central

    Ballester, Veroushka; Guo, Xiuqing; Vendrell, Roberto; Haritunians, Talin; Klomhaus, Alexandra M.; Li, Dalin; McGovern, Dermot P. B.; Rotter, Jerome I.; Torres, Esther A.; Taylor, Kent D.

    2014-01-01

    The Puerto Rico population may be modeled as an admixed population with contributions from three continents: Sub-Saharan Africa, Ancient America, and Europe. Extending the study of the genetics of inflammatory bowel disease (IBD) to an admixed population such as Puerto Rico has the potential to shed light on IBD genes identified in studies of European populations, find new genes contributing to IBD susceptibility, and provide basic information on IBD for the care of US patients of Puerto Rican and Latino descent. In order to study the association between immune-related genes and Crohn’s disease (CD) and ulcerative colitis (UC) in Puerto Rico, we genotyped 1159 Puerto Rican cases, controls, and family members with the ImmunoChip. We also genotyped 832 subjects from the Human Genome Diversity Panel to provide data for estimation of global and local continental ancestry. Association of SNPs was tested by logistic regression corrected for global continental descent and family structure. We observed the association between Crohn’s disease and NOD2 (rs17313265, 0.28 in CD, 0.19 in controls, OR 1.5, p = 9×10−6) and IL23R (rs11209026, 0.026 in CD, 0.0.071 in controls, OR 0.4, p = 3.8×10−4). The haplotype structure of both regions resembled that reported for European populations and “local” continental ancestry of the IL23R gene was almost entirely of European descent. We also observed suggestive evidence for the association of the BAZ1A promoter SNP with CD (rs1200332, 0.45 in CD, 0.35 in controls, OR 1.5, p = 2×10−6). Our estimate of continental ancestry surrounding this SNP suggested an origin in Ancient America for this putative susceptibility region. Our observations underscored the great difference between global continental ancestry and local continental ancestry at the level of the individual gene, particularly for immune-related loci. PMID:25259511

  9. Maternal Micronutrient Supplementation and Long Term Health Impact in Children in Rural Bangladesh

    PubMed Central

    Mannan, Tania; Ahmed, Sultan; Akhtar, Evana; Roy, Anjan Kumar; Haq, Md Ahsanul; Roy, Adity; Kippler, Maria; Ekström, Eva-Charlotte; Wagatsuma, Yukiko; Raqib, Rubhana

    2016-01-01

    Background Limited data is available on the role of prenatal nutritional status on the health of school-age children. We aimed to determine the impact of maternal micronutrient supplementation on the health status of Bangladeshi children. Methods Children (8.6–9.6 years; n = 540) were enrolled from a longitudinal mother-child cohort, where mothers were supplemented daily with either 30mg iron and 400μg folic acid (Fe30F), or 60mg iron and 400μg folic acid (Fe60F), or Fe30F including 15 micronutrients (MM), in rural Matlab. Blood was collected from children to determine the concentration of hemoglobin (Hb) and several micronutrients. Anthropometric and Hb data from these children were also available at 4.5 years of age and mothers at gestational week (GW) 14 and 30. Results MM supplementation significantly improved (p≤0.05) body mass index-for-age z-score (BAZ), but not Hb levels, in 9 years old children compared to the Fe30F group. MM supplementation also reduced markers of inflammation (p≤0.05). About 28%, 35% and 23% of the women were found to be anemic at GW14, GW30 and both time points, respectively. The prevalence of anemia was 5% and 15% in 4.5 and 9 years old children, respectively. The adjusted odds of having anemia in 9 year old children was 3-fold higher if their mothers were anemic at both GW14 and GW30 [Odds Ratio (OR) = 3.05; 95% Confidence Interval (CI) 1.42, 6.14, P = 0.002] or even higher if they were also anemic at 4.5 years of age [OR = 5.92; 95% CI 2.64, 13.25; P<0.001]. Conclusion Maternal micronutrient supplementation imparted beneficial effects on child health. Anemia during pregnancy and early childhood are important risk factors for the occurrence of anemia in school-age children. PMID:27537051

  10. Koncepcja resilience. Kluczowe pojęcia i wybrane zagadnienia

    PubMed Central

    Borucka, Anna; Ostaszewski, Krzysztof

    2009-01-01

    Streszczenie Celem niniejszej pracy jest przybliżenie kluczowych pojęć związanych koncepcją resilience. Ta koncepcja wyjaśnia fenomen pozytywnej adaptacji dzieci i młodzieży narażonych na duże ryzyko, przeciwności losu i/lub zdarzenia traumatyczne. Koncepcja resilience akcentuje znaczenie czynników i mechanizmów chroniących w wieku rozwojowym. Z tych przyczyn może być bardzo użyteczna dla rozwijania programów profilaktyki i promocji zdrowia psychicznego wśród dzieci i młodzieży. W niniejszym przeglądzie wykorzystano prace znaczących Autorów zajmujących się tą dziedziną m.in. M. Ruttera. N. Garmezy, E. Werner, S. Luthar, A. Sameroffa, K. Kumpfer, A. Masten, M. Zimmermana, D. Cicchetti. W przeglądzie uwzględniono ponad 20 artykułów i rozdziałów książkowych, które ukazały się w ostatnich 25 latach. Zostały one wybrane z elektronicznej bazy publikacji dostępnej na Uniwersytecie Michigan: elektronicznej bazy SAMSHA oraz z elektronicznych baz publikacji naukowych dostępnych w naszym kraju. W artykule przytoczono kilka definicji resilience, które wskazują na jej interaktywny i dynamiczny charakter. Uwzględniają one wzajemny wpływ czynników ryzyka i czynników chroniących (i ich interakcję) na zachowanie człowieka, jego kompetencje i zdrowie psychiczne. W pracy opisano podstawowe pojęcia związane z resilience: ryzyko, czynniki ryzyka, czynniki chroniące, pozytywną adaptację oraz teoretyczne modele i mechanizmy resilience. Przedstawiono różnice między mechanizmami ryzyka a mechanizmami chroniącymi. Zasygnalizowano też trudności związane z wykorzystaniem podstawowych pojęć resilience w badaniach empirycznych m.in. w określeniu wskaźników ryzyka, wyodrębnieniu grup ryzyka, określeniu wskaźników pozytywnej adaptacji. PMID:19301507

  11. Large Multiethnic Candidate Gene Study for C-Reactive Protein Levels: Identification of a Novel Association at CD36 in African Americans

    PubMed Central

    Ellis, Jaclyn; Lange, Ethan M.; Li, Jin; Dupuis, Josee; Baumert, Jens; Walston, Jeremy D.; Keating, Brendan J.; Durda, Peter; Fox, Ervin R.; Palmer, Cameron D.; Meng, Yan A.; Young, Taylor; Farlow, Deborah N.; Schnabel, Renate B.; Marzi, Carola S.; Larkin, Emma; Martin, Lisa W.; Bis, Joshua C.; Auer, Paul; Ramachandran, Vasan S.; Gabriel, Stacey B.; Willis, Monte S.; Pankow, James S.; Papanicolaou, George J.; Rotter, Jerome I.; Ballantyne, Christie M.; Gross, Myron D.; Lettre, Guillaume; Wilson, James G.; Peters, Ulrike; Koenig, Wolfgang; Tracy, Russell P.; Redline, Susan; Reiner, Alex P.; Benjamin, Emelia J.; Lange, Leslie A.

    2014-01-01

    C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multi-ethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7570 African Americans (AA) from the Candidate gene Association Resource (CARe) study and race-combined meta-analyses that included 29,939 additional individuals of European descent from CARe, the Women’s Health Initiative (WHI) and KORA studies. We observed array-wide significance (p<2.2×10−6) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p=2.0×10−6; CRP, p=4.2×10−71; APOE, p=1.6×10−6). The fourth significant locus, CD36 (p=1.6×10−6), was observed at a functional variant (rs3211938) that is extremely rare in individuals of European descent. We replicated the CD36 finding (p=1.8×10−5) in an independent sample of 8041 AA women from WHI; a meta-analysis combining the CARe and WHI AA results at rs3211938 reached genome-wide significance (p=1.5×10−10). In the race-combined meta-analyses, 13 loci reached significance, including ten (CRP, TOMM40/APOE/APOC1, HNF1A, LEPR, GCKR, IL6R, IL1RN, NLRP3, HNF4A and BAZ1B/BCL7B) previously associated with CRP, and one (ARNTL) previously reported to be nominally associated with CRP. Two novel loci were also detected (RPS6KB1, p=2.0×10−6; CD36, p=1.4×10−6). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent. PMID:24643644

  12. Large multiethnic Candidate Gene Study for C-reactive protein levels: identification of a novel association at CD36 in African Americans.

    PubMed

    Ellis, Jaclyn; Lange, Ethan M; Li, Jin; Dupuis, Josee; Baumert, Jens; Walston, Jeremy D; Keating, Brendan J; Durda, Peter; Fox, Ervin R; Palmer, Cameron D; Meng, Yan A; Young, Taylor; Farlow, Deborah N; Schnabel, Renate B; Marzi, Carola S; Larkin, Emma; Martin, Lisa W; Bis, Joshua C; Auer, Paul; Ramachandran, Vasan S; Gabriel, Stacey B; Willis, Monte S; Pankow, James S; Papanicolaou, George J; Rotter, Jerome I; Ballantyne, Christie M; Gross, Myron D; Lettre, Guillaume; Wilson, James G; Peters, Ulrike; Koenig, Wolfgang; Tracy, Russell P; Redline, Susan; Reiner, Alex P; Benjamin, Emelia J; Lange, Leslie A

    2014-08-01

    C-reactive protein (CRP) is a heritable biomarker of systemic inflammation and a predictor of cardiovascular disease (CVD). Large-scale genetic association studies for CRP have largely focused on individuals of European descent. We sought to uncover novel genetic variants for CRP in a multiethnic sample using the ITMAT Broad-CARe (IBC) array, a custom 50,000 SNP gene-centric array having dense coverage of over 2,000 candidate CVD genes. We performed analyses on 7,570 African Americans (AA) from the Candidate gene Association Resource (CARe) study and race-combined meta-analyses that included 29,939 additional individuals of European descent from CARe, the Women's Health Initiative (WHI) and KORA studies. We observed array-wide significance (p < 2.2 × 10(-6)) for four loci in AA, three of which have been reported previously in individuals of European descent (IL6R, p = 2.0 × 10(-6); CRP, p = 4.2 × 10(-71); APOE, p = 1.6 × 10(-6)). The fourth significant locus, CD36 (p = 1.6 × 10(-6)), was observed at a functional variant (rs3211938) that is extremely rare in individuals of European descent. We replicated the CD36 finding (p = 1.8 × 10(-5)) in an independent sample of 8,041 AA women from WHI; a meta-analysis combining the CARe and WHI AA results at rs3211938 reached genome-wide significance (p = 1.5 × 10(-10)). In the race-combined meta-analyses, 13 loci reached significance, including ten (CRP, TOMM40/APOE/APOC1, HNF1A, LEPR, GCKR, IL6R, IL1RN, NLRP3, HNF4A and BAZ1B/BCL7B) previously associated with CRP, and one (ARNTL) previously reported to be nominally associated with CRP. Two novel loci were also detected (RPS6KB1, p = 2.0 × 10(-6); CD36, p = 1.4 × 10(-6)). These results highlight both shared and unique genetic risk factors for CRP in AA compared to populations of European descent. PMID:24643644

  13. A Reliable Method of Completing and Compensating the Results of Measurements of Flow Parameters in a Network of Headings / O Pewnej Metodzie Uzupełniania I Wyrównywania Wyników Pomiarów Parametrów Przepływu W Sieci Wyrobisk Górniczych

    NASA Astrophysics Data System (ADS)

    Dziurzyński, Wacław; Krach, Andrzej; Pałka, Teresa

    2015-03-01

    pressure values on the basis of the available results of measurements carried out in adjacent nodes, as well as the pressure value calculated on the basis of the heading geometry and the given volumetric flow rate. The present paper discusses the methodology of compensating and balancing the volumetric air flow rates within a network of headings (Chapter 2) and the methodology of determining pressure values (Chapter 3) in the nodes of the network. The developed calculation algorithms - verified by means of sample calculations performed for a selected area of a mine ventilation network - were introduced into the VentGraph software system. The calculation results were presented in tabular form. The Summary section discusses the minuses and pluses of the adopted methodology. Podstawą prognozy procesu przewietrzania jest posługiwanie się zwalidowanym programem komputerowym (Dziurzyński i in., 2011; Pritchard, 2010) oraz poprawnie przygotowaną bazą danych zawierającą parametry opisujące przepływ powietrza i gazów, zgodną z przyjętym modelem matematycznym w programie komputerowym VentGraph (Dziurzyński, 2002). Dysponując bazą danych pomiarowych oraz przyjętym do obliczeń komputerowych i symulacji procesu przewietrzania modelem matematycznym przystępujemy do opracowania modelu numerycznego dla wybranej sieci wyrobisk kopalni. Przygotowanie modelu numerycznego sieci wentylacyjnej danej kopalni wymaga dostarczenia zestawu danych dotyczących struktury sieci i własności fizycznych jej elementów, tj. wyrobisk, wentylatorów, tam, a przy symulacji pożaru dodatkowo wymagane jest podanie parametrów opisujących ognisko pożaru oraz własności skał górotworu. Obecna praktyka postępowania polega na tym, że wykonuje się ręczne pomiary wentylacyjne w wyrobiskach górniczych, a uzyskane wyniki stanowią podstawę do wyznaczenia parametrów fizycznych takich jak: opór aerodynamiczny wyrobiska, gęstość przepływającego powietrza i

  14. Selected Properties of Flotation Tailings Wastes Deposited in the Gilów and Żelazny Most Waste Reservoirs Regarding Their Potential Environmental Management / Wybrane Właściwości Odpadów Poflotacyjnych Zdeponowanych W Zbiornikach Gilów I Żelazny Most W Aspekcie Możliwości Ich Zagospodarowania Przyrodniczego

    NASA Astrophysics Data System (ADS)

    Baran, Agnieszka; Śliwka, Małgorzata; Lis, Marcin

    2013-09-01

    Wastes originating from copper mining, particularly generated during the ore enrichment process constitute a considerable percentage of industrial wastes in Poland, which theoretically are supposed to provide a raw material base but remain wholly unmanaged. Wastes from copper flotation are deposited on the waste dumps which pose a significant eco-toxicological hazard. The paper discussed the results of analysis of selected post-floatation waste properties deposited in the Żelazny Most and Gilów reservoirs from the perspective of their environmental management. Odpady pochodzące z górnictwa miedzi, szczególnie powstające w procesie wzbogacania rudy, stanowią znaczny odsetek odpadów przemysłowych w naszym kraju, które teoretycznie zasilić mają bazę surowcową i w całości pozostają niezagospodarowane. Odpady z procesu flotacji miedzi są deponowane na składowiskach i stanowią zagrożeniem ekologicznym i ekotoksykologicznym dla środowiska przyrodniczego i człowieka. Niekorzystne oddziaływanie składowisk odpadów poflotacyjnych na środowisko to przede wszystkim deformacje terenu, zanieczyszczenia gleb zanieczyszczeń roślinności metalami ciężkimi, oraz zanieczyszczenie wód powierzchniowych i podziemnych. W artykule zostały omówione niektóre właściwości fizykochemiczne oraz ekotoksykologiczne odpadów poflotacyjnych deponowanych w zbiornikach Żelazny Most i Gilów pod kątem ich biologicznego zagospodarowania. Próbki pobranych osadów, po odpowiednim przygotowaniu, poddano ocenie wybranych parametrów fizycznych, analizie chemicznej oraz serii testów ekotoksykologicznych. Właściwości ekotoksykologiczne osadów oceniono przy użyciu baterii biotestów składającej się z dwóch biotestów pracujących na pięciu organizmach (tab. 1). W teście Phytotoxkit do pomiaru toksyczności osadu wykorzystano trzy rośliny: Sorghum saccharatum, Lepidium sativum i Sinapis alba. Mierzonym parametrem było zahamowanie kiełkowania nasion oraz d

  15. Ages of Lunar Light Plains

    NASA Astrophysics Data System (ADS)

    Hiesinger, Harald; Howes van der Bogert, Carolyn; Thiessen, Fiona; Robinson, Mark

    2013-04-01

    light plains are necessary to corroborate this preliminary observation. In general, our new absolute model ages are similar to model ages derived for light plains north of Mare Frigoris (3.65-4.0 Ga) [6], light plains within the SPA basin (3.43-3.81 Ga) [7], and light plains in the surroundings of the Orientale and Imbrium basins (3.8-4.3 Ga) [8]. The ages are not only similar, but also show similar ranges. While our model ages vary by about 300 Ma, model ages of [6,7] exhibit ranges of ~350 Ma and ~380 Ma, respectively. Ages of [8] show a somewhat wider range of ~500 Ma. From this wide range in ages it has been concluded that a formation of the light plains by a single event (i.e., Orientale or Imbrium) is unlikely [6-8]. References: [1] Wilhelms and McCauley (1971), USGS I-703; [2] Stuart-Alexander (1978), USGS I-1047; [3] Wilhelms et al. (1979), USGS I-1162; [4] Scott et al. (1977), USGS I-1034; [5] Wilhelms and El-Baz (1977), USGS I-948; [6] Köhler et al. (2000), LPSC 31, #1822; [7] Thiessen et al. (2012), LPSC 43, #2060; [8] Neukum (1977b), Moon 17, 383-393.

  16. Inventory of Multiring Basins on the Moon After the Clementine Mission

    NASA Astrophysics Data System (ADS)

    Spudis, P. D.

    1995-09-01

    topography for a basin is that of the degraded Lomonosov-Fleming basin [3,6]. This feature appears as a quasi-circular, smooth plateau of nearly constant elevation about 500 km across. Such an expression is likely caused by infilling of the basin with ancient mare basalts, covered by highland plains and reexposed as the ejecta of dark halo impact craters [7,8]. This interpretation is supported by the mafic signature of the plains in this region in the Clementine global color image [9] and the presense of elevated amounts of iron in the highland crust here [10]. The altimetry data also show many depressions that are likely to be previously unrecognized basins. For example, depressions near the crater Darwin (20 degrees S, 70 degrees W; basin about 300 km diameter), eastern Mare Frigoris (55 degrees N, 30 degrees W; basin about 700 km across), and east of Mare Humboldtianum (60 degrees N, 130 degrees E; basin about 400 km diameter) are probably degraded impact basins. To date, over 45 basins and their rings have been mapped on the Moon and the relief and volumes of the basins have been measured. Work continues on the analysis of this numerical data, which should give insight into the processes of basin formation and planetary evolution. References: [1] Wilhelms D. E. (1987) USGS Prof. Pap. 1348, 302 pp. [2] Spudis P. D. (1993) Geology of Multi-Ring Impact Basins, Cambridge Univ., 263 pp. [3] Nozette S. et al. (1994) Science, 266, 1835. [4] Zuber M. T. et al. (1994) Science, 266, 1839. [5] Spudis P. D. et al. (1994) Science, 266, 1848. [6] Wilhelms D. and El-Baz F. (1977) USGS Map I-948. [7] Schultz P. H. and Spudis P. D. (1979) Proc. LPSC 10th, 2899. [8] Schultz P. H. and Spudis P. D. (1982) Nature, 302, 233. [9] Lucey P. G. et al. (1994) Science, 266, 1855. [10] Lucey P. G. et al. (1995) Science, 268, 1150.

  17. New Criteria to Assess Seismic and Rock Burst Hazard in Coal Mines / Nowe Kryteria Dla Oceny Zagrożenia Sejsmicznego I Tąpaniami W Kopalniach Węgla Kamiennego

    NASA Astrophysics Data System (ADS)

    Mutke, Grzegorz; Dubiński, Józef; Lurka, Adam

    2015-09-01

    niektórych przypadkach również wypadki śmiertelne. Przedstawiono podstawowe parametry sejsmologiczne stosowane w kraju i w świecie do oceny zagrożenia sejsmicznego. Opisano podstawowe zasady metody kompleksowej oceny stanu zagrożenia tąpnięciem, w skład której wchodzi metoda sejsmologiczna bieżącej (pomiarowej) oceny stanu zagrożenia. Od wielu lat, wraz z ciągłym rozwojem bazy aparaturowej i możliwości w zakresie cyfrowej rejestracji sejsmogramów oraz przetwarzania i interpretacji danych pomiarowych wzrasta znaczenie metod sejsmicznych, które są dzisiaj powszechnie stosowane w polskich kopalniach zagrożonych tąpaniami. Ciągła obserwacja zjawisk sejsmicznych indukowanych w trakcie rozwoju procesu eksploatacji pokładów węgla umożliwiła, w oparciu o zgromadzoną bazę danych, opracowywanie nowych kryteriów zagrożenia sejsmicznego oraz zagrożenia tąpnięciem, które winny wyraźnie poprawić efektywność metody sejsmologii górniczej. W artykule przedstawiono nowe kryteria oceny stanu bieżącego zagrożenia tąpaniami zaproponowane do stosowania w polskich kopalniach węgla kamiennego, które prowadzą eksploatację systemem ścianowym. Kryteria te są oparte na wynikach ciągłej rejestracji sejsmologicznej, połączonej z bieżącą analizą zarejestrowanych wstrząsów i obliczaniem wybranych parametrów sejsmologicznych. Parametry te to położenie ognisk wstrząsów w stosunku do wyrobisk eksploatacyjnych, energia sejsmiczna wstrząsów, suma energii sejsmicznej wyzwolona na każde 5m postępu ściany eksploatacyjnej, wartość wagowanego parametru amplitudy prędkości drgań PPVW, moment sejsmiczny M0, indeks energii EI oraz parametr b rozkładu wstrząsów według relacji Gutenberga-Richtera. Wartości powyższych parametrów są określane dla każdej doby lub w przesuwających się co dobę oknach czasowych lub oknach zawierających określoną liczbę wstrząsów, a następnie porównywane, raz na dobę, z ich wartościami

  18. New Criteria to Assess Seismic and Rock Burst Hazard in Coal Mines / Nowe Kryteria Dla Oceny Zagrożenia Sejsmicznego I Tąpaniami W Kopalniach Węgla Kamiennego

    NASA Astrophysics Data System (ADS)

    Mutke, Grzegorz; Dubiński, Józef; Lurka, Adam

    2015-09-01

    niektórych przypadkach również wypadki śmiertelne. Przedstawiono podstawowe parametry sejsmologiczne stosowane w kraju i w świecie do oceny zagrożenia sejsmicznego. Opisano podstawowe zasady metody kompleksowej oceny stanu zagrożenia tąpnięciem, w skład której wchodzi metoda sejsmologiczna bieżącej (pomiarowej) oceny stanu zagrożenia. Od wielu lat, wraz z ciągłym rozwojem bazy aparaturowej i możliwości w zakresie cyfrowej rejestracji sejsmogramów oraz przetwarzania i interpretacji danych pomiarowych wzrasta znaczenie metod sejsmicznych, które są dzisiaj powszechnie stosowane w polskich kopalniach zagrożonych tąpaniami. Ciągła obserwacja zjawisk sejsmicznych indukowanych w trakcie rozwoju procesu eksploatacji pokładów węgla umożliwiła, w oparciu o zgromadzoną bazę danych, opracowywanie nowych kryteriów zagrożenia sejsmicznego oraz zagrożenia tąpnięciem, które winny wyraźnie poprawić efektywność metody sejsmologii górniczej. W artykule przedstawiono nowe kryteria oceny stanu bieżącego zagrożenia tąpaniami zaproponowane do stosowania w polskich kopalniach węgla kamiennego, które prowadzą eksploatację systemem ścianowym. Kryteria te są oparte na wynikach ciągłej rejestracji sejsmologicznej, połączonej z bieżącą analizą zarejestrowanych wstrząsów i obliczaniem wybranych parametrów sejsmologicznych. Parametry te to położenie ognisk wstrząsów w stosunku do wyrobisk eksploatacyjnych, energia sejsmiczna wstrząsów, suma energii sejsmicznej wyzwolona na każde 5m postępu ściany eksploatacyjnej, wartość wagowanego parametru amplitudy prędkości drgań PPVW, moment sejsmiczny M0, indeks energii EI oraz parametr b rozkładu wstrząsów według relacji Gutenberga-Richtera. Wartości powyższych parametrów są określane dla każdej doby lub w przesuwających się co dobę oknach czasowych lub oknach zawierających określoną liczbę wstrząsów, a następnie porównywane, raz na dobę, z ich wartościami

  19. The Application of Coreless Inductors for Displacement Measurements in Laboratory Investigations of Rock Properties

    NASA Astrophysics Data System (ADS)

    Nurkowski, Janusz

    2014-12-01

    ści termicznej (rys. 7). Zmiany częstotliwości z czujnika referencyjnego są poprawkami do wskazań czujnika pomiarowego. Oba czujniki są naprzemiennie podłączane do tego samego generatora poprzez elektroniczny przełącznik (rys. 5). Zastosowanie jednego generatora powoduje, że poprawki te umożliwiają również praktycznie całkowitą eliminację błędu pomiaru ze względu na zmiany temperatury otoczenia i napięcia zasilania na generator i częstościomierz. Charakterystyka przetwornika długość-częstotliwość jest nieliniowa (rys. 3), co wynika z zależności między długością cewki czujnika, więc jej indukcyjnością, a częstotliwością rezonansową obwodu LC (1). Najdokładniej charakterystykę czujnika otrzymać można przez wzorcowanie. Uwzględnione są wtedy głównie pasożytnicze indukcyjności i pojemności połączeń, których wartości trudno obliczyć lub zmierzyć. W pomiarach należy dążyć, na ile to możliwe, do montowania krótkiego czujnika do długich próbek, w ten sposób zmiany długości badanego materiału będą większe, a krótszy czujnik dozna większego odkształcenia, więc czułość pomiaru będzie duża. Jednak zbyt krótki czujnik ma małą indukcyjność i wtedy jego czułość ograniczy indukcyjność połączeń (2). Opracowano dwa podstawowe typy takiego czujnika. Pierwszy, do pomiaru odkształceń liniowych, np. do pomiaru ściśliwości (rys. 2 i 6), o prostej cewce, który jest mocowany do próbki za pośrednictwem zaczepów przytwierdzonych do niej. W ten sposób czujnik nie kontaktuje się bezpośrednio z powierzchnią próbki, i odkształca się bez tarcia, co umożliwia precyzyjny pomiar, szczególnie przy obciążaniu cyklicznym. Bazę pomiarową można dostosowywać do długości próbki, mocując czujnik do zaczepów poprzez łączniki, uzyskując globalny pomiar odkształceń. Czujnik mierzy zmiany długości z rozdzielczością poniżej 1 μm, przy maksymalnych odkształceniach czujnika o kilkadziesi