Science.gov

Sample records for 4a figure 4b

  1. Characterization of Dengue Virus NS4A and NS4B Protein Interaction

    PubMed Central

    Zou, Jing; Xie, Xuping; Wang, Qing-Yin; Dong, Hongping; Lee, Michelle Yueqi; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus replication is mediated by a membrane-associated replication complex where viral membrane proteins NS2A, NS2B, NS4A, and NS4B serve as the scaffold for the replication complex formation. Here, we used dengue virus serotype 2 (DENV-2) as a model to characterize viral NS4A-NS4B interaction. NS4A interacts with NS4B in virus-infected cells and in cells transiently expressing NS4A and NS4B in the absence of other viral proteins. Recombinant NS4A and NS4B proteins directly bind to each other with an estimated Kd (dissociation constant) of 50 nM. Amino acids 40 to 76 (spanning the first transmembrane domain, consisting of amino acids 50 to 73) of NS4A and amino acids 84 to 146 (also spanning the first transmembrane domain, consisting of amino acids 101 to 129) of NS4B are the determinants for NS4A-NS4B interaction. Nuclear magnetic resonance (NMR) analysis suggests that NS4A residues 17 to 80 form two amphipathic helices (helix α1, comprised of residues 17 to 32, and helix α2, comprised of residues 40 to 47) that associate with the cytosolic side of endoplasmic reticulum (ER) membrane and helix α3 (residues 52 to 75) that transverses the ER membrane. In addition, NMR analysis identified NS4A residues that may participate in the NS4A-NS4B interaction. Amino acid substitution of these NS4A residues exhibited distinct effects on viral replication. Three of the four NS4A mutations (L48A, T54A, and L60A) that affected the NS4A-NS4B interaction abolished or severely reduced viral replication; in contrast, two NS4A mutations (F71A and G75A) that did not affect NS4A-NS4B interaction had marginal effects on viral replication, demonstrating the biological relevance of the NS4A-NS4B interaction to DENV-2 replication. Taken together, the study has provided experimental evidence to argue that blocking the NS4A-NS4B interaction could be a potential antiviral approach. IMPORTANCE Flavivirus NS4A and NS4B proteins are essential components of the ER membrane

  2. Specificity of the hepatitis C virus NS3 serine protease: effects of substitutions at the 3/4A, 4A/4B, 4B/5A, and 5A/5B cleavage sites on polyprotein processing.

    PubMed Central

    Kolykhalov, A A; Agapov, E V; Rice, C M

    1994-01-01

    Cleavage at four sites (3/4A, 4A/4B, 4B/5A, and 5A/5B) in the hepatitis C virus polyprotein requires a viral serine protease activity residing in the N-terminal one-third of the NS3 protein. Sequence comparison of the residues flanking these cleavage sites reveals conserved features including an acidic residue (Asp or Glu) at the P6 position, a Cys or Thr residue at the P1 position, and a Ser or Ala residue at the P1' position. In this study, we used site-directed mutagenesis to assess the importance of these and other residues for NS3 protease-dependent cleavages. Substitutions at the P7 to P2' positions of the 4A/4B site had varied effects on cleavage efficiency. Only Arg at the P1 position or Pro at P1' substantially blocked processing at this site. Leu was tolerated at the P1 position, whereas five other substitutions allowed various degrees of cleavage. Substitutions with positively charged or other hydrophilic residues at the P7, P3, P2, and P2' positions did not reduce cleavage efficiency. Five substitutions examined at the P6 position allowed complete cleavage, demonstrating that an acidic residue at this position is not essential. Parallel results were obtained with substrates containing an active NS3 protease domain in cis or when the protease domain was supplied in trans. Selected substitutions blocking or inhibiting cleavage at the 4A/4B site were also examined at the 3/4A, 4B/5A, and 5A/5B sites. For a given substitution, a site-dependent gradient in the degree of inhibition was observed, with a 3/4A site being least sensitive to mutagenesis, followed by the 4A/4B, 4B/5A, and 5A/5B sites. In most cases, mutations abolishing cleavage at one site did not affect processing at the other serine protease-dependent sites. However, mutations at the 3/4A site which inhibited cleavage also interfered with processing at the 4B/5A site. Finally, during the course of these studies an additional NS3 protease-dependent cleavage site has been identified in the NS4B

  3. The gene history of zebrafish tlr4a and tlr4b is predictive of their divergent functions.

    PubMed

    Sullivan, Con; Charette, Jeremy; Catchen, Julian; Lage, Christopher R; Giasson, Gregory; Postlethwait, John H; Millard, Paul J; Kim, Carol H

    2009-11-01

    Mammalian immune responses to LPS exposure are typified by the robust induction of NF-kappaB and IFN-beta responses largely mediated by TLR4 signal transduction pathways. In contrast to mammals, Tlr4 signal transduction pathways in nontetrapods are not well understood. Comprehensive syntenic and phylogenetic analyses support our hypothesis that zebrafish tlr4a and tlr4b genes are paralogous rather than orthologous to human TLR4. Furthermore, we provide evidence to support our assertion that the in vivo responsiveness of zebrafish to LPS exposure is not mediated by Tlr4a and Tlr4b paralogs because they fail to respond to LPS stimulation in vitro. Zebrafish Tlr4a and Tlr4b paralogs were also unresponsive to heat-killed Escherichia coli and Legionella pneumophila. Using chimeric molecules in which portions of the zebrafish Tlr4 proteins were fused to portions of the mouse TLR4 protein, we show that the lack of responsiveness to LPS was most likely due to the inability of the extracellular portions of zebrafish Tlr4a and Tlr4b to recognize the molecule, rather than to changes in their capacities to transduce signals through their Toll/IL-1 receptor (TIR) domains. Taken together, these findings strongly support the notion that zebrafish tlr4a and tlr4b paralogs have evolved to provide alternative ligand specificities to the Tlr immune defense system in this species. These data demonstrate that intensive examination of gene histories when describing the Tlr proteins of basally diverging vertebrates is required to obtain fuller appreciation of the evolution of their function. These studies provide the first evidence for the functional evolution of a novel Tlr.

  4. Distinct and overlapping functions of the cullin E3 ligase scaffolding proteins CUL4A and CUL4B

    PubMed Central

    Hannah, Jeffrey

    2016-01-01

    The cullin 4 subfamily of genes includes CUL4A and CUL4B, which share a mostly identical amino acid sequence aside from the elongated N-terminal region in CUL4B. Both act as scaffolding proteins for modular cullin RING ligase 4 (CRL4) complexes which promote the ubiquitination of a variety of substrates. CRL4 function is vital to cells as loss of both genes or their shared substrate adaptor protein DDB1 halts proliferation and eventually leads to cell death. Due to their high structural similarity, CUL4A and CUL4B share a substantial overlap in function. However, in some cases, differences in subcellular localization, spatiotemporal expression patterns and stress-inducibility preclude functional compensation. In this review, we highlight the most essential functions of the CUL4 genes in: DNA repair and replication, chromatin-remodeling, cell cycle regulation, embryogenesis, hematopoiesis and spermatogenesis. CUL4 genes are also clinically relevant as dysregulation can contribute to the onset of cancer and CRL4 complexes are often hijacked by certain viruses to promote viral replication and survival. Also, mutations in CUL4B have been implicated in a subset of patients suffering from syndromic X-linked intellectual disability (AKA mental retardation). Interestingly, the antitumor effects of immunomodulatory drugs are caused by their binding to the CRL4CRBN complex and re-directing the E3 ligase towards the Ikaros transcription factors IKZF1 and IKZF3. Because of their influence over key cellular functions and relevance to human disease, CRL4s are considered promising targets for therapeutic intervention. PMID:26344709

  5. Cell surface trafficking of TLR1 is differentially regulated by the chaperones PRAT4A and PRAT4B.

    PubMed

    Hart, Bryan E; Tapping, Richard I

    2012-05-11

    The subcellular localization of Toll-like receptors (TLRs) is critical to their ability to function as innate immune sensors of microbial infection. We previously reported that an I602S polymorphism of human TLR1 is associated with aberrant trafficking of the receptor to the cell surface, loss of responses to TLR1 agonists, and differential susceptibility to diseases caused by pathogenic mycobacteria. Through an extensive analysis of receptor deletion and point mutants we have discovered that position 602 resides within a short 6 amino acid cytoplasmic region that is required for TLR1 surface expression. This short trafficking motif, in conjunction with the adjacent transmembrane domain, is sufficient to direct TLR1 to the cell surface. A serine at position 602 interrupts this trafficking motif and prevents cell surface expression of TLR1. Additionally, we have found that ER-resident TLR chaperones, PRAT4A and PRAT4B, act as positive and negative regulators of TLR1 surface trafficking, respectively. Importantly, either over-expression of PRAT4A or knock-down of PRAT4B rescues cell surface expression of the TLR1 602S variant. We also report that IFN-γ treatment of primary human monocytes derived from homozygous 602S individuals rescues TLR1 cell surface trafficking and cellular responses to soluble agonists. This event appears to be mediated by PRAT4A whose expression is strongly induced in human monocytes by IFN-γ. Collectively, these results provide a mechanism for the differential trafficking of TLR1 I602S variants, and highlight the distinct roles for PRAT4A and PRAT4B in the regulation of TLR1 surface expression.

  6. Monoclonal antipeptide antibodies against amino acid residues 1101-1106 of human C4 distinguish C4A from C4B.

    PubMed

    Reilly, B D; Levine, P; Rothbard, J; Skanes, V M

    1991-01-01

    Comparison of amino acid sequences of the alpha-chain fragment of human C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 in which the aspartic acid-histidine substitution at position 1106 may be related to the amide and ester bond forming properties of these molecules. Peptides containing twelve amino acid residues of the C4A- or C4B-specific sequences were synthesized and injected into female Balb/c mice. Serum from 2 mice, one immunized with the C4A-specific peptide and the other with the C4B-specific peptide, gave strong isotype-specific responses in an enzyme-linked immunosorbent assay against affinity-purified C4A3 and C4B2B1. Spleen cells from these mice were fused with the mouse myeloma SP2/0-Ag 14, and two cloned cell lines, AII-1 and BII-1, were established from hybrids. Enzyme-linked immunosorbent assay and western blotting of monoclonal antibodies AII-1 and BII-1 show that the former reacts with the C4A but not with the C4B alpha-chain and the latter with C4B but not with the C4A alpha-chain. Furthermore, immunoblotting of C4 allelic variants showed that AII-1 reacted with all C4A allotypes tested, including A6, A4, A3 and A2, whereas BII-1 reacted with all C4B allotypes tested, including B5, B3, B2, and B1.

  7. Cleavage at a novel site in the NS4A region by the yellow fever virus NS2B-3 proteinase is a prerequisite for processing at the downstream 4A/4B signalase site.

    PubMed Central

    Lin, C; Amberg, S M; Chambers, T J; Rice, C M

    1993-01-01

    Flavivirus proteins are produced by co- and posttranslational proteolytic processing of a large polyprotein by both host- and virus-encoded proteinases. The viral serine proteinase, which consists of NS2B and NS3, is responsible for cleavage of at least four dibasic sites (2A/2B, 2B/3, 3/4A, and 4B/5) in the nonstructural region. Since the amino acid sequence preceding NS4B shares characteristics with signal peptides used for translocation of nascent polypeptides into the lumen of the endoplasmic reticulum, it has been proposed that cleavage at the 4A/4B site is mediated by a cellular signal peptidase. In this report, cell-free translation and in vivo transient expression assays were used to study processing in the NS4 region of the yellow fever virus polyprotein. With a construct which contained NS4B preceded by 17 residues constituting the putative signal peptide (sig4B), membrane-dependent cleavage at the 4A/4B site was demonstrated in vitro. Surprisingly, processing of NS4A-4B was not observed in cell-free translation studies, and in vivo expression of several yellow fever virus polyproteins revealed that the 4A/4B cleavage occurred only during coexpression of NS2B and the proteinase domain of NS3. Examination of mutant derivatives of the NS3 proteinase domain demonstrated that cleavage at the 4A/4B site correlated with expression of an active NS2B-3 proteinase. From these results, we propose a model in which the signalase cleavage generating the N terminus of NS4B requires a prior NS2B-3 proteinase-mediated cleavage at a novel site (called the 4A/2K site) which is conserved among flaviviruses and located 23 residues upstream of the signalase site. In support of this model, mutations at the 4A/4B signalase site did not eliminate processing in the NS4 region. In contrast, substitutions at the 4A/2K site, which were engineered to block NS2B-3 proteinase-mediated cleavage, eliminated signalase cleavage at the 4A/4B site. In addition, the size of the 3(502)-4A

  8. KDM4B and KDM4A promote endometrial cancer progression by regulating androgen receptor, c-myc, and p27kip1

    PubMed Central

    Kwan, Suet-Ying; Chen, Limo; Chen, Jin-Hong; Ying, Zuo-Lin; Zhou, Ye; Gu, Wei; Wang, Li-Hua; Cheng, Wei-Wei; Zeng, Jianfang; Wan, Xiao-Ping; Mok, Samuel C.; Wong, Kwong-Kwok; Bao, Wei

    2015-01-01

    Epidemiological evidence suggests that elevated androgen levels and genetic variation related to the androgen receptor (AR) increase the risk of endometrial cancer (EC). However, the role of AR in EC is poorly understood. We report that two members of the histone demethylase KDM4 family act as major regulators of AR transcriptional activityin EC. In the MFE-296 cell line, KDM4B and AR upregulate c-myc expression, while in AN3CA cells KDM4A and AR downregulate p27kip1. Additionally, KDM4B expression is positively correlated with AR expression in EC cell lines with high baseline AR expression, while KDM4A and AR expression are positively correlated in low-AR cell lines. In clinical specimens, both KDM4B and KDM4A expression are significantly higher in EC tissues than that in normal endometrium. Finally, patients with alterations in AR, KDM4B, KDM4A, and c-myc have poor overall and disease-free survival rates. Together, these findings demonstrate that KDM4B and KDM4A promote EC progression by regulating AR activity. PMID:26397136

  9. Coriolis Interactions in the nu2, nu4a, nu4b, and nu3a States of Phosphine-d1

    PubMed

    Kshirsagar; Job

    1997-10-01

    Spectra of the nu4a (HPH bend) and nu4b (HPD bend) bands of the PH2D molecule have been recorded and analyzed. The Coriolis interactions between the two states as well as the various Coriolis interactions of the nu4a and nu4b states with the nu2 state have been included in the analysis. Several new assignments of transitions which occur with enhanced intensity in the nu2 band also have been made. The parameters of the nu4a and nu4b states, improved parameters of the nu2 state, and the interaction parameters have been determined. The data on the nu3a band of PH2D have been reanalyzed by taking into account the b-axis Coriolis interaction of the nu3a state with the 2nu2 state. Copyright 1997 Academic Press. Copyright 1997Academic Press

  10. Roles of p15Ink4b and p16Ink4a in myeloid differentiation and RUNX1-ETO-associated acute myeloid leukemia

    PubMed Central

    Ko, Rose M.; Kim, Hyung-Gyoon; Wolff, Linda; Klug, Christopher A.

    2008-01-01

    Inactivation of p15Ink4b expression by promoter hypermethylation occurs in up to 80% of acute myeloid leukemia (AML) cases and is particularly common in the FAB-M2 subtype of AML, which is characterized by the presence of the RUNX1-ETO translocation in 40% of cases. To establish whether the loss of p15Ink4b contributes to AML progression in association with RUNX1-ETO, we have expressed the RUNX1-ETO fusion protein from a retroviral vector in hematopoietic progenitor cells isolated from wild-type, p15Ink4b or p16Ink4a knockout bone marrow. Analysis of lethally irradiated recipient mice reconstituted with RUNX1-ETO-expressing cells showed that neither p15Ink4b or p16Ink4a loss significantly accelerated disease progression over the time period of one year post-transplantation. Loss of p15Ink4b alone resulted in increased myeloid progenitor cell frequencies in bone marrow by 10 months post-transplant and a 19-fold increase in the frequency of Lin-c-Kit+Sca-1+ (LKS) cells that was not associated with expansion of long-term reconstituting HSC. These results strongly suggest that p15Ink4b loss must be accompanied by additional oncogenic changes for RUNX1-ETO-associated AML to develop. PMID:18037485

  11. Complement components C2, C3, and C4 (C4A and C4B) and BF polymorphisms in populations of the Indian subcontinent.

    PubMed

    Ad'hiah, A H; Papiha, S S

    1996-10-01

    Genetic polymorphisms of the complement components (five loci: C2, C3, C4A, C4B, and BF) have been investigated in the Telugu-speaking Hindu population of Hyderabad, Andhra Pradesh, India, and the Bangali-speaking Muslim population of Dacca, Bangladesh. The available data are compared to understand the genetic variation of complement components in populations of the Indian subcontinent. The C3*F and BF*F alleles show wide frequency variations in different ethnic groups of India. The range of variation in the C3*F allele is intermediate between European whites and southeast Asian populations, whereas the BF*F allele places the Indian frequencies between European whites and African blacks. This is the first population study to investigate the C2 and C4 (C4A and C4B) polymorphisms in two distinct groups of the Indian subcontinent. For the C2 polymorphism only the C2*B variant allele was observed, and its frequency was slightly higher than in European populations. In both populations the C4A and C4B loci were highly polymorphic, with a high frequency of the null alleles C4A*QO and C4B*QO, which may account for the greater susceptibility to certain autoimmune diseases in populations of South Asia.

  12. eIF4B stimulates eIF4A ATPase and unwinding activities by direct interaction through its 7-repeats region.

    PubMed

    Andreou, Alexandra Zoi; Harms, Ulf; Klostermeier, Dagmar

    2017-01-02

    Eukaryotic translation initiation starts with binding of the eIF4F complex to the 5'-m(7)G cap of the mRNA. Recruitment of the 43S pre-initiation complex (PIC), formed by the 40S ribosomal subunit and other translation initiation factors, leads to formation of the 48S PIC that then scans the 5'-untranslated region (5'-UTR) toward the start codon. The eIF4F complex consists of eIF4E, the cap binding protein, eIF4A, a DEAD-box RNA helicase that is believed to unwind secondary structures in the 5'-UTR during scanning, and eIF4G, a scaffold protein that binds to both eIF4E and eIF4A. The ATPase and helicase activities of eIF4A are jointly stimulated by eIF4G and the translation initiation factor eIF4B. Yeast eIF4B mediates recruitment of the 43S PIC to the cap-bound eIF4F complex by interacting with the 40S subunit and possibly with eIF4A. However, a direct interaction between yeast eIF4A and eIF4B has not been demonstrated yet. Here we show that eIF4B binds to eIF4A in the presence of RNA and ADPNP, independent of the presence of eIF4G. A stretch of seven moderately conserved repeats, the r1-7 region, is responsible for complex formation, for modulation of the conformational energy landscape of eIF4A by eIF4B, and for stimulating the RNA-dependent ATPase- and ATP-dependent RNA unwinding activities of eIF4A. The isolated r1-7 region only slightly stimulates eIF4A conformational changes and activities, suggesting that communication of the repeats with other regions of eIF4B is required for full stimulation of eIF4A activity, for recruitment of the PIC to the mRNA and for translation initiation.

  13. Association between C4, C4A, and C4B copy number variations and susceptibility to autoimmune diseases: a meta-analysis

    PubMed Central

    Li, Na; Zhang, Jun; Liao, Dan; Yang, Lu; Wang, Yingxiong; Hou, Shengping

    2017-01-01

    Although several studies have investigated the association between C4, C4A, and C4B gene copy number variations (CNVs) and susceptibility to autoimmune diseases, the results remain inconsistency for those diseases. Thus, in this study, a comprehensive meta-analysis was conducted to assess the role of C4, C4A, and C4B CNVs in autoimmune diseases in different ethnic groups. A total of 16 case-control studies described in 12 articles (8663 cases and 11099 controls) were included in this study. The pooled analyses showed that a low C4 gene copy number (GCN) (<4) was treated as a significant risk factor (odds ratio [OR] = 1.46, 95% confidence interval [CI] = 1.19–1.78) for autoimmune diseases compared with a higher GCN (>4). The pooled statistical results revealed that low C4 (<4) and low C4A (<2) GCNs could be risk factors for systemic lupus erythematosus (SLE) in Caucasian populations. Additionally, the correlation between C4B CNVs and all type of autoimmune diseases could not be confirmed by the current meta-analysis (OR = 1.07, 95% CI = 0.93–1.24). These data suggest that deficiency or absence of C4 and C4A CNVs may cause susceptibility to SLE. PMID:28205620

  14. The Function of HMG-Box Transcription Factors Sox4a and Sox4b in Zebrafish Bone Development and Homeostasis

    NASA Astrophysics Data System (ADS)

    Aceto, J.; Motte, P.; Martial, J. A.; Muller, M.

    2008-06-01

    In mammals, the Sox4 gene is involved in development of endocardial crests, the brain, the lung, teeth, gonads and lymphocytes. Recently, Sox4 was shown to control bone mass and mineralization in mice. In zebrafish, two homologs for the mammalian Sox4 are present, sox4a and sox4b. Here we investigate the function of the sox4a and sox4b genes in cartilage and bone development in zebrafish. Therefore, we focus our attention on the first bone structures to be formed, the head skeleton and more precisely the pharyngeal cartilage. We show that both genes are expressed in the pharyngeal region, albeit at different time points during development. Double in situ hybridization experiments are used to exactly define the particular tissues where they are expressed. Furthermore, microinjection experiments of antisense oligonucleotides are used to block translation of these specific genes and to define their precise function during cartilage and bone development.

  15. The plasma membrane Ca2+ pump isoform 4a differs from isoform 4b in the mechanism of calmodulin binding and activation kinetics: implications for Ca2+ signaling.

    PubMed

    Caride, Ariel J; Filoteo, Adelaida G; Penniston, John T; Strehler, Emanuel E

    2007-08-31

    The inhibition by the regulatory domain and the interaction with calmodulin (CaM) vary among plasma membrane calcium pump (PMCA) isoforms. To explore these differences, the kinetics of CaM effects on PMCA4a were investigated and compared with those of PMCA4b. The maximal apparent rate constant for CaM activation of PMCA4a was almost twice that for PMCA4b, whereas the rates of activation for both isoforms showed similar dependence on Ca2+. The inactivation of PMCA4a by CaM removal was also faster than for PMCA4b, and Ca2+ showed a much smaller effect (2- versus 30-fold modification). The rate constants of the individual steps that determine the overall rates were obtained from stopped-flow experiments in which binding of TA-CaM was observed by changes in its fluorescence. TA-CaM binds to two conformations of PMCA4a, an "open" conformation with high activity, and a "closed" one with lower activity. Compared with PMCA4b (Penheiter, A. R., Bajzer, Z., Filoteo, A. G., Thorogate, R., Török, K., and Caride, A. J. (2003) Biochemistry 41, 12115-12124), the model for PMCA4a predicts less inhibition in the closed form and a much faster equilibrium between the open and closed forms. Based on the available kinetic parameters, we determined the constants to fit the shape of a Ca2+ signal in PMCA4b-overexpressing Chinese hamster ovary cells. Using the constants for PMCA4a, and allowing small variations in parameters of other systems contributing to a Ca2+ signal, we then simulated the effect of PMCA4a on the shape of a Ca2+ signal in Chinese hamster ovary cells. The results reproduce the published data (Brini, M., Coletto, L., Pierobon, N., Kraev, N., Guerini, D., and Carafoli, E. (2003) J. Biol. Chem. 278, 24500-24508), and thereby demonstrate the importance of altered regulatory kinetics for the different functional properties of PMCA isoforms.

  16. Methylation of CpG island of p14(ARK), p15(INK4b) and p16(INK4a) genes in coke oven workers.

    PubMed

    Zhang, H; Li, X; Ge, L; Yang, J; Sun, J; Niu, Q

    2015-02-01

    To detect the blood genomic DNA methylation in coke oven workers and find a possible early screening index for occupational lung cancer, 74 coke oven workers as the exposed group and 47 water pump workers as the controls were surveyed, and urine samples and peripheral blood mononuclear cells (PBMCs) were collected. Airborne benzo[a]pyrene (B[a]P) levels in workplace and urinary 1-hydroxypyrene (1-OH-Py) levels were determined by high-performance liquid chromatography. DNA damage of PBMCs and the p14(ARK), p15(INK4b) and p16(INK4a) gene CpG island methylation in the promoter region were detected by comet assay and methylation-specific polymerase chain reaction techniques, respectively. Results show that compared with the controls, concentration of airborne B[a]Ps was elevated in the coke plant, and urinary 1-OH-Py's level and DNA olive tail moment in comet assay were significantly increased in the coke oven workers, and p14(ARK), p15(INK4b) and p16(INK4a) gene methylation rates were also significantly increased. With the working years and urinary 1-OH-Py's level, the rates of p14(ARK) and p16(INK4a) gene methylation were significantly increased while that of p15(INK4b) gene methylation displayed no statistical change. We conclude that PBMCs' p14(ARK) and p16(INK4a) gene methylation may be used for screening and warning lung cancer in coke oven workers.

  17. Substitution of a single amino acid (aspartic acid for histidine) converts the functional activity of human complement C4B to C4A.

    PubMed Central

    Carroll, M C; Fathallah, D M; Bergamaschini, L; Alicot, E M; Isenman, D E

    1990-01-01

    The C4B isotype of the fourth component of human complement (C4) displays 3- to 4-fold greater hemolytic activity than does its other isotype C4A. This correlates with differences in their covalent binding efficiencies to erythrocytes coated with antibody and complement C1. C4A binds to a greater extent when C1 is on IgG immune aggregates. The differences in covalent binding properties correlate only with amino acid changes between residues 1101 and 1106 (pro-C4 numbering)--namely, Pro-1101, Cys-1102, Leu-1105, and Asp-1106 in C4A and Leu-1101, Ser-1102, Ile-1105, and His-1106 in C4B, which are located in the C4d region of the alpha chain. To more precisely identify the residues that are important for the functional differences, C4A-C4B hybrid proteins were constructed by using recombinant DNA techniques. Comparison of these by hemolytic assay and binding to IgG aggregates showed that the single substitution of aspartic acid for histidine at position 1106 largely accounted for the change in functional activity and nature of the chemical bond formed (ester vs. amide). Surprisingly, substitution of a neutral residue, alanine, for histidine at position 1106 resulted in an increase in binding to immune aggregates without subsequent reduction in the hemolytic activity. This result strongly suggests that position 1106 is not "catalytic" as previously proposed but interacts sterically/electrostatically with potential acceptor sites and serves to "select" binding sites on potential acceptor molecules. Images PMID:2395880

  18. 16 CFR Figure 1 to Part 1513 - Wedge Block for Tests in § 1513.4 (a), (b), and (c)

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Wedge Block for Tests in § 1513.4 (a), (b), and (c) 1 Figure 1 to Part 1513 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR BUNK BEDS Pt. 1513, Fig. 1 Figure 1 to Part...

  19. 16 CFR Figure 1 to Part 1513 - Wedge Block for Tests in § 1513.4 (a), (b), and (c)

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Wedge Block for Tests in § 1513.4 (a), (b), and (c) 1 Figure 1 to Part 1513 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR BUNK BEDS Pt. 1513, Fig. 1 Figure 1 to Part...

  20. NOGO-A/RTN4A and NOGO-B/RTN4B are simultaneously expressed in epithelial, fibroblast and neuronal cells and maintain ER morphology

    PubMed Central

    Rämö, Olli; Kumar, Darshan; Gucciardo, Erika; Joensuu, Merja; Saarekas, Maiju; Vihinen, Helena; Belevich, Ilya; Smolander, Olli-Pekka; Qian, Kui; Auvinen, Petri; Jokitalo, Eija

    2016-01-01

    Reticulons (RTNs) are a large family of membrane associated proteins with various functions. NOGO-A/RTN4A has a well-known function in limiting neurite outgrowth and restricting the plasticity of the mammalian central nervous system. On the other hand, Reticulon 4 proteins were shown to be involved in forming and maintaining endoplasmic reticulum (ER) tubules. Using comparative transcriptome analysis and qPCR, we show here that NOGO-B/RTN4B and NOGO-A/RTN4A are simultaneously expressed in cultured epithelial, fibroblast and neuronal cells. Electron tomography combined with immunolabelling reveal that both isoforms localize preferably to curved membranes on ER tubules and sheet edges. Morphological analysis of cells with manipulated levels of NOGO-B/RTN4B revealed that it is required for maintenance of normal ER shape; over-expression changes the sheet/tubule balance strongly towards tubules and causes the deformation of the cell shape while depletion of the protein induces formation of large peripheral ER sheets. PMID:27786289

  1. NOGO-A/RTN4A and NOGO-B/RTN4B are simultaneously expressed in epithelial, fibroblast and neuronal cells and maintain ER morphology.

    PubMed

    Rämö, Olli; Kumar, Darshan; Gucciardo, Erika; Joensuu, Merja; Saarekas, Maiju; Vihinen, Helena; Belevich, Ilya; Smolander, Olli-Pekka; Qian, Kui; Auvinen, Petri; Jokitalo, Eija

    2016-10-27

    Reticulons (RTNs) are a large family of membrane associated proteins with various functions. NOGO-A/RTN4A has a well-known function in limiting neurite outgrowth and restricting the plasticity of the mammalian central nervous system. On the other hand, Reticulon 4 proteins were shown to be involved in forming and maintaining endoplasmic reticulum (ER) tubules. Using comparative transcriptome analysis and qPCR, we show here that NOGO-B/RTN4B and NOGO-A/RTN4A are simultaneously expressed in cultured epithelial, fibroblast and neuronal cells. Electron tomography combined with immunolabelling reveal that both isoforms localize preferably to curved membranes on ER tubules and sheet edges. Morphological analysis of cells with manipulated levels of NOGO-B/RTN4B revealed that it is required for maintenance of normal ER shape; over-expression changes the sheet/tubule balance strongly towards tubules and causes the deformation of the cell shape while depletion of the protein induces formation of large peripheral ER sheets.

  2. Purification and characterization of two novel antimicrobial peptides Subpeptin JM4-A and Subpeptin JM4-B produced by Bacillus subtilis JM4.

    PubMed

    Wu, Shimei; Jia, Shifang; Sun, Dandan; Chen, Meiling; Chen, Xiuzhu; Zhong, Jin; Huan, Liandong

    2005-11-01

    An antimicrobial peptides-producing strain was isolated from soil and identified as Bacillus subtilis JM4 according to biochemical tests and 16S rDNA sequence analysis. The corresponding antimicrobial peptides were purified to homogeneity by ammonium sulfate precipitation, sequential SP-Sepharose Fast Flow, Sephadex G-25 and C18 reverse-phase chromatography, and in the final purification step, two active fractions were harvested, designated as Subpeptin JM4-A and Subpeptin JM4-B. The molecular weights, determined by mass spectrometry, were 1422.71 Da for Subpeptin JM4-A and 1422.65 Da for Subpeptin JM4-B, respectively. Amino acid sequencing showed that they differed from each other only at the seventh amino acid except for three unidentified residues, and the two peptides had no significant sequence homology to the known peptides in the database, indicating that they are two novel antimicrobial peptides. In addition, characteristic measurements indicated that both peptides had a relatively broad inhibitory spectrum and remained active over a wide pH and temperature range.

  3. Mutational analysis of genes p14ARF, p15INK4b, p16INK4a, and PTEN in human nervous system tumors.

    PubMed

    Almeida, L O; Custódio, A C; Araújo, J J; Rey, J A; Almeida, J R W; Santos, M J; Clara, C A; Casartelli, C

    2008-05-27

    Cancer is one of the most common and severe problems in clinical medicine, and nervous system tumors represent about 2% of the types of cancer. The central role of the nervous system in the maintenance of vital activities and the functional consequences of the loss of neurons can explain how severe brain cancers are. The cell cycle is a highly complex process, with a wide number of regulatory proteins involved, and such proteins can suffer alterations that transform normal cells into malignant ones. The INK4 family members (CDK inhibitors) are the cell cycle regulators that block the progression of the cycle through the R point, causing an arrest in G1 stage. The p14ARF (alternative reading frame) gene is a tumor suppressor that inhibits p53 degradation during the progression of the cell cycle. The PTEN gene is related to the induction of growth suppression through cell cycle arrest, to apoptosis and to the inhibition of cell adhesion and migration. The purpose of the present study was to assess the mutational state of the genes p14ARF, p15INK4b, p16INK4a, and PTEN in 64 human nervous system tumor samples. Homozygous deletions were found in exon 2 of the p15INK4b gene and exon 3 of the p16INK4a gene in two schwannomas. Three samples showed a guanine deletion (63 codon) which led to a loss of heterozygosity in the p15 gene, and no alterations could be seen in the PTEN gene. Although the group of patients was heterogeneous, our results are in accordance with other different studies that indicate that homozygous deletion and loss of heterozygosity in the INK4 family members are frequently observed in nervous system tumors.

  4. 16 CFR Figure 1 to Part 1213 - Wedge Block for Tests in § 1213.4(a), (b) and (c)

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Wedge Block for Tests in § 1213.4(a), (b) and (c) 1 Figure 1 to Part 1213 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ENTRAPMENT HAZARDS IN BUNK BEDS Pt. 1213, Fig. 1...

  5. 16 CFR Figure 1 to Part 1213 - Wedge Block for Tests in § 1213.4(a), (b), and (c)

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Wedge Block for Tests in § 1213.4(a), (b), and (c) 1 Figure 1 to Part 1213 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ENTRAPMENT HAZARDS IN BUNK BEDS Pt. 1213, Fig. 1...

  6. AtCCR4a and AtCCR4b are Involved in Determining the Poly(A) Length of Granule-bound starch synthase 1 Transcript and Modulating Sucrose and Starch Metabolism in Arabidopsis thaliana.

    PubMed

    Suzuki, Yuya; Arae, Toshihiro; Green, Pamela J; Yamaguchi, Junji; Chiba, Yukako

    2015-05-01

    Removing the poly(A) tail is the first and rate-limiting step of mRNA degradation and apparently an effective step not only for modulating mRNA stability but also for translation of many eukaryotic transcripts. Carbon catabolite repressor 4 (CCR4) has been identified as a major cytoplasmic deadenylase in Saccharomyces cerevisiae. The Arabidopsis thaliana homologs of the yeast CCR4, AtCCR4a and AtCCR4b, were identified by sequence-based analysis; however, their role and physiological significance in plants remain to be elucidated. In this study, we revealed that AtCCR4a and AtCCR4b are localized to cytoplasmic mRNA processing bodies, which are specific granules consisting of many enzymes involved in mRNA turnover. Double mutants of AtCCR4a and AtCCR4b exhibited tolerance to sucrose application but not to glucose. The levels of sucrose in the seedlings of the atccr4a/4b double mutants were reduced, whereas no difference was observed in glucose levels. Further, amylose levels were slightly but significantly increased in the atccr4a/4b double mutants. Consistent with this observation, we found that the transcript encoding granule-bound starch synthase 1 (GBSS1), which is responsible for amylose synthesis, is accumulated to a higher level in the atccr4a/4b double mutant plants than in the control plants. Moreover, we revealed that GBSS1 has a longer poly(A) tail in the double mutant than in the control plant, suggesting that AtCCR4a and AtCCR4b can influence the poly(A) length of transcripts related to starch metabolism. Our results collectively suggested that AtCCR4a and AtCCR4b are involved in sucrose and starch metabolism in A. thaliana.

  7. A single-amino acid substitution in West Nile virus 2K peptide between NS4A and NS4B confers resistance to lycorine, a flavivirus inhibitor

    PubMed Central

    Zou, Gang; Puig-Basagoiti, Francesc; Zhang, Bo; Qing, Min; Chen, Liqiang; Pankiewicz, Krzysztof W.; Felczak, Krzysztof; Yuan, Zhiming; Shi, Pei-Yong

    2017-01-01

    Lycorine potently inhibits flaviviruses in cell culture. At 1.2-μM concentration, lycorine reduced viral titers of West Nile (WNV), dengue, and yellow fever viruses by 102- to 104-fold. However, the compound did not inhibit an alphavirus (Western equine encephalitis virus) or a rhabdovirus (vesicular stomatitis virus), indicating a selective antiviral spectrum. The compound exerts its antiviral activity mainly through suppression of viral RNA replication. A Val→Met substitution at the 9th amino acid position of the viral 2K peptide (spanning the endoplasmic reticulum membrane between NS4A and NS4B proteins) confers WNV resistance to lycorine, through enhancement of viral RNA replication. Initial chemistry synthesis demonstrated that modifications of the two hydroxyl groups of lycorine can increase the compound’s potency, while reducing its cytotoxicity. Taken together, the results have established lycorine as a flavivirus inhibitor for antiviral development. The lycorine-resistance results demonstrate a direct role of the 2K peptide in flavivirus RNA synthesis. PMID:19062063

  8. Accidental Conical Intersections in Mixed Trimers of Potassium and Rubidium: a Vibronic Analysis of the 4^4B_2 and 3^4A_1 States

    NASA Astrophysics Data System (ADS)

    Hauser, A. W.; Auböck, G.; Callegari, C.; Ernst, W. E.

    2010-06-01

    We compare the 3^4A_1 and 4^4B_2 states of homonuclear and heteronuclear alkali trimers formed of potassium and rubidium. The Multireference Rayleigh Schrödinger Perturbation Theory of second order is applied to obtain the corresponding adiabatic potential energy surfaces. In the case of homonuclear trimers these pairs of states correspond to the two branches of the E×{}e Jahn-Teller distorted 2^4E^' state. For heteronuclear trimers, the vibrational modes Q_x and Q_y are no longer degenerate, but the two electronic states still show a conical intersection at obtuse (KRb_2) or acute (K_2Rb) isosceles geometries. Spectroscopic consequences of this situation are discussed, vibronic spectra are predicted and compared to LIF spectra obtained in helium droplet isolation spectroscopy experiments of our group. J. Nagl, G. Auböck, A.W. Hauser, O. Allard, C. Callegari and W.E. Ernst, Phys. Rev. Lett. 100, 063001 (2008) J. Nagl, G. Auböck, A.W. Hauser, O. Allard, C. Callegari and W.E. Ernst, J. Chem. Phys. 128, 154320 (2008)

  9. APEX-CHAMP+ high-J CO observations of low-mass young stellar objects. III. NGC 1333 IRAS 4A/4B envelope, outflow, and ultraviolet heating

    NASA Astrophysics Data System (ADS)

    Yıldız, Umut A.; Kristensen, Lars E.; van Dishoeck, Ewine F.; Belloche, Arnaud; van Kempen, Tim A.; Hogerheijde, Michiel R.; Güsten, Rolf; van der Marel, Nienke

    2012-06-01

    Context. The NGC 1333 IRAS 4A and IRAS 4B sources are among the most well-studied Stage 0 low-mass protostars, which drive prominent bipolar outflows. Spectrally resolved molecular emission lines provide crucial information about the physical and chemical structure of the circumstellar material as well as the dynamics of the different components. Most studies have so far concentrated on the colder parts (T ≤ 30 K) of these regions. Aims: The aim is to characterize the warmer parts of the protostellar envelope using the new generation of submillimeter instruments. This will allow us to quantify the feedback of the protostars on their surroundings in terms of shocks, ultraviolet (UV) heating, photodissociation, and outflow dispersal. Methods: The dual frequency 2 × 7 pixel 650/850 GHz array receiver CHAMP+ mounted on APEX was used to obtain a fully sampled, large-scale ~4' × 4' map at 9″ resolution of the IRAS 4A/4B region in the 12CO J = 6-5 line. Smaller maps were observed in the 13CO 6-5 and [C i] J = 2-1 lines. In addition, a fully sampled 12CO J = 3-2 map made with HARP-B on the JCMT is presented and deep isotopolog observations are obtained at selected outflow positions to constrain the optical depth. Complementary Herschel-HIFI and ground-based lines of CO and its isotopologs, from J = 1-0 up to 10-9 (Eu/k ≈ 300 K), are collected at the source positions and used to construct velocity-resolved CO ladders and rotational diagrams. Radiative-transfer models of the dust and lines are used to determine the temperatures and masses of the outflowing and photon-heated gas and infer the CO abundance structure. Results: Broad CO emission-line profiles trace entrained shocked gas along the outflow walls, which have an average temperature of ~100 K. At other positions surrounding the outflow and the protostar, the 6-5 line profiles are narrow indicating UV excitation. The narrow 13CO 6-5 data directly reveal the UV heated gas distribution for the first time. The

  10. Gene Copy-Number Variations (CNVs) and Protein Levels of Complement C4A and C4B as Novel Biomarkers for Partial Disease Remissions in New-Onset Type 1 Diabetes Patients

    PubMed Central

    Kingery, Suzanne E.; Wu, Yee Ling; Zhou, Bi; Hoffman, Robert P.; Yu, C. Yung

    2014-01-01

    Objective To determine the roles of complement C4A and C4B gene CNVs and their plasma protein concentrations in residual insulin secretion and loss of pancreatic beta-cell function in new-onset type 1 diabetes patients. Methods We studied 34 patients of European ancestry with new-onset type 1 diabetes, aged between 3 and 17 years (10.7±3.45), at Nationwide Children's Hospital in Columbus, Ohio. Gene copy-number and size variations of complement C4A and C4B were determined by genomic Southern blot analyses. C4A and C4B protein phenotypes were elucidated by immunofixation and radial immunodiffusion. Two-digit HLA-DRB1 genotypes were determined by sequence-specific PCR. At 1 month and 9-month post diagnosis, stimulated C-peptide levels were measured after a standardized mixed-meal tolerance test. Results The diploid gene copy-numbers of C4A varied from 0 to 4, and those of C4B from 0 to 3. Patients with higher copy-number of C4A or higher C4A plasma protein concentrations at diagnosis had higher C-peptide levels at 1 month post diagnosis (p=0.008; p=0.008). When controlled by the Z-score of body-mass index, C4A copy-numbers, C4A protein concentrations, the age of disease-onset, the number of HLA-DR3 but not DR4 alleles were significant parameters in determining C-peptide levels. At 9-month post diagnosis, 42.3% of patients remained in partial remission, and these patients were characterized by lower total C4B copy-numbers or lower C4B protein concentrations (p=0.02, p=0.0004). Conclusions C4A appears to associate with the protection of residual beta-cell function in new-onset type 1 diabetes; C4B is correlated with the end of disease remission at 9-month post diagnosis. PMID:22151770

  11. Duplex unwinding and ATPase activities of the DEAD-box helicase eIF4A are coupled by eIF4G and eIF4B.

    PubMed

    Özeş, Ali R; Feoktistova, Kateryna; Avanzino, Brian C; Fraser, Christopher S

    2011-09-30

    Eukaryotic initiation factor (eIF) 4A is a DEAD-box helicase that stimulates translation initiation by unwinding mRNA secondary structure. The accessory proteins eIF4G, eIF4B, and eIF4H enhance the duplex unwinding activity of eIF4A, but the extent to which they modulate eIF4A activity is poorly understood. Here, we use real-time fluorescence assays to determine the kinetic parameters of duplex unwinding and ATP hydrolysis by these initiation factors. To ensure efficient duplex unwinding, eIF4B and eIF4G cooperatively activate the duplex unwinding activity of eIF4A. Our data reveal that eIF4H is much less efficient at stimulating eIF4A unwinding activity than eIF4B, implying that eIF4H is not able to completely substitute for eIF4B in duplex unwinding. By monitoring unwinding and ATPase assays under identical conditions, we demonstrate that eIF4B couples the ATP hydrolysis cycle of eIF4A with strand separation, thereby minimizing nonproductive unwinding events. Using duplex substrates with altered GC contents but similar predicted thermal stabilities, we further show that the rate of formation of productive unwinding complexes is strongly influenced by the local stability per base pair, in addition to the stability of the entire duplex. This finding explains how a change in the GC content of a hairpin is able to influence translation initiation while maintaining the overall predicted thermal stability.

  12. Luminescent Immunoprecipitation System (LIPS) for Detection of Autoantibodies Against ATP4A and ATP4B Subunits of Gastric Proton Pump H+,K+-ATPase in Atrophic Body Gastritis Patients

    PubMed Central

    Lahner, Edith; Brigatti, Cristina; Marzinotto, Ilaria; Carabotti, Marilia; Scalese, Giulia; Davidson, Howard W; Wenzlau, Janet M; Bosi, Emanuele; Piemonti, Lorenzo; Annibale, Bruno; Lampasona, Vito

    2017-01-01

    Objectives: Circulating autoantibodies targeting the H+/K+-ATPase proton pump of gastric parietal cells are considered markers of autoimmune gastritis, whose diagnostic accuracy in atrophic body gastritis, the pathological lesion of autoimmune gastritis, remains unknown. This study aimed to assess autoantibodies against ATP4A and ATP4B subunits of parietal cells H+, K+-ATPase in atrophic body gastritis patients and controls. Methods: One-hundred and four cases with atrophic body gastritis and 205 controls were assessed for serological autoantibodies specific for ATP4A or ATP4B subunits using luminescent immunoprecipitation system (LIPS). Recombinant luciferase-reporter-fused-antigens were expressed by in vitro transcription-translation (ATP4A) or after transfection in Expi293F cells (ATP4B), incubated with test sera, and immune complexes recovered using protein-A-sepharose. LIPS assays were compared with a commercial enzyme immunoassay (EIA) for parietal cell autoantibodies. Results: ATP4A and ATP4B autoantibody titers were higher in cases compared to controls (P<0.0001). The area under the receiver-operating characteristic curve was 0.98 (95% CI 0.965–0.996) for ATP4A, and 0.99 (95% CI 0.979–1.000) for ATP4B, both higher as compared with that of EIA: 0.86 (95% CI 0.809–0.896), P<0.0001. Sensitivity-specificity were 100–89% for ATP4A and 100–90% for ATP4B assay. Compared with LIPS, EIA for parietal cell autoantibodies showed a lower sensitivity (72%, P<0.0001) at a similar specificity (92%, P=0.558). Conclusions: Positivity to both, ATP4A and ATP4B autoantibodies is closely associated with atrophic body gastritis. Both assays had the highest sensitivity, at the cost of diagnostic accuracy (89 and 90% specificity), outperforming traditional EIA. Once validated, these LIPS assays should be valuable screening tools for detecting biomarkers of damaged atrophic oxyntic mucosa. PMID:28102858

  13. An allele-specific PCR system for rapid detection and discrimination of the CYP2C19∗4A, ∗4B, and ∗17 alleles: implications for clopidogrel response testing.

    PubMed

    Scott, Stuart A; Tan, Qian; Baber, Usman; Yang, Yao; Martis, Suparna; Bander, Jeffrey; Kornreich, Ruth; Hulot, Jean-Sébastien; Desnick, Robert J

    2013-11-01

    CYP2C19 is involved in the metabolism of clinically relevant drugs, including the antiplatelet prodrug clopidogrel, which has prompted interest in clinical CYP2C19 genotyping. The CYP2C19∗4B allele is defined by both gain-of-function [c.-806C>T (∗17)] and loss-of-function [c.1A>G (∗4)] variants on the same haplotype; however, current genotyping and sequencing assays are unable to determine the phase of these variants. Thus, the aim of this study was to develop an assay that could rapidly detect and discriminate the related ∗4A, ∗4B, and ∗17 alleles. An allele-specific PCR assay, composed of four unique primer mixes that specifically interrogate the defining ∗17 and ∗4 variants, was developed by using samples (n = 20) with known genotypes, including the ∗4A, ∗4B, and/or ∗17 alleles. The assay was validated by testing 135 blinded samples, and the results were correlated with CYP2C19 genotyping and allele-specific cloning/sequencing. Importantly, among the six ∗4 carriers in the validation cohort, after allele-specific PCR testing both samples with a ∗1/∗4 genotype were reclassified to ∗1/∗4A, all three samples with a ∗4/∗17 genotype were reclassified to ∗1/∗4B, and a sample with a ∗4/∗17/∗17 genotype was reclassified to ∗4B/∗17. In conclusion, this rapid and robust allele-specific PCR assay can refine CYP2C19 genotyping and metabolizer phenotype classification by determining the phase of the defining ∗17 and ∗4 variants, which may have utility when testing CYP2C19 for clopidogrel response.

  14. International Conference on Harmonisation; guidance on Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on Harmonisation Regions; Annex 4A on Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests General Chapter; availability. Notice.

    PubMed

    2009-04-08

    The Food and Drug Administration (FDA) is announcing the availability of a guidance entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 4A: Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests General Chapter." The guidance was prepared under the auspices of the International Conference on Harmonisation of Technical Requirements for Registration of Pharmaceuticals for Human Use (ICH). The guidance provides the results of the ICH Q4B evaluation of the Microbiological Examination of Nonsterile Products: Microbial Enumeration Tests General Chapter harmonized text from each of the three pharmacopoeias (United States, European, and Japanese) represented by the Pharmacopoeial Discussion Group (PDG). The guidance conveys recognition of the three pharmacopoeial methods by the three ICH regulatory regions and provides specific information regarding the recognition. The guidance is intended to recognize the interchangeability between the local regional pharmacopoeias, thus avoiding redundant testing in favor of a common testing strategy in each regulatory region. In the Federal Register of February 21, 2008 (73 FR 9575), FDA made available a guidance on the Q4B process entitled "Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions."

  15. Endothelial nitric oxide synthase (eNOS) T-786C, 4a4b, and G894T polymorphisms and male infertility: study for idiopathic asthenozoospermia and meta-analysis.

    PubMed

    Song, Pingping; Zou, Shasha; Chen, Tingting; Chen, Jianhua; Wang, Yanan; Yang, Juanjuan; Song, Zhijian; Jiang, Huayu; Shi, Huijuan; Huang, Yiran; Li, Zheng; Shi, Yongyong; Hu, Hongliang

    2015-02-01

    Recent studies on the eNOS gene and male infertility show that expression of eNOS regulates normal spermatogenesis in the testis, and the eNOS gene variants (T-786C, 4a4b, and G894T) are potentially involved in impairment of spermatogenesis and sperm function. Thus, we conducted this association and meta-analysis study to further validate whether variants of those three loci affected the risk of idiopathic asthenozoospermia (AZS) and male infertility. Approximately 340 Chinese idiopathic AZS patients and 342 healthy men were included for this case-control study, genotyped by gel electrophoresis analysis or direct sequencing of PCR products. The eNOS mRNA isolated from the semen of patients was further examined by quantitative real-time PCR. Also, a meta-analysis of association between eNOS gene polymorphisms and male infertility was performed. A significant association was identified on allelic level between 4a4b variant and AZS in our study (chi-squared = 7.53, corrected P = 0.018, odds ratio (OR) = 1.808), while there were no significant difference of T-786C and G894T for asthenozoospermia in both genotype and allele distributions. In addition, expression of eNOS was up-regulated in patients compared with controls (about 2.4-fold, P < 0.001). Furthermore, the results of the meta-analysis support the conclusion that the T-786C and 4a4b loci were associated with male infertility in both Asian and Caucasian populations. Our study provides genetic evidence for the eNOS gene being a risk factor for idiopathic AZS and male infertility. Considering genetic differences among populations and complex pathogenesis of male infertility, more validating studies using independent samples are suggested in the future.

  16. Conspirators in a capital crime: co-deletion of p18INK4c and p16INK4a/p14ARF/p15INK4b in glioblastoma multiforme.

    PubMed

    Solomon, David A; Kim, Jung-Sik; Jean, Walter; Waldman, Todd

    2008-11-01

    Glioblastoma multiforme (GBM) is one of the most dreaded cancer diagnoses due to its poor prognosis and the limited treatment options. Homozygous deletion of the p16(INK4a)/p14(ARF)/p15(INK4b) locus is among the most common genetic alterations in GBM. Two recent studies have shown that deletion and mutation of another INK4 family member, p18(INK4c), also drives the pathogenesis of GBM. This minireview will discuss the known roles for p18(INK4c) in the initiation and progression of cancer and suggest opportunities for future studies.

  17. Results of hydrologic tests and water-chemistry analyses, wells H-4A, H-4B, and H-4C, at the proposed waste isolation pilot plant site, southeastern New Mexico

    USGS Publications Warehouse

    Mercer, Jerry W.; Davis, Paul; Dennehy, K.F.; Goetz, C.L.

    1981-01-01

    Data were collected during hydrologic testing at wells H-4A, H-4B, and H-4C in the southern part of the proposed Waste Isolation Pilot Plant site in southeastern New Mexico. The three water-bearing zones tested, the Magenta and Culebra Dolomite Members of the Rustler Formation and the Rustler Formation-Salado Formation contact, yield water to wells at rates less than 0.9 gallon per minute. Throughout the testing, water-pressure response in the tested zone was monitored by a pressure transducer system. Shut-in and slug tests were conducted to acquire the data from which the following values were derived. Calculated transmissivities for the Magenta, Culebra and the Rustler-Salado contact at wells H-4A, H-4B, and H-4C were 0.06, 0.9, and 0.0006 foot squared per day respectively. Water samples from the Magenta and Culebra had dissolved-solids concentrations of 22,300 and 18,100 milligrams per liter, respectively. The major chemical constituents of ground-water samples from these two zones were sodium, chloride, and sulfate. Water samples from the Rustler-Salado contact had a dissolved-solids concentration of 322,000 milligrams per liter and magnesium, sodium, and chloride were the major constituents. Radium-226, a naturally occurring radioactive element, was present in samples from all three zones. (USGS)

  18. Species-specific but not genotype-specific primary and secondary isotype-specific NSP4 antibody responses in gnotobiotic calves and piglets infected with homologous host bovine (NSP4[A]) or porcine (NSP4[B]) rotavirus.

    PubMed

    Yuan, Lijuan; Honma, Shinjiro; Ishida, Shin-Ichi; Yan, Xiao-Yi; Kapikian, Albert Z; Hoshino, Yasutaka

    2004-12-05

    Using recombinant baculoviruses expressing rotavirus NSP4 [A], [B], [C], and [D] genotypes of bovine, porcine, human, simian, or murine origin, we analyzed serum antibody responses to NSP4s in gnotobiotic calves and piglets infected by the oral/alimentary or intraamniotic route with bovine (NSP4[A]) (Wyatt, R.G., Mebus, C.A., Yolken, R.H., Kalica, A.R., James, H.D., Jr., Kapikian, A.Z., Chanock, R.M., 1979. Rotaviral immunity in gnotobiotic calves: heterologous resistance to human virus induced by bovine virus. Science 203(4380), 548-550) or porcine (NSP4[B]) (Hoshino, Y., Saif, L.J., Sereno, M.M., Chanock, R.M., Kapikian, A.Z., 1988. Infection immunity of piglets to either VP3 or VP7 outer capsid protein confers resistance to challenge with a virulent rotavirus bearing the corresponding antigen. J. Virol. 62(3), 744-748) rotaviruses. Following primary infection and challenge with virulent rotaviruses, the animals developed higher or significantly higher antibody titers to homologous host homotypic NSP4s than to heterologous host homotypic or heterologous host heterotypic NSP4s, indicating that antibody responses were species specific rather than genotype specific. Antibody responses to NSP4s corresponded closely with the phylogenetic relationships of NSP4s within a species-specific region of amino acids (aa) 131-141. In contrast, NSP4 genotypes determined by amino acid full-length sequence identity predicted poorly their "serotypes". In piglets, antibodies to NSP4 induced by previous oral infection failed to confer protection against challenge from a porcine rotavirus bearing serotypically different VP4 and VP7 but essentially identical NSP4 to the porcine rotavirus in primary infection. Thus, in an approach to immunization with a live oral rotavirus vaccine, the NSP4 protein does not appear to play an important role in protection against rotavirus disease and infection.

  19. Deregulated E2F-1 blocks terminal differentiation and loss of leukemogenicity of M1 myeloblastic leukemia cells without abrogating induction of p15(INK4B) and p16(INK4A).

    PubMed

    Amanullah, A; Hoffman, B; Liebermann, D A

    2000-07-15

    The transcription factor E2F-1 has been postulated to play a crucial role in the control of cell cycle progression because of its ability to be bound and regulated by the retinoblastoma gene product (pRb). Exogenous expression of E2F-1, under growth restrictive conditions, was shown to result in p53-dependent programmed cell death. The consequences of deregulated expression of E2F-1 on terminal differentiation of hematopoietic cells in the absence of E2F-1-mediated apoptosis, as well as mechanistic insights into how deregulated E2F-1 may affect terminal differentiation, have not been established. The autonomously proliferating M1 myeloblastic leukemia cell line, which is null for p53 expression and can be induced by interleukin-6 (IL-6) to undergo terminal macrophage differentiation with concomitant loss of leukemogenicity, provides a particularly attractive model system to address these issues. Deregulated and continued expression of E2F-1 blocked the IL-6-induced terminal differentiation program at an early blast stage, giving rise to immature cells, which continued to proliferate without undergoing apoptosis and retained their leukemogenic phenotype. Although E2F-1 blocked IL-6-mediated terminal differentiation and its associated growth arrest, it did not prevent the rapid induction of both p15(INK4B) and p16(INK4A), inhibition of cdk4 kinase activity, and subsequent hypophosphorylation of pRb. The results obtained imply that genetic alterations that both impair p53 function and deregulate E2F-1 expression may render hematopoietic cells refractory to the induction of differentiation and are, thereby, likely to play a major role in the progression of leukemias. (Blood. 2000;96:475-482)

  20. Carcinogen-specific mutational and epigenetic alterations in INK4A, INK4B and p53 tumour-suppressor genes drive induced senescence bypass in normal diploid mammalian cells.

    PubMed

    Yasaei, H; Gilham, E; Pickles, J C; Roberts, T P; O'Donovan, M; Newbold, R F

    2013-01-10

    Immortalization (senescence bypass) is a critical rate-limiting step in the malignant transformation of mammalian somatic cells. Human cells must breach at least two distinct senescence barriers to permit unfettered clonal evolution during cancer development: (1) stress- or oncogene-induced premature senescence (SIPS/OIS), mediated via the p16-Rb and/or ARF-p53-p21 tumour-suppressive pathways, and (2) replicative senescence triggered by telomere shortening. In contrast, because their telomerase is constitutively active, cells from small rodents possess only the SIPS/OIS barrier, and are therefore useful for studying SIPS/OIS bypass in isolation. Dermal fibroblasts from the Syrian hamster (SHD cells) are exceptionally resistant to spontaneous SIPS bypass, but it can be readily induced following exposure to a wide range of chemical and physical carcinogens. Here we show that a spectrum of carcinogen-specific mutational and epigenetic alterations involving the INK4A (p16), p53 and INK4B (p15) genes are associated with induced SIPS bypass. With ionizing radiation, immortalization is invariably accompanied by efficient biallelic deletion of the complete INK4/CDKN2 locus. In comparison, SHD cells immortalized by the powerful polycyclic hydrocarbon carcinogen benzo(a)pyrene display transversion point mutations in the DNA-binding domain of p53 coupled with INK4 alterations such as loss of expression of p15. Epimutational silencing of p16 is the primary event associated with immortalization by nickel, a human non-genotoxic carcinogen. As SIPS/OIS bypass is a prerequisite for the immortalization of normal diploid human epithelial cells, our results with the SHD model will provide a basis for delineating combinations of key molecular changes underpinning this important event in human carcinogenesis.

  1. Strong HCV NS3/4a, NS4b, NS5a, NS5b-specific cellular immune responses induced in Rhesus macaques by a novel HCV genotype 1a/1b consensus DNA vaccine.

    PubMed

    Latimer, Brian; Toporovski, Roberta; Yan, Jian; Pankhong, Panyupa; Morrow, Matthew P; Khan, Amir S; Sardesai, Niranjan Y; Welles, Seth L; Jacobson, Jeffrey M; Weiner, David B; Kutzler, Michele A

    2014-01-01

    Chronic HCV is a surreptitious disease currently affecting approximately 3% of the world's population that can lead to liver failure and cancer decades following initial infection. However, there are currently no vaccines available for the prevention of chronic HCV. From patients who acutely resolve HCV infection, it is apparent that a strong and broad cytotoxic T lymphocyte (CTL) response is important in HCV clearance. DNA vaccines are naked plasmid DNA molecules that encode pathogen antigens to induce a pathogen-specific immune response. They are inexpensive to produce and have an excellent safety profile in animals and humans. Additionally, DNA vaccines are able to induce strong CTL responses, making them well-suited for an HCV vaccine. We aimed to maximize vaccine recipients' opportunity to induce a broad T cell response with a novel antigenic sequence, multi-antigen vaccine strategy. We have generated DNA plasmids encoding consensus sequences of HCV genotypes 1a and 1b non-structural proteins NS3/4a, NS4b, NS5a, and NS5b. Rhesus macaques were used to study the immunogenicity of these constructs. Four animals were immunized 3 times, 6 weeks apart, at a dose of 1.0mg per antigen construct, as an intramuscular injection followed by in vivo electroporation, which greatly increases DNA uptake by local cells. Immune responses were measured 2 weeks post-immunization regimen (PIR) in immunized rhesus macaques and showed a broad response to multiple HCV nonstructural antigens, with up to 4680 spot-forming units per million peripheral blood mononuclear cells (PBMCs) as measured by Interferon-γ ELISpot. In addition, multiparametric flow cytometry detected HCV-specific CD4+ and CD8+ T cell responses by intracellular cytokine staining and detected HCV-specific CD107a+/GrzB+ CD8+ T cells indicating an antigen specific cytolytic response 2 weeks PIR compared with baseline measurements. At the final study time point, 6 weeks PIR, HCV-specific CD45RA- memory-like T cells

  2. Boeing F4B-4

    NASA Technical Reports Server (NTRS)

    1932-01-01

    The Boeing F4B-4 was seen to differ from earlier F4Bs in having a vertical fin with slightly more area. The Boeing model 235 was not fitted with a NACA cowling, but rather the less efficient 'Townend' ring around the Pratt & Whitney Wasp radials cylinders. This aircraft was much used by both the Navy and the Army Air Corps in the late 1920's and early 1930's. The Army variation was known as the P-12E. The engine cowling was a British development known as the 'Townend' ring. It differed from the NACA cowling and was less effective in reducing the drag.

  3. Anxiogenic-Like Behavioral Phenotype of Mice Deficient in Phosphodiesterase 4B (PDE4B)

    PubMed Central

    Zhang, Han-Ting; Huang, Ying; Masood, Anbrin; Stolinski, Lisa R; Li, Yunfeng; Zhang, Lei; Dlaboga, Daniel; Jin, S-L Catherine; Conti, Marco; O’Donnell, James M

    2009-01-01

    Phosphodiesterase-4 (PDE4), an enzyme that catalyzes the hydrolysis of cyclic AMP and plays a critical role in controlling its intracellular concentration, has been implicated in depression- and anxiety-like behaviors. However, the functions of the four PDE4 subfamilies (PDE4A, PDE4B, PDE4C, and PDE4D) remain largely unknown. In animal tests sensitive to anxiolytics, antidepressants, memory enhancers, or analgesics, we examined the behavioral phenotype of mice deficient in PDE4B (PDE4B−/−). Immunoblot analysis revealed loss of PDE4B expression in the cerebral cortex and amygdala of PDE4B−/− mice. The reduction of PDE4B expression was accompanied by decreases in PDE4 activity in the brain regions of PDE4B−/− mice. Compared to PDE4B + / + littermates, PDE4B−/− mice displayed anxiogenic-like behavior, as evidenced by decreased head-dips and time spent in head-dipping in the holeboard test, reduced transitions and time on the light side in the light–dark transition test, and decreased initial exploration and rears in the open-field test. Consistent with anxiogenic-like behavior, PDE4B−/− mice displayed increased levels of plasma corticosterone. In addition, these mice also showed a modest increase in the proliferation of neuronal cells in the hippocampal dentate gyrus. In the forced-swim test, PDE4B−/− mice exhibited decreased immobility; however, this was not supported by the results from the tail-suspension test. PDE4B−/− mice did not display changes in memory, locomotor activity, or nociceptive responses. Taken together, these results suggest that the PDE4B subfamily is involved in signaling pathways that contribute to anxiogenic-like effects on behavior PMID:17700644

  4. Go Figure.

    ERIC Educational Resources Information Center

    Greenman, Geri

    2000-01-01

    Describes the first assignment for an intermediate oil painting class in which the students painted the human figure. Explains that the assignment involved three techniques: (1) abstract application of acrylic paint; (2) oil "Paintstiks" from Shiva; and (3) a final layer of actual oil paint. (CMK)

  5. Selective Phosphodiesterase 4B Inhibitors: A Review

    PubMed Central

    Azam, Mohammed Afzal; Tripuraneni, Naga Srinivas

    2014-01-01

    Abstract Phosphodiesterase 4B (PDE4B) is a member of the phosphodiesterase family of proteins that plays a critical role in regulating intracellular levels of cyclic adenosine monophosphate (cAMP) by controlling its rate of degradation. It has been demonstrated that this isoform is involved in the orchestra of events which includes inflammation, schizophrenia, cancers, chronic obstructive pulmonary disease, contractility of the myocardium, and psoriatic arthritis. Phosphodiesterase 4B has constituted an interesting target for drug development. In recent years, a number of PDE4B inhibitors have been developed for their use as therapeutic agents. In this review, an up-to-date status of the inhibitors investigated for the inhibition of PDE4B has been given so that this rich source of structural information of presently known PDE4B inhibitors could be helpful in generating a selective and potent inhibitor of PDE4B. PMID:25853062

  6. Familial C4B Deficiency and Immune Complex Glomerulonephritis

    PubMed Central

    Soto, K; Wu, YL; Ortiz, A; Aparício, SR; Yu, CY

    2010-01-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient’s deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits. PMID:20580617

  7. Familial C4B deficiency and immune complex glomerulonephritis.

    PubMed

    Soto, K; Wu, Y L; Ortiz, A; Aparício, S R; Yu, C Y

    2010-10-01

    Homozygous complement C4B deficiency is described in a Southern European young female patient with Membranoproliferative Glomerulonephritis (MPGN) type III characterized by renal biopsies with strong complement C4 and IgG deposits. Low C4 levels were independent of clinical evolution or type of immunosuppression and were found in three other family members without renal disease or infections. HLA typing revealed that the patient has homozygous A*02, Cw*06, B*50 at the class I region, and DRB1*08 and DQB1*03 at the class II region. Genotypic and phenotypic studies demonstrated that the patient has homozygous monomodular RCCX in the HLA class III region, with single long C4A genes coding for C4A3 and complete C4B deficiency. Her father, mother, son and niece have heterozygous C4B deficiency. The patient's deceased brother had a history of Henoch-Schönlein Purpura (HSP), an immune complex-mediated proliferative glomerulonephritis. These findings challenge the putative pathophysiological roles of C4A and C4B and underscore the need to perform functional assays, C4 allotyping and genotyping on patients with persistently low serum levels of a classical pathway complement component and glomerulopathy associated with immune deposits.

  8. RDR-4B doppler weather radar with forward looking wind shear detection capability

    NASA Technical Reports Server (NTRS)

    Grasley, Steven S.

    1992-01-01

    The topics are presented in viewgraph form and include the following: Bendix/King atmospheric transport and dispersion (ATAD) position; RDR-4A technical baseline; RTA-4A characteristics; RDR-4 antenna characteristics; modification of RDR-4A to RDR-4B; RDR-4A functional block diagram; RDR-4B characteristics; development/test plan; CV-580 testing capability; CV-580 test results; Continental A300 test configuration; Continental Data Recording Program operational considerations; Continental A300 test results; and display considerations.

  9. Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis*

    PubMed Central

    Yin, Yan; Liu, Liren; Yang, Chenyi; Lin, Congxing; Veith, George Michael; Wang, Caihong; Sutovsky, Peter; Zhou, Pengbo; Ma, Liang

    2016-01-01

    CUL4B ubiquitin ligase belongs to the cullin-RING ubiquitin ligase family. Although sharing many sequence and structural similarities, CUL4B plays distinct roles in spermatogenesis from its homologous protein CUL4A. We previously reported that genetic ablation of Cul4a in mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4b germ cell-specific conditional knock-out (Cul4bVasa),as well as Cul4b global knock-out (Cul4bSox2) mouse, to investigate its roles in spermatogenesis. Germ cell-specific deletion of Cul4b led to male infertility, despite normal testicular morphology and comparable numbers of spermatozoa. Notably, significantly impaired sperm mobility caused by reduced mitochondrial activity and glycolysis level were observed in the majority of the mutant spermatozoa, manifested by low, if any, sperm ATP production. Furthermore, Cul4bVasa spermatozoa exhibited defective arrangement of axonemal microtubules and flagella outer dense fibers. Our mass spectrometry analysis identified INSL6 as a novel CUL4B substrate in male germ cells, evidenced by its direct polyubiquination and degradation by CUL4B E3 ligase. Nevertheless, Cul4b global knock-out males lost their germ cells in an age-dependent manner, implying failure of maintaining the spermatogonial stem cell niche in somatic cells. Taken together, our results show that CUL4B is indispensable to spermatogenesis, and it functions cell autonomously in male germ cells to ensure spermatozoa motility, whereas it functions non-cell-autonomously in somatic cells to maintain spermatogonial stemness. Thus, CUL4B links two distinct spermatogenetic processes to a single E3 ligase, highlighting the significance of ubiquitin modification during spermatogenesis. PMID:26846852

  10. All about Lissajous Figures.

    ERIC Educational Resources Information Center

    Greenslade, Thomas B.

    1993-01-01

    Uses diagrams and text to illustrate the use of Lissajous figures (the figures that are traced out when two simple harmonic motions are combined at right angles to each other) in teaching basic physics concepts. Covers the mathematics of the Lissajous Figure; demonstrating Lissajous Figures; and a typical class. (ZWH)

  11. Structural Basis for the Design of Selective Phosphodiesterase 4B Inhibitors

    PubMed Central

    Fox, David; Burgin, Alex B.; Gurney, Mark E.

    2014-01-01

    Phosphodiesterase-4B (PDE4B) regulates the pro-inflammatory Toll Receptor –Tumor Necrosis Factor α (TNFα) pathway in monocytes, macrophages and microglial cells. As such, it is an important, although under-exploited molecular target for anti-inflammatory drugs. This is due in part to the difficulty of developing selective PDE4B inhibitors as the amino acid sequence of the PDE4 active site is identical in all PDE4 subtypes (PDE4A-D). We show that highly selective PDE4B inhibitors can be designed by exploiting sequence differences outside the active site. Specifically, PDE4B selectivity can be achieved by capture of a C-terminal regulatory helix, now termed CR3 (Control Region 3), across the active site in a conformation that closes access by cAMP. PDE4B selectivity is driven by a single amino acid polymorphism in CR3 (Leu674 in PDE4B1 versus Gln594 in PDE4D). The reciprocal mutations in PDE4B and PDE4D cause a 70-80 fold shift in selectivity. Our structural studies show that CR3 is flexible and can adopt multiple orientations and multiple registries in the closed conformation. The new co-crystal structure with bound ligand provides a guide map for the design of PDE4B selective anti-inflammatory drugs. PMID:24361374

  12. Cell Autonomous and Nonautonomous Function of CUL4B in Mouse Spermatogenesis.

    PubMed

    Yin, Yan; Liu, Liren; Yang, Chenyi; Lin, Congxing; Veith, George Michael; Wang, Caihong; Sutovsky, Peter; Zhou, Pengbo; Ma, Liang

    2016-03-25

    CUL4B ubiquitin ligase belongs to the cullin-RING ubiquitin ligase family. Although sharing many sequence and structural similarities, CUL4B plays distinct roles in spermatogenesis from its homologous protein CUL4A. We previously reported that genetic ablation ofCul4ain mice led to male infertility because of aberrant meiotic progression. In the present study, we generated Cul4bgerm cell-specific conditional knock-out (Cul4b(Vasa)),as well asCul4bglobal knock-out (Cul4b(Sox2)) mouse, to investigate its roles in spermatogenesis. Germ cell-specific deletion of Cul4bled to male infertility, despite normal testicular morphology and comparable numbers of spermatozoa. Notably, significantly impaired sperm mobility caused by reduced mitochondrial activity and glycolysis level were observed in the majority of the mutant spermatozoa, manifested by low, if any, sperm ATP production. Furthermore,Cul4b(Vasa)spermatozoa exhibited defective arrangement of axonemal microtubules and flagella outer dense fibers. Our mass spectrometry analysis identified INSL6 as a novel CUL4B substrate in male germ cells, evidenced by its direct polyubiquination and degradation by CUL4B E3 ligase. Nevertheless,Cul4bglobal knock-out males lost their germ cells in an age-dependent manner, implying failure of maintaining the spermatogonial stem cell niche in somatic cells. Taken together, our results show that CUL4B is indispensable to spermatogenesis, and it functions cell autonomously in male germ cells to ensure spermatozoa motility, whereas it functions non-cell-autonomously in somatic cells to maintain spermatogonial stemness. Thus, CUL4B links two distinct spermatogenetic processes to a single E3 ligase, highlighting the significance of ubiquitin modification during spermatogenesis.

  13. Facts and Figures

    MedlinePlus

    ... Saves Lives Facts & Figures My Blood, Your Blood Blood Donation Types Did you know there is more than one type of blood donation? Learn more about blood donation types here. Blood Safety and Testing The blood supply ...

  14. Accelerated hepatocellular carcinoma development in CUL4B transgenic mice.

    PubMed

    Yuan, Jupeng; Jiang, Baichun; Zhang, Aizhen; Qian, Yanyan; Tan, Haining; Gao, Jiangang; Shao, Changshun; Gong, Yaoqin

    2015-06-20

    Cullin 4B (CUL4B) is a component of the Cullin 4B-Ring E3 ligase (CRL4B) complex that functions in proteolysis and in epigenetic regulation. CUL4B possesses tumor-promoting properties and is markedly upregulated in many types of human cancers. To determine the role of CUL4B in liver tumorigenesis, we generated transgenic mice that expressed human CUL4B in livers and other tissues and evaluated the development of spontaneous and chemically-induced hepatocellular carcinomas. We observed that CUL4B transgenic mice spontaneously developed liver tumors at a high incidence at old ages and exhibited enhanced DEN-induced hepatocarcinogenesis. There was a high proliferation rate in the livers of CUL4B transgenic mice that was accompanied by increased levels of Cdk1, Cdk4 and cyclin D1 and decreased level of p16. The transgenic mice also exhibited increased compensatory proliferation after DEN-induced liver injury, which was accompanied by activation of Akt, Erk, p38 and NF-κB. We also found that Prdx3 was downregulated and that DEN induced a higher level of reactive oxygen species in the livers of transgenic mice. Together, our results demonstrate a critical role of CUL4B in hepatocarcinogenesis in mice.

  15. Variants in CUL4B are Associated with Cerebral Malformations

    PubMed Central

    Vulto-van Silfhout, Anneke T.; Nakagawa, Tadashi; Bahi-Buisson, Nadia; Haas, Stefan A.; Hu, Hao; Bienek, Melanie; Vissers, Lisenka E.L.M.; Gilissen, Christian; Tzschach, Andreas; Busche, Andreas; Müsebeck, Jörg; Rump, Patrick; Mathijssen, Inge B.; Avela, Kristiina; Somer, Mirja; Doagu, Fatma; Philips, Anju K.; Rauch, Anita; Baumer, Alessandra; Voesenek, Krysta; Poirier, Karine; Vigneron, Jacqueline; Amram, Daniel; Odent, Sylvie; Nawara, Magdalena; Obersztyn, Ewa; Lenart, Jacek; Charzewska, Agnieszka; Lebrun, Nicolas; Fischer, Ute; Nillesen, Willy M.; Yntema, Helger G.; Järvelä, Irma; Ropers, Hans-Hilger; de Vries, Bert B.A.; Brunner, Han G.; van Bokhoven, Hans; Raymond, F. Lucy; Willemsen, Michèl A.A.P.; Chelly, Jamel; Xiong, Yue; Barkovich, A. James; Kalscheuer, Vera M.; Kleefstra, Tjitske; de Brouwer, Arjan P.M.

    2015-01-01

    Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B. PMID:25385192

  16. Variants in CUL4B are associated with cerebral malformations.

    PubMed

    Vulto-van Silfhout, Anneke T; Nakagawa, Tadashi; Bahi-Buisson, Nadia; Haas, Stefan A; Hu, Hao; Bienek, Melanie; Vissers, Lisenka E L M; Gilissen, Christian; Tzschach, Andreas; Busche, Andreas; Müsebeck, Jörg; Rump, Patrick; Mathijssen, Inge B; Avela, Kristiina; Somer, Mirja; Doagu, Fatma; Philips, Anju K; Rauch, Anita; Baumer, Alessandra; Voesenek, Krysta; Poirier, Karine; Vigneron, Jacqueline; Amram, Daniel; Odent, Sylvie; Nawara, Magdalena; Obersztyn, Ewa; Lenart, Jacek; Charzewska, Agnieszka; Lebrun, Nicolas; Fischer, Ute; Nillesen, Willy M; Yntema, Helger G; Järvelä, Irma; Ropers, Hans-Hilger; de Vries, Bert B A; Brunner, Han G; van Bokhoven, Hans; Raymond, F Lucy; Willemsen, Michèl A A P; Chelly, Jamel; Xiong, Yue; Barkovich, A James; Kalscheuer, Vera M; Kleefstra, Tjitske; de Brouwer, Arjan P M

    2015-01-01

    Variants in cullin 4B (CUL4B) are a known cause of syndromic X-linked intellectual disability. Here, we describe an additional 25 patients from 11 families with variants in CUL4B. We identified nine different novel variants in these families and confirmed the pathogenicity of all nontruncating variants. Neuroimaging data, available for 15 patients, showed the presence of cerebral malformations in ten patients. The cerebral anomalies comprised malformations of cortical development (MCD), ventriculomegaly, and diminished white matter volume. The phenotypic heterogeneity of the cerebral malformations might result from the involvement of CUL-4B in various cellular pathways essential for normal brain development. Accordingly, we show that CUL-4B interacts with WDR62, a protein in which variants were previously identified in patients with microcephaly and a wide range of MCD. This interaction might contribute to the development of cerebral malformations in patients with variants in CUL4B.

  17. Advanced figure sensor operations and maintenance manual

    NASA Technical Reports Server (NTRS)

    Robertson, H. J.

    1972-01-01

    This manual contains procedures for installing, operating, and maintaining the optical figure sensor and its associated electronic controls. The optical figure sensor, a system of integrated components, comprises: (1) a phase measuring modified interferometer employing a single frequency 6328 A laser, and a Vidissector; (2) a two-axis automatic thermal compensation control mount; (3) a five degree of freedom manual adjustment stand; and (4) a control console. This instrument provides real time output data of optical figure errors for spherical mirrors, and is also capable of measuring aspherical mirrors if a null corrector is added.

  18. PROCEEDINGS: 1993 SO2 CONTROL SYMPOSIUM - VOLUME 2. SESSIONS 4A, 4B, AND 5A

    EPA Science Inventory

    The report documents more than 100 presentations at the 1993 SO2 Control Symposium in Boston, MA, August 24-27, 1993. The presentations covered a wide range of topics: industry's strategies for dealing with Clean Air Act Amendments of 1990, including Phase I strategies, the emiss...

  19. Figurative Language Awards Ceremony.

    ERIC Educational Resources Information Center

    Fink, Lisa

    Figurative language enlivens a text, providing visuals in the minds of readers. This lesson will have students listening to and reading selected texts as they seek out their favorite literary devices. During the five to seven 50-minute sessions, grade three through five students will: acquire a clear understanding of the concept of figurative…

  20. OECD in Figures, 2008

    ERIC Educational Resources Information Center

    OECD Publishing (NJ1), 2008

    2008-01-01

    "OECD in Figures" is a primary statistical source for key data on OECD countries, ranging from economic growth and employment to inflation, trade and environment. Information is presented in tabular form for: (1) Demography and Health; (2) Economy; (3) Energy; (4) Labour; (5) Science and Technology; (6) Environment; (7) Education; (8)…

  1. High resolution crystal structure of human Dim2/TXNL4B

    Technology Transfer Automated Retrieval System (TEKTRAN)

    TXNL4A (thioredoxin like 4A) is an essential protein conserved from yeast to human and is a component of the pre-mRNA splicing machinery. TXNL4B was identified as a TXNL4 family protein that also interacts with prp6, an integral component of the U4/U6•U5 tri-snRNP complex, and was shown to function...

  2. Phosphorylation of mammalian initiation factor eIF-4B

    SciTech Connect

    Duncan, R.F.; Milburn, S.C.; Cooper, R.; Gould, K.; Hunter, T.; Hershey, J.W.B.

    1987-05-01

    The phosphorylation of initiation factors appears to be an important mechanism for regulating the rate of translation in mammalian cells. eIF-4B (80 kDa) purified from HeLa cells exhibits a complex array of 8 to 12 spots when analyzed by 2-dimensional isoelectric focusing - SDS polyacrylamide gel electrophoresis. A similar array of eIF-4B spots is seen when total lysate proteins are analyzed by immunoblotting with anti-eIF-4B antiserum or with antibodies affinity-purified from the most basic eIF-4B spot. The multiple forms of eIF-4B are due to phosphorylation, since all but the most basic spot are labeled with (/sup 32/P)phosphate in vivo and the action of alkaline phosphatase in vitro reduces the array to only two spots. Tryptic peptide maps of phosphopeptides from each of the various isoelectric variants of eIF-4B show a similar complexity, suggesting that a number of different sites are phosphorylated in a random order. When serum-deprived HeLa cells are treated with phorbol ester, both the protein synthesis rate and the extent of eIF-4B phosphorylation increase, suggesting that C kinase may be a regulator of translation. Purified C kinase phosphorylates a number of pure initiation factors in vitro, but eIF-4B is the strongest target protein. When pure eIF-4B is treated, the entire mass of eIF-4B is shifted to the most acidic spots, indicating very strong phosphorylation. Attempts are being made to detect differences in the in vitro activities of the non-phosphorylated and highly phosphorylated forms.

  3. Category 4b - A Regulatory Alternative to TMDLs

    EPA Pesticide Factsheets

    The paper describes the extent to which states have successfully employed TMDL alternatives to address impaired waters and assigned these waters to Category 4b, and includes several Washington State examples.

  4. Nanog regulates primordial germ cell migration through Cxcr4b.

    PubMed

    Sánchez-Sánchez, Ana Virginia; Camp, Esther; Leal-Tassias, Aránzazu; Atkinson, Stuart P; Armstrong, Lyle; Díaz-Llopis, Manuel; Mullor, José L

    2010-09-01

    Gonadal development in vertebrates depends on the early determination of primordial germ cells (PGCs) and their correct migration to the sites where the gonads develop. Several genes have been implicated in PGC specification and migration in vertebrates. Additionally, some of the genes associated with pluripotency, such as Oct4 and Nanog, are expressed in PGCs and gonads, suggesting a role for these genes in maintaining pluripotency of the germ lineage, which may be considered the only cell type that perpetually maintains stemness properties. Here, we report that medaka Nanog (Ol-Nanog) is expressed in the developing PGCs. Depletion of Ol-Nanog protein causes aberrant migration of PGCs and inhibits expression of Cxcr4b in PGCs, where it normally serves as the receptor of Sdf1a to guide PGC migration. Moreover, chromatin immunoprecipitation analysis demonstrates that Ol-Nanog protein binds to the promoter region of Cxcr4b, suggesting a direct regulation of Cxcr4b by Ol-Nanog. Simultaneous overexpression of Cxcr4b mRNA and depletion of Ol-Nanog protein in PGCs rescues the migration defective phenotype induced by a loss of Ol-Nanog, whereas overexpression of Sdf1a, the ligand for Cxcr4b, does not restore proper PGC migration. These results indicate that Ol-Nanog mediates PGC migration by regulating Cxcr4b expression.

  5. Lunar Regolith Figures of Merit

    NASA Technical Reports Server (NTRS)

    Rickman, Doug; Scjrader. Cjrostoam; Jpe (zer. Jams); Fourroux, Kathy

    2009-01-01

    This viewgraph presentation reviews the lunar regolith figures of merit. The contents include: 1) A quick review of Figures-of-Merit (FoM); 2) Software Implementation of FoM Algorithms; and 3) Demonstration of the Software.

  6. Making better scientific figures

    NASA Astrophysics Data System (ADS)

    Hawkins, Ed; McNeall, Doug

    2016-04-01

    In the words of the UK government chief scientific adviser "Science is not finished until it's communicated" (Walport 2013). The tools to produce good visual communication have never been so easily accessible to scientists as at the present. Correspondingly, it has never been easier to produce and disseminate poor graphics. In this presentation, we highlight some good practice and offer some practical advice in preparing scientific figures for presentation to peers or to the public. We identify common mistakes in visualisation, including some made by the authors, and offer some good reasons not to trust defaults in graphics software. In particular, we discuss the use of colour scales and share our experiences in running a social media campaign (http://tiny.cc/endrainbow) to replace the "rainbow" (also "jet", or "spectral") colour scale as the default in (climate) scientific visualisation.

  7. The Theory of Figural Concepts.

    ERIC Educational Resources Information Center

    Fischbein, Efraim

    1993-01-01

    The main thesis of the paper is that geometry deals with mental entities (the so-called geometrical figures) which possess simultaneously conceptual and figural characters. The paper analyzes the internal tensions which may arise in figural concepts because of their double nature, developmental aspects, and didactical implications. (Author/MDH)

  8. A Genetic Interaction between Hepatitis C Virus NS4B and NS3 Is Important for RNA Replication▿

    PubMed Central

    Paredes, Anne M.; Blight, Keril J.

    2008-01-01

    Hepatitis C virus (HCV) nonstructural protein 4B (NS4B), a poorly characterized integral membrane protein, is thought to function as a scaffold for replication complex assembly; however, functional interactions with the other HCV nonstructural proteins within this complex have not been defined. We report that a Con1 chimeric subgenomic replicon containing the NS4B gene from the closely related H77 isolate is defective for RNA replication in a transient assay, suggesting that H77 NS4B is unable to productively interact with the Con1 replication machinery. The H77 NS4B sequences that proved detrimental for Con1 RNA replication resided in the predicted N- and C-terminal cytoplasmic domains as well as the central transmembrane region. Selection for Con1 derivatives that could utilize the entire H77 NS4B or hybrid Con1-H77 NS4B proteins yielded mutants containing single amino acid substitutions in NS3 and NS4A. The second-site mutations in NS3 partially restored the replication of Con1 chimeras containing the N-terminal or transmembrane domains of H77 NS4B. In contrast, the deleterious H77-specific sequences in the C terminus of NS4B, which mapped to a cluster of four amino acids, were completely suppressed by second-site substitutions in NS3. Collectively, these results provide the first evidence for a genetic interaction between NS4B and NS3 important for productive HCV RNA replication. PMID:18715921

  9. Pyrazolopyridines as potent PDE4B inhibitors: 5-Heterocycle SAR

    SciTech Connect

    Mitchell, Charlotte J.; Ballantine, Stuart P.; Coe, Diane M.; Cook, Caroline M.; Delves, Christopher J.; Dowle, Mike D.; Edlin, Chris D.; Hamblin, J. Nicole; Holman, Stuart; Johnson, Martin R.; Jones, Paul S.; Keeling, Sue E.; Kranz, Michael; Lindvall, Mika; Lucas, Fiona S.; Neu, Margarete; Solanke, Yemisi E.; Somers, Don O.; Trivedi, Naimisha A.; Wiseman, Joanne O.

    2012-05-03

    Following the discovery of 4-(substituted amino)-1-alkyl-pyrazolo[3,4-b]pyridine-5-carboxamides as potent and selective phosphodiesterase 4B inhibitors, [Hamblin, J. N.; Angell, T.; Ballentine, S., et al. Bioorg. Med. Chem. Lett.2008, 18, 4237] the SAR of the 5-position was investigated further. A range of substituted heterocycles showed good potencies against PDE4. Optimisation using X-ray crystallography and computational modelling led to the discovery of 16, with sub-nM inhibition of LPS-induced TNF-{alpha} production from isolated human peripheral blood mononuclear cells.

  10. MCNP4B{sup {trademark}} verification and validation

    SciTech Connect

    Hendricks, J.S.; Court, J.D.

    1996-08-01

    Several new features and bug fixes have been incorporated into the new release of MCNP. As required by the MCNP Software Quality Assurance Plan, these changes to the code and the test set are documented here for user reference. This document summarizes the new MCNP4B features and corrections, separated into major and minor groupings. Also included are a code cleanup section and a section delineating problems identified in LA-12839 which have not been corrected. Finally, we document the MCNP4B test set modifications and explain how test set coverage has been improved.

  11. Figure-ground organization in real and subjective contours: a new ambiguous figure, some novel measures of ambiguity, and apparent distance across regions of figure and ground.

    PubMed

    Shank, M D; Walker, J T

    1989-08-01

    This study was designed to assess the effects of organization, luminance contrast, sector angle, and orientation on a new, highly ambiguous Cs-keyhole figure. Organization and contrast were the most important factors, and sector angle also influenced figure-ground relationships. There was no significant effect of orientation, nor was there any significant interaction between any of the factors. Several new measures of figure-ground organization were developed, such as ambiguity ratios based on reaction times and on ratings of the strength of perceived organizations, providing new quantitative measures of figure-ground relationships. Distances measured across figural regions appeared smaller than equal distances across the ground in the new reversible figure, and also in Rubin's classic vase-face figure presented in real and subjective contours. Inducing a perceptual set to see a particular organization in a reversible figure influenced the apparent distance across that organization. Several possible explanations of the observed effects are considered: (1) an instance of Emmert's law, based on the difference in apparent depth of figure and ground; (2) an aspect of the Müller-Lyer illusion; (3) a feature-detector model of contour attraction; (4) a natural set or predisposition to see a figure as smaller; and (5) framing effects. The first two explanations appear the most promising.

  12. RAMONA-4B code for BWR systems analysis

    SciTech Connect

    Cheng, H.S.; Rohatgi, U.S.

    1996-12-31

    The RAMONA-4B code is a coupled thermal-hydraulic, 3D kinetics code for plant transient analyses of a complete Boiling Water Reactor (BWR) system including Reactor Pressure Vessel (RPV), Balance of Plant (BOP) and containment. The complete system representation enables an integrated and coupled systems analysis of a BWR without recourse to prescribed boundary conditions.

  13. Amino acid residues 1101-1105 of the isotypic region of human C4B is important to the covalent binding activity of complement component C4.

    PubMed

    Reilly, B D; Levine, R P; Skanes, V M

    1991-11-01

    The C4A and C4B isotypes of human C4 show certain functional differences that stem from their relative preference for transacylation to amino (-NH2) vs hydroxyl (-OH) nucleophiles, respectively, on complement-activating surfaces. Comparison of amino acid sequences of the alpha-chain fragment of C4, C4d, has shown C4A- and C4B-specific sequences at residues 1101-1106 are the only consistent structural difference between isotype, i.e., Pro, Cys, Pro, Val, Leu, Asp in C4A and Leu, Ser, Pro, Val Ile, His in C4B. These residues may be responsible either in part or entirely for properties associated with isotype. To examine the functional role of residues 1101-1106 in C4B-mediated hemolysis, whole serum or immunopurified human C4 with allotypes, A3B1, A3, B2B1, or B1 were preincubated in the presence or absence of an antipeptide mAb (BII-1) specific for amino acid residues 1101-1105 of C4B. Sensitized sheep E and C4-deficient guinea pig serum was then added and lysis measured by absorbance at 415 nm. Our results show lysis of antibody-sensitized sheep E is inhibited by antibody and C4B2B1, C4B1, or C4A3B1 but not antibody and C4A3. The interference of hemolysis by BII-1 could not be explained by inhibition of activation of C4B or inhibition of C3 or C5 convertase activity. Furthermore, results from uptake experiments show that BII-1 interferes with the covalent binding activity of C4B, indicating residues 1101-1105 play a role in the covalent binding reaction of C4B to the target E-antibody complex.

  14. Figure Analysis: An Implementation Dialogue

    ERIC Educational Resources Information Center

    Wiles, Amy M.

    2016-01-01

    Figure analysis is a novel active learning teaching technique that reinforces visual literacy. Small groups of students discuss diagrams in class in order to learn content. The instructor then gives a brief introduction and later summarizes the content of the figure. This teaching technique can be used in place of lecture as a mechanism to deliver…

  15. Three-Dimensional Lissajous Figures.

    ERIC Educational Resources Information Center

    D'Mura, John M.

    1989-01-01

    Described is a mechanically driven device for generating three-dimensional harmonic space figures with different frequencies and phase angles on the X, Y, and Z axes. Discussed are apparatus, viewing stereo pairs, equations of motion, and using space figures in classroom. (YP)

  16. Discovery of Dengue Virus NS4B Inhibitors

    PubMed Central

    Wang, Qing-Yin; Dong, Hongping; Zou, Bin; Karuna, Ratna; Wan, Kah Fei; Zou, Jing; Susila, Agatha; Yip, Andy; Shan, Chao; Yeo, Kim Long; Xu, Haoying; Ding, Mei; Chan, Wai Ling; Gu, Feng; Seah, Peck Gee; Liu, Wei; Lakshminarayana, Suresh B.; Kang, CongBao; Lescar, Julien; Blasco, Francesca; Smith, Paul W.

    2015-01-01

    ABSTRACT The four serotypes of dengue virus (DENV-1 to -4) represent the most prevalent mosquito-borne viral pathogens in humans. No clinically approved vaccine or antiviral is currently available for DENV. Here we report a spiropyrazolopyridone compound that potently inhibits DENV both in vitro and in vivo. The inhibitor was identified through screening of a 1.8-million-compound library by using a DENV-2 replicon assay. The compound selectively inhibits DENV-2 and -3 (50% effective concentration [EC50], 10 to 80 nM) but not DENV-1 and -4 (EC50, >20 μM). Resistance analysis showed that a mutation at amino acid 63 of DENV-2 NS4B (a nonenzymatic transmembrane protein and a component of the viral replication complex) could confer resistance to compound inhibition. Genetic studies demonstrate that variations at amino acid 63 of viral NS4B are responsible for the selective inhibition of DENV-2 and -3. Medicinal chemistry improved the physicochemical properties of the initial “hit” (compound 1), leading to compound 14a, which has good in vivo pharmacokinetics. Treatment of DENV-2-infected AG129 mice with compound 14a suppressed viremia, even when the treatment started after viral infection. The results have proven the concept that inhibitors of NS4B could potentially be developed for clinical treatment of DENV infection. Compound 14a represents a potential preclinical candidate for treatment of DENV-2- and -3-infected patients. IMPORTANCE Dengue virus (DENV) threatens up to 2.5 billion people and is now spreading in many regions in the world where it was not previously endemic. While there are several promising vaccine candidates in clinical trials, approved vaccines or antivirals are not yet available. Here we describe the identification and characterization of a spiropyrazolopyridone as a novel inhibitor of DENV by targeting the viral NS4B protein. The compound potently inhibits two of the four serotypes of DENV (DENV-2 and -3) both in vitro and in vivo. Our

  17. Characterization of Nuclear Localization Signal in the N Terminus of CUL4B and Its Essential Role in Cyclin E Degradation and Cell Cycle Progression*

    PubMed Central

    Zou, Yongxin; Mi, Jun; Cui, Jinpeng; Lu, Defen; Zhang, Xiyu; Guo, Chenhong; Gao, Guimin; Liu, Qiji; Chen, Bingxi; Shao, Changshun; Gong, Yaoqin

    2009-01-01

    CUL4A and CUL4B, which are derived from the same ancestor, CUL4, encode scaffold proteins that organize cullin-RING ubiquitin ligase (E3) complexes. Recent genetic studies have shown that germ line mutation in CUL4B can cause mental retardation, short stature, and other abnormalities in humans. CUL4A was observed to be overexpressed in breast and hepatocellular cancers, although no germ line mutation in human CUL4A has been reported. Although CUL4A has been known to be involved in a number of cellular processes, including DNA repair and cell cycle regulation, little is known about whether CUL4B has similar functions. In this report, we tested the functional importance of CUL4B in cell proliferation and characterized the nuclear localization signal (NLS) that is essential for its function. We found that RNA interference silencing of CUL4B led to an inhibition of cell proliferation and a prolonged S phase, due to the overaccumulation of cyclin E, a substrate targeted by CUL4B for ubiquitination. We showed that, unlike CUL4A and other cullins that carry their NLS in their C termini, NLS in CUL4B is located in its N terminus, between amino acid 37 and 40, KKRK. This NLS could bind to importin α1, α3, and α5. NLS-deleted CUL4B was distributed in cytoplasm and failed to promote cell proliferation. Therefore, the nuclear localization of CUL4B mediated by NLS is critical for its normal function in cell proliferation. PMID:19801544

  18. R-X Modeling Figures

    SciTech Connect

    Goda, Joetta Marie; Miller, Thomas; Grogan, Brandon

    2016-10-26

    This document contains figures that will be included in an ORNL final report that details computational efforts to model an irradiation experiment performed on the Godiva IV critical assembly. This experiment was a collaboration between LANL and ORNL.

  19. Facts and Figures on Pain

    MedlinePlus

    ... Room Position Statements AAPM Facts and Figures on Pain Overview What is Chronic Pain? Incidence of Pain, ... of them. Back to Top What is Chronic Pain? While acute pain is a normal sensation triggered ...

  20. A region rich in aspartic acid, arginine, tyrosine, and glycine (DRYG) mediates eukaryotic initiation factor 4B (eIF4B) self-association and interaction with eIF3.

    PubMed Central

    Méthot, N; Song, M S; Sonenberg, N

    1996-01-01

    The binding of mRNA to the ribosome is mediated by eukaryotic initiation factors eukaryotic initiation factor 4F (eIF4F), eIF4B, eIF4A, and eIF3, eIF4F binds to the mRNA cap structure and, in combination with eIF4B, is believed to unwind the secondary structure in the 5' untranslated region to facilitate ribosome binding. eIF3 associates with the 40S ribosomal subunit prior to mRNA binding. eIF4B copurifies with eIF3 and eIF4F through several purification steps, suggesting the involvement of a multisubunit complex during translation initiation. To understand the mechanism by which eIF4B promotes 40S ribosome binding to the mRNA, we studied its interactions with partner proteins by using a filter overlay (protein-protein [far Western]) assay and the two-hybrid system. In this report, we show that eIF4B self-associates and also interacts directly with the p170 subunit of eIF3. A region rich in aspartic acid, arginine, tyrosine, and glycine, termed the DRYG domain, is sufficient for self-association of eIF4B, both in vitro and in vivo, and for interaction with the p170 subunit of eIF3. These experiments suggest that eIF4B participates in mRNA-ribosome binding by acting as an intermediary between the mRNA and eIF3, via a direct interaction with the p170 subunit of eIF3. PMID:8816444

  1. Generation and characterization of a Cyp4b1 null mouse and the role of CYP4B1 in the activation and toxicity of Ipomeanol.

    PubMed

    Parkinson, Oliver T; Liggitt, H Denny; Rettie, Allan E; Kelly, Edward J

    2013-08-01

    4-Ipomeanol (IPO) is a prototypical pulmonary toxin that requires P450-mediated metabolic activation to reactive intermediates in order to elicit its toxic effects. CYP4B1 is a pulmonary enzyme that has been shown, in vitro, to have a high capacity for bioactivating IPO. In order to determine, unambiguously, the role of CYP4B1 in IPO bioactivation in vivo, we generated Cyp4b1 null mice following targeted disruption of the gene downstream of exon 1. Cyp4b1 (-/-) mice are viable and healthy, with no overt phenotype, and no evidence of compensatory upregulation of other P450 isoforms in any of the tissues examined. Pulmonary and renal microsomes prepared from male Cyp4b1 (-/-) mice exhibited no detectable expression of the protein and catalyzed the in vitro bioactivation of IPO at < 10% of the rates observed in tissue microsomes from Cyp4b1 (+/+) animals. Administration of IPO (20mg/kg) to Cyp4b1 (+/+) mice resulted in characteristic lesions in the lung, and to a lesser extent in the kidney, which were completely absent in Cyp4b1 (-/-) mice. We conclude that CYP4B1 is a critical enzyme for the bioactivation of IPO in vivo and that the Cyp4b1 (-/-) mouse is a useful model for studying CYP4B1-dependent metabolism and toxicity.

  2. SECONDARY ECLIPSE PHOTOMETRY OF WASP-4b WITH WARM SPITZER

    SciTech Connect

    Beerer, Ingrid M.; Knutson, Heather A.; Burrows, Adam; Fortney, Jonathan J.; Laughlin, Gregory; Agol, Eric; Cowan, Nicolas B.; Charbonneau, David; Desert, Jean-Michel; Deming, Drake; Langton, Jonathan; Lewis, Nikole K.; Showman, Adam P.

    2011-01-20

    We present photometry of the giant extrasolar planet WASP-4b at 3.6 and 4.5 {mu}m taken with the Infrared Array Camera on board the Spitzer Space Telescope as part of Spitzer's extended warm mission. We find secondary eclipse depths of 0.319% {+-} 0.031% and 0.343% {+-} 0.027% for the 3.6 and 4.5 {mu}m bands, respectively, and show model emission spectra and pressure-temperature profiles for the planetary atmosphere. These eclipse depths are well fit by model emission spectra with water and other molecules in absorption, similar to those used for TrES-3 and HD 189733b. Depending on our choice of model, these results indicate that this planet has either a weak dayside temperature inversion or no inversion at all. The absence of a strong thermal inversion on this highly irradiated planet is contrary to the idea that highly irradiated planets are expected to have inversions, perhaps due the presence of an unknown absorber in the upper atmosphere. This result might be explained by the modestly enhanced activity level of WASP-4b's G7V host star, which could increase the amount of UV flux received by the planet, therefore reducing the abundance of the unknown stratospheric absorber in the planetary atmosphere as suggested in Knutson et al. We also find no evidence for an offset in the timing of the secondary eclipse and place a 2{sigma} upper limit on |ecos {omega}| of 0.0024, which constrains the range of tidal heating models that could explain this planet's inflated radius.

  3. Figure analysis: An implementation dialogue.

    PubMed

    Wiles, Amy M

    2016-07-08

    Figure analysis is a novel active learning teaching technique that reinforces visual literacy. Small groups of students discuss diagrams in class in order to learn content. The instructor then gives a brief introduction and later summarizes the content of the figure. This teaching technique can be used in place of lecture as a mechanism to deliver information to students. Here, a "how to" guide is presented in the form of an in-class dialogue, displaying the difficulties in visual interpretation that some students may experience while figure analysis is being implemented in an upper-level, cell biology course. Additionally, the dialogue serves as a guide for instructors who may implement the active learning technique as they consider how to respond to students' concerns in class. © 2016 by The International Union of Biochemistry and Molecular Biology, 44(4):345-348, 2016.

  4. Concepts and Figures in Geometric Reasoning.

    ERIC Educational Resources Information Center

    Fischbein, Efraim; Nachlieli, Talli

    1998-01-01

    Opens with the theoretical construct of figural concepts. Argues that geometrical figures are characterized by both conceptual and sensorial properties. Investigates the effects of interaction between conceptual and figural components. Contains 19 references. (DDR)

  5. Choreography Styles in Figure Skating

    ERIC Educational Resources Information Center

    Moormann, Peter Paul

    2006-01-01

    Fifty-eight figure skating trainers from fifteen different countries acted as volunteers in this study on choreography styles. The styles were based on reports of artistic-creative strategies in composing music, drawing, writing poems or novels, and in making dances. The prevalence of the Mozartian (at the onset the choreographer already has a…

  6. Storytelling Figures: A Pueblo Tradition.

    ERIC Educational Resources Information Center

    Kraus, Nancy

    1997-01-01

    In a collaborative unit on pueblo storytelling figures involving art, music, language arts, and physical education, a teacher describes how she helped second graders understand the Pueblo pottery tradition by reading aloud literature covering the past and present. Lists folklore, fiction, poetry, nonfiction, professional resources, videos, CDs,…

  7. Electron photon verification calculations using MCNP4B

    SciTech Connect

    Gierga, D.P.; Adams, K.J.

    1998-07-01

    MCNP4B was released in February 1997 with significant enhancements to electron/photon transport methods. These enhancements have been verified against a wide range of published electron/photon experiments, spanning high energy bremsstrahlung production to electron transmission and reflection. Three sets of bremsstrahlung experiments were simulated. The first verification calculations for bremsstrahlung production used the experimental results in Faddegon for 15 MeV electrons incident on lead, aluminum, and beryllium targets. The calculated integrated bremsstrahlung yields, the bremsstrahlung energy spectra, and the mean energy of the bremsstrahlung beam were compared with experiment. The impact of several MCNP tally options and physics parameters was explored in detail. The second was the experiment of O`Dell which measured the bremsstrahlung spectra from 10 and 20.9 MeV electrons incident on a gold/tungsten target. The final set was a comparison of relative experimental spectra with calculated results for 9.66 MeV electrons incident on tungsten based on the experiment of Starfelt and Koch. The transmission experiments of Ebert were also studied, including comparisons of transmission coefficients for 10.2 MeV electrons incident on carbon, silver, and uranium foils. The agreement between experiment and simulation was usually within two standard deviations of the experimental and calculational errors.

  8. Theory in Biology: Figure 1 or Figure 7?

    PubMed Central

    2015-01-01

    The pace of modern science is staggering. The quantities of data now flowing from DNA sequencers, fluorescence and electron microscopes, mass spectrometers and other mind-blowing instruments leave us faced with information overload. This explosion in data has brought on its heels a concomitant need for efforts at the kinds of synthesis and unification we see in theoretical physics. Often in cell biology, when theoretical modeling takes place, it is as a figure 7 reflection on experiments that have already been done, with data fitting providing a metric of success. Figure 1 theory, by way of contrast, is about living dangerously by turning our thinking into formal mathematical predictions and confronting that math with experiments that have not yet been done. PMID:26584768

  9. Theory in Biology: Figure 1 or Figure 7?

    PubMed

    Phillips, Rob

    2015-12-01

    The pace of modern science is staggering. The quantities of data now flowing from DNA sequencers, fluorescence and electron microscopes, mass spectrometers, and other mind-blowing instruments leave us faced with information overload. This explosion in data has brought on its heels a concomitant need for efforts at the kinds of synthesis and unification we see in theoretical physics. Often in cell biology, when theoretical modeling takes place, it is as a figure 7 reflection on experiments that have already been done, with data fitting providing a metric of success. Figure 1 theory, by way of contrast, is about living dangerously by turning our thinking into formal mathematical predictions and confronting that math with experiments that have not yet been done.

  10. Figural symbolism in Chinese ideographs.

    PubMed

    Koriat, A; Levy, I

    1979-07-01

    Hebrew-speaking subjects were presented with 42 pairs of Chinese characters designating antonymic concepts and were required to match them with their corresponding Hebrew words. Correct translation was significant and was related to foreign language study and academic experience. Highest success was found for the activity domain of the semantic differential and for attributes judged to afford a diagrammatic representation. Examination of the character-referent relationships suggested that translation success was due to principles of figural symbolism rather than to pictographic representation of the attributes in question. The results are seen as suggestive of the effects of figural symbolization on the invention and/or evolution of natural scripts and are discussed in terms of the manner in which the graphic medium has been fashioned to convey abstract concepts.

  11. 49 CFR 178.50 - Specification 4B welded or brazed steel cylinders.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 3 2013-10-01 2013-10-01 false Specification 4B welded or brazed steel cylinders... FOR PACKAGINGS Specifications for Cylinders § 178.50 Specification 4B welded or brazed steel cylinders. (a) Type, size, and service pressure. A DOT 4B is a welded or brazed steel cylinder with...

  12. 49 CFR 178.50 - Specification 4B welded or brazed steel cylinders.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 3 2011-10-01 2011-10-01 false Specification 4B welded or brazed steel cylinders... FOR PACKAGINGS Specifications for Cylinders § 178.50 Specification 4B welded or brazed steel cylinders. (a) Type, size, and service pressure. A DOT 4B is a welded or brazed steel cylinder with...

  13. 49 CFR 178.50 - Specification 4B welded or brazed steel cylinders.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 3 2014-10-01 2014-10-01 false Specification 4B welded or brazed steel cylinders... FOR PACKAGINGS Specifications for Cylinders § 178.50 Specification 4B welded or brazed steel cylinders. (a) Type, size, and service pressure. A DOT 4B is a welded or brazed steel cylinder with...

  14. 49 CFR 178.50 - Specification 4B welded or brazed steel cylinders.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 3 2012-10-01 2012-10-01 false Specification 4B welded or brazed steel cylinders... FOR PACKAGINGS Specifications for Cylinders § 178.50 Specification 4B welded or brazed steel cylinders. (a) Type, size, and service pressure. A DOT 4B is a welded or brazed steel cylinder with...

  15. Determinants of the tumor suppressor INPP4B protein and lipid phosphatase activities.

    PubMed

    Lopez, Sandra M; Hodgson, Myles C; Packianathan, Charles; Bingol-Ozakpinar, Ozlem; Uras, Fikriye; Rosen, Barry P; Agoulnik, Irina U

    2013-10-18

    The tumor suppressor INPP4B is an important regulator of phosphatidyl-inositol signaling in the cell. Reduced INPP4B expression is associated with poor outcomes for breast, prostate, and ovarian cancer patients. INPP4B contains a CX5R catalytic motif characteristic of dual-specificity phosphatases, such as PTEN. Lipid phosphatase activity of INPP4B has previously been described. In this report we show that INPP4B can dephosphorylate para-nitrophenyl phosphate (pNPP) and 6,8-difluoro-4-methylumbelliferyl (DiFMUP), synthetic phosphotyrosine analogs, suggesting that INPP4B has protein tyrosine phosphatase (PTP) activity. Using mutagenesis, we examined the functional role of specific amino acids within the INPP4B C842KSAKDR catalytic site. The K843M mutant displayed increased pNPP hydrolysis, the K846M mutant lost lipid phosphatase activity with no effect on PTP activity, and the D847E substitution ablated PTP activity and significantly reduced lipid phosphatase activity. Further, we show that INPP4B but not PTEN is able to reduce tyrosine phosphorylation of Akt1 and both the lipid and PTP activity of INPP4B likely contribute to the reduction of Akt1 phosphorylation. Taken together our data identified key residues in the INPP4B catalytic domain associated with lipid and protein phosphatase activities and found a robust downstream target regulated by INPP4B but not PTEN.

  16. The HMG-box transcription factor Sox4b is required for pituitary expression of gata2a and specification of thyrotrope and gonadotrope cells in zebrafish.

    PubMed

    Quiroz, Yobhana; Lopez, Mauricio; Mavropoulos, Anastasia; Motte, Patrick; Martial, Joseph A; Hammerschmidt, Matthias; Muller, Marc

    2012-06-01

    The pituitary is a complex gland comprising different cell types each secreting specific hormones. The extensive network of signaling molecules and transcription factors required for determination and terminal differentiation of specific cell types is still not fully understood. The SRY-like HMG-box (SOX) transcription factor Sox4 plays important roles in many developmental processes and has two homologs in zebrafish, Sox4a and Sox4b. We show that the sox4b gene is expressed in the pituitary anlagen starting at 24 h after fertilization (hpf) and later in the entire head region including the pituitary. At 48 hpf, sox4b mRNA colocalizes with that for TSH (tshβ), glycoprotein subunit α (gsuα), and the Zn finger transcription factor Gata2a. Loss of Sox4b function, using morpholino knockdown or expression of a dominant-negative Sox4 mutant, leads to a drastic decrease in tshβ and gsuα expression and reduced levels of gh, whereas other anterior pituitary gland markers including prl, slβ, pomc, and lim3 are not affected. Sox4b is also required for expression of gata2a in the pituitary. Knockdown of gata2a leads to decreased tshβ and gsuα expression at 48 hpf, similar to sox4b morphants. Injection of gata2a mRNA into sox4b morphants rescued tshβ and gsuα expression in thyrotrope cells. Finally, sox4b or gata2a knockdown causes a significant decrease of gonadotropin expression (lhβ and fshβ) at 4 d after fertilization. In summary, our results indicate that Sox4b is expressed in zebrafish during pituitary development and plays a crucial role in the differentiation of thyrotrope and gonadotrope cells through induction of gata2a expression in the developing pituitary.

  17. Hooke's figurations: a figural drawing attributed to Robert Hooke.

    PubMed

    Hunter, Matthew C

    2010-09-20

    The experimental philosopher Robert Hooke (1635-1703) is known to have apprenticed to the leading painter Peter Lely on his first arrival in London in the late 1640s. Yet the relevance of Hooke's artistic training to his mature draughtsmanship and identity has remained unclear. Shedding light on that larger interpretive problem, this article argues for the attribution to Hooke of a figural drawing now in Tate Britain (T10678). This attributed drawing is especially interesting because it depicts human subjects and bears Hooke's name functioning as an artistic signature, both highly unusual features for his draughtsmanship. From evidence of how this drawing was collected and physically placed alongside images by leading artists in the early eighteenth century, I suggest how it can offer new insight into the reception of Hooke and his graphic work in the early Enlightenment.

  18. Androgen Receptor Coactivator ARID4B Is Required for the Function of Sertoli Cells in Spermatogenesis.

    PubMed

    Wu, Ray-Chang; Zeng, Yang; Pan, I-Wen; Wu, Mei-Yi

    2015-09-01

    Defects in spermatogenesis, a process that produces spermatozoa inside seminiferous tubules of the testis, result in male infertility. Spermatogenic progression is highly dependent on a microenvironment provided by Sertoli cells, the only somatic cells and epithelium of seminiferous tubules. However, genes that regulate such an important activity of Sertoli cells are poorly understood. Here, we found that AT-rich interactive domain 4B (ARID4B), is essential for the function of Sertoli cells to regulate spermatogenesis. Specifically, we generated Sertoli cell-specific Arid4b knockout (Arid4bSCKO) mice, and showed that the Arid4bSCKO male mice were completely infertile with impaired testis development and significantly reduced testis size. Importantly, severe structural defects accompanied by loss of germ cells and Sertoli cell-only phenotype were found in many seminiferous tubules of the Arid4bSCKO testes. In addition, maturation of Sertoli cells was significantly delayed in the Arid4bSCKO mice, associated with delayed onset of spermatogenesis. Spermatogenic progression was also defective, showing an arrest at the round spermatid stage in the Arid4bSCKO testes. Interestingly, we showed that ARID4B functions as a "coactivator" of androgen receptor and is required for optimal transcriptional activation of reproductive homeobox 5, an androgen receptor target gene specifically expressed in Sertoli cells and critical for spermatogenesis. Together, our study identified ARID4B to be a key regulator of Sertoli cell function important for male germ cell development.

  19. PHOBOS Experiment: Figures and Data

    DOE Data Explorer

    The PHOBOS Collaboration

    PHOBOS consists of many silicon detectors surrounding the interaction region. With these detectors physicists can count the total number of produced particles and study the angular distributions of all the products. Physicists know from other branches of physics that a characteristic of phase transitions are fluctuations in physical observables. With the PHOBOS array they look for unusual events or fluctuations in the number of particles and angular distribution. The articles that have appeared in refereed science journals are listed here with separate links to the supporting data plots, figures, and tables of numeric data.  See also supporting data for articles in technical journals at http://www.phobos.bnl.gov/Publications/Technical/phobos_technical_publications.htm and from conference proceedings at http://www.phobos.bnl.gov/Publications/Proceedings/phobos_proceedings_publications.htm

  20. BPO4@B2O3 and (BPO4@B2O3):Eu3+: The novel single-emitting-component phosphors for near UV-white LEDs

    NASA Astrophysics Data System (ADS)

    Cao, Xiyu; Liu, Wei; Jiang, Yu; Cao, Lixin; Su, Ge; Gao, Rongjie

    2016-08-01

    Nowadays much effort has been devoted to exploring novel luminescent materials with low-cost, high stability and excellent luminescent properties. In this paper, a new kind of luminescent material BPO4@B2O3 was prepared by using a facile method. The as-obtained samples contain numerous BPO4 nanoparticles enclosed by amorphous and crystalline B2O3 homogeneously, which exhibits a broad emission band ranging from 380 to 700 nm under near-UV irradiation. More importantly, it is worth noting that the BPO4@B2O3 phosphor exhibits the excellent thermal quenching property, which endows it with a promising prospect as phosphors for high power white LEDs. To further promote its application as white light phosphors, Eu3+ ions were doped into the BPO4@B2O3 samples and prepared the (BPO4@B2O3):Eu3+ phosphors with chromaticity coordinates (0.3022, 0.3122). The corresponding packaging of LEDs indicates that both BPO4@B2O3 and (BPO4@B2O3):Eu3+ can be considered as the promising phosphors for WLEDs.

  1. Finding Figurative Language in "The Phantom Tollbooth."

    ERIC Educational Resources Information Center

    Hinton, Lisa

    This lesson is an exploration of figurative language using the novel "The Phantom Tollbooth" and various Web resources. Students examine figurative language in the story and create a chart representing the literal and figurative meanings of words and phrases. During the four to eight 40-minute class sessions, middle school students will: read the…

  2. LAPTM4B: an oncogene in various solid tumors and its functions

    PubMed Central

    Meng, Y; Wang, L; Chen, D; Chang, Y; Zhang, M; XU, J-J; Zhou, R; Zhang, Q-Y

    2016-01-01

    The oncogene Lysosome-associated protein transmembrane-4β (LAPTM4B) gene was identified, and the polymorphism region in the 5′-UTR of this gene was certified to be associated with tumor susceptibility. LAPTM4B-35 protein was found to be highly expressed in various solid tumors and could be a poor prognosis marker. The functions of LAPTM4B in solid tumors were also explored. It is suggested that LAPTM4B could promote the proliferation of tumor cells, boost invasion and metastasis, resist apoptosis, initiate autophagy and assist drug resistance. PMID:27212036

  3. The transcription activity of heat shock factor 4b is regulated by FGF2.

    PubMed

    Hu, Yan-Zhong; Zhang, Jun; Li, Shulian; Wang, Chuan; Chu, Liujie; Zhang, Zhi; Ma, Zengyi; Wang, Mingli; Jiang, Qiying; Liu, Guangchao; Qi, Yijun; Ma, Yuanfang

    2013-02-01

    Heat shock factor 4b has been found to be closely associated with postnatal lens development. It expresses in postnatal lens epithelial and secondary fiber cells and controls the expression of small heat shock proteins which are important for lens homeostasis. However, the signal pathways underlying Hsf4b are still not completely understood. Here we present that Hsf4b transcription activity is regulated by FGF2 a key growth factor that is involved in regulating lens development at multiple stages. FGF2 can promote Hsf4b nuclear-translocation and the expression of Hsp25 and αB-crystallin, the key downstream targets of Hsf4b in the Hsf4b-reconstituted mouse hsf4-/- lens epithelial cells. Further study indicates that FGF2 can induce Hsf4b protein stabilization through ERK1/2-mediated posttranslational phosphorylation or sumoylation. Hsf4b can promote FGF2-induced morphology transition from lens epithelial cell to the fiber cell, and this morphology transition can be inhibited by ERK1/2 inhibitor U0126. Taken together, our data demonstrate that Hsf4b is a novel downstream transcription factor of FGF2, and its transcription activity is associated with FGF2-modulated lens epithelial cell-fiber cell transition.

  4. Mapping the Interactions between the NS4B and NS3 Proteins of Dengue Virus

    PubMed Central

    Zou, Jing; Lee, Le Tian; Wang, Qing Yin; Xie, Xuping; Lu, Siyan; Yau, Yin Hoe; Yuan, Zhiming; Geifman Shochat, Susana; Kang, Congbao

    2015-01-01

    ABSTRACT Flavivirus RNA synthesis is mediated by a multiprotein complex associated with the endoplasmic reticulum membrane, named the replication complex (RC). Within the flavivirus RC, NS4B, an integral membrane protein with a role in virulence and regulation of the innate immune response, binds to the NS3 protease-helicase. NS4B modulates the RNA helicase activity of NS3, but the molecular details of their interaction remain elusive. Here, we used dengue virus (DENV) to map the determinants for the NS3-NS4B interaction. Coimmunoprecipitation and an in situ proximity ligation assay confirmed that NS3 colocalizes with NS4B in both DENV-infected cells and cells coexpressing both proteins. Surface plasmon resonance demonstrated that subdomains 2 and 3 of the NS3 helicase region and the cytoplasmic loop of NS4B are required for binding. Using nuclear magnetic resonance (NMR), we found that the isolated cytoplasmic loop of NS4B is flexible, with a tendency to form a three-turn α-helix and two short β-strands. Upon binding to the NS3 helicase, 12 amino acids within the cytoplasmic loop of NS4B exhibited line broadening, suggesting a participation in the interaction. Sequence alignment showed that 4 of these 12 residues are strictly conserved across different flaviviruses. Mutagenesis analysis showed that three (Q134, G140, and N144) of the four evolutionarily conserved NS4B residues are essential for DENV replication. The mapping of the NS3/NS4B-interacting regions described here can assist the design of inhibitors that disrupt their interface for antiviral therapy. IMPORTANCE NS3 and NS4B are essential components of the flavivirus RC. Using DENV as a model, we mapped the interaction between the viral NS3 and NS4B proteins. The subdomains 2 and 3 of NS3 helicase as well as the cytoplasmic loop of NS4B are critical for the interaction. Functional analysis delineated residues within the NS4B cytoplasmic loop that are crucial for DENV replication. Our findings reveal

  5. Mutations in classical swine fever virus NS4B affect virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), a virus causing a severe disease in swine. Protein domain analysis of the predicted amino acid sequence of NS4B in highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Interleukin-1 receptor like domain (TIR...

  6. Mutations in the classical swine fever virus NS4B protein affects virulence in swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    NS4B is one of the non-structural proteins of Classical Swine Fever Virus (CSFV), the etiological agent of a severe, highly lethal disease of swine. Protein domain analysis of the predicted amino acid sequence of the NS4B protein of highly pathogenic CSFV strain Brescia (BICv) identified a Toll/Inte...

  7. 78 FR 63221 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... ICH Q4B evaluation of the Bacterial Endotoxins Test General Chapter harmonized text from each of...

  8. 76 FR 37129 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-24

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... ] availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... published ICH guidance, ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the...

  9. Atypical Listeria monocytogenes Serotype 4b strains harboring a lineage II-specific gene cassette

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes is the etiological agent of listeriosis, a severe foodborne illness. The population of L. monocytogenes is divided into four lineages (I-IV) and serotype 4b in lineage I has been involved in numerous outbreaks. Several serotype 4b epidemic-associated clonal groups (ECI, II, an...

  10. TAF4b Regulates Oocyte-Specific Genes Essential for Meiosis

    PubMed Central

    Grive, Kathryn J.; Gustafson, Eric A.; Seymour, Kimberly A.; Baddoo, Melody; Schorl, Christoph; Golnoski, Kayla; Rajkovic, Aleksandar; Brodsky, Alexander S.; Freiman, Richard N.

    2016-01-01

    TAF4b is a gonadal-enriched subunit of the general transcription factor TFIID that is implicated in promoting healthy ovarian aging and female fertility in mice and humans. To further explore the potential mechanism of TAF4b in promoting ovarian follicle development, we analyzed global gene expression at multiple time points in the human fetal ovary. This computational analysis revealed coordinate expression of human TAF4B and critical regulators and effectors of meiosis I including SYCP3, YBX2, STAG3, and DAZL. To address the functional relevance of this analysis, we turned to the embryonic Taf4b-deficient mouse ovary where, for the first time, we demonstrate, severe deficits in prophase I progression as well as asynapsis in Taf4b-deficient oocytes. Accordingly, TAF4b occupies the proximal promoters of many essential meiosis and oogenesis regulators, including Stra8, Dazl, Figla, and Nobox, and is required for their proper expression. These data reveal a novel TAF4b function in regulating a meiotic gene expression program in early mouse oogenesis, and support the existence of a highly conserved TAF4b-dependent gene regulatory network promoting early oocyte development in both mice and women. PMID:27341508

  11. Identification of breast cancer cell subtypes sensitive to ATG4B inhibition

    PubMed Central

    Bortnik, Svetlana; Choutka, Courtney; Horlings, Hugo M.; Leung, Samuel; Baker, Jennifer H.; Lebovitz, Chandra; Dragowska, Wieslawa H.; Go, Nancy E.; Bally, Marcel B.; Minchinton, Andrew I.; Gelmon, Karen A.; Gorski, Sharon M.

    2016-01-01

    Autophagy, a lysosome-mediated degradation and recycling process, functions in advanced malignancies to promote cancer cell survival and contribute to cancer progression and drug resistance. While various autophagy inhibition strategies are under investigation for cancer treatment, corresponding patient selection criteria for these autophagy inhibitors need to be developed. Due to its central roles in the autophagy process, the cysteine protease ATG4B is one of the autophagy proteins being pursued as a potential therapeutic target. In this study, we investigated the expression of ATG4B in breast cancer, a heterogeneous disease comprised of several molecular subtypes. We examined a panel of breast cancer cell lines, xenograft tumors, and breast cancer patient specimens for the protein expression of ATG4B, and found a positive association between HER2 and ATG4B protein expression. We showed that HER2-positive cells, but not HER2-negative breast cancer cells, require ATG4B to survive under stress. In HER2-positive cells, cytoprotective autophagy was dependent on ATG4B under both starvation and HER2 inhibition conditions. Combined knockdown of ATG4B and HER2 by siRNA resulted in a significant decrease in cell viability, and the combination of ATG4B knockdown with trastuzumab resulted in a greater reduction in cell viability compared to trastuzumab treatment alone, in both trastuzumab-sensitive and -resistant HER2 overexpressing breast cancer cells. Together these results demonstrate a novel association of ATG4B positive expression with HER2 positive breast cancers and indicate that this subtype is suitable for emerging ATG4B inhibition strategies. PMID:27556700

  12. Recommended reference figures for geophysics and geodesy

    NASA Technical Reports Server (NTRS)

    Khan, M. A.; Okeefe, J. A.

    1973-01-01

    Specific reference figures are recommended for consistent use in geophysics and geodesy. The selection of appropriate reference figure for geophysical studies suggests a relationship between the Antarctic negative gravity anomaly and the great shrinkage of the Antarctic ice cap about 4-5 million years ago. The depression of the south polar regions relative to the north polar regions makes the Southern Hemisphere flatter than the Northern Hemisphere, thus producing the third harmonic (pear-shaped) contribution to the earth's figure.

  13. Incomplete figure perception and invisible masking.

    PubMed

    Chikhman, Valery; Shelepin, Yuri; Foreman, Nigel; Merkuljev, Aleksey; Pronin, Sergey

    2006-01-01

    The Gollin test (measuring recognition thresholds for fragmented line drawings of everyday objects and animals) has traditionally been regarded as a test of incomplete figure perception or 'closure', though there is a debate about how such closure is achieved. Here, figural incompleteness is considered to be the result of masking, such that absence of contour elements of a fragmented figure is the result of the influence of an 'invisible' mask. It is as though the figure is partly obscured by a mask having parameters identical to those of the background. This mask is 'invisible' only consciously, but for the early stages of visual processing it is real and has properties of multiplicative noise. Incomplete Gollin figures were modeled as the figure covered by the mask with randomly distributed transparent and opaque patches. We adjusted the statistical characteristics of the contour image and empty noise patches and processed those using spatial and spatial-frequency measures. Across 73 figures, despite inter-subject variability, mean recognition threshold was always approximately 15% of total contour in naive observers. Recognition worsened with increasing spectral similarity between the figure and the 'invisible' mask. Near threshold, the spectrum of the fragmented image was equally similar to that of the 'invisible' mask and complete image. The correlation between spectral parameters of figures at threshold and complete figures was greatest for figures that were most easily recognised. Across test sessions, thresholds reduced when either figure or mask parameters were familiar. We argue that recognition thresholds for Gollin stimuli in part reflect the extraction of signal from noise.

  14. Figure-ground assignment in pigeons: evidence for a figural benefit.

    PubMed

    Lazareva, Olga E; Castro, Leyre; Vecera, Shaun P; Wasserman, Edward A

    2006-07-01

    Four pigeons discriminated whether a target spot appeared on a colored figural shape or on a differently colored background by first pecking the target and then reporting its location: on the figure or the background. We recorded three dependent variables: target detection time, choice response time, and choice accuracy. The birds were faster to detect the target, to report its location, and to learn the correct response on figure trials than on background trials. Later tests suggested that the pigeons might have attended to the figural region as a whole rather than using local properties in performing the figure-background discrimination. The location of the figural region did not affect figure-ground assignment. Finally, when 4 other pigeons had to detect and peck the target without making a choice report, no figural advantage emerged in target detection time, suggesting that the birds' attention may not have been automatically summoned to the figural region.

  15. The Structural Basis of Oncogenic Mutations G12, G13 and Q61 in Small GTPase K-Ras4B

    PubMed Central

    Lu, Shaoyong; Jang, Hyunbum; Nussinov, Ruth; Zhang, Jian

    2016-01-01

    Ras mediates cell proliferation, survival and differentiation. Mutations in K-Ras4B are predominant at residues G12, G13 and Q61. Even though all impair GAP-assisted GTP → GDP hydrolysis, the mutation frequencies of K-Ras4B in human cancers vary. Here we aim to figure out their mechanisms and differential oncogenicity. In total, we performed 6.4 μs molecular dynamics simulations on the wild-type K-Ras4B (K-Ras4BWT-GTP/GDP) catalytic domain, the K-Ras4BWT-GTP–GAP complex, and the mutants (K-Ras4BG12C/G12D/G12V-GTP/GDP, K-Ras4BG13D-GTP/GDP, K-Ras4BQ61H-GTP/GDP) and their complexes with GAP. In addition, we simulated ‘exchanged’ nucleotide states. These comprehensive simulations reveal that in solution K-Ras4BWT-GTP exists in two, active and inactive, conformations. Oncogenic mutations differentially elicit an inactive-to-active conformational transition in K-Ras4B-GTP; in K-Ras4BG12C/G12D-GDP they expose the bound nucleotide which facilitates the GDP-to-GTP exchange. These mechanisms may help elucidate the differential mutational statistics in K-Ras4B-driven cancers. Exchanged nucleotide simulations reveal that the conformational transition is more accessible in the GTP-to-GDP than in the GDP-to-GTP exchange. Importantly, GAP not only donates its R789 arginine finger, but stabilizes the catalytically-competent conformation and pre-organizes catalytic residue Q61; mutations disturb the R789/Q61 organization, impairing GAP-mediated GTP hydrolysis. Together, our simulations help provide a mechanistic explanation of key mutational events in one of the most oncogenic proteins in cancer. PMID:26902995

  16. (4bS,8aS)-1-Isopropyl-4b,8,8-trimethyl-4b,5,6,7,8,8a,9,10-octa­hydro­phenan­thren-2-yl acetate

    PubMed Central

    Oubabi, Radouane; Auhmani, Aziz; Ait Itto, My Youssef; Auhmani, Abdelwahed; Daran, Jean-Claude

    2014-01-01

    The hemisynthesis of the title compound, C22H32O2, was carried out through direct acetyl­ation reaction of the naturally occurring diterpene totarol [systematic name: (4bS,8aS)-4b,8,8-trimethyl-1-propan-2-yl-5,6,7,8a,9,10-hexa­hydro­phen­an­thren-2-ol]. The mol­ecule is built up from three fused six membered rings, one saturated and two unsaturated. The central unsaturated ring has a half-chair conformation, whereas the other unsaturated ring displays a chair conformation. The absolute configuration is deduced from the chemical pathway. The value of the Hooft parameter [−0.10 (6)] allowed this absolute configuration to be confirmed. PMID:24765017

  17. INPP4B is an oncogenic regulator in human colon cancer

    PubMed Central

    Guo, S T; Chi, M N; Yang, R H; Guo, X Y; Zan, L K; Wang, C Y; Xi, Y F; Jin, L; Croft, A; Tseng, H-Y; Yan, X G; Farrelly, M; Wang, F H; Lai, F; Wang, J F; Li, Y P; Ackland, S; Scott, R; Agoulnik, I U; Hondermarck, H; Thorne, R F; Liu, T; Zhang, X D; Jiang, C C

    2016-01-01

    Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates phosphatidylinositol 3-kinase signaling and is a tumor suppressor in some types of cancers. However, we have found that it is frequently upregulated in human colon cancer cells. Here we show that silencing of INPP4B blocks activation of Akt and serum- and glucocorticoid-regulated kinase 3 (SGK3), inhibits colon cancer cell proliferation and retards colon cancer xenograft growth. Conversely, overexpression of INPP4B increases proliferation and triggers anchorage-independent growth of normal colon epithelial cells. Moreover, we demonstrate that the effect of INPP4B on Akt and SGK3 is associated with inactivation of phosphate and tensin homolog through its protein phosphatase activity and that the increase in INPP4B is due to Ets-1-mediated transcriptional upregulation in colon cancer cells. Collectively, these results suggest that INPP4B may function as an oncogenic driver in colon cancer, with potential implications for targeting INPP4B as a novel approach to treat this disease. PMID:26411369

  18. Mitotic MELK-eIF4B signaling controls protein synthesis and tumor cell survival

    PubMed Central

    Wang, Yubao; Begley, Michael; Li, Qing; Huang, Hai-Tsang; Lako, Ana; Eck, Michael J.; Gray, Nathanael S.; Mitchison, Timothy J.; Cantley, Lewis C.; Zhao, Jean J.

    2016-01-01

    The protein kinase maternal and embryonic leucine zipper kinase (MELK) is critical for mitotic progression of cancer cells; however, its mechanisms of action remain largely unknown. By combined approaches of immunoprecipitation/mass spectrometry and peptide library profiling, we identified the eukaryotic translation initiation factor 4B (eIF4B) as a MELK-interacting protein during mitosis and a bona fide substrate of MELK. MELK phosphorylates eIF4B at Ser406, a modification found to be most robust in the mitotic phase of the cell cycle. We further show that the MELK–eIF4B signaling axis regulates protein synthesis during mitosis. Specifically, synthesis of myeloid cell leukemia 1 (MCL1), an antiapoptotic protein known to play a role in cancer cell survival during cell division, depends on the function of MELK-elF4B. Inactivation of MELK or eIF4B results in reduced protein synthesis of MCL1, which, in turn, induces apoptotic cell death of cancer cells. Our study thus defines a MELK–eIF4B signaling axis that regulates protein synthesis during mitosis, and consequently influences cancer cell survival. PMID:27528663

  19. ATG4B/autophagin-1 regulates intestinal homeostasis and protects mice from experimental colitis

    PubMed Central

    Cabrera, Sandra; Fernández, Álvaro F.; Mariño, Guillermo; Aguirre, Alina; Suárez, María F.; Español, Yaiza; Vega, José A.; Laurà, Rosaria; Fueyo, Antonio; Fernández-García, M. Soledad; Freije, José M.P.; Kroemer, Guido; López-Otín, Carlos

    2013-01-01

    The identification of inflammatory bowel disease (IBD) susceptibility genes by genome-wide association has linked this pathology to autophagy, a lysosomal degradation pathway that is crucial for cell and tissue homeostasis. Here, we describe autophagy-related 4B, cysteine peptidase/autophagin-1 (ATG4B) as an essential protein in the control of inflammatory response during experimental colitis. In this pathological condition, ATG4B protein levels increase in parallel with the induction of autophagy. Moreover, ATG4B expression is significantly reduced in affected areas of the colon from IBD patients. Consistently, atg4b−/− mice present Paneth cell abnormalities, as well as an increased susceptibility to DSS-induced colitis. atg4b-deficient mice exhibit significant alterations in proinflammatory cytokines and mediators of the immune response to bacterial infections, which are reminiscent of those found in patients with Crohn disease or ulcerative colitis. Additionally, antibiotic treatments and bone marrow transplantation from wild-type mice reduced colitis in atg4b−/− mice. Taken together, these results provided additional evidence for the importance of autophagy in intestinal pathologies and describe ATG4B as a novel protective protein in inflammatory colitis. Finally, we propose that atg4b-null mice are a suitable model for in vivo studies aimed at testing new therapeutic strategies for intestinal diseases associated with autophagy deficiency. PMID:23782979

  20. Heat capacity, resistivity, and angular dependent magnetization studies of single crystal Nd1+ϵFe4B4 for ϵ≈17

    DOE PAGES

    Conner, Benjamin S.; Susner, Michael A.; Lampen-Kelley, Paula; ...

    2017-04-04

    Advances in crystal growth have allowed for synthesis of large single crystals of Nd1+ϵFe4B4, a well-known phase with a modulated structure. As a result we are able to report heat capacity and resistivity measurements on a single crystal Nd1+ϵFe4B4 sample with a distribution of ϵ that skews towards the solubility limit of Nd near ϵ ≈ 17. Heat capacity measurements show evidence of crystal field splitting at temperatures higher than the long-range ferromagnetic Curie temperature. Heat capacity, resistivity, and magnetization measurements all confirm a Curie temperature of 7 K which is lower than previously reported values in the Nd1+ϵFe4B4 system.more » Here, we also perform measurements of the angular dependence of the magnetization and discover behavior associated with the magnetic anisotropy that is inconsistent with the simple description previously proposed.« less

  1. A C-terminal di-leucine motif controls plasma membrane expression of PMCA4b.

    PubMed

    Antalffy, Géza; Pászty, Katalin; Varga, Karolina; Hegedűs, Luca; Enyedi, Agnes; Padányi, Rita

    2013-12-01

    Recent evidences show that the localization of different plasma membrane Ca(2+) ATPases (PMCAs) is regulated in various complex, cell type-specific ways. Here we show that in low-density epithelial and endothelial cells PMCA4b localized mostly in intracellular compartments and its plasma membrane localization was enhanced upon increasing density of cells. In good correlation with the enhanced plasma membrane localization a significantly more efficient Ca(2+) clearance was observed in confluent versus non-confluent HeLa cell cultures expressing mCherry-PMCA4b. We analyzed the subcellular localization and function of various C-terminally truncated PMCA4b variants and found that a truncated mutant PMCA4b-ct24 was mostly intracellular while another mutant, PMCA4b-ct48, localized more to the plasma membrane, indicating that a protein sequence corresponding to amino acid residues 1158-1181 contained a signal responsible for the intracellular retention of PMCA4b in non-confluent cultures. Alteration of three leucines to alanines at positions 1167-1169 resulted in enhanced cell surface expression and an appropriate Ca(2+) transport activity of both wild type and truncated pumps, suggesting that the di-leucine-like motif (1167)LLL was crucial in targeting PMCA4b. Furthermore, upon loss of cell-cell contact by extracellular Ca(2+) removal, the wild-type pump was translocated to the early endosomal compartment. Targeting PMCA4b to early endosomes was diminished by the L(1167-69)A mutation, and the mutant pump accumulated in long tubular cytosolic structures. In summary, we report a di-leucine-like internalization signal at the C-tail of PMCA4b and suggest an internalization-mediated loss of function of the pump upon low degree of cell-cell contact.

  2. LAPTM4B Gene Expression and Polymorphism as Diagnostic Markers of Breast Cancer in Egyptian Patients

    PubMed Central

    Shaker, Olfat; Taha, Fatma; Salah, Maha; El-Marzouky, Mohamed

    2015-01-01

    Summary Background The aim of this study was to investigate the association between LAPTM4B gene polymorphism and the risk of breast cancer among Egyptian female patients. Also, measurement was done of its serum level to evaluate its significance as a diagnostic marker for breast cancer. Methods This case control study was done on 88 breast cancer patients, 40 with fibroadenoma and 80 healthy subjects. Genotyping of the LAPTM4B polymorphism was determined by PCR. Serum LAPTM4B level was measured using ELISA. Results There was a significant difference in the (*1/2+ *2/2) genotypes in breast cancer patients (59.1) compared to the control subjects (43.8%) (P=0.047; OR=1.86; 95% CI =1.01–3.43). The frequency of the allele 2* of the LAPTM4B gene was significantly higher in breast cancer patients (36.4%) than in the control (25.6%) (p=0.034; OR=1.66; 95% CI =1.04–2.65). Genotypes (*1/2+*2/2) were significantly associated with the differential classification of TNM. Serum level of LAPTM4B was significantly higher in breast cancer patients than in control and fibroadenoma and in fibroadenoma patients than in control. In breast cancer patients, serum LAPTM4B was significantly higher in stage III and in large tumor size. Serum LAPTM4B was significantly higher in the cancer patients’ genotypes (*1/2+*2/2). Conclusions Genetic polymorphism of LAPTM4B is a potential risk factor for the development of breast cancer. Serum LAPTM4B may be used as a diagnostic and prognostic marker for breast cancer. PMID:28356847

  3. Chronic Cognitive Dysfunction after Traumatic Brain Injury Is Improved with a Phosphodiesterase 4B Inhibitor

    PubMed Central

    Titus, David J.; Wilson, Nicole M.; Freund, Julie E.; Carballosa, Melissa M.; Sikah, Kevin E.; Furones, Concepcion; Dietrich, W. Dalton; Gurney, Mark E.

    2016-01-01

    Learning and memory impairments are common in traumatic brain injury (TBI) survivors. However, there are no effective treatments to improve TBI-induced learning and memory impairments. TBI results in decreased cAMP signaling and reduced cAMP-response-element binding protein (CREB) activation, a critical pathway involved in learning and memory. TBI also acutely upregulates phosphodiesterase 4B2 (PDE4B2), which terminates cAMP signaling by hydrolyzing cAMP. We hypothesized that a subtype-selective PDE4B inhibitor could reverse the learning deficits induced by TBI. To test this hypothesis, adult male Sprague-Dawley rats received sham surgery or moderate parasagittal fluid-percussion brain injury. At 3 months postsurgery, animals were administered a selective PDE4B inhibitor or vehicle before cue and contextual fear conditioning, water maze training and a spatial working memory task. Treatment with the PDE4B inhibitor significantly reversed the TBI-induced deficits in cue and contextual fear conditioning and water maze retention. To further understand the underlying mechanisms of these memory impairments, we examined hippocampal long-term potentiation (LTP). TBI resulted in a significant reduction in basal synaptic transmission and impaired expression of LTP. Treatment with the PDE4B inhibitor significantly reduced the deficits in basal synaptic transmission and rescued LTP expression. The PDE4B inhibitor reduced tumor necrosis factor-α levels and increased phosphorylated CREB levels after TBI, suggesting that this drug inhibited molecular pathways in the brain known to be regulated by PDE4B. These results suggest that a subtype-selective PDE4B inhibitor is a potential therapeutic to reverse chronic learning and memory dysfunction and deficits in hippocampal synaptic plasticity following TBI. SIGNIFICANCE STATEMENT Currently, there are an estimated 3.2–5.3 million individuals living with disabilities from traumatic brain injury (TBI) in the United States, and 8 of

  4. Occipital network for figure/ground organization.

    PubMed

    Likova, Lora T; Tyler, Christopher W

    2008-08-01

    To study the cortical mechanism of figure/ground categorization in the human brain, we employed fMRI and the temporal-asynchrony paradigm. This paradigm is able to eliminate any differential activation for local stimulus features, and thus to identify only global perceptual interactions. Strong segmentation of the image into different spatial configurations was generated solely from temporal asynchronies between zones of homogeneous dynamic noise. The figure/ground configuration was a single geometric figure enclosed in a larger surround region. In a control condition, the figure/ground organization was eliminated by segmenting the noise field into many identical temporal-asynchrony stripes. The manipulation of the type of perceptual organization triggered dramatic reorganization in the cortical activation pattern. The figure/ground configuration generated suppression of the ground representation (limited to early retinotopic visual cortex, V1 and V2) and strong activation in the motion complex hMT+/V5+; conversely, both responses were abolished when the figure/ground organization was eliminated. These results suggest that figure/ground processing is mediated by top-down suppression of the ground representation in the earliest visual areas V1/V2 through a signal arising in the motion complex. We propose a model of a recurrent cortical architecture incorporating suppressive feedback that operates in a topographic manner, forming a figure/ground categorization network distinct from that for "pure" scene segmentation and thus underlying the perceptual organization of dynamic scenes into cognitively relevant components.

  5. Feature Assignment in Perception of Auditory Figure

    ERIC Educational Resources Information Center

    Gregg, Melissa K.; Samuel, Arthur G.

    2012-01-01

    Because the environment often includes multiple sounds that overlap in time, listeners must segregate a sound of interest (the auditory figure) from other co-occurring sounds (the unattended auditory ground). We conducted a series of experiments to clarify the principles governing the extraction of auditory figures. We distinguish between auditory…

  6. Key Figures on Vocational Education and Training.

    ERIC Educational Resources Information Center

    Mossoux, Anne France, Ed.

    This brochure identifies key figures on vocational education and training (VET) and VET-related topics in Europe using harmonized data from Eurostat. Throughout, figures of candidate countries are compared to those of European Union (EU) member states. Background information on the education and training systems is as follows: increasing numbers…

  7. "Blessed": Musical Talent, Smartness, & Figured Identities

    ERIC Educational Resources Information Center

    Hoffman, Adria R.

    2015-01-01

    The purpose of this study is to explore smartness and talent as social constructs. Drawing on Holland et al.'s (1998) figured identities, this article explores the figuring of abilities by elucidating the voices of African American high school chorus students. Critical Race Theory (CRT) helps to unpack normalized language and practices that…

  8. Automatic figure classification in bioscience literature.

    PubMed

    Kim, Daehyun; Ramesh, Balaji Polepalli; Yu, Hong

    2011-10-01

    Millions of figures appear in biomedical articles, and it is important to develop an intelligent figure search engine to return relevant figures based on user entries. In this study we report a figure classifier that automatically classifies biomedical figures into five predefined figure types: Gel-image, Image-of-thing, Graph, Model, and Mix. The classifier explored rich image features and integrated them with text features. We performed feature selection and explored different classification models, including a rule-based figure classifier, a supervised machine-learning classifier, and a multi-model classifier, the latter of which integrated the first two classifiers. Our results show that feature selection improved figure classification and the novel image features we explored were the best among image features that we have examined. Our results also show that integrating text and image features achieved better performance than using either of them individually. The best system is a multi-model classifier which combines the rule-based hierarchical classifier and a support vector machine (SVM) based classifier, achieving a 76.7% F1-score for five-type classification. We demonstrated our system at http://figureclassification.askhermes.org/.

  9. Detector array evaluation and figures of merit

    NASA Technical Reports Server (NTRS)

    Dereniak, Eustace L.

    1990-01-01

    The commonly used methods to evaluate the performance of a two-dimensional focal-plane array using charge transfer devices are reviewed. Two figures of merit that attempt to combine quantum efficiency, read noise and dark-current generation into a single parameter are discussed. The figures of merit are suggested as possible alternatives to the D asterisk.

  10. Analysis of That Mysterious Figure 8

    ERIC Educational Resources Information Center

    Leyden, Michael B.

    1974-01-01

    Presents a quantitative analysis of the "figure 8" found on the globes of most earth science textbooks, using an exercise of year's eccentric shadow plotting techniques. Indicates that the exercise can serve to change a student's abstract "figure 8" to his real learning experience. (CC)

  11. The Vernier Caliper and Significant Figures.

    ERIC Educational Resources Information Center

    Oberhofer, E. S.

    1985-01-01

    Misconceptions occur because the caliper is often read with the same significant figures as a meter stick; however, the precision of the vernier caliper is greater than the precision of a meter stick. Clarification of scale reading, precision of both tools, and significant figures are discussed. (JN)

  12. The Development of Ambiguous Figure Perception

    ERIC Educational Resources Information Center

    Wimmer, Marina C.; Doherty, Martin J.

    2011-01-01

    Ambiguous figures have fascinated researchers for almost 200 years. The physical properties of these figures remain constant, yet two distinct interpretations are possible; these reverse (switch) from one percept to the other. The consensus is that reversal requires complex interaction of perceptual bottom-up and cognitive top-down elements. The…

  13. Evolution of the Significant Figure Rules

    ERIC Educational Resources Information Center

    Carter, Ashley R.

    2013-01-01

    Today, almost all introductory physics textbooks include standardized "rules" on how to find the number of significant figures in a calculated value. And yet, 30 years ago these rules were almost nonexistent. Why have we increased the role of significant figures in introductory classes, and should we continue this trend? A look back at…

  14. Two New Copper Borates with Mesoscale Cubic Supramolecular Cages Assembled from {Cu4 @B20 } Clusters.

    PubMed

    Wang, Jia-Jia; Wei, Qi; Yang, Bai-Feng; Yang, Guo-Yu

    2017-02-24

    Two new copper borates, namely H6 [(μ4 -O)Cu4 @B20 O32 (OH)8 ]⋅25 H2 O (1) and H6 [(μ4 -O)Cu4 @B20 O32 (OH)8 ]⋅34 H2 O⋅8 H3 BO3 (2), with 3D supramolecular framework have been made under solvothermal conditions, which built by novel cubic supramolecular cages with mesoscale cavities via the H-bondings. Interestingly, the cage is assembled by [(μ4 -O)Cu4 @B20 O32 (OH)8 ] ({Cu4 @B20 }) cluster units with different point-group symmetry. Owing to extra H3 BO3 molecules participated in building the supramolecular framework, 2 has a larger cubic cage size and higher non-framework volume, leading to the cage size extended to mesoporous size set as a version of ''1 plus".

  15. VizieR Online Data Catalog: XO-4b 3yr observations with DEMONEX (Villanueva+, 2016)

    NASA Astrophysics Data System (ADS)

    Villanueva, S. Jr; Eastman, J. D.; Gaudi, B. S.

    2016-06-01

    New observations of XO-4b were made using DEdicated MONitor of EXotransits (DEMONEX). DEMONEX monitored bright stars hosting known transiting planets over a 3yr period from 2008 to 2011 in order to provide a homogeneous data set of precise relative photometry for over 40 transiting systems. There are 20 nights of data from 2008 November to 2010 May taken during primary transits of XO-4b. All observations were made in the Sloan z band. (1 data file).

  16. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 3 Figure 3 to Part 1508...

  17. 16 CFR Figure 3 to Part 1509 - Figure 3 to Part 1509

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Figure 3 to Part 1509 3 Figure 3 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 3 Figure 3 to Part 1509 EC03OC91.066...

  18. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS Pt. 1508, Fig. 3 Figure 3 to Part 1508 EC03OC91.063...

  19. 16 CFR Figure 1 to Part 1509 - Figure 1 to Part 1509

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Figure 1 to Part 1509 1 Figure 1 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 1 Figure 1 to Part 1509 EC03OC91.064...

  20. 16 CFR Figure 1 to Part 1509 - Figure 1 to Part 1509

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Figure 1 to Part 1509 1 Figure 1 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 1 Figure 1 to Part 1509 EC03OC91.064...

  1. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS Pt. 1508, Fig. 3 Figure 3 to Part 1508 EC03OC91.063...

  2. 16 CFR Figure 3 to Part 1509 - Figure 3 to Part 1509

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Figure 3 to Part 1509 3 Figure 3 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 3 Figure 3 to Part 1509 EC03OC91.066...

  3. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 3 Figure 3 to Part 1508...

  4. 16 CFR Figure 3 to Part 1508 - Figure 3 to Part 1508

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Figure 3 to Part 1508 3 Figure 3 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 3 Figure 3 to Part 1508...

  5. Current Drug Discovery for Anti-hepatitis C Virus Targeting NS4B.

    PubMed

    Wang, Zhenya; Chen, Xinli; Wu, Chunli; Xu, Haiwei; Liu, Hongmin

    2016-01-01

    Hepatitis C virus (HCV) infection is a major worldwide epidemic disease. It is estimated that more than 170 million individuals are infected with HCV and with three to four million new cases each year. Many new direct-acting antiviral (DAA) agents that specifically target HCV NS3 protease or NS5B polymerase inhibitors are therefore in development, with a significant effect for the patient and for the market recently. The non-structural 4B (NS4B) protein, is among the least characterized of the HCV proteins. A variety of functions have been recognized for NS4B, such as the ability to induce the membranous web replication platform, RNA binding and NTPase activity. In order to maximize antiviral efficacy and prevent the emergence of resistance, novel NS4B inhibitors have been subjected to pharmacological studies. In this review, we discussed current understanding of the structure and function of NS4B, and novel drug discoveries targeting NS4B as anti-hepatitis C virus such as sulfonamide, piperidine, carboxamide, piperazinone and quinoline derivatives within the last three years.

  6. UBE4B targets phosphorylated p53 at serines 15 and 392 for degradation

    PubMed Central

    Du, Cheng; Wu, Hong; Leng, Roger P.

    2016-01-01

    Phosphorylation of p53 is a key mechanism responsible for the activation of its tumor suppressor functions in response to various stresses. In unstressed cells, p53 is rapidly turned over and is maintained at a low basal level. After DNA damage or other forms of cellular stress, the p53 level increases, and the protein becomes metabolically stable. However, the mechanism of phosphorylated p53 regulation is unclear. In this study, we studied the kinetics of UBE4B, Hdm2, Pirh2, Cop1 and CHIP induction in response to p53 activation. We show that UBE4B coimmunoprecipitates with phosphorylated p53 at serines 15 and 392. Notably, the affinity between UBE4B and Hdm2 is greatly decreased after DNA damage. Furthermore, we observe that UBE4B promotes endogenous phospho-p53(S15) and phospho-p53(S392) degradation in response to IR. We demonstrate that UBE4B and Hdm2 repress p53S15A, p53S392A, and p53-2A(S15A, S392A) functions, including p53-dependent transactivation and growth inhibition. Overall, our results reveal that UBE4B plays an important role in regulating phosphorylated p53 following DNA damage. PMID:26673821

  7. O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity.

    PubMed

    Jo, Yoon Kyung; Park, Na Yeon; Park, So Jung; Kim, Byung-Gyu; Shin, Ji Hyun; Jo, Doo Sin; Bae, Dong-Jun; Suh, Young-Ah; Chang, Jeong Ho; Lee, Eun Kyung; Kim, Sang-Yeob; Kim, Jin Cheon; Cho, Dong-Hyung

    2016-08-30

    Autophagy is a catabolic degradation process and maintains cellular homeostasis. And autophagy is activated in response to various stress conditions. Although O-GlcNAcylation functions a sensor for nutrient and stress, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we identified that ATG4B is novel target for O-GlcNAcylation under metabolic stress condition. Treatment with PugNAc, an O-GlcNAcase inhibitor increased activation of autophagy in SH-SY5Y cells. Both bimolecular fluorescence complementation and immunoprecipitation assay indicated that OGT directly interacts with ATG4B in SH-SY5Y cells. We also found that the O-GlcNAcylated ATG4B was increased in autophagy activation conditions, and down-regulation of OGT reduces O-GlcNAcylation of ATG4B under low glucose condition. Furthermore, the proteolytic activity of ATG4B for LC3 cleavage was enhanced in PugNAc-treated cells. Taken together, these results imply that O-GlcNAcylation of ATG4B regulates autophagy activation by increasing its proteolytic activity under metabolic stress condition.

  8. O-GlcNAcylation of ATG4B positively regulates autophagy by increasing its hydroxylase activity

    PubMed Central

    Jo, Yoon Kyung; Park, Na Yeon; Park, So Jung; Kim, Byung-Gyu; Shin, Ji Hyun; Jo, Doo Sin; Bae, Dong-Jun; Suh, Young-Ah; Chang, Jeong Ho; Lee, Eun Kyung; Kim, Sang-Yeob; Kim, Jin Cheon; Cho, Dong-Hyung

    2016-01-01

    Autophagy is a catabolic degradation process and maintains cellular homeostasis. And autophagy is activated in response to various stress conditions. Although O-GlcNAcylation functions a sensor for nutrient and stress, the relationship between O-GlcNAcylation and autophagy is largely unknown. Here, we identified that ATG4B is novel target for O-GlcNAcylation under metabolic stress condition. Treatment with PugNAc, an O-GlcNAcase inhibitor increased activation of autophagy in SH-SY5Y cells. Both bimolecular fluorescence complementation and immunoprecipitation assay indicated that OGT directly interacts with ATG4B in SH-SY5Y cells. We also found that the O-GlcNAcylated ATG4B was increased in autophagy activation conditions, and down-regulation of OGT reduces O-GlcNAcylation of ATG4B under low glucose condition. Furthermore, the proteolytic activity of ATG4B for LC3 cleavage was enhanced in PugNAc-treated cells. Taken together, these results imply that O-GlcNAcylation of ATG4B regulates autophagy activation by increasing its proteolytic activity under metabolic stress condition. PMID:27527864

  9. Mechanisms of Membrane Binding of Small GTPase K-Ras4B Farnesylated Hypervariable Region*

    PubMed Central

    Jang, Hyunbum; Abraham, Sherwin J.; Chavan, Tanmay S.; Hitchinson, Ben; Khavrutskii, Lyuba; Tarasova, Nadya I.; Nussinov, Ruth; Gaponenko, Vadim

    2015-01-01

    K-Ras4B belongs to a family of small GTPases that regulates cell growth, differentiation and survival. K-ras is frequently mutated in cancer. K-Ras4B association with the plasma membrane through its farnesylated and positively charged C-terminal hypervariable region (HVR) is critical to its oncogenic function. However, the structural mechanisms of membrane association are not fully understood. Here, using confocal microscopy, surface plasmon resonance, and molecular dynamics simulations, we observed that K-Ras4B can be distributed in rigid and loosely packed membrane domains. Its membrane binding domain interaction with phospholipids is driven by membrane fluidity. The farnesyl group spontaneously inserts into the disordered lipid microdomains, whereas the rigid microdomains restrict the farnesyl group penetration. We speculate that the resulting farnesyl protrusion toward the cell interior allows oligomerization of the K-Ras4B membrane binding domain in rigid microdomains. Unlike other Ras isoforms, K-Ras4B HVR contains a single farnesyl modification and positively charged polylysine sequence. The high positive charge not only modulates specific HVR binding to anionic phospholipids but farnesyl membrane orientation. Phosphorylation of Ser-181 prohibits spontaneous farnesyl membrane insertion. The mechanism illuminates the roles of HVR modifications in K-Ras4B targeting microdomains of the plasma membrane and suggests an additional function for HVR in regulation of Ras signaling. PMID:25713064

  10. KDM4B is a master regulator of the estrogen receptor signalling cascade.

    PubMed

    Gaughan, Luke; Stockley, Jacqueline; Coffey, Kelly; O'Neill, Daniel; Jones, Dominic L; Wade, Mark; Wright, Jamie; Moore, Madeleine; Tse, Sandy; Rogerson, Lynsey; Robson, Craig N

    2013-08-01

    The importance of the estrogen receptor (ER) in breast cancer (BCa) development makes it a prominent target for therapy. Current treatments, however, have limited effectiveness, and hence the definition of new therapeutic targets is vital. The ER is a member of the nuclear hormone receptor superfamily of transcription factors that requires co-regulator proteins for complete regulation. Emerging evidence has implicated a small number of histone methyltransferase (HMT) and histone demethylase (HDM) enzymes as regulators of ER signalling, including the histone H3 lysine 9 tri-/di-methyl HDM enzyme KDM4B. Two recent independent reports have demonstrated that KDM4B is required for ER-mediated transcription and depletion of the enzyme attenuates BCa growth in vitro and in vivo. Here we show that KDM4B has an overarching regulatory role in the ER signalling cascade by controlling expression of the ER and FOXA1 genes, two critical components for maintenance of the estrogen-dependent phenotype. KDM4B interacts with the transcription factor GATA-3 in BCa cell lines and directly co-activates GATA-3 activity in reporter-based experiments. Moreover, we reveal that KDM4B recruitment and demethylation of repressive H3K9me3 marks within upstream regulatory regions of the ER gene permits binding of GATA-3 to drive receptor expression. Ultimately, our findings confirm the importance of KDM4B within the ER signalling cascade and as a potential therapeutic target for BCa treatment.

  11. Neuroblastoma patient outcomes, tumor differentiation, and ERK activation are correlated with expression levels of the ubiquitin ligase UBE4B

    PubMed Central

    Woodfield, Sarah E.; Guo, Rong Jun; Liu, Yin; Major, Angela M.; Hollingsworth, Emporia Faith; Indiviglio, Sandra; Whittle, Sarah B.; Mo, Qianxing; Bean, Andrew J.; Ittmann, Michael; Lopez-Terrada, Dolores; Zage, Peter E.

    2016-01-01

    Background UBE4B is an E3/E4 ubiquitin ligase whose gene is located in chromosome 1p36.22. We analyzed the associations of UBE4B gene and protein expression with neuroblastoma patient outcomes and with tumor prognostic features and histology. Methods We evaluated the association of UBE4B gene expression with neuroblastoma patient outcomes using the R2 Platform. We screened neuroblastoma tumor samples for UBE4B protein expression using immunohistochemistry. FISH for UBE4B and 1p36 deletion was performed on tumor samples. We then evaluated UBE4B expression for associations with prognostic factors and with levels of phosphorylated ERK in neuroblastoma tumors and cell lines. Results Low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma and with worse outcomes in all patient subgroups. UBE4B protein expression was associated with neuroblastoma tumor differentiation, and decreased UBE4B protein levels were associated with high-risk features. UBE4B protein levels were also associated with levels of phosphorylated ERK. Conclusions We have demonstrated associations between UBE4B gene expression and neuroblastoma patient outcomes and prognostic features. Reduced UBE4B protein expression in neuroblastoma tumors was associated with high-risk features, a lack of differentiation, and with ERK activation. These results suggest UBE4B may contribute to the poor prognosis of neuroblastoma tumors with 1p36 deletions and that UBE4B expression may mediate neuroblastoma differentiation. PMID:27014418

  12. eIF4B stimulates translation of long mRNAs with structured 5′ UTRs and low closed-loop potential but weak dependence on eIF4G

    PubMed Central

    Sen, Neelam Dabas; Zhou, Fujun; Harris, Michael S.; Ingolia, Nicholas T.

    2016-01-01

    DEAD-box RNA helicases eukaryotic translation initiation factor 4A (eIF4A) and Ded1 promote translation by resolving mRNA secondary structures that impede preinitiation complex (PIC) attachment to mRNA or scanning. Eukaryotic translation initiation factor 4B (eIF4B) is a cofactor for eIF4A but also might function independently of eIF4A. Ribosome profiling of mutants lacking eIF4B or with impaired eIF4A or Ded1 activity revealed that eliminating eIF4B reduces the relative translational efficiencies of many more genes than does inactivation of eIF4A, despite comparable reductions in bulk translation, and few genes display unusually strong requirements for both factors. However, either eliminating eIF4B or inactivating eIF4A preferentially impacts mRNAs with longer, more structured 5′ untranslated regions (UTRs). These findings reveal an eIF4A-independent role for eIF4B in addition to its function as eIF4A cofactor in promoting PIC attachment or scanning on structured mRNAs. eIF4B, eIF4A, and Ded1 mutations also preferentially impair translation of longer mRNAs in a fashion mitigated by the ability to form closed-loop messenger ribonucleoprotein particles (mRNPs) via eIF4F–poly(A)-binding protein 1 (Pab1) association, suggesting cooperation between closed-loop assembly and eIF4B/helicase functions. Remarkably, depleting eukaryotic translation initiation factor 4G (eIF4G), the scaffold subunit of eukaryotic translation initiation factor 4F (eIF4F), preferentially impacts short mRNAs with strong closed-loop potential and unstructured 5′ UTRs, exactly the opposite features associated with hyperdependence on the eIF4B/helicases. We propose that short, highly efficient mRNAs preferentially depend on the stimulatory effects of eIF4G-dependent closed-loop assembly. PMID:27601676

  13. Phosphodiesterase 4B negatively regulates endotoxin-activated interleukin-1 receptor antagonist responses in macrophages

    PubMed Central

    Yang, Jing-Xing; Hsieh, Kou-Chou; Chen, Yi-Ling; Lee, Chien-Kuo; Conti, Marco; Chuang, Tsung-Hsien; Wu, Chin-Pyng; Jin, S.-L. Catherine

    2017-01-01

    Activation of TLR4 by lipopolysaccharide (LPS) induces both pro-inflammatory and anti-inflammatory cytokine production in macrophages. Type 4 phosphodiesterases (PDE4) are key cAMP-hydrolyzing enzymes, and PDE4 inhibitors are considered as immunosuppressors to various inflammatory responses. We demonstrate here that PDE4 inhibitors enhance the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1Ra) secretion in LPS-activated mouse peritoneal macrophages, and this response was regulated at the transcriptional level rather than an increased IL-1Ra mRNA stability. Studies with PDE4-deficient macrophages revealed that the IL-1Ra upregulation elicited by LPS alone is PKA-independent, whereas the rolipram-enhanced response was mediated by inhibition of only PDE4B, one of the three PDE4 isoforms expressed in macrophages, and it requires PKA but not Epac activity. However, both pathways activate CREB to induce IL-1Ra expression. PDE4B ablation also promoted STAT3 phosphorylation (Tyr705) to LPS stimulation, but this STAT3 activation is not entirely responsible for the IL-1Ra upregulation in PDE4B-deficient macrophages. In a model of LPS-induced sepsis, only PDE4B-deficient mice displayed an increased circulating IL-1Ra, suggesting a protective role of PDE4B inactivation in vivo. These findings demonstrate that PDE4B negatively modulates anti-inflammatory cytokine expression in innate immune cells, and selectively targeting PDE4B should retain the therapeutic benefits of nonselective PDE4 inhibitors. PMID:28383060

  14. The higher level of complexity of K-Ras4B activation at the membrane

    PubMed Central

    Jang, Hyunbum; Banerjee, Avik; Chavan, Tanmay S.; Lu, Shaoyong; Zhang, Jian; Gaponenko, Vadim; Nussinov, Ruth

    2016-01-01

    Is nucleotide exchange sufficient to activate K-Ras4B? To signal, oncogenic rat sarcoma (Ras) anchors in the membrane and recruits effectors by exposing its effector lobe. With the use of NMR and molecular dynamics (MD) simulations, we observed that in solution, farnesylated guanosine 5′-diphosphate (GDP)-bound K-Ras4B is predominantly autoinhibited by its hypervariable region (HVR), whereas the GTP-bound state favors an activated, HVR-released state. On the anionic membrane, the catalytic domain adopts multiple orientations, including parallel (∼180°) and perpendicular (∼90°) alignments of the allosteric helices, with respect to the membrane surface direction. In the autoinhibited state, the HVR is sandwiched between the effector lobe and the membrane; in the active state, with membrane-anchored farnesyl and unrestrained HVR, the catalytic domain fluctuates reinlessly, exposing its effector-binding site. Dimerization and clustering can reduce the fluctuations. This achieves preorganized, productive conformations. Notably, we also observe HVR-autoinhibited K-Ras4B-GTP states, with GDP-bound-like orientations of the helices. Thus, we propose that the GDP/GTP exchange may not be sufficient for activation; instead, our results suggest that the GDP/GTP exchange, HVR sequestration, farnesyl insertion, and orientation/localization of the catalytic domain at the membrane conjointly determine the active or inactive state of K-Ras4B. Importantly, K-Ras4B-GTP can exist in active and inactive states; on its own, GTP binding may not compel K-Ras4B activation.—Jang, H., Banerjee, A., Chavan, T. S, Lu, S., Zhang, J., Gaponenko, V., Nussinov, R. The higher level of complexity of K-Ras4B activation at the membrane. PMID:26718888

  15. Past to Present: Undergrowth with Two Figures

    ERIC Educational Resources Information Center

    School Arts: The Art Education Magazine for Teachers, 2004

    2004-01-01

    This brief article describes the historical, cultural, and artistic elements of Vincent van Gogh's oil on canvas "Undergrowth with Two Figures" of 1980. The article concludes with questions for students to consider in relation to these aspects of the painting.

  16. Rhetoric Denuded and Redressed: Figs and Figures.

    ERIC Educational Resources Information Center

    Poulakos, John; Whitson, Steve

    1995-01-01

    Replies to an article in this issue that responds to an earlier article by these authors. Replies aesthetically in aphorisms, subsuming philosophical argument within a vortex of figuration and thus troping the knowledge drive while privileging "doxa" over "episteme." (SR)

  17. Comparison of the Pharmacological Profiles of Selective PDE4B and PDE4D Inhibitors in the Central Nervous System

    PubMed Central

    Zhang, Chong; Xu, Ying; Zhang, Han-Ting; Gurney, Mark E.; O’Donnell, James M.

    2017-01-01

    Inhibition of cyclic AMP (cAMP)-specific phosphodiesterase 4 (PDE4) has been proposed as a potential treatment for a series of neuropsychological conditions such as depression, anxiety and memory loss. However, the specific involvement of each of the PDE4 subtypes (PDE4A, 4B and 4C) in different categories of behavior has yet to be elucidated. In the present study, we compared the possible pharmacological effects of PDE4B and PDE4D selective inhibitors, A-33 and D159687, in mediating neurological function in mice. Both compounds were equally potent in stimulating cAMP signaling in the mouse hippocampal cell line HT-22 leading to an increase in CREB phosphorylation. In contrast, A-33 and D159687 displayed distinct neuropharmacological effects in mouse behavioral tests. A-33 has an antidepressant-like profile as indicated by reduced immobility time in the forced swim and tail suspension tasks, as well as reduced latency to feed in the novelty suppressed feeding test. D159687, on the other hand, had a procognitive profile as it improved memory in the novel object recognition test but had no antidepressant or anxiolytic benefit. The present data suggests that inhibitors targeting specific subtypes of PDE4 may exhibit differential pharmacological effects and aid a more efficient pharmacotherapy towards neuropsychological conditions. PMID:28054669

  18. Evolution of the Significant Figure Rules

    NASA Astrophysics Data System (ADS)

    Carter, Ashley R.

    2013-09-01

    Today, almost all introductory physics textbooks include standardized "rules" on how to find the number of significant figures in a calculated value. And yet, 30 years ago these rules were almost nonexistent. Whyhave we increased the role of significant figures in introductory classes, and should we continue this trend? A look back at the evolution of significant figures over the last 300 years, from Newton to Millikan to modern authors, sheds some light on their purpose moving forward. While there is much discussion for and against their use, especially in chemistry, a review of earlier versions of the rules suggests that we have lost some items of value, most notably, a significant figure rule for angles. In addition, we have lost the emphasis that the significant figure rules were designed to calculate an approximate (not exact) precision. Now that the significant figure rules are ingrained into our introductory physics sequence, we would be wise to reiterate that these are just general "rules of thumb."

  19. Ion beam figuring of small optical components

    NASA Astrophysics Data System (ADS)

    Drueding, Thomas W.; Fawcett, Steven C.; Wilson, Scott R.; Bifano, Thomas G.

    1995-12-01

    Ion beam figuring provides a highly deterministic method for the final precision figuring of optical components with advantages over conventional methods. The process involves bombarding a component with a stable beam of accelerated particles that selectively removes material from the surface. Figure corrections are achieved by rastering the fixed-current beam across the workplace at appropriate, time-varying velocities. Unlike conventional methods, ion figuring is a noncontact technique and thus avoids such problems as edge rolloff effects, tool wear, and force loading of the workpiece. This work is directed toward the development of the precision ion machining system at NASA's Marshall Space Flight Center. This system is designed for processing small (approximately equals 10-cm diam) optical components. Initial experiments were successful in figuring 8-cm-diam fused silica and chemical-vapor-deposited SiC samples. The experiments, procedures, and results of figuring the sample workpieces to shallow spherical, parabolic (concave and convex), and non-axially-symmetric shapes are discussed. Several difficulties and limitations encountered with the current system are discussed. The use of a 1-cm aperture for making finer corrections on optical components is also reported.

  20. Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis

    PubMed Central

    Cabrera, Sandra; Maciel, Mariana; Herrera, Iliana; Nava, Teresa; Vergara, Fabián; Gaxiola, Miguel; López-Otín, Carlos; Selman, Moisés; Pardo, Annie

    2015-01-01

    Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of autophagy in lung fibrosis is still undefined. In this study, we show for the first time, how autophagy disruption contributes to bleomycin-induced lung fibrosis in vivo using an Atg4b-deficient mouse as a model. Atg4b-deficient mice displayed a significantly higher inflammatory response at 7 d after bleomycin treatment associated with increased neutrophilic infiltration and significant alterations in proinflammatory cytokines. Likewise, we found that Atg4b disruption resulted in augmented apoptosis affecting predominantly alveolar and bronchiolar epithelial cells. At 28 d post-bleomycin instillation Atg4b-deficient mice exhibited more extensive and severe fibrosis with increased collagen accumulation and deregulated extracellular matrix-related gene expression. Together, our findings indicate that the ATG4B protease and autophagy play a crucial role protecting epithelial cells against bleomycin-induced stress and apoptosis, and in the regulation of the inflammatory and fibrotic responses. PMID:25906080

  1. Essential role for the ATG4B protease and autophagy in bleomycin-induced pulmonary fibrosis.

    PubMed

    Cabrera, Sandra; Maciel, Mariana; Herrera, Iliana; Nava, Teresa; Vergara, Fabián; Gaxiola, Miguel; López-Otín, Carlos; Selman, Moisés; Pardo, Annie

    2015-04-03

    Autophagy is a critical cellular homeostatic process that controls the turnover of damaged organelles and proteins. Impaired autophagic activity is involved in a number of diseases, including idiopathic pulmonary fibrosis suggesting that altered autophagy may contribute to fibrogenesis. However, the specific role of autophagy in lung fibrosis is still undefined. In this study, we show for the first time, how autophagy disruption contributes to bleomycin-induced lung fibrosis in vivo using an Atg4b-deficient mouse as a model. Atg4b-deficient mice displayed a significantly higher inflammatory response at 7 d after bleomycin treatment associated with increased neutrophilic infiltration and significant alterations in proinflammatory cytokines. Likewise, we found that Atg4b disruption resulted in augmented apoptosis affecting predominantly alveolar and bronchiolar epithelial cells. At 28 d post-bleomycin instillation Atg4b-deficient mice exhibited more extensive and severe fibrosis with increased collagen accumulation and deregulated extracellular matrix-related gene expression. Together, our findings indicate that the ATG4B protease and autophagy play a crucial role protecting epithelial cells against bleomycin-induced stress and apoptosis, and in the regulation of the inflammatory and fibrotic responses.

  2. Discover natural compounds as potential phosphodiesterase-4B inhibitors via computational approaches.

    PubMed

    Li, Jing; Zhou, Nan; Liu, Wen; Li, Jianzong; Feng, Yu; Wang, Xiaoyun; Wu, Chuanfang; Bao, Jinku

    2016-05-01

    cAMP, intracellular cyclic adenosine monophosphate, is a ubiquitous second messenger that plays a key role in many physiological processes. PDE4B which can reduce the cAMP level by hydrolyzing cAMP to 5'-AMP has become a therapeutic target for the treatment of human diseases such as respiratory disorders, inflammation diseases, neurological and psychiatric disorders. However, the use of currently available PDE4B inhibitors is restricted due to serious side effects caused by targeting PDE4D. Hence, we are attempting to find out subfamily-selective PDE4B inhibitors from natural products, using computer-aided approaches such as virtual screening, docking, and molecular dynamics simulation. Finally, four potential PDE4B-selective inhibitors (ZINC67912770, ZINC67912780, ZINC72320169, and ZINC28882432) were found. Compared to the reference drug (roflumilast), they scored better during the virtual screening process. Binding free energy for them was -317.51, -239.44, -215.52, and -165.77 kJ/mol, better than -129.05 kJ/mol of roflumilast. The pharmacophore model of the four candidate inhibitors comprised six features, including one hydrogen bond donor, four hydrogen bond acceptors, and one aromatic ring feature. It is expected that our study will pave the way for the design of potent PDE4B-selective inhibitors of new drugs to treat a wide variety of diseases such as asthma, COPD, psoriasis, depression, etc.

  3. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors.

    PubMed

    Akin, Debra; Wang, S Keisin; Habibzadegah-Tari, Pouran; Law, Brian; Ostrov, David; Li, Min; Yin, Xiao-Ming; Kim, Jae-Sung; Horenstein, Nicole; Dunn, William A

    2014-01-01

    Autophagy has been implicated in the progression and chemoresistance of various cancers. In this study, we have shown that osteosarcoma Saos-2 cells lacking ATG4B, a cysteine proteinase that activates LC3B, are defective in autophagy and fail to form tumors in mouse models. By combining in silico docking with in vitro and cell-based assays, we identified small compounds that suppressed starvation-induced protein degradation, LC3B lipidation, and formation of autophagic vacuoles. NSC185058 effectively inhibited ATG4B activity in vitro and in cells while having no effect on MTOR and PtdIns3K activities. In addition, this ATG4B antagonist had a negative impact on the development of Saos-2 osteosarcoma tumors in vivo. We concluded that tumor suppression was due to a reduction in ATG4B activity, since we found autophagy suppressed within treated tumors and the compound had no effects on oncogenic protein kinases. Our findings demonstrate that ATG4B is a suitable anti-autophagy target and a promising therapeutic target to treat osteosarcoma.

  4. A novel ATG4B antagonist inhibits autophagy and has a negative impact on osteosarcoma tumors

    PubMed Central

    Akin, Debra; Wang, S Keisin; Habibzadegah-Tari, Pouran; Law, Brian; Ostrov, David; Li, Min; Yin, Xiao-Ming; Kim, Jae-Sung; Horenstein, Nicole; Dunn, William A

    2014-01-01

    Autophagy has been implicated in the progression and chemoresistance of various cancers. In this study, we have shown that osteosarcoma Saos-2 cells lacking ATG4B, a cysteine proteinase that activates LC3B, are defective in autophagy and fail to form tumors in mouse models. By combining in silico docking with in vitro and cell-based assays, we identified small compounds that suppressed starvation-induced protein degradation, LC3B lipidation, and formation of autophagic vacuoles. NSC185058 effectively inhibited ATG4B activity in vitro and in cells while having no effect on MTOR and PtdIns3K activities. In addition, this ATG4B antagonist had a negative impact on the development of Saos-2 osteosarcoma tumors in vivo. We concluded that tumor suppression was due to a reduction in ATG4B activity, since we found autophagy suppressed within treated tumors and the compound had no effects on oncogenic protein kinases. Our findings demonstrate that ATG4B is a suitable anti-autophagy target and a promising therapeutic target to treat osteosarcoma. PMID:25483883

  5. Wetting of microstructured alumina fabricated by epitaxial growth of Al4B2O9 whiskers

    NASA Astrophysics Data System (ADS)

    Wang, Yifeng; Feng, Jicai; Chen, Zhe; Song, Xiaoguo; Cao, Jian

    2015-12-01

    Topographical microstructures were fabricated on alumina by epitaxial growth of Al4B2O9 whiskers in air. The products were characterized via scanning electron microscopy, transmission electron microscopy, and X-ray diffraction. The whiskers were found to grow along the [0 0 1] crystallographic direction, and the lattice mismatch between Al2O3 and Al4B2O9 was determined to be 0.03%. The wetting of the Al4B2O9-whisker-coated surfaces by Ag-36.7Cu-8.0Ti at.% alloy was studied. The time needed to reach the equilibrium stage reduced as the temperature increased, and the final contact angle for liquid alloy on the rough surface was 27° at 880 °C. The wetting dynamics of the whiskers coated surfaces was investigated. After wetting, a whisker-interconnected region was formed between alumina and the alloy.

  6. Alternative pathways for association and dissociation of the calmodulin-binding domain of plasma membrane Ca(2+)-ATPase isoform 4b (PMCA4b).

    PubMed

    Penniston, John T; Caride, Ariel J; Strehler, Emanuel E

    2012-08-24

    The calmodulin (CaM)-binding domain of isoform 4b of the plasma membrane Ca(2+) -ATPase (PMCA) pump is represented by peptide C28. CaM binds to either PMCA or C28 by a mechanism in which the primary anchor residue Trp-1093 binds to the C-terminal lobe of the extended CaM molecule, followed by collapse of CaM with the N-terminal lobe binding to the secondary anchor Phe-1110 (Juranic, N., Atanasova, E., Filoteo, A. G., Macura, S., Prendergast, F. G., Penniston, J. T., and Strehler, E. E. (2010) J. Biol. Chem. 285, 4015-4024). This is a relatively rapid reaction, with an apparent half-time of ~1 s. The dissociation of CaM from PMCA4b or C28 is much slower, with an overall half-time of ~10 min. Using targeted molecular dynamics, we now show that dissociation of Ca(2+)-CaM from C28 may occur by a pathway in which Trp-1093, although deeply embedded in a pocket in the C-terminal lobe of CaM, leaves first. The dissociation begins by relatively rapid release of Trp-1093, followed by very slow release of Phe-1110, removal of C28, and return of CaM to its conformation in the free state. Fluorescence measurements and molecular dynamics calculations concur in showing that this alternative path of release of the PMCA4b CaM-binding domain is quite different from that of binding. The intermediate of dissociation with exposed Trp-1093 has a long lifetime (minutes) and may keep the PMCA primed for activation.

  7. Identification of New ATG4B Inhibitors Based on a Novel High-Throughput Screening Platform.

    PubMed

    Xu, Danqing; Xu, Zhiheng; Han, Li; Liu, Cheng; Zhou, Zheng; Qiu, Zongxing; Lin, Xianfeng; Tang, Guozhi; Shen, Hong; Aebi, Johannes; Riemer, Claus; Kuhn, Bernd; Stahl, Martin; Mark, David; Qin, Ning; Ding, Haiyuan

    2017-04-01

    Autophagy is an evolutionarily conserved homeostasis process through which aggregated proteins or damaged organelles are enveloped in a double-membrane structure called an autophagosome and then digested in a lysosome-dependent manner. Growing evidence suggests that malfunction of autophagy contributes to the pathogenesis of a variety of diseases, including cancer, viral infection, and neurodegeneration. However, autophagy is a complicated process, and understanding of the relevance of autophagy to disease is limited by lack of specific and potent autophagy modulators. ATG4B, a Cys-protease that cleaves ATG8 family proteins, such as LC3B, is a key protein in autophagosome formation and maturation process. A novel time-resolved fluorescence resonance energy transfer (TR-FRET) assay measuring protease activity of ATG4B was developed, validated, and adapted into a high-throughput screening (HTS) format. HTS was then conducted with a Roche focus library of 57,000 compounds. After hit confirmation and a counterscreen to filter out fluorescence interference compounds, 267 hits were confirmed, constituting a hit rate of 0.49%. Furthermore, among 65 hits with an IC50 < 50 µM, one compound mimics the LC3 peptide substrate (-TFG-). Chemistry modification based on this particular hit gave preliminary structure activity relationship (SAR) resulting in a compound with a 10-fold increase in potency. This compound forms a stable covalent bond with Cys74 of ATG4B in a 1:1 ratio as demonstrated by liquid chromatography/tandem mass spectrometry (LC/MS/MS). Furthermore, this compound displayed cellular ATG4B inhibition activity. Overall, the novel TR-FRET ATG4B protease assay plus counterscreen assay provides a robust platform to identify ATG4B inhibitors, which would help to elucidate the mechanism of the autophagy pathway and offer opportunities for drug discovery.

  8. Wet-Etch Figuring Optical Figuring by Controlled Application of Liquid Etchant

    SciTech Connect

    Britten, J

    2001-02-13

    WET-ETCH FIGURING (WEF) is an automated method of precisely figuring optical materials by the controlled application of aqueous etchant solution. This technology uses surface-tension-gradient-driven flow to confine and stabilize a wetted zone of an etchant solution or other aqueous processing fluid on the surface of an object. This wetted zone can be translated on the surface in a computer-controlled fashion for precise spatial control of the surface reactions occurring (e.g. chemical etching). WEF is particularly suitable for figuring very thin optical materials because it applies no thermal or mechanical stress to the material. Also, because the process is stress-free the workpiece can be monitored during figuring using interferometric metrology, and the measurements obtained can be used to control the figuring process in real-time--something that cannot be done with traditional figuring methods.

  9. Hepatitis C Virus NS4B Can Suppress STING Accumulation To Evade Innate Immune Responses

    PubMed Central

    Wen, Yahong; Shu, Chang; Han, Qingxia; Konan, Kouacou V.; Li, Pingwei; Kao, C. Cheng

    2015-01-01

    ABSTRACT The cyclic dinucleotide 2′,3′-cGAMP can bind the adaptor protein STING (stimulator of interferon [IFN] genes) to activate the production of type I IFNs and proinflammatory cytokines. We found that cGAMP added to the culture medium could suppress the replication of the hepatitis C virus (HCV) genotype 1b strain Con1 subgenomic replicon in human hepatoma cells. Knockdown of STING expression diminished the inhibitory effect on replicon replication, while overexpression of STING enhanced the inhibitory effects of cGAMP. The addition of cGAMP into 1b/Con1 replicon cells significantly increased the expression of type I IFNs and antiviral interferon-stimulated genes. Unexpectedly, replication of the genotype 2a JFH1 replicon and infectious JFH1 virus was less sensitive to the inhibitory effect of cGAMP than was that of 1b/Con1 replicon. Using chimeric replicons, 2a NS4B was identified to confer resistance to cGAMP. Transient expression of 2a NS4B resulted in a pronounced inhibitory effect on STING-mediated beta IFN (IFN-β) reporter activation compared to that of 1b NS4B. 2a NS4B was found to suppress STING accumulation in a dose-dependent manner. The predicted transmembrane domain of 2a NS4B was required to inhibit STING accumulation. These results demonstrate a novel genotype-specific inhibition of the STING-mediated host antiviral immune response. IMPORTANCE The cyclic dinucleotide cGAMP was found to potently inhibit the replication of HCV genotype 1b Con1 replicon but was less effective for the 2a/JFH1 replicon and infectious JFH1 virus. The predicted transmembrane domain in 2a NS4B was shown to be responsible for the decreased sensitivity to cGAMP. The N terminus of NS4B has been reported to suppress STING-mediated signaling by disrupting the interaction of STING and TBK1 and/or MAVS. We show that 2a/JFH1 NS4B has an additional mechanism to evade STING signaling through suppressing STING accumulation. PMID:26468527

  10. Genome-first approach diagnosed Cabezas syndrome via novel CUL4B mutation detection.

    PubMed

    Okamoto, Nobuhiko; Watanabe, Miki; Naruto, Takuya; Matsuda, Keiko; Kohmoto, Tomohiro; Saito, Masako; Masuda, Kiyoshi; Imoto, Issei

    2017-01-01

    Cabezas syndrome is a syndromic form of X-linked intellectual disability primarily characterized by a short stature, hypogonadism and abnormal gait, with other variable features resulting from mutations in the CUL4B gene. Here, we report a clinically undiagnosed 5-year-old male with severe intellectual disability. A genome-first approach using targeted exome sequencing identified a novel nonsense mutation [NM_003588.3:c.2698G>T, p.(Glu900*)] in the last coding exon of CUL4B, thus diagnosing this patient with Cabezas syndrome.

  11. Genome-first approach diagnosed Cabezas syndrome via novel CUL4B mutation detection

    PubMed Central

    Okamoto, Nobuhiko; Watanabe, Miki; Naruto, Takuya; Matsuda, Keiko; Kohmoto, Tomohiro; Saito, Masako; Masuda, Kiyoshi; Imoto, Issei

    2017-01-01

    Cabezas syndrome is a syndromic form of X-linked intellectual disability primarily characterized by a short stature, hypogonadism and abnormal gait, with other variable features resulting from mutations in the CUL4B gene. Here, we report a clinically undiagnosed 5-year-old male with severe intellectual disability. A genome-first approach using targeted exome sequencing identified a novel nonsense mutation [NM_003588.3:c.2698G>T, p.(Glu900*)] in the last coding exon of CUL4B, thus diagnosing this patient with Cabezas syndrome. PMID:28144446

  12. Mutation in the AP4B1 gene cause hereditary spastic paraplegia type 47 (SPG47) .

    PubMed

    Bauer, Peter; Leshinsky-Silver, Esther; Blumkin, Lubov; Schlipf, Nina; Schröder, Christopher; Schicks, Julia; Lev, Dorit; Riess, Olaf; Lerman-Sagie, Tally; Schöls, Ludger

    2012-02-01

    We recently identified a new locus for spastic paraplegia type 47 (SPG47) in a consanguineous Arabic family with two affected siblings with progressive spastic paraparesis,intellectual disability, seizures, periventricular white matter changes and thin corpus callosum. Using exome sequencing, we now identified a novel AP4B1 frameshift mutation (c.664delC) in this family. This mutation was homozygous in both affected siblings and heterozygous in both parents. The mutant allele was absent in 316 Caucasian and 200 ethnically matched control chromosomes. We propose that AP4B1 mutations cause SPG47 and should be considered in early onset spastic paraplegia with intellectual disability.

  13. Overview of the Lockheed Martin Compact Fusion Reactor (CFR) T4B Experiment

    NASA Astrophysics Data System (ADS)

    McGuire, Thomas

    2016-10-01

    The Lockheed Martin Compact Fusion Reactor (CFR) Program endeavors to quickly develop a compact fusion power plant with favorable commercial economics and military utility. The CFR uses a diamagnetic, high beta, magnetically encapsulated, linear ring cusp plasma confinement scheme. The goal of the T4B experiment is to demonstrate a suitable plasma target for heating experiments and to characterize the behavior of plasma sources in the CFR configuration. The design of the T4B experiment will be presented, including discussion of predicted behavior, plasma sources, heating mechanisms, diagnostics suite and relevant numerical modeling. ©2016 Lockheed Martin Corporation. All Rights Reserved.

  14. Loss of p15/Ink4b accompanies tumorigenesis triggered by complex DNA double-strand breaks

    PubMed Central

    Camacho, Cristel V.; Mukherjee, Bipasha; McEllin, Brian; Ding, Liang-Hao; Hu, Burong; Habib, Amyn A.; Xie, Xian-Jin; Nirodi, Chaitanya S.; Saha, Debabrata; Story, Michael D.; Balajee, Adayabalam S.; Bachoo, Robert M.; Boothman, David A.; Burma, Sandeep

    2010-01-01

    DNA double-strand breaks (DSBs) are the most deleterious lesion inflicted by ionizing radiation. Although DSBs are potentially carcinogenic, it is not clear whether complex DSBs that are refractory to repair are more potently tumorigenic compared with simple breaks that can be rapidly repaired, correctly or incorrectly, by mammalian cells. We previously demonstrated that complex DSBs induced by high-linear energy transfer (LET) Fe ions are repaired slowly and incompletely, whereas those induced by low-LET gamma rays are repaired efficiently by mammalian cells. To determine whether Fe-induced DSBs are more potently tumorigenic than gamma ray-induced breaks, we irradiated ‘sensitized’ murine astrocytes that were deficient in Ink4a and Arf tumor suppressors and injected the surviving cells subcutaneously into nude mice. Using this model system, we find that Fe ions are potently tumorigenic, generating tumors with significantly higher frequency and shorter latency compared with tumors generated by gamma rays. Tumor formation by Fe-irradiated cells is accompanied by rampant genomic instability and multiple genomic changes, the most interesting of which is loss of the p15/Ink4b tumor suppressor due to deletion of a chromosomal region harboring the CDKN2A and CDKN2B loci. The additional loss of p15/Ink4b in tumors derived from cells that are already deficient in p16/Ink4a bolsters the hypothesis that p15 plays an important role in tumor suppression, especially in the absence of p16. Indeed, we find that reexpression of p15 in tumor-derived cells significantly attenuates the tumorigenic potential of these cells, indicating that p15 loss may be a critical event in tumorigenesis triggered by complex DSBs. PMID:20663777

  15. Minimizing Uncertainty in Cryogenic Surface Figure Measurement

    NASA Technical Reports Server (NTRS)

    Blake, Peter; Mink, Ronald G.; Chambers, John; Robinson, F. David; Content, David; Davila, Pamela

    2005-01-01

    A new facility at the Goddard Space Flight Center is designed to measure with unusual accuracy the surface figure of mirrors at cryogenic temperatures down to 12 K. The facility is currently configured for spherical mirrors with a radius of curvature (ROC) of 600 mm, and apertures of about 150 mm or less. The goals of the current experiment were to 1) Obtain the best possible estimate of test mirror surface figure, S(x,y) at 87 K and 20 K; 2) Obtain the best estimate of the cryo-change, Delta (x,y): the change in surface figure between room temperature and the two cryo-temperatures; and 3) Determine the uncertainty of these measurements, using the definitions and guidelines of the ISO Guide to the Expression of Uncertainty in Measurement. A silicon mirror was tested, and the cry-change from room temperature to 20K was found to be 3.7 nm rms, with a standard uncertainty of 0.23 nm in the rms statistic. Both the cryo-change figure and the uncertainty are among the lowest such figures yet published. This report describes the facilities, experimental methods, and uncertainty analysis of the measurements.

  16. [Knockdown of Larp4b in Lin(-) cells does not affect the colony forming ability of mouse hematopoietic cells].

    PubMed

    Wang, Xiao-Juan; Pang, Ya-Kun; Cheng, Hui; Dong, Fang; Liang, Hao-Yue; Zhang, Ying-Chi; Wang, Xiao-Min; Xu, Jing; Cheng, Tao; Yuan, Wei-Ping

    2013-06-01

    Larp4b is a member of the LARP family, which can interact with RNA and generally stimulate the translation of mRNA. Abnormal expression of Larp4b can be found in leukemia patients in our previous study. This study was purposed to detect the relative expression of Larp4b mRNA in different subpopulations of mouse hematopoietic cells, to construct lentivirus vector containing shLarp4b targeting mouse gene Larp4b and to explore its effects on mouse Lin(-) cells infected with shLarp4b by lentivirus. SF-LV-shLarP4b-EGFP and control vectors were constructed and two-plasmid lentivirus packing system was used to transfect 293T cells. After 48 h and 72 h, lentivirus SF-LV-shLarp4b-EGFP was harvested and was used to infect Lin(-) cells. After 48 h, EGFP(+) cells was sorted by flow cytometry (FCM). Meanwhile, semi-quantitative real time-PCR, AnnexinV-PE/7-AAD staining, PI staining and colony forming cell assay (CFC) were performed to determine the expression of Larp4b and its effect on the proliferation of hematopoietic progenitor cells. The results showed that Larp4b was highly expressed in myeloid cells. SF-LV-shLarp4b-EGFP was successfully constructed according to the restriction endonuclease digestion assay. RT-PCR confirmed that Larp4b was efficiently knockdown in mouse Lin(-) cells. The low expression of Larp4b did not affect the colony forming number, the apoptosis and cell cycle of Lin(-) cells. It is concluded that knockdown of Larp4b in mouse Lin(-) cells do not contribute to the colony forming ability and the growth of Lin(-) cells in vitro. This useful knockdown system will be used to study in vivo Larp4b in future.

  17. Software systems for modeling articulated figures

    NASA Technical Reports Server (NTRS)

    Phillips, Cary B.

    1989-01-01

    Research in computer animation and simulation of human task performance requires sophisticated geometric modeling and user interface tools. The software for a research environment should present the programmer with a powerful but flexible substrate of facilities for displaying and manipulating geometric objects, yet insure that future tools have a consistent and friendly user interface. Jack is a system which provides a flexible and extensible programmer and user interface for displaying and manipulating complex geometric figures, particularly human figures in a 3D working environment. It is a basic software framework for high-performance Silicon Graphics IRIS workstations for modeling and manipulating geometric objects in a general but powerful way. It provides a consistent and user-friendly interface across various applications in computer animation and simulation of human task performance. Currently, Jack provides input and control for applications including lighting specification and image rendering, anthropometric modeling, figure positioning, inverse kinematics, dynamic simulation, and keyframe animation.

  18. Intrathecal injection of phosphodiesterase 4B-specific siRNA attenuates neuropathic pain in rats with L5 spinal nerve ligation.

    PubMed

    Ji, Qing; Di, Yan; He, Xiaoyun; Liu, Qingzhen; Liu, Jian; Li, Weiyan; Zhang, Lidong

    2016-02-01

    Phosphodiesterase 4 (PDE4) is an adenosine cyclic 3,5-monophosphate-specific degradative enzyme, which is closely associated with the inflammatory response. Among its four subtypes (A-D), it remains unclear which one exerts suppressive effects on inflammation and reduces neuropathic pain. The present study aimed to examine the modulation of neuroinflammation by PDE4 subtypes in the spinal cord of a rat model of L5 spinal nerve ligation (SNL)-induced neuropathic pain. The expression levels of PDE4A-D were measured in the lumbar spinal cords of naïve rats. The rats were then divided into seven groups: The sham group (sham surgery + saline), the saline group (SNL + saline), the vehicle group (SNL + Lipofectamine® RNAiMAX), the mismatch small interfering (si)RNA group (SNL + mismatch siRNA), the PDE4A-siRNA group (SNL + PDE4A-siRNA), the PDE4B-siRNA group (SNL + PDE4B-siRNA) and the PDE4D-siRNA group (SNL + PDE4D-siRNA). In order to determine behavioral changes, mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were recorded. The mRNA and protein expression levels of PDE4s were also detected. Furthermore, the association between behavioral changes and individual subtypes of PDE4 were studied following intrathecal administration of PDE4A, B and D-specific siRNA. The expression levels of protein kinases, including phosphorylated-extracellular signal-regulated kinases (p-ERK), and inflammatory cytokines were measured, in order to explore the underlying mechanisms. Subtypes A, B and D, but not C, were detected in the naïve rats. After SNL, both MWT and TWL were reduced. The mRNA and protein expression levels of PDE4A, B and D were significantly upregulated after 2, 4, 6 and 8 days of SNL. Subtype-specific siRNA significantly suppressed the elevated expression levels; however, only rats treated with PDE4B siRNA exhibited improved MWT and TWL. Further analysis of the PDE4B siRNA-treated rats demonstrated that 8 days after SNL, the intensity of p

  19. Identification of an NTPase motif in classical swine fever virus NS4B protein

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Classical swine fever (CSF) is a highly contagious and often fatal disease of swine caused by CSF virus (CSFV), a positive sense single-stranded RNA virus in the genus Pestivirus of the Flaviviridae family. Here, we have identified, within CSFV non-structural (NS) protein NS4B, conserved sequence el...

  20. Identification of immunogenic MAGED4B peptides for vaccine development in oral cancer immunotherapy.

    PubMed

    Lim, Kue Peng; Chun, Nicole Ai Leng; Gan, Chai Phei; Teo, Soo-Hwang; Rahman, Zainal Ariff Abdul; Abraham, Mannil Thomas; Zain, Rosnah Binti; Ponniah, Sathibalan; Cheong, Sok Ching

    2014-01-01

    The ever-increasing number of tumor-associated antigens has provided a major stimulus for the development of therapeutic peptides vaccines. Tumor-associated peptides can induce high immune response rates and have been developed as vaccines for several types of solid tumors, and many are at various stages of clinical testing. MAGED4B, a melanoma antigen, is overexpressed in oral squamous cell carcinoma (OSCC) and this expression promotes proliferation and cell migration. In this study, we have identified 9 short peptides derived from MAGED4B protein that are restricted in binding to the HLA subtypes common in the Asian population (HLA-A2, A11, and A24). The peptides had good binding affinity with the MHC-Class I molecules and stimulated ex-vivo IFN-gamma and Granzyme-B production in blood samples from OSCC patients, suggesting that they are immunogenic. Further, T cells stimulated with peptide-pulsed dendritic cells showed enhanced T-cell cytotoxic activity against MAGED4B-overexpressing OSCC cell lines. In summary, we have identified MAGED4B peptides that induce anti-tumor immune responses advocating that they could be further developed as vaccine candidates for the treatment of OSCC.

  1. 16 CFR 1508.5 - Component spacing test method for § 1508.4(b).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Component spacing test method for § 1508.4(b). 1508.5 Section 1508.5 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS § 1508.5 Component spacing test method...

  2. 20. FOUR 4B17Gs BEING CONVERTED TO F9Cs. Photographic copy of ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    20. FOUR 4B-17Gs BEING CONVERTED TO F-9Cs. Photographic copy of historic photograph. Jan.-June 1947 OAMA (original print located at Ogden Air Logistics Center, Hill Air Force Base, Utah). Photographer unknown. - Hill Field, Airplane Repair Hangars No. 1-No. 4, 5875 Southgate Avenue, Layton, Davis County, UT

  3. PSD-95 mediates membrane clustering of the human plasma membrane Ca2+ pump isoform 4b.

    PubMed

    Padányi, Rita; Pászty, Katalin; Strehler, Emanuel E; Enyedi, Agnes

    2009-06-01

    Besides the control of global calcium changes, specific plasma membrane calcium ATPase (PMCA) isoforms are involved in the regulation of local calcium signals. Although local calcium signaling requires the confinement of signaling molecules into microdomains, little is known about the specific organization of PMCA molecules within the plasma membrane. Here we show that co-expression with the postsynaptic density-95 (PSD-95) scaffolding protein increased the plasma membrane expression of PMCA4b and redistributed the pump into clusters. The clustering of PMCA4b was fully dependent on the presence of its PDZ-binding sequence. Using the fluorescence recovery after photobleaching (FRAP) technique, we show that the lateral membrane mobility of the clustered PMCA4b is significantly lower than that of the non-clustered molecules. Disruption of the actin-based cytoskeleton by cytochalasin D resulted in increased cluster size. Our results suggest that PSD-95 promotes the formation of high-density PMCA4b microdomains in the plasma membrane and that the membrane cytoskeleton plays an important role in the regulation of this process.

  4. 75 FR 54153 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-03

    ... Recommendation of Pharmacopoeial Texts for Use in the International Conference on Harmonisation Regions; Annex 11... guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the ICH Regions... Electrophoresis General Chapter harmonized text from each of the three pharmacopoeias (United States,...

  5. 75 FR 18509 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-12

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... Texts for Use in the ICH Regions; Annex 10: Polyacrylamide Gel Electrophoresis General Chapter.'' The... ICH Q4B evaluation of the Polyacrylamide Gel Electrophoresis General Chapter harmonized text from...

  6. 75 FR 17148 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-05

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... Dissolution Test General Chapter harmonized text from each of the three pharmacopoeias (United...

  7. 75 FR 53973 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-02

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... Sieving General Chapter harmonized text from each of the three pharmacopoeias (United States,...

  8. 75 FR 17147 - International Conference on Harmonisation; Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-05

    ... Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the... Friability General Chapter harmonized text from each of the three pharmacopoeias (United States,...

  9. DISC1, PDE4B, and NDE1 at the centrosome and synapse

    SciTech Connect

    Bradshaw, Nicholas J.; Ogawa, Fumiaki; Antolin-Fontes, Beatriz; Chubb, Jennifer E.; Carlyle, Becky C.; Christie, Sheila; Claessens, Antoine; Porteous, David J.; Millar, J. Kirsty

    2008-12-26

    Disrupted-In-Schizophrenia 1 (DISC1) is a risk factor for schizophrenia and other major mental illnesses. Its protein binding partners include the Nuclear Distribution Factor E Homologs (NDE1 and NDEL1), LIS1, and phosphodiesterases 4B and 4D (PDE4B and PDE4D). We demonstrate that NDE1, NDEL1 and LIS1, together with their binding partner dynein, associate with DISC1, PDE4B and PDE4D within the cell, and provide evidence that this complex is present at the centrosome. LIS1 and NDEL1 have been previously suggested to be synaptic, and we now demonstrate localisation of DISC1, NDE1, and PDE4B at synapses in cultured neurons. NDE1 is phosphorylated by cAMP-dependant Protein Kinase A (PKA), whose activity is, in turn, regulated by the cAMP hydrolysis activity of phosphodiesterases, including PDE4. We propose that DISC1 acts as an assembly scaffold for all of these proteins and that the NDE1/NDEL1/LIS1/dynein complex is modulated by cAMP levels via PKA and PDE4.

  10. [Figures of anima in the Odyssey].

    PubMed

    Meneghello, Mauro

    2012-01-01

    Feminine characters in the Odyssey show different aspects of the archetype: Mother and Anima (C.G. Jung). From an Analytical Psychology perspective the encounters of Odysseus with goddesses: Circe, Calypso, Ino are looked at as different and successive stages of the hero's way into the inconscious, who shows himself in feminine figures, being masculine the consciousness of the hero. Nausicaa is a new, nearly-human figure of Anima who appears after the symbolic death of Odysseus and leads him to the royal couple Alcinous-Arete: in front of them all he finds his new, reborn, personality by creating and narrating his own myth.

  11. Metrics of Justice. A Sundial's Nomological Figuration.

    PubMed

    Behrmann, Carolin

    2015-01-01

    This paper examines a polyhedral dial from the British Museum made by the instrument maker Ulrich Schniep, and discusses the status of multifunctional scientific instruments. It discerns a multifaceted iconic meaning considering different dimensions such as scientific functionality (astronomy), the complex allegorical figure of Justice (iconography), and the representation of the sovereign (politics), the court and the Kunstkammer of Albrecht v of Bavaria. As a numen mixtum the figure of "Justicia" touches different fields that go far beyond pure astronomical measurement and represents the power of the ruler as well as the rules of economic justice.

  12. 50 CFR Figure 1 to Part 640 - Figure 1 to Part 640

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 10 2011-10-01 2011-10-01 false Figure 1 to Part 640 1 Figure 1 to Part 640 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Pt....

  13. 50 CFR Figure 1 to Part 640 - Figure 1 to Part 640

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 12 2012-10-01 2012-10-01 false Figure 1 to Part 640 1 Figure 1 to Part 640 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Pt....

  14. 50 CFR Figure 1 to Part 640 - Figure 1 to Part 640

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 8 2010-10-01 2010-10-01 false Figure 1 to Part 640 1 Figure 1 to Part 640 Wildlife and Fisheries FISHERY CONSERVATION AND MANAGEMENT, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE SPINY LOBSTER FISHERY OF THE GULF OF MEXICO AND SOUTH ATLANTIC Pt....

  15. The Offerings of Fringe Figures and Migrants

    ERIC Educational Resources Information Center

    Engels-Schwarzpaul, A.-Chr.

    2015-01-01

    "The Western tradition", as passe-partout, includes fringe figures, émigrés and migrants. Rather than looking to resources at the core of the Western tradition to overcome its own blindnesses, I am more interested in its gaps and peripheries, where other thoughts and renegade knowledges take hold. It is in the contact zones with…

  16. Cylindrical optic figuring dwell time optimization

    NASA Astrophysics Data System (ADS)

    Waluschka, Eugene

    2000-11-01

    The Constellation-X, grazing incidence, x-ray telescope may be fabricated from replicated segments. A series of mandrels will serve as the 'masters' in the replication processes. Diamond turning (milling) followed by abrasive figuring followed by a super polishing are the steps currently envisioned in making just one (of many) mandrel. The abrasive figuring of a mandrel is accomplished by moving a grinding tool along a helical path on this almost cylindrical surface. The measurement of the surface is, however, performed along 'axial' scan lines which intercept this helical path. This approach to figuring and measuring permits a relatively simple scheme to be implemented for the determination of the optimal dwell times of the figuring tool. These optimal dwell times are determined by a deconvolution which approaches the problem in a linear programming context and uses the Simplex Method. The approach maximizes the amount of material removed at any point subject to inequality constraints. The effects of using these 'optimum' dwell times is to significantly improve the tools effectiveness at removing the higher spatial frequencies while staying (strictly) within the bounds and constraints imposed by the hardware. In addition, the ringing at the edges of the optic, frequently present in deconvolution problems, is completely eliminated.

  17. Go Figure. HEADJAM. Teaching Guide [and Videotape].

    ERIC Educational Resources Information Center

    MATHCOUNTS Foundation, Alexandria, VA.

    The HeadJam series is comprised of six programs exploring mathematics, science, and critical thinking skills. It is an award-winning, educational videotape series for middle school students that explores multi-disciplinary skills in a highly entertaining way. The teacher's guide and 22-minute video, "Go Figure," demonstrate how math is used in the…

  18. Noise figure of hybrid optical parametric amplifiers.

    PubMed

    Marhic, Michel E

    2012-12-17

    Following a fiber optical parametric amplifier, used as a wavelength converter or in the phase-sensitive mode, by a phase-insensitive amplifier (PIA) can significantly reduce four-wave mixing between signals in broadband systems. We derive the quantum mechanical noise figures (NF) for these two hybrid configurations, and show that adding the PIA only leads to a moderate increase in NF.

  19. Computerized Testing: The Hidden Figures Test.

    ERIC Educational Resources Information Center

    Jacobs, Ronald L.; And Others

    1985-01-01

    This study adapted the Hidden Figures Test for use on PLATO and determined the reliability of the computerized version compared to the paper and pencil version. Results indicate the test was successfully adapted with some modifications, and it was judged reliable although it may be measuring additional constructs. (MBR)

  20. Human Figure Drawings of Vietnamese Children.

    ERIC Educational Resources Information Center

    Delatte, Joseph G. Jr.

    1978-01-01

    Some characteristics of the human figure drawings of 93 Vietnamese children were investigated. Drawings were scored according to the Goodenough method. Mental age scores were high in relation to chronological age and this result is explained in terms of cultural emphasis on the value of copying well. (SE)

  1. Facts and Figures about Chinese Americans.

    ERIC Educational Resources Information Center

    Association of Chinese Teachers, San Francisco, CA.

    In this brief collection of facts and figures about Chinese Americans, information and data are presented on the geographic location of Chinese in America, the pattern of Chinese immigration to the United States, and income and occupations of Chinese Americans. In addition, a brief chronology of Chinese American history is presented. (Author/AM)

  2. Data Behind the Figures in AAS Journals

    NASA Astrophysics Data System (ADS)

    Biemesderfer, Chris

    2013-01-01

    Substantial amounts of digital data are produced in the scientific enterprise, and much of it is carefully analyzed and processed. Often resulting from a good deal of intellectual effort, many of these highly-processed products are published in the scholarly literature. Many of these data - or more precisely, representations of these data - are committed to the scholarly record in the forms of figures and tables that appear within articles: the AAS journals publish more than 30,000 figures and nearly 10,000 tables each year. For more than a decade, the AAS journals have accepted machine-readable tables that provide the data behind (some of) the tables, and recently the journals have started to encourage the submission of the data behind figures. (See the related poster by Greg Schwarz.) During this time, the journals have been refining techniques for acquiring and managing the digital data that underlie figures and tables. In 2012 the AAS was awarded a grant by the US NSF so that the journals can extend the methods for providing access to these data objects, through a deeper collaboration with the VO and with organizations like DataCite, and by spearheading discussions about the formats and metadata that will best facilitate long-term data management and access. An important component of these activities is educating scientists about the importance and benefits of making such data sets available.

  3. Cultural Impact on Human Figure Drawings.

    ERIC Educational Resources Information Center

    De La Serna, Marcelo; And Others

    1979-01-01

    A human figure drawing instrument was administered to Black children from the Virgin Islands and Georgia and to White children from Mexico. Both cultural and sex differences occurred, influencing the drawings. Black children from different cultures differed from each other on this instrument. (Author/BEF)

  4. 36 CFR Appendix - Figures to Part 1194

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Figures to Part 1194 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY STANDARDS Information, Documentation, and Support Information, documentation, and support. Pt. 1194,...

  5. 36 CFR Appendix - Figures to Part 1192

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 3 2011-07-01 2011-07-01 false Figures to Part 1192 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, similar vehicles and systems. Pt....

  6. 36 CFR Appendix - Figures to Part 1192

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Figures to Part 1192 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD AMERICANS WITH DISABILITIES ACT (ADA) ACCESSIBILITY GUIDELINES FOR TRANSPORTATION VEHICLES Other Vehicles and Systems Trams, similar vehicles and systems. Pt....

  7. 36 CFR Appendix - Figures to Part 1194

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Figures to Part 1194 Parks, Forests, and Public Property ARCHITECTURAL AND TRANSPORTATION BARRIERS COMPLIANCE BOARD ELECTRONIC AND INFORMATION TECHNOLOGY ACCESSIBILITY STANDARDS Information, Documentation, and Support Information, documentation, and support. Pt. 1194,...

  8. T'ang Dynasty Tomb Figure.

    ERIC Educational Resources Information Center

    Selle, Penny

    1988-01-01

    Uses a print of a T'ang Dynasty tomb figure to acquaint grades 10-12 students with the tools needed for developing aesthetic judgement and artistic criticism. Includes background on the artwork and instructional strategies to help students describe the object, analyze the artmaking process, and formulate their own opinions. (GEA)

  9. Fading-Figure Tracing in Williams Syndrome

    ERIC Educational Resources Information Center

    Nagai, Chiyoko; Inui, Toshio; Iwata, Makoto

    2011-01-01

    Williams syndrome (WS) is a neurodevelopmental disorder characterized by severe impairment of visuospatial abilities. Figure-drawing abilities, which are thought to reflect visuospatial abilities, have yet to be fully investigated in WS. The purpose of the present study was to clarify whether drawing abilities differ between WS individuals and…

  10. Participation in the Figured World of Graffiti

    ERIC Educational Resources Information Center

    Valle, Imuris; Weiss, Eduardo

    2010-01-01

    This article is based on ethnographic work with two "crews" of young graffiti artists in southern Mexico City. The crews share certain characteristics with gangs or urban tribes, but more with "communities of practice": they live in the "figured world" of graffiti, a community of practice at the local and global…

  11. The Crystal Structure of Cytochrome P450 4B1 (CYP4B1) Monoxygenase Complexed with Octane Discloses Several Structural Adaptations for ω-Hydroxylation.

    PubMed

    Hsu, Mei-Hui; Baer, Brian R; Rettie, Allan E; Johnson, Eric F

    2017-02-06

    P450 family 4 fatty acid ω-hydroxylases preferentially oxygenate primary C-H bonds over adjacent, energetically favored secondary C-H bonds, but the mechanism explaining this intriguing preference is unclear. To this end, the structure of rabbit P450 4B1 complexed with its substrate octane was determined by X-ray crystallography to define features of the active site that contribute to a preference for ω-hydroxylation. The structure indicated that octane is bound in a narrow active site cavity that limits access of the secondary C-H bond to the reactive intermediate. A highly conserved sequence motif on helix I contributes to positioning the terminal carbon of octane for ω-hydroxylation. Glu-310 of this motif auto-catalytically forms an ester bond with the heme 5-methyl, and the immobilized E310 contributes to substrate positioning. The preference for ω-hydroxylation was decreased in a E310A mutant having a shorter side-chain, but overall rates of metabolism were retained. E310D and E310Q substitutions having longer side-chains exhibit lower overall rates, likely due to higher conformational entropy for these residues, but they retained high preferences for octane ω-hydroxylation. Sequence comparisons indicated that active-site residues constraining octane for ω-hydroxylation are conserved in family 4 P450s. Moreover, the heme 7-propionate is positioned in the active site and provides additional restraints on substrate binding. In conclusion, P450 4B1 exhibits structural adaptations for ω-hydroxylation that include changes in the conformation of the heme and changes in a highly conserved helix I motif that is associated with selective oxygenation of un-activated primary C-H bonds.

  12. Mirror Figuring Techniques of Sir William Herschel

    NASA Astrophysics Data System (ADS)

    Albin, E. F.

    2004-05-01

    Between the years 1773 to 1818, Sir William Herschel constructed dozens of speculum telescope mirrors, with diameters ranging from 6 - 48 inches. Very little, if any, detailed information has ever been published on the specifics of his mirror figuring efforts. The reason for this certainly relates to his desire to closely guard mirror production trade secrets. Upon Herschel's death, all telescope-making documents were passed on to his only son, Sir John Herschel. These materials are now in the possession of the British RAS and primarily consist of: a) a four volume series entitled "Experiments on the Construction of Specula," b) a 129 page treaty called "On the Construction of Specula," and c) a 179 page manuscript entitled "Results of Experiments on the Construction of Mirrors." It is suggested that publication was further delayed and then eventually abandoned due to silver-coated glass mirrors coming into favor. A recent investigation by the author, of the unpublished manuscripts on the construction of specula, suggests that Herschel's mirror figuring techniques did not involve any guess work; in fact, his methods were highly refined -- never leaving to chance the evolution of a spherical surface into the required paraboloid. At the heart of Herschel's figuring techniques were a series of aperture diaphragms (similar to the Couder masks used by modern telescope makers) that were placed over the mirror, which allowed for the precise determination of its curvature at various predefined zones. With this information, Herschel was able to vary his figuring strokes with his polishing tool accordingly. In addition, all mirrors were subsequently "star tested," sometimes with aperture diaphragms in place, allowing for field examination of the mirror's "distinctness" or performance. Double stars and the planet Saturn were favorite targets used to analyze and then correct a mirror's figure.

  13. Development and characterization of a replicon-based phenotypic assay for assessing HCV NS4B from clinical isolates.

    PubMed

    Rajyaguru, Sonal; Yang, Huiling; Martin, Ross; Miller, Michael D; Mo, Hongmei

    2013-11-01

    The hepatitis C virus (HCV) NS4B inhibitors have shown potent inhibition of HCV replication in vitro. To assess the effect of viral diversity on the susceptibility to NS4B inhibitors, genotype (GT)-specific GT1a and GT1b replicon shuttle vectors were designed and created for cloning HCV NS4B genes from clinical isolates. For the GT1b NS4B shuttle vector, the S2204I adaptive mutation was introduced in NS5A to improve replication due to the replacement of the K1846T adaptive mutation in NS4B with NS4B from the clinical isolates. In addition to the adaptive mutations, a newly identified Huh-7 cell line, Huh-7-1C, which is highly permissive for both GT1a and GT1b replication, was used to further enhance the replication levels. HCV NS4B gene from clinical isolates was amplified and inserted into the corresponding GT1a and GT1b modified lab strain chimeric replicons. GT1a and GT1b chimeric replicons expressing diverse NS4B genes from corresponding subtypes of clinical isolates replicated at highly efficient levels for phenotypic analysis. Due to natural variation in their amino acid residues in NS4B, these isolates displayed varying drug susceptibilities to an NS4B inhibitor. In mixed populations with wild-type, the sensitivity of resistance detection of NS4B resistant mutants H94R and V105M was between 20% and 80%. The chimeric shuttle vectors can be used to characterize the activity of antiviral drugs targeting NS4B from diverse natural clinical isolates and aid in the development of novel compounds against HCV NS4B.

  14. Expression of human inducible nitric oxide synthase in a tetrahydrobiopterin (H4B)-deficient cell line: H4B promotes assembly of enzyme subunits into an active dimer.

    PubMed Central

    Tzeng, E; Billiar, T R; Robbins, P D; Loftus, M; Stuehr, D J

    1995-01-01

    Murine inducible nitric oxide (NO) synthase (iNOS) is catalytically active only in dimeric form. Assembly of its purified subunits into a dimer requires H4B. To understand the structure-activity relationships of human iNOS, we constitutively expressed recombinant human iNOS in NIH 3T3 cells by using a retroviral vector. These cells are deficient in de novo H4B biosynthesis and the role of H4B in the expression and assembly of active iNOS in an intact cell system could be studied. In the absence of added H4B, NO synthesis by the cells was minimal, whereas cells grown with supplemental H4B or the H4B precursor sepiapterin generated NO (74.1 and 63.3 nmol of nitrite per 10(6) cells per 24 h, respectively). NO synthesis correlated with an increase in intracellular H4B but no increase in iNOS protein. Instead, an increased percentage of dimeric iNOS was observed, rising from 20% in cytosols from unsupplemented cells to 66% in H4B-supplemented cell cytosols. In all cases, only dimeric iNOS displayed catalytic activity. Cytosols prepared from H4B-deficient cells exhibited little iNOS activity but acquired activity during a 60- to 120-min incubation with H4B, reaching final activities of 60-72 pmol of citrulline per mg of protein per min. Reconstitution of cytosolic NO synthesis activity was associated with conversion of monomers into dimeric iNOS during the incubation. Thus, human iNOS subunits dimerize to form an active enzyme, and H4B plays a critical role in promoting dimerization in intact cells. This reveals a post-translational mechanism by which intracellular H4B can regulate iNOS expression. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 PMID:8524846

  15. Optical and Near-UV Observations of the Transiting Extrasolar Planet TrES-4b

    NASA Astrophysics Data System (ADS)

    Smith, Carter-Thaxton; Turner, J.; Carleton, T.; Crawford, B.; Guvenen, B.; Hardegree-Ullman, K.; Small, L.; Towner, A. P.; Walker-LaFollette, A.; Henz, T.

    2013-01-01

    Using the Steward Observatory 61” Kuiper Telescope, The University of Arizona Astronomy Club conducted photometric observations of the transiting extrasolar planet TrES-4b as part of the Exoplanet Observation Project. Observations were made in the Bessell U, Harris B, and Harris R filters. Initial observations were made in 2009, with follow up observations in 2011. Basic data reduction and photometry was done using IRAF and determination of transit parameters was done using Transit Analysis Package (TAP) and JKTEBOP transit modeling code. We present an updated planetary mass, radius, density, surface gravity, Safronov number, equilibrium temperature, orbital distance, and orbital inclination for TrES-4b. In addition, we also searched for asymmetries between the near-UV and optical light curves. This project, started in spring 2009, has introduced many undergraduate students to research and given them valuable experience with data reduction and observation techniques.

  16. Qatar Exoplanet Survey : Qatar-3b, Qatar-4b, and Qatar-5b

    NASA Astrophysics Data System (ADS)

    Alsubai, Khalid; Mislis, Dimitris; Tsvetanov, Zlatan I.; Latham, David W.; Bieryla, Allyson; Buchhave, Lars A.; Esquerdo, Gilbert A.; Bramich, D. M.; Pyrzas, Stylianos; Vilchez, Nicolas P. E.; Mancini, Luigi; Southworth, John; Evans, Daniel F.; Henning, Thomas; Ciceri, Simona

    2017-04-01

    We report the discovery of Qatar-3b, Qatar-4b, and Qatar-5b, three new transiting planets identified by the Qatar Exoplanet Survey. The three planets belong to the hot Jupiter family, with orbital periods of {P}{{Q}3{{b}}} = 2.50792 days, {P}{{Q}4{{b}}} = 1.80539 days, and {P}{{Q}5{{b}}} = 2.87923 days. Follow-up spectroscopic observations reveal the masses of the planets to be {M}{{Q}3{{b}}} = 4.31 ± 0.47 {M}{{J}}, {M}{{Q}4{{b}}} = 6.10 ± 0.54 {M}{{J}}, and {M}{{Q}5{{b}}} = 4.32 ± 0.18 {M}{{J}}, while model fits to the transit light curves yield radii of {R}{{Q}3{{b}}} = 1.096 ± 0.14 {R}{{J}}, {R}{{Q}4{{b}}} = 1.135 ± 0.11 {R}{{J}}, and {R}{{Q}5{{b}}} = 1.107 ± 0.064 {R}{{J}}. The host stars are low-mass main sequence stars with masses and radii M Q3 = 1.145 ± 0.064 M ⊙, M Q4 = 0.896 ± 0.048 M ⊙, M Q5 = 1.128 ± 0.056 M ⊙ and R Q3 = 1.272 ± 0.14 R ⊙, R Q4 = 0.849 ± 0.063 R ⊙, and R Q5 = 1.076 ± 0.051 R ⊙ for Qatar-3, 4, and 5 respectively. The V magnitudes of the three host stars are V Q3 = 12.88, V Q4 = 13.60, and V Q5 = 12.82. All three new planets can be classified as heavy hot Jupiters (M > 4 M J).

  17. A Novel Benzodiazepine Compound Inhibits Yellow Fever Virus Infection by Specifically Targeting NS4B Protein.

    PubMed

    Guo, Fang; Wu, Shuo; Julander, Justin; Ma, Julia; Zhang, Xuexiang; Kulp, John; Cuconati, Andrea; Block, Timothy M; Du, Yanming; Guo, Ju-Tao; Chang, Jinhong

    2016-09-21

    Although a highly effective vaccine is available, the number of yellow fever cases has increased over the past two decades, which highlights the pressing need for antiviral therapeutics. In a high throughput screening campaign, we identified an acetic acid benzodiazepine (BDAA) compound, which potently inhibits yellow fever virus (YFV). Interestingly, while treatment of YFV infected cultures with 2 μM of BDAA reduced the virion production by greater than 2 logs, the compound is not active against 21 other viruses from 14 different viral families. Selection and genetic analysis of drug resistant viruses revealed that substitution of proline at amino acid 219 (P219) of the nonstructural protein 4B (NS4B) with serine, threonine or alanine confers YFV resistance to BDAA without apparent loss of replication fitness in cultured mammalian cells. However, substitution of P219 with glycine confers BDAA resistance with significant loss of replication ability. Bioinformatics analysis predicts that the P219 localizes at the endoplasmic reticulum lumen side of the fifth putative trans-membrane domain of NS4B and the mutation may render the viral protein incapable of interacting with BDAA. Our studies thus revealed important role and structural basis for NS4B protein in supporting YFV replication. Moreover, in YFV-infected hamsters, oral administration of BDAA protected 90% of the animals from death, significantly reduced viral load by greater than 2 logs and attenuated viral infection-induced liver injury and body weight loss. The encouraging preclinical results thus warrant further development of BDAA or its derivatives as antiviral agents to treat yellow fever.

  18. Molecular docking NS4B of DENV 1-4 with known bioactive phyto-chemicals

    PubMed Central

    Paul, Anubrata; Vibhuti, Arpana; Raj, Samuel

    2016-01-01

    Dengue disease is a global disease that has no effective treatment. The dengue virus (DENV) NS4B is a target for designing specific antivirals due to its importance in viral replication. Medicinal plants have been a savior for dengue virus as they consist of a class of phytochemicals having anti-viral activity and can pose a new approach ofstrong drug against viruses. The present study analyzes the activity of compounds against NS4B of DENV (1-4) serotypes. In this study Catechin, Cianidanol, Epicatechin, Eupatoretin, Glabranin, Laurifolin, DL-Catechin, astherapeutic agents were filtered by using Lipinski rule’s five and the drug-likeness property of these agents were used for assessment of pharmacological properties. The molecular docking results presented the 2-D structures of bioactive complex, which interacted with especially conserved residues of target domains. Interestingly, we find the Catechin, Laurifolin, Cianidanol have highest binding energy against NS4B in DENV-1,2,4 which is evident by the formation of more hydrogen bonds with the amino acid residues at the binding site of the receptor. Our results revealed that the bioactive compound, especially Catechin has significant anti-dengue activities. In addition, this study may be helpful in further experimental investigations. PMID:28149049

  19. DISTRIBUTION OF CH{sub 3}OH IN NGC 1333 IRAS4B

    SciTech Connect

    Sakai, Nami; Yamamoto, Satoshi; Ceccarelli, Cecilia; Bottinelli, Sandrine; Sakai, Takeshi

    2012-07-20

    Distribution of the CH{sub 3}OH (J{sub K} = 2{sub K}-1{sub K}, 96.7 GHz) emission has been investigated toward NGC 1333 IRAS4B, a low-mass Class 0 protostar which harbors a hot corino, with Nobeyama Millimeter Array. The CH{sub 3}OH emission is found to be prominent in the shocked region caused by an impact of the molecular outflow from the protostars. The direction of the outflow which is responsible for the shock seems to be opposite to that of a compact outflow known previously in the CO (J = 2-1), HCN (J = 1-0), H{sub 2}CO (3{sub 12}-2{sub 11}), and CH{sub 3}OH (J{sub K} = 7{sub K}-6{sub K}) emissions, whereas it is the same as that of the faint second outflow found in the H{sub 2}CO emission. This double outflow structure can be interpreted most naturally by the existence of more than two protostars in IRAS4B. On the other hand, a centrally condensed component associated apparently with IRAS4B cannot be recognized in our CH{sub 3}OH observation. Our observation suggests that, in this source, the CH{sub 3}OH (J{sub K} 2{sub K}-1{sub K}) emission preferentially traces the shocked regions rather than the hot corino around the protostar.

  20. HATS-4b: A dense hot Jupiter transiting a super metal-rich G star

    SciTech Connect

    Jordán, Andrés; Brahm, Rafael; Rabus, M.; Suc, V.; Espinoza, N.; Bakos, G. Á.; Penev, K.; Hartman, J. D.; Csubry, Z.; Bhatti, W.; De Val Borro, M.; Bayliss, D.; Zhou, G.; Mancini, L.; Mohler-Fischer, M.; Ciceri, S.; Csák, B.; Henning, T.; Sato, B.; Buchhave, L.; and others

    2014-08-01

    We report the discovery by the HATSouth survey of HATS-4b, an extrasolar planet transiting a V = 13.46 mag G star. HATS-4b has a period of P ≈ 2.5167 days, mass of M{sub p} ≈ 1.32 M {sub Jup}, radius of R{sub p} ≈ 1.02 R {sub Jup}, and density of ρ {sub p} = 1.55 ± 0.16 g cm{sup –3} ≈1.24 ρ{sub Jup}. The host star has a mass of 1.00 M {sub ☉}, a radius of 0.92 R {sub ☉}, and a very high metallicity [Fe/H]=0.43 ± 0.08. HATS-4b is among the densest known planets with masses between 1 and 2 M {sub J} and is thus likely to have a significant content of heavy elements of the order of 75 M {sub ⊕}. In this paper we present the data reduction, radial velocity measurements, and stellar classification techniques adopted by the HATSouth survey for the CORALIE spectrograph. We also detail a technique for simultaneously estimating vsin i and macroturbulence using high resolution spectra.

  1. Inhibition of HCV replication by humanized-single domain transbodies to NS4B.

    PubMed

    Glab-Ampai, Kittirat; Malik, Aijaz Ahmad; Chulanetra, Monrat; Thanongsaksrikul, Jeeraphong; Thueng-In, Kanyarat; Srimanote, Potjanee; Tongtawe, Pongsri; Chaicumpa, Wanpen

    2016-08-05

    NS4B of hepatitis C virus (HCV) initiates membrane web formation, binds RNA and other HCV proteins for viral replication complex (RC) formation, hydrolyses NTP, and inhibits innate anti-viral immunity. Thus, NS4B is an attractive target of a novel anti-HCV agent. In this study, humanized-nanobodies (VHs/VHHs) that bound to recombinant NS4B were produced by means of phage display technology. The nanobodies were linked molecularly to a cell penetrating peptide, penetratin (PEN), for making them cell penetrable (become transbodies). Human hepatic (Huh7) cells transfected with HCV JFH1-RNA that were treated with transbodies from four Escherichia coli clones (PEN-VHH7, PEN-VHH9, PEN-VH33, and PEN-VH43) had significant reduction of HCV RNA amounts in their culture fluids and intracellularly when compared to the transfected cells treated with control transbody and medium alone. The results were supported by the HCV foci assay. The transbody treated-transfected cells also had upregulation of the studied innate cytokine genes, IRF3, IFNβ and IL-28b. The transbodies have high potential for testing further as a novel anti-HCV agent, either alone, adjunct of existing anti-HCV agents/remedies, or in combination with their cognates specific to other HCV enzymes/proteins.

  2. (4R,4aS,4bS,7R,10aR)-4-Hy­droxy-4a,7-dimethyl-2-(propan-2-yl)-1,4,4a,4b,5,6,7,8,10,10a-deca­hydro­phenanthren-1-one

    PubMed Central

    Caracelli, Ignez; Zukerman-Schpector, Julio; Machado, André T. Lousada; Brocksom, Timothy J.; Ferreira, M. Lúcia; Tiekink, Edward R. T.

    2011-01-01

    In the title compound, C19H28O2, the A ring adopts a chair conformation, and each of the B and C rings adopts a distorted half-chair conformation with the methine C atom in the CH2C(H)C(=O) residue, common to both rings, lying 0.6397 (19) and 0.6328 (18) Å out of the approximate plane defined by the remaining five C atoms (r.m.s. deviations = 0.0791 and 0.0901 Å for rings B and C, respectively). Helical supra­molecular chains along the a axis mediated by hy­droxy–carbonyl O—H⋯O hydrogen bonds feature in the crystal packing. PMID:22220138

  3. (4R*,4aS*,4bS*,5R*,10aR*)-4-Hy­droxy-4a,5-dimethyl-2-(propan-2-yl)-1,4,4a,4b,5,6,7,8,10,10a-deca­hydro­phenan­thren-1-one

    PubMed Central

    Caracelli, Ignez; Zukerman-Schpector, Julio; Machado, André T. Lousada; Brocksom, Timothy J.; Ferreira, M. Lúcia; Tiekink, Edward R. T.

    2011-01-01

    In the title compound, C19H28O2, the A ring adopts a chair conformation. Both the B and C rings adopt envelope conformations with the C atoms common to both rings and adjacent to the carbonyl and hydroxyl groups, respectively, lying 0.604 (3) and 0.634 (3) Å out of the mean planes defined by the remaining five C atoms of rings B and C, respectively (r.m.s. deviations = 0.0100 and 0.0157 Å, respectively). The formation of linear supra­molecular C(7) chains along the a axis mediated by hy­droxy-O—H⋯O(carbon­yl) hydrogen bonds is the most prominent feature of the crystal packing. PMID:22199834

  4. Figure correction of multilayer coated optics

    DOEpatents

    Chapman; Henry N. , Taylor; John S.

    2010-02-16

    A process is provided for producing near-perfect optical surfaces, for EUV and soft-x-ray optics. The method involves polishing or otherwise figuring the multilayer coating that has been deposited on an optical substrate, in order to correct for errors in the figure of the substrate and coating. A method such as ion-beam milling is used to remove material from the multilayer coating by an amount that varies in a specified way across the substrate. The phase of the EUV light that is reflected from the multilayer will be affected by the amount of multilayer material removed, but this effect will be reduced by a factor of 1-n as compared with height variations of the substrate, where n is the average refractive index of the multilayer.

  5. Recommended Figures of Merit for Green Monopropellants

    NASA Technical Reports Server (NTRS)

    Marshall. William M.; Deans, Matthew C.

    2013-01-01

    Hydrazine propellant has historically been used as a rocket thruster monopropellant since the mid-1960s. Mission managers are well aware of its characteristics and performance. However, it is a known toxic chemical and a wide effort is underway to reduce and/or eliminate its use worldwide. Several new propellant combinations have been developed in the last few years which tout or promise to provide same or better performance as hydrazine while being "non-toxic" or "green". Yet, there is no consistent definition for what constitutes "non-toxic" or "green", and thus no good figure of merit for which to compare. This paper seeks to review the three major categories of figures of merit, and discusses how they might be used to assess the viability of a propellant.

  6. LETTER TO THE EDITOR: Significant figures

    NASA Astrophysics Data System (ADS)

    Wheeler, David

    2000-05-01

    The interesting article on `University students' conceptions of basic astronomy concepts' by Ricardo Trumper (2000 Phys. Educ. 35 9-15) was spoiled by a lack of attention to detail. The percentages for the student responses were mostly quoted to three figures but the sample size of 76 allows for only two at most. As well as making the article much less `readable', the decimal point in the percentage figure implies a measurement accuracy that is just not there in reality. Sociologists and newspaper reporters have long been guilty of this kind of accidental deception. If we physicists don't set an example in our own journals how can we ever expect it to stop?

  7. Figure and finish of grazing incidence mirrors

    SciTech Connect

    Takacs, P.Z. ); Church, E.L. . Army Armament Research, Development and Engineering Center)

    1989-08-01

    Great improvement has been made in the past several years in the quality of optical components used in synchrotron radiation (SR) beamlines. Most of this progress has been the result of vastly improved metrology techniques and instrumentation permitting rapid and accurate measurement of the surface finish and figure on grazing incidence optics. A significant theoretical effort has linked the actual performance of components used as x-ray wavelengths to their topological properties as measured by surface profiling instruments. Next-generation advanced light sources will require optical components and systems to have sub-arc second surface figure tolerances. This paper will explore the consequences of these requirements in terms of manufacturing tolerances to see if the present manufacturing state-of-the-art is capable of producing the required surfaces. 15 refs., 14 figs., 2 tabs.

  8. High figure of merit thermoelectrics - Theoretical considerations

    NASA Technical Reports Server (NTRS)

    Vining, Cronin B.

    1990-01-01

    The thermoelectric figure of merit of a semiconductor, ZT, can be calculated from a small number of microscopic material parameters, the material composition, the doping level, and the temperature. The functional dependence of ZT on these parameters has been studied for a range of material parameters using a recently developed model which accurately and self-consistently describes the thermoelectric properties of n-type silicon-germanium alloys. ZT values several times larger than current state-of-the-art values of ZT of about 1 are shown to be entirely consistent with existing theory, even using material parameters already observed. A search for materials with much higher figure of merit values therefore remains of interest, in spite of several decades of relatively slow progress in this area.

  9. Adolescent girls' parasocial interactions with media figures.

    PubMed

    Theran, Sally A; Newberg, Emily M; Gleason, Tracy R

    2010-01-01

    We examined aspects of adolescent girls' parasocial interactions in the context of typical development. Parasocial interactions are defined as symbolic, one-sided quasi-interactions between a viewer and a media figure. In total, 107 adolescent girls were examined; 94% reported engaging in parasocial interactions to some degree. Preoccupied attachment style predicted the degree of involvement in and emotional intensity of parasocial interactions. Results suggest that parasocial interactions are characteristic of girls with preoccupied attachment, but are also part of normative development.

  10. Figure-Ground Segmentation Using Factor Graphs.

    PubMed

    Shen, Huiying; Coughlan, James; Ivanchenko, Volodymyr

    2009-06-04

    Foreground-background segmentation has recently been applied [26,12] to the detection and segmentation of specific objects or structures of interest from the background as an efficient alternative to techniques such as deformable templates [27]. We introduce a graphical model (i.e. Markov random field)-based formulation of structure-specific figure-ground segmentation based on simple geometric features extracted from an image, such as local configurations of linear features, that are characteristic of the desired figure structure. Our formulation is novel in that it is based on factor graphs, which are graphical models that encode interactions among arbitrary numbers of random variables. The ability of factor graphs to express interactions higher than pairwise order (the highest order encountered in most graphical models used in computer vision) is useful for modeling a variety of pattern recognition problems. In particular, we show how this property makes factor graphs a natural framework for performing grouping and segmentation, and demonstrate that the factor graph framework emerges naturally from a simple maximum entropy model of figure-ground segmentation.We cast our approach in a learning framework, in which the contributions of multiple grouping cues are learned from training data, and apply our framework to the problem of finding printed text in natural scenes. Experimental results are described, including a performance analysis that demonstrates the feasibility of the approach.

  11. Generating Ambiguous Figure-Ground Images.

    PubMed

    Kuo, Ying-Miao; Chu, Hung-Kuo; Chi, Ming-Te; Lee, Ruen-Rone; Lee, Tong-Yee

    2016-02-26

    Ambiguous figure-ground images, mostly represented as binary images, are fascinating as they present viewers a visual phenomena of perceiving multiple interpretations from a single image. In one possible interpretation, the white region is seen as a foreground figure while the black region is treated as shapeless background. Such perception can reverse instantly at any moment. In this paper, we investigate the theory behind this ambiguous perception and present an automatic algorithm to generate such images. We model the problem as a binary image composition using two object contours and approach it through a three-stage pipeline. The algorithm first performs a partial shape matching to find a good partial contour matching between objects. This matching is based on a content-aware shape matching metric, which captures features of ambiguous figure-ground images. Then we combine matched contours into a compound contour using an adaptive contour deformation, followed by computing an optimal cropping window and image binarization for the compound contour that maximize the completeness of object contours in the final composition. We have tested our system using a wide range of input objects and generated a large number of convincing examples with or without user guidance. The efficiency of our system and quality of results are verified through an extensive experimental study.

  12. Vacuolar protein sorting 4B regulates apoptosis of intestinal epithelial cells via p38 MAPK in Crohn's disease.

    PubMed

    Zhang, Dongmei; Wang, Liang; Yan, Lijun; Miao, Xianjing; Gong, Chen; Xiao, Min; Ni, Runzhou; Tang, Qiyun

    2015-02-01

    Vacuolar protein sorting 4B (VPS4B), a member of ATPase family proteins, reportedly possesses multiple biological functions, such as regulating the development of breast cancer and non-small-cell lung cancer, participating in Parkinson's disease, and modulating neuronal apoptosis after cerebral ischemia. However, its expression and potential functions in Crohn's disease (CD) has not been understood. In this study, we reported for the first time that VPS4B was over-expressed in intestinal epithelial cell (IECs) of patients with CD. In TNBS-induced mouse colitis models, we observed the up-regulation of VPS4B was accompanied with the elevated levels of IEC apoptotic markers (active caspase-3 and cleaved PARP) and phosphorylated p38 in colitis IECs. Co-localization of VPS4B and active caspase-3 in IECs of the TNBS group further indicated the possible involvement of VPS4B in IEC apoptosis. Employing the TNF-α-treated HT29 cells as an in vitro IEC apoptosis model, we confirmed the positive correlation of VPS4B with caspase-dependent cellular apoptosis. Knocking VPS4B down by siRNA significantly alleviated TNF-α-induced p38 phosphorylation and cellular apoptosis in HT29 cells. Taken together, our findings suggested that VPS4B may facilitate the IEC apoptosis in CD via p38 MAPK signaling pathway.

  13. Changes in area affect figure-ground assignment in pigeons.

    PubMed

    Castro, Leyre; Lazareva, Olga F; Vecera, Shaun P; Wasserman, Edward A

    2010-03-05

    A critical cue for figure-ground assignment in humans is area: smaller regions are more likely to be perceived as figures than are larger regions. To see if pigeons are similarly sensitive to this cue, we trained birds to report whether a target appeared on a colored figure or on a differently colored background. The initial training figure was either smaller than (Experiments 1 and 2) or the same area as (Experiment 2) the background. After training, we increased or decreased the size of the figure. When the original training shape was smaller than the background, pigeons' performance improved with smaller figures (and worsened with larger figures); when the original training shape was the same area as the background, pigeons' performance worsened when they were tested with smaller figures. A smaller figural region appeared to improve the figure-ground discrimination only when size was a relevant cue in the initial discrimination.

  14. 16 CFR 1508.5 - Component spacing test method for § 1508.4(b).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ..., aluminum, or equivalent) as shown in figure 1. (b) Place the wedge midway between two vertical components... DPP-50, or equivalent spring scale) to the eyebolt and exert a 9-kilogram (20-pound) direct pull on the wedge. The test may be performed by suspending a 9-kilogram (20-pound) weight from the...

  15. INPP4B is upregulated and functions as an oncogenic driver through SGK3 in a subset of melanomas

    PubMed Central

    Wilmott, James S.; Guo, Xiang Yun; Yan, Xu Guang; Wang, Chun Yan; Liu, Xiao Ying; Jin, Lei; Tseng, Hsin-Yi; Liu, Tao; Croft, Amanda; Hondermarck, Hubert; Scolyer, Richard A.; Jiang, Chen Chen; Zhang, Xu Dong

    2015-01-01

    Inositol polyphosphate 4-phosphatase type II (INPP4B) negatively regulates PI3K/Akt signalling and has a tumour suppressive role in some types of cancers. However, we have found that it is upregulated in a subset of melanomas. Here we report that INPP4B can function as an oncogenic driver through activation of serum- and glucocorticoid-regulated kinase 3 (SGK3) in melanoma. While INPP4B knockdown inhibited melanoma cell proliferation and retarded melanoma xenograft growth, overexpression of INPP4B enhanced melanoma cell and melanocyte proliferation and triggered anchorage-independent growth of melanocytes. Noticeably, INPP4B-mediated melanoma cell proliferation was not related to activation of Akt, but was mediated by SGK3. Upregulation of INPP4B in melanoma cells was associated with loss of miRNA (miR)-494 and/or miR-599 due to gene copy number reduction. Indeed, overexpression of miR-494 or miR-599 downregulated INPP4B, reduced SGK3 activation, and inhibited melanoma cell proliferation, whereas introduction of anti-miR-494 or anti-miR-599 upregulated INPP4B, enhanced SGK3 activation, and promoted melanoma cell proliferation. Collectively, these results identify upregulation of INPP4B as an oncogenic mechanism through activation of SGK3 in a subset of melanomas, with implications for targeting INPP4B and restoring miR-494 and miR-599 as novel approaches in the treatment of melanomas with high INPP4B expression. PMID:26573229

  16. The Cry4B toxin of Bacillus thuringiensis subsp. israelensis kills Permethrin-resistant Anopheles gambiae, the principal vector of malaria.

    PubMed

    Ibrahim, Mohamed A; Griko, Natalya B; Bulla, Lee A

    2013-04-01

    Resurgence of malaria has been attributed, in part, to the development of resistance by Anopheles gambiae, a principal vector of the disease, to various insecticidal compounds such as Permethrin. Permethrin, a neurotoxicant, is widely used to impregnate mosquito nets. An alternative strategy to control mosquitoes is the use of Bacillus thuringiensis subsp. israelensis (Bti) because there is no observable resistance in the field to the bacterium. Bti kills mosquitoes by targeting cadherin molecules residing in the midgut epithelium of larvae of the insect. Cry proteins (Cry4A, Cry4B, Cry10A and Cry11A) produced by the bacterium during the sporulation phase of its life cycle bind to the cadherin molecules, which serve as receptors for the proteins. These Cry proteins have variable specificity to a variety of mosquitoes, including Culex and Aedes as well as Anopheles. Importantly, selective mosquitocidal action is occasioned by binding of the respective Cry toxins to cadherins distinctive to individual mosquito species. Differential fractionation of the four Cry proteins from a novel Bti isolate (M1) and cloning and expression of their genes in Escherichia coli revealed that Cry4B is the only Cry protein that exerts insecticidal action against An. gambiae. Indeed, it does so against a Permethrin-resistant strain of the mosquito. The other three Cry proteins are ineffective. Multiple sequence alignments of the four Cry proteins revealed a divergent sequence motif in the Cry4B toxin, which most likely determines binding of the toxin to its cognate receptor, BT-R3, in An. gambiae and to its specific toxicity. A model showing Cry4B toxin binding to BT-R3 is presented.

  17. New AP4B1 mutation in an African-American child associated with intellectual disability.

    PubMed

    Lamichhane, Dronacharya

    2013-12-01

    Prevalence of intellectual disability (ID) varies from 1-3%. Genetic causes of ID are being increasingly recognized. Although multiple mutations have been identified as a cause of syndromic ID, the genetic etiology of non-syndromic ID is poorly understood. However, more than 100 loci have been mapped that are associated with non-syndromic ID. There have been a couple of reports of AP4B1 gene mutation causing severe intellectual disability, absent speech, shy character, stereotypic laughter, muscular hypotonia that progressed to spastic paraplegia, microcephaly, foot deformity, decreased muscle mass of the lower limbs, inability to walk, and growth retardation. They had structural brain abnormalities and seizures. The reported cases were from Arab families where consanguineous marriage is common. We encountered an African-American child who presented first at the age of 24 mo with language difficulties and was subsequently found to have moderate to severe intellectual disability by standardized tests. Shortly, he started to have seizures and problems with ambulation. Although he was hypotonic at the time of presentation, legs slowly became spastic at the age of 4 yr. After a thorough work up, he was found to have heterozygous mutation in the AP4B1 gene along with another missense mutation in the same gene. There has been no report of mutation in this gene in the North American population. Although AP4B1 typically is said to be an autosomal recessive disease-causing gene, our case is different in the sense that there are two mutations in the same gene one of which has never been reported before and co-exists with a known disease causing mutation. Yet, the phenotype of the case closely resembles those published previously.

  18. Yersiniosis due to infection by Yersinia pseudotuberculosis 4b in captive meerkats (Suricata suricatta) in Japan.

    PubMed

    Nakamura, Shin-Ichi; Hayashidani, Hideki; Yonezawa, Aya; Suzuki, Isao; Une, Yumi

    2015-09-01

    Two meerkats (Suricata suricatta) housed in the same zoological garden in Japan died due to Yersinia pseudotuberculosis serotype 4b infection. Gross and microscopic lesions included necrotizing enteritis and enlargement of the spleen and liver with multifocal necrosis. Inflammatory cells, primarily neutrophils, and nuclear debris were associated with clusters of Gram-negative bacilli. Additionally, there were aberrant organism forms that were larger than bacilli and appeared as basophilic globular bodies. Immunohistochemical examination showed that the bacilli and globular bodies were strongly positive for Y. pseudotuberculosis O4 antigen. The globular bodies were considered a shape-changed form of Y. pseudotuberculosis, and these morphologically abnormal bacteria could present a diagnostic challenge.

  19. Input files with ORNL—mathematical phantoms of the human body for MCNP-4B

    NASA Astrophysics Data System (ADS)

    Krstić, D.; Nikezić, D.

    2007-01-01

    Protection against ionizing radiation requires information on the absorbed doses in organs of the human body. Implantation of many dosimeters in the human body is undesirable (or impossible), so the doses in organs are not measurable and some kind of dose calculation has to be applied. Calculation of doses in organs requests: (a) an exact description of the geometry of organs, (b) the chemical constitution of tissues, and (c) appropriate computer programs. The first two items, (a) and (b), make a so-called "phantom". In another words, the "phantom of a human body" is a mathematical representation of the human body including all other relevant information. All organs are represented with geometrical bodies (like cylinders, ellipsoids, tori, cones etc.), which are described with suitable mathematical equations. A corresponding chemical constitution for various types of organ tissues is also defined. MCNP-4B ( Monte Carlo N- Particle) is often used as transport code. Users of this software prepare an "input file" providing all necessary information for program execution. This information includes: (a) source definition—type of ionizing radiation, energy spectrum, and geometry of the source; (b) target definition—material constitution, geometry, location in respect to the source etc.; (c) characterization of absorbing media between the source and target; (d) output tally, etc. This paper presents input files with "human phantoms" for the MCNP-4B code. The input files with "phantoms" were prepared based on publications issued by the Oak Ridge National Laboratory (ORNL). Seven input files relating to different age groups (newborn, 1, 5, 10, 15 years, as well as, male and female adults) are presented here. A test example and comparison with other data found in literature are also given. Program summaryTitle of program: INPUT FILES, AMALE, AFEMALE, AGE15, AGE10, AGE5, AGE01, NEWB Catalogue identifier:ADYF_v1_0 Program summary URL

  20. Synergistic interactions between PDE4B and GSK-3: DISC1 mutant mice.

    PubMed

    Lipina, Tatiana V; Wang, Min; Liu, Fang; Roder, John C

    2012-03-01

    Disrupted-In-Schizophrenia-1 (DISC1) is a strong genetic risk factor associated with psychiatric disorders. Two distinct mutations in the second exon of the DISC1 gene (Q31L and L100P) lead to either depression- or schizophrenia-like behavior in mice. Both phosphodiesterase-4B (PDE4B) and glycogen synthase kinase-3 (GSK-3) have common binding sites on N-terminal region of DISC1 and are implicated into etiology of schizophrenia and depression. It is not known if PDE4B and GSK-3 could converge signals in the cell via DISC1 at the same time. The purpose of the present study was to assess whether rolipram (PDE4 inhibitor) might synergize with TDZD-8 (GSK-3 blocker) to produce antipsychotic effects at low doses on the DISC1-L100P genetic model. Indeed, combined treatment of DISC1-L100P mice with rolipram (0.1 mg/kg) and TDZD-8 (2.5 mg/kg) in sub-threshold doses corrected their Pre-Pulse Inhibition (PPI) deficit and hyperactivity, without any side effects at these doses. We have suggested that rolipram-induced increase of cAMP level might influence GSK-3 function and, hence the efficacy of TDZD-8. Our second goal was to estimate how DISC1-Q31L with reduced PDE4B activity, and therefore mimicking rolipram-induced conditions, could alter pharmacological response to TDZD-8, GSK-3 activity and its interaction with DISC1. DISC1-Q31L mutants showed increased sensitivity to GSK-3 inhibitor compare to DISC1-L100P mice. TDZD-8 (2.5 mg/kg) was able to correct PPI deficit, reduce immobility in the forced swim test (FST) and increased social motivation/novelty. In parallel, biochemical analysis revealed significantly reduced binding of GSK-3 to the mutated DISC1-Q31L and increased enzymatic activity of GSK-3. Taken together, genetic variations in DISC1 influence formation of biochemical complex with PDE4 and GSK-3 and strength the possibility of synergistic interactions between these proteins.

  1. Crystal structure features in a new compound C4B25Mg1.42

    NASA Astrophysics Data System (ADS)

    Konovalikhin, S. V.; Ponomarev, V. I.

    2015-09-01

    The composition of C4B25Mg1.42 crystal obtained by self-propagating high-temperature synthesis was determined using X-ray diffraction. This is the first crystalline structure where all boron atoms in the В12 icosahedron occupy crystallographically independent positions; this circumstance allowed us to analyze the effect of substituents on bond lengths in the icosahedron. The crystal structure features, including the channels filled with disordered Mg atoms and the spread of В—В endo- and exo-bond lengths in the icosahedra, are described. A crystallochemical analysis of pair bonds has been performed for the first time.

  2. Complete Genome Sequence of the Larvicidal Bacterium Lysinibacillus sphaericus Strain OT4b.25

    PubMed Central

    Rey, Andrés; Silva-Quintero, Laura

    2016-01-01

    Lysinibacillus sphaericus OT4b.25 is a native Colombian strain isolated from coleopteran larvae in an oak forest near Bogotá D.C.; this strain has shown high levels of pathogenic activity against Culex quinquefasciatus larvae in laboratory assays compared to that of other members of the same species. Using Pacific Biosciences sequencing technology, we propose a chromosomal contig of 4,665,775 bp that, according to comparative analysis, is highly similar to that of reference strain L. sphaericus C3-41. PMID:27151786

  3. Population Structure of Listeria monocytogenes Serotype 4b Isolates from Sporadic Human Listeriosis in the United States, 2003-2008

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Listeria monocytogenes can cause severe foodborne disease (listeriosis). Serotype 4b strains have resulted in numerous outbreaks, repeatedly involving three epidemic clones (ECI, ECII, and ECIa). Little is known about population structure of L. monocytogenes serotype 4b from sporadic listeriosis, ev...

  4. 75 FR 41871 - International Conference on Harmonisation; Draft Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-19

    ... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... availability of a draft guidance entitled ``Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use... evaluation of the Bacterial Endotoxins Test General Chapter harmonized text from each of the...

  5. Thermoelectric figure of merit in topological insulators

    NASA Astrophysics Data System (ADS)

    Takahashi, Ryuji; Murakami, Shuichi

    2011-07-01

    Transport behavior of two-dimensional topological insulators is theoretically studied in narrow ribbon geometry. The system has perfectly conducting edge channels, which are free from backscattering. At high temperature, the bulk states dominate in the transport phenomenon. However, at low temperature the conducting channels along the edges become dominant. It causes a bulk-to-edge crossover. Namely, by lowering temperature, the figure of merit first decreases by a competition between the bulk and the edge transport, and then increases again because the edge transport become larger.

  6. Identification of Amino Acid Determinants in CYP4B1 for Optimal Catalytic Processing of 4-Ipomeanol

    PubMed Central

    Wiek, Constanze; Schmidt, Eva M; Roellecke, Katharina; Freund, Marcel; Nakano, Mariko; Kelly, Edward J; Kaisers, Wolfgang; Yarov-Yarovoy, Vladimir; Kramm, Christof M; Rettie, Allan E; Hanenberg, Helmut

    2014-01-01

    Mammalian CYP4B1 enzymes are cytochrome P450 monooxygenases that are responsible for the bioactivation of several exogenous pro-toxins including 4-ipomeanol (4-IPO). In contrast to the orthologous rabbit enzyme, we show here that native human CYP4B1 with a serine at position 427 is unable to bio-activate 4-IPO and does not cause cytotoxicity in HepG2 cells and primary human T-cells that overexpress these enzymes. We also demonstrate that a proline residue in the meander region at position 427 in human CYB4B1 and 422 in rabbit CYP4B1 is important for protein stability and rescues the 4-IPO bioactivation of the human enzyme, but is not essential for the catalytic activity of the rabbit CYP4B1 protein. Systematic substitution of native and p.S427P human CYP4B1 with peptide regions from the highly active rabbit enzyme reveals that 18 amino acids in the wild-type rabbit CYP4B1 protein are key for conferring high 4-IPO metabolizing activity. Introduction of 12 of the 18 amino acids that are also present at corresponding positions in other human CYP4 family members into the p.S427P human CYP4B1 protein results in a mutant human enzyme (P+12) that is as stable and as active as the rabbit wild-type CYP4B1 protein. These 12 mutations cluster in the predicted B–C loop through F-helix regions and reveal new amino acid regions important to P450 enzyme stability. Finally, by minimally re-engineering the human CYP4B1 enzyme for efficient activation of 4-IPO, we have developed a novel human suicide gene system that is a candidate for adoptive cellular therapies in humans. PMID:25247810

  7. The plasma membrane Ca(2+) pump PMCA4b inhibits the migratory and metastatic activity of BRAF mutant melanoma cells.

    PubMed

    Hegedũs, Luca; Garay, Tamás; Molnár, Eszter; Varga, Karolina; Bilecz, Ágnes; Török, Szilvia; Padányi, Rita; Pászty, Katalin; Wolf, Matthias; Grusch, Michael; Kállay, Enikõ; Döme, Balázs; Berger, Walter; Hegedũs, Balázs; Enyedi, Agnes

    2016-11-04

    Oncogenic mutations of BRAF lead to constitutive ERK activity that supports melanoma cell growth and survival. While Ca(2+) signaling is a well-known regulator of tumor progression, the crosstalk between Ca(2+) signaling and the Ras-BRAF-MEK-ERK pathway is much less explored. Here we show that in BRAF mutant melanoma cells the abundance of the plasma membrane Ca(2+) ATPase isoform 4b (PMCA4b, ATP2B4) is low at baseline but markedly elevated by treatment with the mutant BRAF specific inhibitor vemurafenib. In line with these findings gene expression microarray data also shows decreased PMCA4b expression in cutaneous melanoma when compared to benign nevi. The MEK inhibitor selumetinib-similarly to that of the BRAF-specific inhibitor-also increases PMCA4b levels in both BRAF and NRAS mutant melanoma cells suggesting that the MAPK pathway is involved in the regulation of PMCA4b expression. The increased abundance of PMCA4b in the plasma membrane enhances [Ca(2+) ]i clearance from cells after Ca(2+) entry. Moreover we show that both vemurafenib treatment and PMCA4b overexpression induce marked inhibition of migration of BRAF mutant melanoma cells. Importantly, reduced migration of PMCA4b expressing BRAF mutant cells is associated with a marked decrease in their metastatic potential in vivo. Taken together, our data reveal an important crosstalk between Ca(2+) signaling and the MAPK pathway through the regulation of PMCA4b expression and suggest that PMCA4b is a previously unrecognized metastasis suppressor.

  8. LARP4B is an AU-rich sequence associated factor that promotes mRNA accumulation and translation.

    PubMed

    Küspert, Maritta; Murakawa, Yasuhiro; Schäffler, Katrin; Vanselow, Jens T; Wolf, Elmar; Juranek, Stefan; Schlosser, Andreas; Landthaler, Markus; Fischer, Utz

    2015-07-01

    mRNAs are key molecules in gene expression and subject to diverse regulatory events. Regulation is accomplished by distinct sets of trans-acting factors that interact with mRNAs and form defined mRNA-protein complexes (mRNPs). The resulting "mRNP code" determines the fate of any given mRNA and thus controlling gene expression at the post-transcriptional level. The La-related protein 4B (LARP4B) belongs to an evolutionarily conserved family of RNA-binding proteins characterized by the presence of a La-module implicated in direct RNA binding. Biochemical experiments have shown previously direct interactions of LARP4B with factors of the translation machinery. This finding along with the observation of an association with actively translating ribosomes suggested that LARP4B is a factor contributing to the mRNP code. To gain insight into the function of LARP4B in vivo we tested its mRNA association at the transcriptome level and its impact on the proteome. PAR-CLIP analyses allowed us to identify the in vivo RNA targets of LARP4B. We show that LARP4B binds to a distinct set of cellular mRNAs by contacting their 3' UTRs. Biocomputational analysis combined with in vitro binding assays identified the LARP4B-binding motif on mRNA targets. The reduction of cellular LARP4B levels leads to a marked destabilization of its mRNA targets and consequently their reduced translation. Our data identify LARP4B as a component of the mRNP code that influences the expression of its mRNA targets by affecting their stability.

  9. The electron and energy transfer between oligothiophenes and thieno[3,4-b]thiophene units

    NASA Astrophysics Data System (ADS)

    Szarko, Jodi; Guo, Jianchang; Liang, Yongye; Rolczynski, Brian; Yu, Luping; Chen, Lin X.

    2008-08-01

    In a recent study, it has been shown that organic photovoltaic (OPV) solar cells consisting of polymers with certain stoichiometric ratios of alkyl thiophene:thieno[3,4-b]thiophene monomeric units in random sequences, when combined with [6,6]-phenyl-C61-butyric acid methyl ester (PCBM), may have potentials for creating more efficient devices. Such a potential enhancement is mainly due to the light harvesting in most of the visible and near infrared region by these low band-gap polymers. However, very little is known about the photoinduced energy/electron transfer and transport within these copolymers. It is important to understand both the ultrafast interactions between these two monomeric units when they are linked in the copolymers and their interactions with the electron acceptor PCBM in order to determine the transport mechanisms in these systems, and then to create the architectures that optimize electronic transport properties. Therefore, three oligomer molecules have been synthesized to model the local interactions in the copolymers, each of which consists of a thieno[3,4-b] thiophene derivative at its center linked with two alkyl oligothiophene side units. The alkyl oligothiophene units for the three molecules are 2, 4, or 8 units in length. By performing transient absorption and fluorescence upconversion measurements, the nature of the early exciton diffusion and energy transfer between these different units is elucidated.

  10. Geopotential Model Improvement Using POCM_4B Dynamic Ocean Topography Information: PGM2000A

    NASA Technical Reports Server (NTRS)

    Pavlis, N. K.; Chinn, D. S.; Cox, C. M.; Lemoine, Frank G.; Smith, David E. (Technical Monitor)

    2000-01-01

    The two-year mean (1993-1994) Dynamic Ocean Topography (DOT) field implied by the POCM_4B circulation model was used to develop normal equations for DOT, in a surface spherical harmonic representation. These normal equations were combined with normal equations from satellite tracking data, surface gravity data, and altimeter data from TOPEX/Poseidon and ERS-1. Several least-squares combination solutions were developed in this fashion, by varying parameters such as the maximum degree of the estimated DOT and the relative weights of the different data. The solutions were evaluated in terms of orbit fit residuals, GPS/Leveling-derived undulations, and independent DOT information from in situ WOCE hydrographic data. An optimal solution was developed in this fashion which was originally presented at the 1998 EGS meeting in Nice, France. This model, designated here PGM2000A, maintains the orbit and land geoid modeling performance of EGM96, while improving its marine geoid modeling capability. In addition, PGM2000A's error spectrum is considerably more realistic than those of other contemporary gravitational models and agrees well with the error spectrum of EGM96. We will present the development and evaluation of PGM2000A, with particular emphasis on the weighting of the DOT information implied by POCM_4B. We will also present an inter-comparison of PGM2000A with the GRIM5-C1 and TEG-4 models. Directions for future work and problematic areas will be identified.

  11. Surface figure control for coated optics

    DOEpatents

    Ray-Chaudhuri, Avijit K.; Spence, Paul A.; Kanouff, Michael P.

    2001-01-01

    A pedestal optical substrate that simultaneously provides high substrate dynamic stiffness, provides low surface figure sensitivity to mechanical mounting hardware inputs, and constrains surface figure changes caused by optical coatings to be primarily spherical in nature. The pedestal optical substrate includes a disk-like optic or substrate section having a top surface that is coated, a disk-like base section that provides location at which the substrate can be mounted, and a connecting cylindrical section between the base and optics or substrate sections. The optic section has an optical section thickness.sup.2 /optical section diameter ratio of between about 5 to 10 mm, and a thickness variation between front and back surfaces of less than about 10%. The connecting cylindrical section may be attached via three spaced legs or members. However, the pedestal optical substrate can be manufactured from a solid piece of material to form a monolith, thus avoiding joints between the sections, or the disk-like base can be formed separately and connected to the connecting section. By way of example, the pedestal optical substrate may be utilized in the fabrication of optics for an extreme ultraviolet (EUV) lithography imaging system, or in any optical system requiring coated optics and substrates with reduced sensitivity to mechanical mounts.

  12. Figures of Merit for Lunar Simulants

    NASA Astrophysics Data System (ADS)

    Slane, Frederick

    The collection and analysis of lunar samples from 1969 to present has yielded large amounts of data. Published analyses give some idea of the complex nature of the regolith at all scales, rocks, soils and the smaller particulates commonly referred to as dust. Data recently acquired in support of NASA's simulant effort has markedly increased our knowledge and quantitatively demonstrates that complexity. It is anticipated that future analyses will further add to the known complexity. In an effort to communicate among the diverse technical communities performing research on or research using regolith samples and simulants, a set of Figures of Merit (FoM) have been devised. The objective is to allow consistent and concise comparative communication between researchers from multiple organizations and nations engaged in lunar exploration. This paper describes Figures of Merit in a working draft of an international standard for Lunar Simulants. The FoM methodology uses scientific understanding of the lunar samples to formulate parameters which are reproducibly quantifiable. Advanced work at NASA has evolved this effort to the point that formal definitions, supporting mathematics and functioning code have implemented the concept for testing.

  13. Figure-ground separation by cue integration.

    PubMed

    Tang, Xiangyu; von der Malsburg, Christoph

    2008-06-01

    This letter presents an improved cue integration approach to reliably separate coherent moving objects from their background scene in video sequences. The proposed method uses a probabilistic framework to unify bottom-up and top-down cues in a parallel, "democratic" fashion. The algorithm makes use of a modified Bayes rule where each pixel's posterior probabilities of figure or ground layer assignment are derived from likelihood models of three bottom-up cues and a prior model provided by a top-down cue. Each cue is treated as independent evidence for figure-ground separation. They compete with and complement each other dynamically by adjusting relative weights from frame to frame according to cue quality measured against the overall integration. At the same time, the likelihood or prior models of individual cues adapt toward the integrated result. These mechanisms enable the system to organize under the influence of visual scene structure without manual intervention. A novel contribution here is the incorporation of a top-down cue. It improves the system's robustness and accuracy and helps handle difficult and ambiguous situations, such as abrupt lighting changes or occlusion among multiple objects. Results on various video sequences are demonstrated and discussed. (Video demos are available at http://organic.usc.edu:8376/ approximately tangx/neco/index.html .).

  14. Prolactin Regulatory Element Binding Protein Is Involved in Hepatitis C Virus Replication by Interaction with NS4B

    PubMed Central

    Kong, Lingbao; Fujimoto, Akira; Nakamura, Mariko; Aoyagi, Haruyo; Matsuda, Mami; Watashi, Koichi; Suzuki, Ryosuke; Arita, Minetaro; Yamagoe, Satoshi; Dohmae, Naoshi; Suzuki, Takehiro; Sakamaki, Yuriko; Ichinose, Shizuko; Suzuki, Tetsuro; Wakita, Takaji

    2016-01-01

    ABSTRACT It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers the membranous HCV replication compartment, but the underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis and identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA identified prolactin regulatory element binding (PREB) to be a novel HCV host cofactor. The interaction between PREB and NS4B was confirmed by immunoprecipitation, immunofluorescence, and proximity ligation assays. PREB colocalized with double-stranded RNA and the newly synthesized HCV RNA labeled with bromouridine triphosphate in HCV replicon cells. Furthermore, PREB shifted to detergent-resistant membranes (DRMs), where HCV replication complexes reside, in the presence of NS4B expression in Huh7 cells. However, a PREB mutant lacking the NS4B-binding region (PREBd3) could not colocalize with double-stranded RNA and did not shift to the DRM in the presence of NS4B. These results indicate that PREB locates at the HCV replication complex by interacting with NS4B. PREB silencing inhibited the formation of the membranous HCV replication compartment and increased the protease and nuclease sensitivity of HCV replicase proteins and RNA in DRMs, respectively. Collectively, these data indicate that PREB promotes HCV RNA replication by participating in the formation of the membranous replication compartment and by maintaining its proper structure by interacting with NS4B. Furthermore, PREB was induced by HCV infection in vitro and in vivo. Our findings provide new insights into HCV host cofactors. IMPORTANCE The hepatitis C virus (HCV) protein NS4B can induce alteration of the endoplasmic reticulum and the formation of a membranous web structure, which provides a platform for the HCV replication complex. The molecular mechanism by which NS4B induces the membranous HCV replication

  15. Advancing Sustainable Materials Management: Facts and Figures Report

    EPA Pesticide Factsheets

    Each year EPA releases the Advancing Sustainable Materials Management: Facts and Figures report, formerly called Municipal Solid Waste in the United States: Facts and Figures. It includes information on Municipal Solid Waste generation, recycling, an

  16. Inhibitor screening and enzymatic activity determination for autophagy target Atg4B using a gel electrophoresis-based assay.

    PubMed

    Cleenewerck, Matthias; Grootaert, Mandy O J; Gladysz, Rafaela; Adriaenssens, Yves; Roelandt, Ria; Joossens, Jurgen; Lambeir, Anne-Marie; De Meyer, Guido R Y; Declercq, Wim; Augustyns, Koen; Martinet, Wim; Van der Veken, Pieter

    2016-11-10

    Atg4B is a cysteine hydrolase that plays a key role in autophagy. Although it has been proposed as an attractive drug target, inhibitor discovery has proven highly challenging. The absence of a standardized, easily implementable enzyme activity/inhibition assay for Atg4B most likely contributes to this situation. Therefore, three different assay types for Atg4B activity/inhibition quantification were first compared: (1) an approach using fluorogenic Atg4B-substrates, (2) an in-gel densitometric quantification assay and (3) a thermal shift protocol. The gel-based approach showed the most promising results and was validated for screening of potential Atg4B inhibitors. A set of 8 literature inhibitors was included. Remarkably, in our hands only 2 literature references were found to have measurable Atg4B affinity. Furthermore, a fragment library (n = 182) was tested for Atg4B inhibition. One library member showed inhibition at high micromolar concentration and was found fit for further, fragment-based inhibitor design.

  17. The LARK/RBM4a protein is highly expressed in cerebellum as compared to cerebrum.

    PubMed

    Pfuhl, Thorsten; Mamiani, Alfredo; Dürr, Matthias; Welter, Susanne; Stieber, Johanna; Ankara, Jasmin; Liss, Michael; Dobner, Thomas; Schmitt, Andrea; Falkai, Peter; Kremmer, Elisabeth; Jung, Volker; Barth, Stephanie; Grässer, Friedrich A

    2008-10-17

    The RNA binding motif protein 4 genes RBM4a and RBM4b are located on human chromosome 11q13.2 and encode highly similar proteins of 363 and 359 amino acids, respectively. They contain two RNA recognition motifs (RRMs) and a retroviral-type Zn-finger. RBM4a binds RNA, is involved in alternative splicing and is also a part of the microRNA-processing RISC complex. In particular, RBM4a is involved in exon 10 inclusion of the tau protein. The function of RBM4b is unknown. With new monoclonal antibodies we show that RBM4a is detectable in virtually all tissues and cell lines tested while RBM4b was only found in kidney and liver. Both RBM4a and RBM4b are nuclear phosphoproteins with half-lives of 2.5h and 4.5h, respectively. To our knowledge, this is the first description of RBM4b protein in human tissue. In human brain, expression of RBM4a was strongly up-regulated in cerebellum as compared to forebrain.

  18. HATS-4b: A Dense Hot Jupiter Transiting a Super Metal-rich G star

    NASA Astrophysics Data System (ADS)

    Jordán, Andrés; Brahm, Rafael; Bakos, G. Á.; Bayliss, D.; Penev, K.; Hartman, J. D.; Zhou, G.; Mancini, L.; Mohler-Fischer, M.; Ciceri, S.; Sato, B.; Csubry, Z.; Rabus, M.; Suc, V.; Espinoza, N.; Bhatti, W.; de Val-Borro, M.; Buchhave, L.; Csák, B.; Henning, T.; Schmidt, B.; Tan, T. G.; Noyes, R. W.; Béky, B.; Butler, R. P.; Shectman, S.; Crane, J.; Thompson, I.; Williams, A.; Martin, R.; Contreras, C.; Lázár, J.; Papp, I.; Sári, P.

    2014-08-01

    We report the discovery by the HATSouth survey of HATS-4b, an extrasolar planet transiting a V = 13.46 mag G star. HATS-4b has a period of P ≈ 2.5167 days, mass of Mp ≈ 1.32 M Jup, radius of Rp ≈ 1.02 R Jup, and density of ρ p = 1.55 ± 0.16 g cm-3 ≈1.24 ρJup. The host star has a mass of 1.00 M ⊙, a radius of 0.92 R ⊙, and a very high metallicity [Fe/H]=0.43 ± 0.08. HATS-4b is among the densest known planets with masses between 1 and 2 M J and is thus likely to have a significant content of heavy elements of the order of 75 M ⊕. In this paper we present the data reduction, radial velocity measurements, and stellar classification techniques adopted by the HATSouth survey for the CORALIE spectrograph. We also detail a technique for simultaneously estimating vsin i and macroturbulence using high resolution spectra. The HATSouth network is operated by a collaboration consisting of Princeton University (PU), the Max Planck Institut für Astronomie (MPIA), and the Australian National University (ANU). The station at Las Campanas Observatory (LCO) of the Carnegie Institution is operated by PU in conjunction with collaborators at the Pontificia Universidad Católica de Chile, the station at the High Energy Spectroscopic Survey site is operated in conjunction with MPIA, and the station at Siding Spring Observatory (SSO) is operated jointly with ANU. This paper includes data gathered with the 6.5 m Magellan Telescopes located at LCO, Chile. Based in part on data collected at Subaru Telescope, which is operated by the National Astronomical Observatory of Japan, and on observations made with the MPG/ESO 2.2 m Telescope at the ESO Observatory in La Silla. This paper uses observations obtained with facilities of the Las Cumbres Observatory Global Telescope.

  19. Characterization of an Additional Splice Acceptor Site Introduced into CYP4B1 in Hominoidae during Evolution.

    PubMed

    Schmidt, Eva M; Wiek, Constanze; Parkinson, Oliver T; Roellecke, Katharina; Freund, Marcel; Gombert, Michael; Lottmann, Nadine; Steward, Charles A; Kramm, Christof M; Yarov-Yarovoy, Vladimir; Rettie, Allan E; Hanenberg, Helmut

    2015-01-01

    CYP4B1 belongs to the cytochrome P450 family 4, one of the oldest P450 families whose members have been highly conserved throughout evolution. The CYP4 monooxygenases typically oxidize fatty acids to both inactive and active lipid mediators, although the endogenous ligand(s) is largely unknown. During evolution, at the transition of great apes to humanoids, the CYP4B1 protein acquired a serine instead of a proline at the canonical position 427 in the meander region. Although this alteration impairs P450 function related to the processing of naturally occurring lung toxins, a study in transgenic mice suggested that an additional serine insertion at position 207 in human CYP4B1 can rescue the enzyme stability and activity. Here, we report that the genomic insertion of a CAG triplet at the intron 5-exon 6 boundary in human CYP4B1 introduced an additional splice acceptor site in frame. During evolution, this change occurred presumably at the stage of Hominoidae and leads to two major isoforms of the CYP4B1 enzymes of humans and great apes, either with or without a serine 207 insertion (insSer207). We further demonstrated that the CYP4B1 enzyme with insSer207 is the dominant isoform (76%) in humans. Importantly, this amino acid insertion did not affect the 4-ipomeanol metabolizing activities or stabilities of the native rabbit or human CYP4B1 enzymes, when introduced as transgenes in human primary cells and cell lines. In our 3D modeling, this functional neutrality of insSer207 is compatible with its predicted location on the exterior surface of CYP4B1 in a flexible side chain. Therefore, the Ser207 insertion does not rescue the P450 functional activity of human CYP4B1 that has been lost during evolution.

  20. SLC4A Transporters

    PubMed Central

    Choi, Inyeong

    2016-01-01

    SLC4A gene family proteins include bicarbonate transporters that move HCO3− across the plasma membrane and regulate intracellular pH and transepithelial movement of acid–base equivalents. These transporters are Cl/HCO3 exchangers, electrogenic Na/HCO3 cotransporters, electroneutral Na/HCO3 cotransporters, and Na+-driven Cl/HCO3 exchanger. Studies of the bicarbonate transporters in vitro and in vivo have demonstrated their physiological importance for acid–base homeostasis at the cellular and systemic levels. Recent advances in structure/function analysis have also provided valuable information on domains or motifs critical for regulation, ion translocation, and protein topology. This chapter focuses on the molecular mechanisms of ion transport along with associated structural aspects from mutagenesis of particular residues and from chimeric constructs. Structure/function studies have helped to understand the mechanism by which ion substrates are moved via the transporters. This chapter also describes some insights into the structure of SLC4A1 (AE1) and SLC4A4 (NBCe1) transporters. Finally, as some SLC4A transporters exist in concert with other proteins in the cells, the structural features associated with protein–protein interactions are briefly discussed. PMID:23177984

  1. Figure Control of Lightweight Optical Structures

    NASA Technical Reports Server (NTRS)

    Main, John A.; Song, Haiping

    2005-01-01

    The goal of this paper is to demonstrate the use of fuzzy logic controllers in modifying the figure of a piezoceramic bimorph mirror. Non-contact electron actuation technology is used to actively control a bimorph mirror comprised two PZT-5H wafers by varying the electron flux and electron voltages. Due to electron blooming generated by the electron flux, it is difficult to develop an accurate control model for the bimorph mirror through theoretical analysis alone. The non-contact shape control system with electron flux blooming can be approximately described with a heuristic model based on experimental data. Two fuzzy logic feedback controllers are developed to control the shape of the bimorph mirror according to heuristic fuzzy inference rules generated from previous experimental results. Validation of the proposed fuzzy logic controllers is also discussed.

  2. Structure analysis for plane geometry figures

    NASA Astrophysics Data System (ADS)

    Feng, Tianxiao; Lu, Xiaoqing; Liu, Lu; Li, Keqiang; Tang, Zhi

    2013-12-01

    As there are increasing numbers of digital documents for education purpose, we realize that there is not a retrieval application for mathematic plane geometry images. In this paper, we propose a method for retrieving plane geometry figures (PGFs), which often appear in geometry books and digital documents. First, detecting algorithms are applied to detect common basic geometry shapes from a PGF image. Based on all basic shapes, we analyze the structural relationships between two basic shapes and combine some of them to a compound shape to build the PGF descriptor. Afterwards, we apply matching function to retrieve candidate PGF images with ranking. The great contribution of the paper is that we propose a structure analysis method to better describe the spatial relationships in such image composed of many overlapped shapes. Experimental results demonstrate that our analysis method and shape descriptor can obtain good retrieval results with relatively high effectiveness and efficiency.

  3. BOREAS Level-4b AVHRR-LAC Ten-Day Composite Images: At-sensor Radiance

    NASA Technical Reports Server (NTRS)

    Cihlar, Josef; Chen, Jing; Nickerson, Jaime; Newcomer, Jeffrey A.; Huang, Feng-Ting; Hall, Forrest G. (Editor)

    2000-01-01

    The BOReal Ecosystem-Atmosphere Study (BOREAS) Staff Science Satellite Data Acquisition Program focused on providing the research teams with the remotely sensed satellite data products they needed to compare and spatially extend point results. Manitoba Remote Sensing Center (MRSC) and BOREAS Information System (BORIS) personnel acquired, processed, and archived data from the Advanced Very High Resolution Radiometer (AVHRR) instruments on the National Oceanic and Atmospheric Administration (NOAA-11) and -14 satellites. The AVHRR data were acquired by CCRS and were provided to BORIS for use by BOREAS researchers. These AVHRR level-4b data are gridded, 10-day composites of at-sensor radiance values produced from sets of single-day images. Temporally, the 10- day compositing periods begin 11-Apr-1994 and end 10-Sep-1994. Spatially, the data cover the entire BOREAS region. The data are stored in binary image format files.

  4. Hexadecanedionic acid-sepharose 4B: A new tool for preparation of albumin-depleted plasma.

    PubMed

    Soskic, Vukic; Schwall, Gerhard; Nyakatura, Elke; Poznanovic, Slobodan; Stegmann, Werner; Schrattenholz, Andre

    2006-12-01

    Serum and plasma are the major sources of human material for clinical molecular diagnostics and drug discovery. However, due to the high abundance of some proteins, of which serum albumin (SA) is most prominent, lower-abundance proteins often remain undetectable in proteomic analysis of these body fluids. We have used hexadecanedionic acid (HDA) immobilized to Sepharose 4B to develop an affinity resin that is effective in the removal of SA from plasma. Two-dimensional gel analysis of the SA-depleted samples shows a significant enhancement of the low-abundance proteins and highly specific capture of serum albumin. The HDA resin shows better performance in terms of specificity than dye-based resins.

  5. [A novel pyridazino-fused ring system: synthesis of pyridazino[3,4-b]diazepam].

    PubMed

    Károlyházy, L; Horváth, G; Mátyus, P

    2001-08-01

    As an analogue of pyridazino-fused ring systems with pharmacological activities, the novel pyridazinol[3,4-b][1,5]diazepine ring system was prepared. The synthetic pathway includes three steps from 4 5-(N-benzyl-N-3-hydroxypropyl)amino derivative which is easily available through nucleophilic substitution reaction of the known 4,5-dichloro-2-methyl-6-nitro-3(2H)-pyridazinone (2) with N-benzyl-N-(3-hydroxypropyl)amine. In the first step, compound 4 was treated with thionyl chloride to give the chloropropyl derivative 5. In the second step, a Bechamp reduction was carried out with Fe in acetic acid to obtain the amino compound 6, and finally the ring closure reaction of 6 was performed in N,N-dimethylformamide in the presence of potassium carbonate at 110 degrees C for 40 hours. In this way the bicyclic compound 7 could be isolated in 48% yield.

  6. Low-energy Be4+/B5+ - H2 cross sections

    NASA Astrophysics Data System (ADS)

    Saha, Bidhan

    2000-06-01

    Single electron capture cross sections from molecular hydrogen by Be4+/B5+ have been calculated using the Molecular Orbital formalism in the semiclassical close-coupling scheme. The important interactions leading to state selective charge transfer are confined at large internuclear seperation. We have found that freezing the molecular details of the target turns out to be a convenient strategy [1]. In our investigation we treat H2 as a pseudo-atom with ionization potential 16.1 eV. The results will be presented in the conference. This work is supported by Research Corporation, NSF CREST and Army High Performance Computing Research. [1] A. Kumar and B C Saha, Phys Rev A 59,1273 (1999).

  7. Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B

    PubMed Central

    Rao, Minxi; Smith, Brian C.

    2015-01-01

    ABSTRACT Nitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis. PMID:25944856

  8. Cul4A is essential for spermatogenesis and male fertility.

    PubMed

    Kopanja, Dragana; Roy, Nilotpal; Stoyanova, Tanya; Hess, Rex A; Bagchi, Srilata; Raychaudhuri, Pradip

    2011-04-15

    The mammalian Cul4 genes, Cul4A and Cul4B, encode the scaffold components of the cullin-based E3 ubiquitin ligases. The two Cul4 genes are functionally redundant. Recent study indicated that mice expressing a truncated CUL4A that fails to interact with its functional partner ROC1 exhibit no developmental phenotype. We generated a Cul4A-/- strain lacking exons 4-8 that does not express any detectable truncated protein. In this strain, the male mice are infertile and exhibit severe deficiencies in spermatogenesis. The primary spermatocytes are deficient in progression through late prophase I, a time point when expression of the X-linked Cul4B gene is silenced due to meiotic sex chromosome inactivation. Testes of the Cul4A-/- mice exhibit extensive apoptosis. Interestingly, the pachytene spermatocytes exhibit persistent double stranded breaks, suggesting a deficiency in homologous recombination. Also, we find that CUL4A localizes to the double stranded breaks generated in pre-pachytene spermatocytes. The observations identify a novel function of CUL4A in meiotic recombination and demonstrate an essential role of CUL4A in spermatogenesis.

  9. Magnetic anisotropy and crystalline electric field effects in RRh{sub 4}B{sub 4} single crystals.

    SciTech Connect

    Zhou, H.; Lambert, S. E.; Maple, M. B.; Dunlap, B. D.; Materials Science Division; Univ. of California at San Diego

    2009-08-01

    Research on polycrystalline RRh{sub 4}B{sub 4} samples has shown that crystalline electric field (CEF) effects play an important role in these compounds. The successful synthesis of single crystal samples of RRh{sub 4}B{sub 4} with R = Y, Sm, Gd, Tb, Dy, Ho, Er, Tm, and Lu has provided an opportunity to further investigate CEF effects in these materials. Magnetization and magnetic susceptibility measurements on the RRh{sub 4}B{sub 4} single crystals revealed strong magnetic anisotropy, and the experimental results could be described well by CEF calculations based on the parameters derived from an analysis of experimental data for ErRh{sub 4}B{sub 4} single crystals. The easy directions of magnetization of these compounds are consistent with the signs of the Stevens factor {alpha}J of the CEF Hamiltonian. A strong influence of magnetic anisotropy on superconductivity was also observed.

  10. 75 FR 43172 - International Conference on Harmonisation; Draft Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-23

    ... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... Recommendation of Pharmacopoeial Texts for Use in the ICH Regions; Annex 13: Bulk Density and Tapped Density...

  11. Possible role for increased C4b-binding-protein level in acquired protein S deficiency in type I diabetes.

    PubMed

    Ceriello, A; Giugliano, D; Quatraro, A; Marchi, E; Barbanti, M; Lefebvre, P

    1990-04-01

    In this study, total protein S (PS) immunological levels, free-PS and C4b-binding-protein (C4bBP) concentrations, and PS functional activity were investigated in insulin-dependent (type I) diabetic patients and compared with nondiabetic subjects. Mean total PS antigen concentration was not different between diabetic patients and nondiabetic subjects, whereas free-PS levels and PS functional activity were significantly reduced in diabetic patients. C4bBP was increased in diabetic patients and correlated with HbA1 levels. This study shows that type I diabetic patients have depressed free PS and PS activity despite the presence of normal total PS concentration and suggests that this phenomenon is probably linked to the increase of circulating C4bBP.

  12. Relationship between LAPTM4B Gene Polymorphism and Prognosis of Patients following Tumor Resection for Colorectal and Esophageal Cancers

    PubMed Central

    Xing, Xiaofang; Du, Hong; Zhou, Chunlian; Zhang, Qingyun; Hao, Chunyi; Wen, Xianzi; Ji, Jiafu

    2016-01-01

    Background Lysosome-associated transmembrane-4 beta (LAPTM4B) is an oncogene that participates tumorgenesis in a variety of human solid tumors, and it has two alleles named as LAPTM4B*1 and *2. The present study aimed to identify the association of LAPTM4B genotype with clinicopathological features and prognosis in colorectal and esophageal cancer patients. Method Genotypes of LAPTM4B were determined by PCR in 167 colon cancer cases (72 patients in a discovery cohort and 95 patients in a testing cohort), 160 rectal cancer cases and 164 esophageal cancer cases. Association between the LAPTM4B gene polymorphism and clinicopathological variables was calculated by Chi-square test or Fisher’s exact test. Patient survival differences were calculated by the Kaplan-Meier method. Prognostic factors were determined with Log-rank test and Cox regression model. Results LAPTM4B *1/1 was more frequently detected in colon cancer patients with lymph node metastasis and TNM III+IV stages in total colon cancer (discovery + testing cohorts). LAPTM4B *2/2 decreased in recurrent patients in total colon cancer patients (P = 0.045). Kaplan-Meier survival curves and Log-rank test showed that LAPTM4B*1 was correlated with shorter overall survival (OS) in discovery and testing cohorts of colon cancer (P = 0.0254 and 0.0292, respectively), but not in rectal and esophageal cancer cases (P = 0.7669 and 0.9356, respectively). Multivariate analysis showed that LAPTM4B genotype was an independent prognostic factor for OS in total colon cancer [P = 0.004, hazard ratio (HR) = 0.432; 95% confidence interval (CI) = 0.243–0.768], but not in rectal and esophageal cancers (P = 0.791, HR = 1.073, 95% CI = 0.638–1.804 and 0.998, HR = 1.000, 95% CI = 0.663–1.530, respectively). Conclusion These findings suggested that LAPTM4B allele *1 was a risk factor associated with poor prognosis in patients with colon cancer, but not in patients with rectal or esophageal cancers. LAPTM4B genotype status might

  13. Escape Mutations in NS4B Render Dengue Virus Insensitive to the Antiviral Activity of the Paracetamol Metabolite AM404.

    PubMed

    van Cleef, Koen W R; Overheul, Gijs J; Thomassen, Michael C; Marjakangas, Jenni M; van Rij, Ronald P

    2016-04-01

    Despite the enormous disease burden associated with dengue virus infections, a licensed antiviral drug is lacking. Here, we show that the paracetamol (acetaminophen) metabolite AM404 inhibits dengue virus replication. Moreover, we find that mutations in NS4B that were previously found to confer resistance to the antiviral compounds NITD-618 and SDM25N also render dengue virus insensitive to AM404. Our work provides further support for NS4B as a direct or indirect target for antiviral drug development.

  14. A Computer Graphics Human Figure Application Of Biostereometrics

    NASA Astrophysics Data System (ADS)

    Fetter, William A.

    1980-07-01

    A study of improved computer graphic representation of the human figure is being conducted under a National Science Foundation grant. Special emphasis is given biostereometrics as a primary data base from which applications requiring a variety of levels of detail may be prepared. For example, a human figure represented by a single point can be very useful in overview plots of a population. A crude ten point figure can be adequate for queuing theory studies and simulated movement of groups. A one hundred point figure can usefully be animated to achieve different overall body activities including male and female figures. A one thousand point figure si-milarly animated, begins to be useful in anthropometrics and kinesiology gross body movements. Extrapolations of this order-of-magnitude approach ultimately should achieve very complex data bases and a program which automatically selects the correct level of detail for the task at hand. See Summary Figure 1.

  15. A case of figurate urticaria by etanercept

    PubMed Central

    Sessa, Maurizio; Sullo, Maria Giuseppa; Mascolo, Annamaria; Cimmaruta, Daniela; Romano, Francesca; Puca, Rosa Valentina; Capuano, Annalisa; Rossi, Francesco; Schiavo, Ada Lo

    2016-01-01

    Etanercept is a competitive inhibitor of tumor necrosis factor-alpha (TNF-α) a polypeptide hormone, involved in the development of the immune system, in host defense and immune surveillance. Even if the etanercept mechanism of action is not completely understood, it is supposed that it negatively modulates biological responses mediated by molecules (cytokines, adhesion molecules, or proteinases) induced or regulated by TNF. For this reason, it is widely used in the treatment of immunologicals diseases, such as rheumatoid and psoriatic arthritis, polyarticular juvenile idiopathic active, ankylosing spondylitis, and plaque psoriasis. Etanercept has a good tolerability profile. Adverse events related to skin are rare, arising usually in about 5% of patients treated with anti-TNF α. In this scenario, we describe a case of figurate urticaria arose after the re-administration of etanercept in a patient affected by psoriasis and hepatitis B. A 65-year-old man, affected by psoriasis, was hospitalized in September 2014 to the Regional Center for the treatment of psoriasis and Biological Drugs of Second University of Naples for progressive extension of psoriatic skin lesions. The laboratory analysis detected positivity for hepatitis B virus (HBV) antigens. For this reason, it was administered to him lamivudine 100 mg/die about 30 days before to start etanercept treatment. The etanercept therapy has resulted in a progressive improving of skin manifestations, and the patient decided individually to stop the therapy. Afterwards, for worsening of the psoriatic lesions, he was again hospitalized and treated with the same therapeutic schedule (lamivudine followed by etanercept). Ten days after the start of therapy, the patient showed the onset of urticarial rash. Due to this, the treatment with lamivudine and etanercept was suspended and the patient's clinical conditions improved. It is probably that immunological disorders due to etanercept therapy and HBV infection could

  16. Retraction: "Activated K-Ras and INK4a/Arf Deficiency Promote Aggressiveness of Pancreatic Cancer by Induction of EMT Consistent With Cancer Stem Cell Phenotype" by Wang et al.

    PubMed

    2016-10-01

    The above article, published online on November 23, 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Gary S. Stein, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation from Wayne State University involving the first author and the corresponding author that found Figure 4B and C to be inappropriately manipulated and re-labeled. Literature Cited Wang Z, Ali S, Banerjee S, Bao B, Li Y, Azmi AS, Korc M, Sarkar FH. 2013. Activated K-Ras and INK4a/Arf deficiency promote aggressiveness of pancreatic cancer by induction of EMT consistent with cancer stem cell phenotype. J Cell Physiol 228:556-562; doi: 10.1002/jcp.24162.

  17. Thermoelectric Figure of Merit in Anisotropic Systems

    NASA Astrophysics Data System (ADS)

    Bies, W.; Radtke, R. J.; Ehrenreich, H.

    1998-03-01

    General expressions for the electrical conductivity, thermopower, and electronic thermal conductivity are derived for anisotropic materials including their full tensorial character and properly treating the effects of the sample boundaries. The thermoelectric figure of merit ZT constructed from these quantities is proved to be maximal only when the electric field (in thermoelectric coolers) or thermal gradient (in power generators) is applied along the direction of highest conductivity. Fields applied along directions for which the conductivity tensor is non-diagonal induce transverse electric fields and thermal gradients which may be larger in magnitude than the applied fields. These fields reduce ZT below that expected from anisotropy alone. Numerical results are presented for bulk n-type Bi_2Te3 and quantum well and quantum wire geometries using semiclassical transport theory in the effective mass and relaxation time approximations. The effects of multi-valley conduction and confinement-induced splitting of the valley degeneracy are included. Surprisingly, this model predicts generally that the thermopower and hence ZT are independent of the direction of the applied fields in the limit of vanishing lattice thermal conductivity.

  18. An economics figure of merit in ALPS

    SciTech Connect

    Shatilla, Y.A.

    2000-07-01

    One of the most pressing issues facing the deregulated nuclear electric power industry is its economic competitiveness when compared to other sources of electrical power. Traditionally, finding the optimum loading pattern (LP) that meets all the safety and operational objective functions and at the same time produces the most attractive economical solutions is an iterative process. This is because (a) LP search tools usually lack the capability to generate equilibrium solutions and (b) economics objective functions are hard to include in the search process. In this paper, the Westinghouse Advanced Loading Pattern Search code (ALPS) has been demonstrated to successfully find LPs that meet user-defined operational and safety as well as economics objectives. This has been made possible by the development of TULIP language that allows the integration of external procedures into the search process of the main program, ALPS. In the example given, an economic figure of merit (EFM) has been defined and included via TULIP script into the fuel management optimization problem of a three-loop Westinghouse core operating an 18-month cycle. The LPs found by ALPS exhibit a clear trend of meeting and, in some cases, exceeding the EFM objective function defined for the ALPS search process a priori.

  19. Birth delays skew developing world's fertility figures.

    PubMed

    1999-09-01

    This article explains that birth delays skew developing world's fertility figures. When successive groups of women who have delayed childbearing start having children, the rapid fertility decline stalls. Such change in the timing of childbearing skews the total fertility rate (TFR). Analysis of the tempo component of TFR trends in Taiwan suggests that tempo effects reduced its TFR by about 10% in the late 1970s and early 1990s and by about 19% in the late 1980s. In Colombia, on the basis of increasing mean maternal age at childbirth between the 1970s and the late 1980s, tempo distortions of the TFR during the most of the 1980s seem likely. Moreover, many developing countries are now experiencing rapid fertility declines that are in part attributable to tempo changes. These changes have accelerated past fertility transitions, but they also make these countries vulnerable to future stalls in fertility when the delays in childbearing end. Since fertility reductions caused by tempo effects lead to real declines in birth rates and hence in population growth, countries that wish to reduce birth rates can take actions that encourage women to delay marriage and the onset of childbearing.

  20. High-temperature mass spectrometry - Vaporization of group 4-B metal carbides. [using Knudsen effusion

    NASA Technical Reports Server (NTRS)

    Stearns, C. A.; Kohl, F. J.

    1974-01-01

    The high temperature vaporization of the metal-carbon systems TiC, ZrC, HfC, and ThC was studied by the Knudsen effusion - mass spectrometric method. For each system the metal dicarbide and tetracarbide molecular species were identified in the gas phase. Relative ion currents of the carbides and metals were measured as a function of temperature. Second- and third-law methods were used to determine enthalpies. Maximum values were established for the dissociation energies of the metal monocarbide molecules TiC, ZrC, HfC, and ThC. Thermodynamic functions used in the calculations are discussed in terms of assumed molecular structures and electronic contributions to the partition functions. The trends shown by the dissociation energies of the carbides of Group 4B are compared with those of neighboring groups and discussed in relation to the corresponding oxides and chemical bonding. The high temperature molecular beam inlet system and double focusing mass spectrometer are described.

  1. Study of Historical 4B/X17 Mega Flare on 28 October 2003 (P58)

    NASA Astrophysics Data System (ADS)

    Uddin, W.; Chandra, R.; Ali, S. S.

    2006-11-01

    wuddin_99@yahoo.com We analysed multi-wavelength data of 28 October 2003 4B/X17.2 class extremely energetic parallel ribbon solar flare, which occurred in NOAA 10486. The flare was well observed in H-alpha at ARIES, Nainital and various space (SOHO, TRACE, RHESSI, WIND etc.) and ground based Observatories. The H-alpha observations show the stretching/detwisting and eruption of helically twisted S shaped (sigmoid) filament in the South-West direction of the active region with bright shock front followed by rapid increase in intensity and area of the gigantic flare. The flare is associated with a bright/fast full halo earth directed CME, strong type II, III and IV radio bursts, an intense proton event and GLE. It seems that the filament eruption triggered the halo CME because the helical structure is clearly visible in the SOHO/LASCO C2, C3 images. This indicates helicity transfer from chromosphere to corona and interplanetary medium. The magnetic field of the flaring region was most complex with high magnetic shear. From the above analysis we feel that the energy buildup/release process of this unique flare support helically twisted magnetic flux rope model.

  2. Intramolecular cycloaddition reactions of furo[3,4-b]indoles for alkaloid synthesis.

    PubMed

    Padwa, Albert; Zou, Yan; Cheng, Bo; Li, Hao; Downer-Riley, Nadale; Straub, Christopher S

    2014-04-04

    Model studies dealing with the Cu(II)- or Rh(II)-catalyzed carbenoid cyclization/cycloaddition cascade of several α-diazo indolo amido esters have been carried out as an approach to the alkaloid scandine. The Cu(II)-catalyzed reaction of an α-diazo indolo diester that contains a tethered oxa-pentenyl side chain was found to give rise to a reactive benzo[c]furan which undergoes a subsequent [4 + 2]-cycloaddition across the tethered π-bond. The reaction proceeds by the initial generation of a copper carbenoid intermediate which cyclizes onto the adjacent carbonyl group to give a reactive benzo[c]furan which in certain cases can be isolated. Disappointingly, the analogous reaction with the related amido indolo ester failed to take place, even when the tethered π-bond contained an electron-withdrawing carbomethoxy group. It would seem that the geometric requirements for the intramolecular cycloaddition of the furo[3,4-b]indole system with the tethered π-bond imposes distinct restrictions upon the bond angles of the reacting centers to prevent the cycloaddition reaction from occurring. However, the incorporation of another carbonyl group on the nitrogen atom of the tethered alkenyl diazo amido indolo ester seemingly provides better orbital overlap between the reacting π-systems and allows the desired cycloaddition reaction to occur.

  3. Inositol polyphosphate 4-phosphatase II (INPP4B) is associated with chemoresistance and poor outcome in AML.

    PubMed

    Rijal, Sewa; Fleming, Shaun; Cummings, Nik; Rynkiewicz, Natalie K; Ooms, Lisa M; Nguyen, Nhu-Y N; Teh, Tse-Chieh; Avery, Sharon; McManus, Julie F; Papenfuss, Anthony T; McLean, Catriona; Guthridge, Mark A; Mitchell, Christina A; Wei, Andrew H

    2015-04-30

    Phosphoinositide signaling regulates diverse cellular functions. Phosphoinositide-3 kinase (PI3K) generates PtdIns(3,4,5)P3 and PtdIns(3,4)P2, leading to the activation of proliferative and anti-apoptotic signaling pathways. Termination of phosphoinositide signaling requires hydrolysis of inositol ring phosphate groups through the actions of PtdIns(3,4,5)P3 3-phosphatase (PTEN), PtdIns(3,4,5)P3 5-phosphatases (eg, SHIP), and PtdIns(3,4)P2 4-phosphatases (eg, INPP4B). The biological relevance of most of these phosphoinositide phosphatases in acute myeloid leukemia (AML) remains poorly understood. Mass spectrometry-based gene expression profiling of 3-, 4- and 5-phosphatases in human AML revealed significant overexpression of INPP4B. Analysis of an expanded panel of 205 AML cases at diagnosis revealed INPP4B overexpression in association with reduced responses to chemotherapy, early relapse, and poor overall survival, independent of other risk factors. Ectopic overexpression of INPP4B conferred leukemic resistance to cytosine arabinoside (ara-C), daunorubicin, and etoposide. Expression of a phosphatase inert variant (INPP4B C842A) failed to abrogate resistance of AML cells to chemotherapy in vitro or in vivo. In contrast, targeted suppression of endogenously overexpressed INPP4B by RNA interference sensitized AML cell lines and primary AML to chemotherapy. These findings demonstrate a previously unsuspected and clinically relevant role for INPP4B gain of function as a mediator of chemoresistance and poor survival outcome in AML independent of its phosphoinositide phosphatase function.

  4. Crystal structure of 7-isopropyl-1,4a,N-trimethyl-1,2,3,4,4a,4b,5,6,7,8,10,10a-dodeca-hydro-phenanthrene-1-carb-ox-amide.

    PubMed

    Liu, Li; Yan, Xin-Yan; Rao, Xiao-Ping

    2015-10-01

    In the title compound, C26H37NO, a new derivative of di-hydro-abietic acid, the two cyclo-hexene rings adopt half chair conformations, whereas the cyclo-hexane ring has a chair conformation. Each of the methyl groups is in an axial position with respect to the tricyclic hydro-phenanthrene residue. In the crystal packing, methyl-ene-C-H⋯π(phen-yl) inter-actions lead to supra-molecular helical chains along [010]; the amide-H atom does not form a significant inter-molecular inter-action owing to steric pressure.

  5. Sport-specific injuries and medical problems of figure skaters.

    PubMed

    Porter, Emily B; Young, Craig C; Niedfeldt, Mark W; Gottschlich, Laura M

    2007-09-01

    Figure skating is becoming increasingly popular as both a recreational and competitive sport. As the number of figure skating participants increases, so will the number of active patients who present to their primary care physician with sport-related injuries and medical problems. Figure skating is a unique sport that continues to evolve and progress with participants partaking in more difficult moves and more rigorous training programs. Common problems in figure skating include acute musculo-skeletal injuries and chronic overuse injuries, which primarily occur in the foot, ankle, knee, leg, hip, and lower back. Figure skaters are also more likely to endure specific medical problems such as exercise-induced bronchospasm and eating disorders. Primary care physicians are able to contribute to their figure skating patient's health by recognition and appropriate treatment of acute injuries and prevention of chronic injuries and other medical problems.

  6. The interaction between the hepatitis C proteins NS4B and NS5A is involved in viral replication.

    PubMed

    David, Naama; Yaffe, Yakey; Hagoel, Lior; Elazar, Menashe; Glenn, Jeffrey S; Hirschberg, Koret; Sklan, Ella H

    2015-01-15

    Hepatitis C virus (HCV) replicates in membrane associated, highly ordered replication complexes (RCs). These complexes include viral and host proteins necessary for viral RNA genome replication. The interaction network among viral and host proteins underlying the formation of these RCs is yet to be thoroughly characterized. Here, we investigated the association between NS4B and NS5A, two critical RC components. We characterized the interaction between these proteins using fluorescence resonance energy transfer and a mammalian two-hybrid system. Specific tryptophan residues within the C-terminal domain (CTD) of NS4B were shown to mediate this interaction. Domain I of NS5A, was sufficient to mediate its interaction with NS4B. Mutations in the NS4B CTD tryptophan residues abolished viral replication. Moreover, one of these mutations also affected NS5A hyperphosphorylation. These findings provide new insights into the importance of the NS4B-NS5A interaction and serve as a starting point for studying the complex interactions between the replicase subunits.

  7. UBE4B protein couples ubiquitination and sorting machineries to enable epidermal growth factor receptor (EGFR) degradation.

    PubMed

    Sirisaengtaksin, Natalie; Gireud, Monica; Yan, Qing; Kubota, Yoshihisa; Meza, Denisse; Waymire, Jack C; Zage, Peter E; Bean, Andrew J

    2014-01-31

    The signaling of plasma membrane proteins is tuned by internalization and sorting in the endocytic pathway prior to recycling or degradation in lysosomes. Ubiquitin modification allows recognition and association of cargo with endosomally associated protein complexes, enabling sorting of proteins to be degraded from those to be recycled. The mechanism that provides coordination between the cellular machineries that mediate ubiquitination and endosomal sorting is unknown. We report that the ubiquitin ligase UBE4B is recruited to endosomes in response to epidermal growth factor receptor (EGFR) activation by binding to Hrs, a key component of endosomal sorting complex required for transport (ESCRT) 0. We identify the EGFR as a substrate for UBE4B, establish UBE4B as a regulator of EGFR degradation, and describe a mechanism by which UBE4B regulates endosomal sorting, affecting cellular levels of the EGFR and its downstream signaling. We propose a model in which the coordinated action of UBE4B, ESCRT-0, and the deubiquitinating enzyme USP8 enable the endosomal sorting and lysosomal degradation of the EGFR.

  8. The caspase-3 cleavage product of the plasma membrane Ca2+-ATPase 4b is activated and appropriately targeted.

    PubMed

    Pászty, Katalin; Antalffy, Géza; Penheiter, Alan R; Homolya, László; Padányi, Rita; Iliás, Attila; Filoteo, Adelaida G; Penniston, John T; Enyedi, Agnes

    2005-11-01

    The calmodulin-activated transporter hPMCA4 (human plasma membrane Ca2+-ATPase isoform 4) is a target for cleavage by caspase-3 during apoptosis. We have demonstrated that caspase-3 generates a 120 kDa fragment of this pump which lacks the complete autoinhibitory sequence [Paszty, Verma, Padanyi, Filoteo, Penniston and Enyedi (2002) J. Biol. Chem. 277, 6822-6829]. In the present study we analysed further the characteristics of the fragment of hPMCA4b produced by caspase-3. We did this by overexpressing the caspase-3 cleavage product of hPMCA4b in COS-7 and MDCKII (Madin-Darby canine kidney II) cells. This technique made it possible to clearly define the properties of this fragment, and we showed that it is constitutively active, as it forms a phosphoenzyme intermediate and has high Ca2+ transport activity in the absence of calmodulin. When this fragment of hPMCA4b was stably expressed in MDCKII cell clones, it was targeted without degradation to the basolateral plasma membrane. In summary, our studies emphasize that the caspase-3 cleavage product of hPMCA4b is constitutively active, and that the C-terminus is not required for proper targeting of hPMCA4b to the plasma membrane. Also, for the first time, we have generated cell clones that stably express a constitutively active PMCA.

  9. Newly isolated Penicillium oxalicum A592-4B secretes enzymes that degrade milled rice straw with high efficiency.

    PubMed

    Aoyama, Akihisa; Kurane, Ryuichiro; Matsuura, Akira; Nagai, Kazuo

    2015-01-01

    An enzyme producing micro-organism, which can directly saccharify rice straw that has only been crushed without undergoing the current acid or alkaline pretreatment, was found. From the homology with the ITS, 28S rDNA sequence, the strain named A592-4B was identified as Penicillium oxalicum. Activities of the A592-4B enzymes and commercial enzyme preparations were compared by Novozymes Cellic CTec2 and Genencore GC220. In the present experimental condition, activity of A592-4B enzymes was 2.6 times higher than that of CTec2 for degrading milled rice straw. Furthermore, even when a quarter amount of A592-4B enzyme was applied to the rice straw, the conversion rate was still higher than that by CTec2. By utilizing A592-4B enzymes, improved lignocellulose degradation yields can be achieved without pre-treatment of the substrates; thus, contributing to cost reduction as well as reducing environmental burden.

  10. Systems Biology Reveals NS4B-Cyclophilin A Interaction: A New Target to Inhibit YFV Replication.

    PubMed

    Vidotto, Alessandra; Morais, Ana T S; Ribeiro, Milene R; Pacca, Carolina C; Terzian, Ana C B; Gil, Laura H V G; Mohana-Borges, Ronaldo; Gallay, Philippe; Nogueira, Mauricio L

    2017-04-07

    Yellow fever virus (YFV) replication is highly dependent on host cell factors. YFV NS4B is reported to be involved in viral replication and immune evasion. Here interactions between NS4B and human proteins were determined using a GST pull-down assay and analyzed using 1-DE and LC-MS/MS. We present a total of 207 proteins confirmed using Scaffold 3 Software. Cyclophilin A (CypA), a protein that has been shown to be necessary for the positive regulation of flavivirus replication, was identified as a possible NS4B partner. 59 proteins were found to be significantly increased when compared with a negative control, and CypA exhibited the greatest difference, with a 22-fold change. Fisher's exact test was significant for 58 proteins, and the p value of CypA was the most significant (0.000000019). The Ingenuity Systems software identified 16 pathways, and this analysis indicated sirolimus, an mTOR pathway inhibitor, as a potential inhibitor of CypA. Immunofluorescence and viral plaque assays showed a significant reduction in YFV replication using sirolimus and cyclosporine A (CsA) as inhibitors. Furthermore, YFV replication was strongly inhibited in cells treated with both inhibitors using reporter BHK-21-rep-YFV17D-LucNeoIres cells. Taken together, these data suggest that CypA-NS4B interaction regulates YFV replication. Finally, we present the first evidence that YFV inhibition may depend on NS4B-CypA interaction.

  11. AMPK antagonizes hepatic glucagon-stimulated cyclic AMP signalling via phosphorylation-induced activation of cyclic nucleotide phosphodiesterase 4B

    PubMed Central

    Johanns, M.; Lai, Y.-C.; Hsu, M.-F.; Jacobs, R.; Vertommen, D.; Van Sande, J.; Dumont, J. E.; Woods, A.; Carling, D.; Hue, L.; Viollet, B.; Foretz, M; Rider, M H

    2016-01-01

    Biguanides such as metformin have previously been shown to antagonize hepatic glucagon-stimulated cyclic AMP (cAMP) signalling independently of AMP-activated protein kinase (AMPK) via direct inhibition of adenylate cyclase by AMP. Here we show that incubation of hepatocytes with the small-molecule AMPK activator 991 decreases glucagon-stimulated cAMP accumulation, cAMP-dependent protein kinase (PKA) activity and downstream PKA target phosphorylation. Moreover, incubation of hepatocytes with 991 increases the Vmax of cyclic nucleotide phosphodiesterase 4B (PDE4B) without affecting intracellular adenine nucleotide concentrations. The effects of 991 to decrease glucagon-stimulated cAMP concentrations and activate PDE4B are lost in hepatocytes deleted for both catalytic subunits of AMPK. PDE4B is phosphorylated by AMPK at three sites, and by site-directed mutagenesis, Ser304 phosphorylation is important for activation. In conclusion, we provide a new mechanism by which AMPK antagonizes hepatic glucagon signalling via phosphorylation-induced PDE4B activation. PMID:26952277

  12. Thieno[3,4-b]thiophene-Based Novel Small-Molecule Optoelectronic Materials.

    PubMed

    Zhang, Cheng; Zhu, Xiaozhang

    2017-04-04

    Because of the tailorable photoelectric properties derived from judicious molecular design and large-area and low-temperature processability especially on flexible substrates, design and synthesis of new organic π-functional materials is always a central topic in the field of organic optoelectronics, which siginificantly contributed to the development of high-performance optoelectronic devices such as organic photovoltaics (OPVs), organic field-effect transistors (OFETs), and organic light-emitting diodes (OLEDs). Compared with polymers, small molecules with well-defined molecular structures benefit the establishment of structure-property relationships, which may provide valuable guidelines for the design of new optoelectronic materials to further promote the device performance. New building blocks are essential for the construction of optoelectronic materials. As is well recognized, thiophene-based functional materials have played an indispensable role in the development of organic optoelectronics. Compared with six-membered benzene, five-membered thiophene shows weaker aromaticity and lower steric hindrance and may provide extra sulfur-sulfur interactions in solid state. Among various thiophene building blocks, thieno[3,4-b]thiophene (TbT) is an asymmetric fused bithiophene containing four functionalization positions, in which the proaromatic thiophene can effectively stabilize the quinoidal resonance of the aromatic thiophene. Thus, TbT exhibits a unique characteristic of quinoid-resonance effect that is powerful to modulate electronic structures. Although the application of TbT in polymer donor materials represented by PTB-7 has achieved a great success, its application in small-molecule optoelectronic materials is almost an untouched field. In this Account, we summerize the rational design of a series of TbT-based small-molecule optoelectronic materials designed and optimized by quinoid-resonance effect, regiochemistry, and side-chain engineering and

  13. Beyond captions: linking figures with abstract sentences in biomedical articles.

    PubMed

    Bockhorst, Joseph P; Conroy, John M; Agarwal, Shashank; O'Leary, Dianne P; Yu, Hong

    2012-01-01

    Although figures in scientific articles have high information content and concisely communicate many key research findings, they are currently under utilized by literature search and retrieval systems. Many systems ignore figures, and those that do not typically only consider caption text. This study describes and evaluates a fully automated approach for associating figures in the body of a biomedical article with sentences in its abstract. We use supervised methods to learn probabilistic language models, hidden Markov models, and conditional random fields for predicting associations between abstract sentences and figures. Three kinds of evidence are used: text in abstract sentences and figures, relative positions of sentences and figures, and the patterns of sentence/figure associations across an article. Each information source is shown to have predictive value, and models that use all kinds of evidence are more accurate than models that do not. Our most accurate method has an F1-score of 69% on a cross-validation experiment, is competitive with the accuracy of human experts, has significantly better predictive accuracy than state-of-the-art methods and enables users to access figures associated with an abstract sentence with an average of 1.82 fewer mouse clicks. A user evaluation shows that human users find our system beneficial. The system is available at http://FigureItOut.askHERMES.org.

  14. Higher-order figure discrimination in fly and human vision.

    PubMed

    Aptekar, Jacob W; Frye, Mark A

    2013-08-19

    Visually-guided animals rely on their ability to stabilize the panorama and simultaneously track salient objects, or figures, that are distinct from the background in order to avoid predators, pursue food resources and mates, and navigate spatially. Visual figures are distinguished by luminance signals that produce coherent motion cues as well as more enigmatic 'higher-order' statistical features. Figure discrimination is thus a complex form of motion vision requiring specialized neural processing. In this minireview, we will highlight recent advances in understanding the perceptual, behavioral, and neurophysiological basis of higher-order figure detection in flies, much of which is grounded in the historical perspective and mechanistic underpinnings of human psychophysics.

  15. Surface reconstruction, figure-ground modulation, and border-ownership.

    PubMed

    Jeurissen, Danique; Self, Matthew W; Roelfsema, Pieter R

    2013-01-01

    The Differentiation-Integration for Surface Completion (DISC) model aims to explain the reconstruction of visual surfaces. We find the model a valuable contribution to our understanding of figure-ground organization. We point out that, next to border-ownership, neurons in visual cortex code whether surface elements belong to a figure or the background and that this is influenced by attention. We furthermore suggest that there must be strong links between object recognition and figure-ground assignment in order to resolve the status of interior contours. Incorporation of these factors in neurocomputational models will further improve our understanding of surface reconstruction, figure-ground organization, and border-ownership.

  16. Investigation of the process chain leading to the development of convection during COP IOP 4b

    NASA Astrophysics Data System (ADS)

    Bauer, H.-S.; Schwitalla, T.; Aoshima, F.; Behrendt, A.; Wulfmeyer, V.

    2012-04-01

    The COPS IOP 4b took place from June 20th to June 21st 2007. It was characterized by widespread convection in the COPS domain. The development was steered by a strong low pressure system southwest of the British Isles. On its eastern side warm and moist subtropical air was directed to central Europe. First convection was triggered over the Vosges Mountains around noon on the 20th of June long before the front approached the COPS region. After a calm early afternoon, severe convection was triggered in wide regions of the COPS region in the evening and moved eastwards to Bavaria during the night to the 21st of June. In contrast to other IOPs, the situation was not captured correctly by most of the involved prediction models, no matter whether they were operated with or without sophisticated data assimilation. Aim of this presentation is to unravel the mechanisms responsible for the triggering of convection and to understand the processes preparing the atmosphere for the development of severe convection during the afternoon and night. For this purpose, many different data sets will be investigated ranging from the high resolution Vienna Enhanced Resolution Analysis (VERA), high resolution radar and satellite images and composites to soundings and data as well as retrieved products from the instruments at the COPS supersites. First impression is that the complicated low-level wind field is the major driver for the preparation of the atmosphere and therefore for the development of convection during the day. The inaccuracies in representing the low level wind field are also expected to be the major reason for the failure of the models to correctly predict the situation.

  17. Skin Involvement and Breast Cancer: Are T4B Lesions of All Sizes Created Equal?

    PubMed Central

    Silverman, Diana; Ruth, Karen; Sigurdson, Elin R.; Egleston, Brian L.; Goldstein, Lori J.; Wong, Yu-Ning; Boraas, Marcia; Bleicher, Richard J.

    2014-01-01

    Background Nonmetastatic non-inflammatory invasive breast cancers having skin involvement (SI) are classified as T4b, regardless of size. This study evaluated disease specific survival (DSS) to determine whether size should be considered for these lesions, rather than grouping them all into Stage III. Study Design Surveillance Epidemiology and End Results data linked to Medicare claims were reviewed. SI and nonSI tumors were reclassified using AJCC 7th Edition groupings using tumor size and nodal involvement alone without considering SI (neostage). DSS was adjusted for demographics, histology and treatment using competing risk methods with propensity score-based weighting and bootstrap standard errors. Results Among 924 SI patients diagnosed between 1992 and 2005, tumors were 0.1–2.0, 2.1–5.0, and >5.0 cm in 11.6%, 51.1%, and 37.3% of cases, respectively. There were no nodal metastases in 22.3%, 1–3 positive nodes in 31.7%, 4–9 positive in 28.6% and ≥10 positive in 17.4% of cases. For SI patients, adjusted 5-year DSS was 95.8% [95%CI: 95.6–96.0] for neostage I, declining progressively to 36.4% [95%CI: 33.8–39.2] for neostage IIIC patients. Adjusted 5-year DSS for SI and nonSI tumors (n=66,185) was similar for neostage I, IIA, and IIB, and markedly lower for IIIA and IIIC. Adjusted DSS for SI IIIA was similar to nonSI IIIC. Conclusions Noninflammatory SI breast cancers have widely varied DSS that differs by tumor size and nodal involvement, and therefore should not all be stage III. SI should be subordinate to T and N groupings to classify SI with nonSI lesions having similar prognoses. PMID:25026875

  18. BOOK REVIEW: Relativistic Figures of Equilibrium

    NASA Astrophysics Data System (ADS)

    Mars, M.

    2009-08-01

    Compact fluid bodies in equilibrium under its own gravitational field are abundant in the Universe and a proper treatment of them can only be carried out using the full theory of General Relativity. The problem is of enormous complexity as it involves two very different regimes, namely the interior and the exterior of the fluid, coupled through the surface of the body. This problem is very challenging both from a purely theoretical point of view, as well as regarding the obtaining of realistic models and the description of their physical properties. It is therefore an excellent piece of news that the book 'Relativistic Figures of Equilibrium' by R Meinel, M Ansorg, A Kleinwächter, G Neugebauer and D Petroff has been recently published. This book approaches the topic in depth and its contents will be of interest to a wide range of scientists working on gravitation, including theoreticians in general relativity, mathematical physicists, astrophysicists and numerical relativists. This is an advanced book that intends to present some of the present-day results on this topic. The most basic results are presented rather succinctly, and without going into the details, of their derivations. Although primarily not intended to serve as a textbook, the presentation is nevertheless self-contained and can therefore be of interest both for experts on the field as well as for anybody wishing to learn more about rotating self-gravitating compact bodies in equilibrium. It should be remarked, however, that this book makes a rather strong selection of topics and concentrates fundamentally on presenting the main results obtained by the authors during their research in this field. The book starts with a chapter where the fundamental aspects of rotating fluids in equilibrium, including its thermodynamic properties, are summarized. Of particular interest are the so-called mass-shedding limit, which is the limit where the body is rotating so fast that it is on the verge of starting

  19. Figures and First Years: Examining first-year Calculus I student ability to incorporate figures into technical reports

    NASA Astrophysics Data System (ADS)

    Antonacci, Nathan; Rogers, Michael; Pfaff, Thomas

    This three-year study focused on first-year Calculus I students and their abilities to incorporate figures into technical reports. Students were handed guidelines as part of their Multidisciplinary Sustainability Education Module meant to aid them in crafting effective figures. Figure-specific questionnaires were added in the class to gain insight into the quantitative literacy skills students possessed both before starting their course and after its completion. Reviews of the figures in 78 technical reports written by 106 students showed repeated failure to refer to figures in discussion sections and use them in evidence-based arguments. Analysis of quantitative literacy skills revealed that the students could both read and interpret figures, suggesting that issues with literacy were not the main contributor to the sub-par graphs.

  20. UBE4B Levels Are Correlated with Clinical Outcomes in Neuroblastoma Patients and with Altered Neuroblastoma Cell Proliferation and Sensitivity to EGFR Inhibitors

    PubMed Central

    Zage, Peter E.; Sirisaengtaksin, Natalie; Liu, Yin; Gireud, Monica; Brown, Brandon S.; Palla, Shana; Richards, Kristen N.; Hughes, Dennis P.M.; Bean, Andrew J.

    2012-01-01

    Background The UBE4B gene, located on chromosome 1p36, encodes a ubiquitin ligase that interacts with Hrs, a protein involved in EGFR trafficking, suggesting a link between EGFR trafficking and neuroblastoma pathogenesis. We have analyzed the roles of UBE4B in the outcomes of neuroblastoma patients and in neuroblastoma tumor cell proliferation, EGFR trafficking, and response to EGFR inhibition. Methods We examined the association of UBE4B expression with neuroblastoma patient survival using available microarray datasets. We measured UBE4B and EGFR protein levels in patient tumor samples and EGFR degradation rates in neuroblastoma cell lines and analyzed the effects of UBE4B on neuroblastoma tumor cell growth. The effects of the EGFR inhibitor cetuximab were examined in neuroblastoma cells expressing wild-type and mutant UBE4B. Results Low UBE4B gene expression is associated with poor outcomes in patients with neuroblastoma. UBE4B overexpression reduced neuroblastoma tumor cell proliferation, and UBE4B expression was inversely related to EGFR expression in patient tumor samples. EGFR degradation rates correlated with cellular UBE4B levels. Enhanced expression of catalytically active UBE4B resulted in reduced sensitivity to EGFR inhibition. Conclusions We have demonstrated associations between UBE4B expression and neuroblastoma patient outcomes and between UBE4B and EGFR expression in neuroblastoma tumor samples. Moreover, levels of UBE4B influenced neuroblastoma tumor cell proliferation, EGFR degradation, and response to EGFR inhibition. These results suggest UBE4B-mediated GFR trafficking may contribute to the poor prognosis of neuroblastoma tumors with 1p36 deletions, and that UBE4B expression may be a marker that can predict responses of neuroblastoma tumors to treatment. PMID:22990745

  1. Genome sequence and description of the heavy metal tolerant bacterium Lysinibacillus sphaericus strain OT4b.31

    PubMed Central

    Peña-Montenegro, Tito David; Dussán, Jenny

    2013-01-01

    Lysinibacillus sphaericus strain OT4b.31 is a native Colombian strain having no larvicidal activity against Culex quinquefasciatus and is widely applied in the bioremediation of heavy-metal polluted environments. Strain OT4b.31 was placed between DNA homology groups III and IV. By gap-filling and alignment steps, we propose a 4,096,672 bp chromosomal scaffold. The whole genome (consisting of 4,856,302 bp long, 94 contigs and 4,846 predicted protein-coding sequences) revealed differences in comparison to the L. sphaericus C3-41 genome, such as syntenial relationships, prophages and putative mosquitocidal toxins. Sphaericolysin B354, the coleopteran toxin Sip1A and heavy metal resistance clusters from nik, ars, czc, cop, chr, czr and cad operons were identified. Lysinibacillus sphaericus OT4b.31 has applications not only in bioremediation efforts, but also in the biological control of agricultural pests. PMID:24501644

  2. Local Outbreak of Listeria monocytogenes Serotype 4b Sequence Type 6 Due to Contaminated Meat Pâté.

    PubMed

    Althaus, Denise; Jermini, Marco; Giannini, Petra; Martinetti, Gladys; Reinholz, Danuta; Nüesch-Inderbinen, Magdalena; Lehner, Angelika; Stephan, Roger

    2017-04-01

    In January and February 2016, five cases of confirmed and two cases of probable infection due to Listeria monocytogenes serotype 4b, sequence type (ST) 6 belonging to a single pulsed-field gel electrophoresis pulsotype pattern were registered in a region of southern Switzerland. L. monocytogenes was detected in blood samples (four cases) and pleural fluid (one case). Furthermore, L. monocytogenes 4b ST6 was detected in a stool sample of an asymptomatic person exposed to a common food. Forthwith, the food safety authority and a local gourmet meat producer reported L. monocytogenes contamination of meat pâté. Analysis of further food and environmental samples from the premises of the producer yielded isolates matching the clinical strains and confirmed the presence of L. monocytogenes 4b ST6 in the mincing machine as the cause of the food contamination.

  3. (4aS,4bR,7R,10aS)-3,7-Dimethyl-10a-(propan-2-yl)-1,4,4a,4b,5,6,7,8,10,10a-deca­hydro­phenanthrene-1,4-dione

    PubMed Central

    Caracelli, Ignez; Zukerman-Schpector, Julio; Machado, André T. Lousada; Brocksom, Timothy J.; Ferreira, M. Lúcia; Tiekink, Edward R. T.

    2011-01-01

    In the title compound, C19H26O2, the A ring adopts a chair conformation, whereas the B and C rings both adopt distorted half-chair conformations with the quaternary C atom common to both rings lying 0.577 (3) and 0.648 (3) Å out of the approximate plane defined by the remaining five C atoms (r.m.s. deviations = 0.1386 and 0.1156 Å) for the B and C rings, respectively. Mol­ecules are assembled in the crystal through C—H⋯O inter­actions involving both carbonyl O atoms, which lead to supra­molecular chains aligned along the b axis. PMID:22199712

  4. Upregulation of LAPTM4B-35 promotes malignant transformation and tumorigenesis in L02 human liver cell line.

    PubMed

    Li, Li; Shan, Yi; Yang, Hua; Zhang, Sha; Lin, Ming; Zhu, Ping; Chen, Xin-Yu; Yi, Jing; McNutt, Michael A; Shao, Gen-Ze; Zhou, Rou-Li

    2011-07-01

    Hepatocellular carcinoma (HCC) is one of the most frequent malignant neoplasms worldwide and is the second leading cause of cancer death in China. We have previously demonstrated that LAPTM4B-35, encoded by lysosomal protein transmembrane 4 beta gene, is overexpressed in over 80% of HCCs and is a novel-independent prognostic factor for metastasis, recurrence, and postoperative survival in HCC. In this study, we investigated the role of LAPTM4B-35 in malignant transformation and tumorigenesis using L02 cells, a cell line originated from human normal liver cells. Our data show that replication-deficient adenovirus vector-mediated upregulation of LAPTM4B-35 promotes anchorage-independent proliferation and resistance to adriamycin-induced apoptosis. Study of the underlying mechanisms demonstrated alterations of molecular events involved in these processes, which included the activation of phosphoinositide 3-kinases (PI3K)/serine/threonine protein kinase B (PKB/AKT)/bcl-xL/bcl-2-associated death promoter homolog (Bad) signaling pathway, inhibition of caspase-3 activation, upregulation of Bcl-2, and downregulation of Bax. In addition, upregulation of LAPTM4B-35 in L02 cells resulted in tumorigenesis in 100% (6/6) of inoculated nude mice and accelerated the death of mice with xenografts in vivo. In conclusion, LAPTM4B-35 promotes malignant transformation and tumorigenesis in human liver L02 cell line through promotion of deregulated proliferation and inhibition of apoptosis. These findings suggest that overexpression of LAPTM4B-35 may play a critical role in hepatocarcinogenesis and therefore, may be a therapeutic target for HCC.

  5. INPP4B-mediated tumor resistance is associated with modulation of glucose metabolism via hexokinase 2 regulation in laryngeal cancer cells

    SciTech Connect

    Min, Joong Won; Kim, Kwang Il; Kim, Hyun-Ah; Kim, Eun-Kyu; Noh, Woo Chul; Jeon, Hong Bae; Cho, Dong-Hyung; Oh, Jeong Su; Park, In-Chul; Hwang, Sang-Gu; Kim, Jae-Sung

    2013-10-11

    Highlights: •HIF-1α-regulated INPP4B enhances glycolysis. •INPP4B regulates aerobic glycolysis by inducing HK2 via Akt-mTOR pathway. •Blockage of INPP4B and HK2 sensitizes radioresistant laryngeal cancer cells to radiation and anticancer drug. •INPP4B is associated with HK2 in human laryngeal cancer tissues. -- Abstract: Inositol polyphosphate 4-phosphatase type II (INPP4B) was recently identified as a tumor resistance factor in laryngeal cancer cells. Herein, we show that INPP4B-mediated resistance is associated with increased glycolytic phenotype. INPP4B expression was induced by hypoxia and irradiation. Intriguingly, overexpression of INPP4B enhanced aerobic glycolysis. Of the glycolysis-regulatory genes, hexokinase 2 (HK2) was mainly regulated by INPP4B and this regulation was mediated through the Akt-mTOR pathway. Notably, codepletion of INPP4B and HK2 markedly sensitized radioresistant laryngeal cancer cells to irradiation or anticancer drug. Moreover, INPP4B was significantly associated with HK2 in human laryngeal cancer tissues. Therefore, these results suggest that INPP4B modulates aerobic glycolysis via HK2 regulation in radioresistant laryngeal cancer cells.

  6. Escape Mutations in NS4B Render Dengue Virus Insensitive to the Antiviral Activity of the Paracetamol Metabolite AM404

    PubMed Central

    van Cleef, Koen W. R.; Overheul, Gijs J.; Thomassen, Michael C.; Marjakangas, Jenni M.

    2016-01-01

    Despite the enormous disease burden associated with dengue virus infections, a licensed antiviral drug is lacking. Here, we show that the paracetamol (acetaminophen) metabolite AM404 inhibits dengue virus replication. Moreover, we find that mutations in NS4B that were previously found to confer resistance to the antiviral compounds NITD-618 and SDM25N also render dengue virus insensitive to AM404. Our work provides further support for NS4B as a direct or indirect target for antiviral drug development. PMID:26856827

  7. Kepler-4b: A Hot Neptune-Like Planet of a G0 Star Near Main-Sequence Turnoff

    DTIC Science & Technology

    2010-04-20

    70 80 90. 100 Planetary Mass (Earth Masses) 1 2 3 4 5 6 7 R ad iu s (E ar th R ad ii) Kepler-4b Uranus Neptune GJ 436b Baraffe Z=0.5, NI, 7Gyr HAT...have masses and radii equal to or larger than those of Neptune and Uranus . The most important differences between the three exoplanets are their host...in Neptune or Uranus ). Nevertheless, we can state with a measure of confidence that there are no possible interior models for Kepler-4b with no H/He

  8. The Development of a Degree 360 Expansion of the Dynamic Ocean Topography of the POCM_4B Global Circulation Model

    NASA Technical Reports Server (NTRS)

    Rapp, Richard H.

    1998-01-01

    This paper documents the development of a degree 360 expansion of the dynamic ocean topography (DOT) of the POCM_4B ocean circulation model. The principles and software used that led to the final model are described. A key principle was the development of interpolated DOT values into land areas to avoid discontinuities at or near the land/ocean interface. The power spectrum of the POCM_4B is also presented with comparisons made between orthonormal (ON) and spherical harmonic magnitudes to degree 24. A merged file of ON and SH computed degree variances is proposed for applications where the DOT power spectrum from low to high (360) degrees is needed.

  9. Synthesis of Substituted 2,3,5,6-tetraarylbenzo(1,2-b:5,4-b')difurans

    NASA Technical Reports Server (NTRS)

    Abdul-Aziz, Mahmoud; Auping, Judith V.; Meador, Michael A.

    1995-01-01

    A series of substituted 2,3,5,6-tetraarylbenzo(l,2-b:5,4-b')difurans 1 was synthesized. This synthesis is based upon the photocyclization of 2,5-dibenzoylresorcinol dibenzyl ethers to the corresponding tetrahydrobenzo(1,2-b:5,4-b')difurans. Treatment of the photoproducts with methanesulfonyl chloride in pyridine afforded 1 in overall yields ranging from 30-72%. A number of these compounds have high fluorescence quantum yields (of phi(sub f) = 0.76-0.90), and their fluorescence spectra exhibit large solvatochromic shifts. These compounds may be suitable for use as fluorescent probes.

  10. Dynamic Reaction Figures: An Integrative Vehicle for Understanding Chemical Reactions

    ERIC Educational Resources Information Center

    Schultz, Emeric

    2008-01-01

    A highly flexible learning tool, referred to as a dynamic reaction figure, is described. Application of these figures can (i) yield the correct chemical equation by simply following a set of menu driven directions; (ii) present the underlying "mechanism" in chemical reactions; and (iii) help to solve quantitative problems in a number of different…

  11. The Young Child's Pictorial Representation of the Human Figure.

    ERIC Educational Resources Information Center

    Cox, Maureen V.; Mason, Sarah

    1998-01-01

    Examined reasons why young children typically omit the torso in human figure drawings. Found that more children produced a conventional figure when they constructed a manikin than when they were asked to draw, suggesting that children omit torsos because they have not yet devised a way of drawing them, rather than forgetting them or having an…

  12. 16 CFR Figures 3 and 4 to Subpart... - Test Specimens

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Test Specimens 3 Figures 3 and 4 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT... Figures 3 and 4 to Subpart A of Part 1201—Test Specimens EC03OC91.006...

  13. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  14. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  15. 49 CFR Appendix A to Subpart F of... - Figures

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Figures A Appendix A to Subpart F of Part 572 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... Percentile Male Pt. 572, Subpt. F, App. A Appendix A to Subpart F of Part 572—Figures EC01AU91.168...

  16. Transformation of the Incomplete Figure in Young Children

    ERIC Educational Resources Information Center

    Noda, Mitsuru

    2014-01-01

    This study aims to examine the developmental changes in young children's perception. A matching completion task consisting of three geometric figures and one bird-like figure were completed by children 3-5 years of age ("N" = 99). The rotation effect, in which the correct response decreased with orientation (45°, 90° 135°, and 180°), was…

  17. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform...

  18. The naked truth about my classical nude figures.

    PubMed

    Burnett, Roger

    2002-02-28

    The story 'Concerns raised over nudes at cancer clinic' (news February 13) does not truly reflect the situation. Although the hospital authorities had concerns about placing the classical nude figures in the hospital environment, the overwhelming response from the public has been positive. Moreover, considerable support for the figures has come from cancer patients.

  19. Distinguishing between Realistic and Fantastical Figures in Iran

    ERIC Educational Resources Information Center

    Davoodi, Telli; Corriveau, Kathleen H.; Harris, Paul L.

    2016-01-01

    Children in the United States come to distinguish historical from fictional story figures between the ages of 3 and 5 years, guided by the plausibility of the story events surrounding the figure (Corriveau, Kim, Schwalen, & Harris, 2009; Woolley & Cox, 2007). However, U.S. children vary in their reactions to stories that include…

  20. 40 CFR Figure B-1 to Subpart B of... - Example

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 40 Protection of Environment 6 2014-07-01 2014-07-01 false Example B Figure B-1 to Subpart B of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... of Automated Methods for SO2, CO, O3, and NO2 Pt. 53, Subpt. B, Fig. B-1 Figure B-1 to Subpart B...

  1. 40 CFR Appendix B to Subpart D of... - Figures

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Figures B Appendix B to Subpart D of Part 90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Provisions Pt. 90, Subpt. D, App. B Appendix B to Subpart D of Part 90—Figures EC01MR92.085 EC01MR92.086...

  2. 40 CFR Appendix B to Subpart E of... - Figures

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Figures B Appendix B to Subpart E of Part 90 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Procedures Pt. 90, Subpt. E, App. B Appendix B to Subpart E of Part 90—Figures EC01MR92.087...

  3. 40 CFR Figure B-1 to Subpart B of... - Example

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 40 Protection of Environment 6 2012-07-01 2012-07-01 false Example B Figure B-1 to Subpart B of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... of Automated Methods for SO2, CO, O3, and NO2 Pt. 53, Subpt. B, Fig. B-1 Figure B-1 to Subpart B...

  4. 40 CFR Appendix B to Subpart D of... - Figures

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Figures B Appendix B to Subpart D of Part 91 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED.... D, App. B Appendix B to Subpart D of Part 91—Figures ER04OC96.013 ER04OC96.014...

  5. 40 CFR Appendix B to Subpart D of... - Figures

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Figures B Appendix B to Subpart D of Part 89 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... Provisions Pt. 89, Subpt. D, App. B Appendix B to Subpart D of Part 89—Figures EC01MR92.000 EC01MR92.001...

  6. 40 CFR Figure B-1 to Subpart B of... - Example

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 6 2013-07-01 2013-07-01 false Example B Figure B-1 to Subpart B of Part 53 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED... of Automated Methods for SO2, CO, O3, and NO2 Pt. 53, Subpt. B, Fig. B-1 Figure B-1 to Subpart B...

  7. 16 CFR Figure 9 to Part 1610 - Brushing Device Template

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Brushing Device Template 9 Figure 9 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 9 Figure 9 to Part 1610—Brushing...

  8. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 46 Shipping 5 2013-10-01 2013-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  9. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  10. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  11. 16 CFR Figure 7 to Part 1610 - Brushing Device

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Brushing Device 7 Figure 7 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 7 Figure 7 to Part 1610—Brushing Device ER25MR08.006...

  12. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  13. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10...

  14. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  15. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  16. 16 CFR Figure 7 to Part 1610 - Brushing Device

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Brushing Device 7 Figure 7 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 7 Figure 7 to Part 1610—Brushing Device ER25MR08.006...

  17. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform Probe EC03OC91.062...

  18. 16 CFR Figure 2 to Part 1610 - Flammability Apparatus Views

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Flammability Apparatus Views 2 Figure 2 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 2 Figure 2 to Part...

  19. 16 CFR Figure 7 to Part 1610 - Brushing Device

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Brushing Device 7 Figure 7 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 7 Figure 7 to Part 1610—Brushing Device ER25MR08.006...

  20. 16 CFR Figure 9 to Part 1610 - Brushing Device Template

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Brushing Device Template 9 Figure 9 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 9 Figure 9 to Part 1610—Brushing...

  1. 16 CFR Figure 1 to Part 1203 - Anatomical Planes

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Anatomical Planes 1 Figure 1 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 1 Figure 1 to Part 1203—Anatomical Planes ER10MR98.001...

  2. 16 CFR Figure 1 to Part 1203 - Anatomical Planes

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Anatomical Planes 1 Figure 1 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 1 Figure 1 to Part 1203—Anatomical Planes ER10MR98.001...

  3. 16 CFR Figure 2 to Part 1610 - Flammability Apparatus Views

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Flammability Apparatus Views 2 Figure 2 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 2 Figure 2 to Part...

  4. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  5. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  6. 16 CFR Figure 1 to Part 1203 - Anatomical Planes

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Anatomical Planes 1 Figure 1 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 1 Figure 1 to Part 1203—Anatomical Planes ER10MR98.001...

  7. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  8. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  9. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  10. 16 CFR Figure 7 to Part 1610 - Brushing Device

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Brushing Device 7 Figure 7 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 7 Figure 7 to Part 1610—Brushing Device ER25MR08.006...

  11. 16 CFR Figure 6 to Part 1610 - Igniter

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Igniter 6 Figure 6 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 6 Figure 6 to Part 1610—Igniter ER20OC08.001...

  12. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 10 2013-10-01 2013-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  13. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  14. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  15. 16 CFR Figure 8 to Part 1610 - Brush

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Brush 8 Figure 8 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 8 Figure 8 to Part 1610—Brush ER25MR08.007...

  16. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10...

  17. 16 CFR Figure 2 to Subpart A of... - Test Frame

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Test Frame 2 Figure 2 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 2 Figure 2...

  18. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR FULL-SIZE BABY CRIBS Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform Probe EC03OC91.062...

  19. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  20. 16 CFR Figure 9 to Part 1610 - Brushing Device Template

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Brushing Device Template 9 Figure 9 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 9 Figure 9 to Part 1610—Brushing...

  1. 16 CFR Figure 6 to Part 1610 - Igniter

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Igniter 6 Figure 6 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 6 Figure 6 to Part 1610—Igniter ER20OC08.001...

  2. 16 CFR Figure 9 to Part 1610 - Brushing Device Template

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Brushing Device Template 9 Figure 9 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 9 Figure 9 to Part 1610—Brushing...

  3. 16 CFR Figure 6 to Part 1610 - Igniter

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Igniter 6 Figure 6 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 6 Figure 6 to Part 1610—Igniter ER20OC08.001...

  4. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10...

  5. 16 CFR Figure 8 to Part 1610 - Brush

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Brush 8 Figure 8 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 8 Figure 8 to Part 1610—Brush ER25MR08.007...

  6. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  7. 16 CFR Figure 1 to Part 1203 - Anatomical Planes

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Anatomical Planes 1 Figure 1 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 1 Figure 1 to Part 1203—Anatomical Planes ER10MR98.001...

  8. 16 CFR Figure 1 to Part 1203 - Anatomical Planes

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Anatomical Planes 1 Figure 1 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 1 Figure 1 to Part 1203—Anatomical Planes ER10MR98.001...

  9. 16 CFR Figure 6 to Part 1610 - Igniter

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Igniter 6 Figure 6 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 6 Figure 6 to Part 1610—Igniter ER20OC08.001...

  10. 16 CFR Figure 6 to Part 1610 - Igniter

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Igniter 6 Figure 6 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 6 Figure 6 to Part 1610—Igniter ER20OC08.001...

  11. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  12. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 46 Shipping 5 2011-10-01 2011-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  13. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 46 Shipping 5 2014-10-01 2014-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  14. 16 CFR Figure 2 to Part 1509 - Headform Probe

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Headform Probe 2 Figure 2 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 2 Figure 2 to Part 1509—Headform Probe EC03OC91.065...

  15. 16 CFR Figure 8 to Part 1610 - Brush

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Brush 8 Figure 8 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 8 Figure 8 to Part 1610—Brush ER25MR08.007...

  16. 16 CFR Figure 8 to Part 1610 - Brush

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Brush 8 Figure 8 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 8 Figure 8 to Part 1610—Brush ER25MR08.007...

  17. 16 CFR Figure 9 to Part 1610 - Brushing Device Template

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Brushing Device Template 9 Figure 9 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 9 Figure 9 to Part 1610—Brushing...

  18. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  19. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  20. 16 CFR Figure 1 to Part 1511 - Pacifier Test Fixture

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Pacifier Test Fixture 1 Figure 1 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt. 1511, Fig. 1 Figure 1 to Part 1511—Pacifier Test Fixture...

  1. 16 CFR Figure 7 to Part 1610 - Brushing Device

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Brushing Device 7 Figure 7 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 7 Figure 7 to Part 1610—Brushing Device ER25MR08.006...

  2. 16 CFR Figure 2 to Subpart A of... - Test Frame

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Test Frame 2 Figure 2 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 2 Figure 2...

  3. 16 CFR Figure 2 to Part 1610 - Flammability Apparatus Views

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Flammability Apparatus Views 2 Figure 2 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt. 1610, Fig. 2 Figure 2 to Part...

  4. 16 CFR Figure 8 to Part 1610 - Brush

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Brush 8 Figure 8 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS STANDARD FOR THE FLAMMABILITY OF CLOTHING TEXTILES Pt.1610, Fig. 8 Figure 8 to Part 1610—Brush ER25MR08.007...

  5. 16 CFR Figure 2 to Part 1509 - Headform Probe

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Headform Probe 2 Figure 2 to Part 1509 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR NON-FULL-SIZE BABY CRIBS Pt. 1509, Fig. 2 Figure 2 to Part 1509—Headform Probe EC03OC91.065...

  6. 46 CFR Figure 1 to Part 150 - Compatibility Chart

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 46 Shipping 5 2010-10-01 2010-10-01 false Compatibility Chart 1 Figure 1 to Part 150 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) CERTAIN BULK DANGEROUS CARGOES COMPATIBILITY OF CARGOES Pt. 150, Fig. 1 Figure 1 to Part 150—Compatibility Chart EC02FE91.079...

  7. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  8. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  9. 16 CFR Figure 2 to Subpart A of... - Test Frame

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Test Frame 2 Figure 2 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 2 Figure 2...

  10. 16 CFR Figure 2 to Subpart A of... - Test Frame

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Test Frame 2 Figure 2 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 2 Figure 2...

  11. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  12. 16 CFR Figure 2 to Part 1511 - Small Parts Gage

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Small Parts Gage 2 Figure 2 to Part 1511 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS REQUIREMENTS FOR PACIFIERS Pt.1511, Fig. 2 Figure 2 to Part 1511—Small Parts Gage EC03OC91.069...

  13. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  14. 16 CFR Figure 9 to Part 1203 - Impact Test Apparatus

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Impact Test Apparatus 9 Figure 9 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 9 Figure 9 to Part 1203—Impact Test Apparatus...

  15. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  16. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 10 2014-10-01 2014-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  17. 16 CFR Figure 5 to Subpart A of... - Impactor

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Impactor 5 Figure 5 to Subpart A of Part 1201 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR ARCHITECTURAL GLAZING MATERIALS The Standard Pt. 1201, Subpt. A, Fig. 5 Figure 5...

  18. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 50 Wildlife and Fisheries 7 2010-10-01 2010-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  19. 16 CFR Figure 7 to Subpart A of... - Specimen Tray

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Specimen Tray 7 Figure 7 to Subpart A of Part 1209 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS INTERIM SAFETY STANDARD FOR CELLULOSE INSULATION The Standard Pt. 1209, Subpt. A, Fig. 7 Figure...

  20. 16 CFR Figure 6 to Part 1203 - Field of Vision

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Field of Vision 6 Figure 6 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 6 Figure 6 to Part 1203—Field of Vision ER10MR98.006...

  1. 16 CFR Figure 6 to Part 1203 - Field of Vision

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Field of Vision 6 Figure 6 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 6 Figure 6 to Part 1203—Field of Vision ER10MR98.006...

  2. 16 CFR Figure 6 to Part 1203 - Field of Vision

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Field of Vision 6 Figure 6 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 6 Figure 6 to Part 1203—Field of Vision ER10MR98.006...

  3. 16 CFR Figure 6 to Part 1203 - Field of Vision

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 2 2014-01-01 2014-01-01 false Field of Vision 6 Figure 6 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 6 Figure 6 to Part 1203—Field of Vision ER10MR98.006...

  4. 16 CFR Figure 6 to Part 1203 - Field of Vision

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Field of Vision 6 Figure 6 to Part 1203 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION CONSUMER PRODUCT SAFETY ACT REGULATIONS SAFETY STANDARD FOR BICYCLE HELMETS Pt. 1203, Fig. 6 Figure 6 to Part 1203—Field of Vision ER10MR98.006...

  5. 40 CFR 89.5 - Table and figure numbering; position.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... 89.5 Section 89.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... will indicate the model year (if applicable) and the topic. (b) Figures for each subpart appear in an... appendix. The figure title will indicate the model year (if applicable) and the topic....

  6. 40 CFR 91.5 - Table and figure numbering; position.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... 91.5 Section 91.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... consecutively by order of appearance in the appendix. The table title will indicate the topic. (b) Figures for... order or appearance in the appendix. The figure title will indicate the topic....

  7. 40 CFR 91.5 - Table and figure numbering; position.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... 91.5 Section 91.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... consecutively by order of appearance in the appendix. The table title will indicate the topic. (b) Figures for... order or appearance in the appendix. The figure title will indicate the topic....

  8. 40 CFR 91.5 - Table and figure numbering; position.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... 91.5 Section 91.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... consecutively by order of appearance in the appendix. The table title will indicate the topic. (b) Figures for... order or appearance in the appendix. The figure title will indicate the topic....

  9. 40 CFR 91.5 - Table and figure numbering; position.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... 91.5 Section 91.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... consecutively by order of appearance in the appendix. The table title will indicate the topic. (b) Figures for... order or appearance in the appendix. The figure title will indicate the topic....

  10. 40 CFR 91.5 - Table and figure numbering; position.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... 91.5 Section 91.5 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... consecutively by order of appearance in the appendix. The table title will indicate the topic. (b) Figures for... order or appearance in the appendix. The figure title will indicate the topic....

  11. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 2 2012-01-01 2012-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform...

  12. 16 CFR Figure 2 to Part 1508 - Headform Probe

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 2 2013-01-01 2013-01-01 false Headform Probe 2 Figure 2 to Part 1508 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS SUBSTANCES ACT REGULATIONS FIREWORKS DEVICES Multiple-tube fireworks devices. Pt. 1508, Fig. 2 Figure 2 to Part 1508—Headform...

  13. Naive Prediction of Pathology from Human Figure Drawings

    ERIC Educational Resources Information Center

    Arkell, R. N.

    1976-01-01

    The present study investigated the degree of accuracy of five groups of judges in inferring pathology in human figure drawings. It was suggested that intuition gained through several years of unsystematic observation of figure drawings played the major role in their interpretation. (Author)

  14. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  15. 50 CFR Figure 4 to Part 223 - Georgia TED

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Georgia TED 4 Figure 4 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 4 Figure 4...

  16. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  17. 50 CFR Figures 1-2 to Part 223 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false 1 Figures 1-2 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Figures 1-2 to Part 223...

  18. 50 CFR Figures 1-2 to Part 223 - [Reserved

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false 1 Figures 1-2 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Figures 1-2 to Part 223...

  19. 50 CFR Figure 3 to Part 223 - Matagorda TED

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Matagorda TED 3 Figure 3 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 3 Figure 3...

  20. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10...

  1. 50 CFR Figure 11 to Part 223 - [Reserved

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false 11 Figure 11 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Figure 11 to Part 223...

  2. 50 CFR Figure 10 to Part 223 - Flounder TED

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 10 2012-10-01 2012-10-01 false Flounder TED 10 Figure 10 to Part 223 Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS THREATENED MARINE AND ANADROMOUS SPECIES Pt. 223, Fig. 10 Figure 10...

  3. Interpreting Children's Human Figure Drawings: Basic Guidelines for School Counselors

    ERIC Educational Resources Information Center

    Foley, Yuehong Chen; Mullis, Fran

    2008-01-01

    The literature was reviewed and summarized to provide common interpretations of human figure drawings. Basic guidelines for interpreting human figure drawings (i.e., face and head, body, arms and hands, and legs and feet) are presented. Expectations for students at different developmental levels (ages 1 1/2 through adolescence) are identified, and…

  4. Heat shock factor-4 (HSF-4a) is a repressor of HSF-1 mediated transcription.

    PubMed

    Zhang, Y; Frejtag, W; Dai, R; Mivechi, N F

    2001-01-01

    Heat shock transcription factors (HSFs) regulate the expression of heat shock proteins and other molecular chaperones that are involved in cellular processes from higher order assembly to protein degradation and apoptosis. Among the human HSFs, HSF-4 is expressed as at least two splice variants. One isoform (HSF-4b) possesses a transcriptional activation domain, but this region is absent in the other isoform (HSF-4a). We have recently shown that the HSF-4a isoform represses basal transcription from heterologous promoters both in vitro and in vivo. Here we show that HSF-4a and HSF-4b have dramatically different effects on HSF-1-containing nuclear bodies, which form after heat shock. While the expression of HSF-4b colocalizes with nuclear granules, the expression of HSF-4a prevents their formation. In addition, there is a concurrent reduction of HSF-1 in the nucleus, and there is reduction in its DNA binding activity and in HSE-dependent transcription of a reporter gene. To better understand the mechanism by which HSF-4a represses transcription, we inducibly expressed HSF-4a in cells and found that HSF-4a binds to the heat shock element (HSE) during attenuation of the heat shock response. Thus HSF-4a is an active repressor of HSF-1-mediated transcription. This repressor function makes the HSF-4a isoform unique within the HSF family.

  5. Egr-1 regulates irradiation-induced autophagy through Atg4B to promote radioresistance in hepatocellular carcinoma cells

    PubMed Central

    Peng, W-x; Wan, Y-y; Gong, A-h; Ge, L; Jin, J; Xu, M; Wu, C-y

    2017-01-01

    Although hepatocellular carcinoma (HCC) is usually response to radiation therapy, radioresistance is still the major obstacle that limits the efficacy of radiotherapy for HCC patients. Therefore, further investigation of underlying mechanisms in radioresistant HCC cells is warranted. In this study, we determined the effect of early growth response factor (Egr-1) on irradiation-induced autophagy and radioresistance in HCC cell lines SMMC-7721 and HepG2. We showed that autophagy-related gene 4B (Atg4B) is induced by Egr-1 upon ionizing radiation (IR) in HCC cells. Luciferase reporter assays and chromatin immunoprecipitation (ChIP) revealed that Egr-1 binds to the Atg4B promoter to upregulate its expression in HCC cells. Suppression of Egr-1 function by dominant-negative Egr-1 dampens IR-induced autophagy, cell migration, and increases cell sensitivity to radiotherapy. Together, these results suggest that Egr-1 contributes to HCC radioresistance through directly upregulating target gene Atg4B, which may serve as a protective mechanism by preferential activation of the autophagy. PMID:28134935

  6. Near-Zero Thermal Expansion and High Ultraviolet Transparency in a Borate Crystal of Zn4 B6 O13.

    PubMed

    Jiang, Xingxing; Molokeev, Maxim S; Gong, Pifu; Yang, Yi; Wang, Wei; Wang, Shuaihua; Wu, Shaofan; Wang, Yingxia; Huang, Rongjin; Li, Laifeng; Wu, Yicheng; Xing, Xianran; Lin, Zheshuai

    2016-09-01

    Intrinsic isotropic near-zero thermal expansion is discovered in borate crystal Zn4 B6 O13 with high transparency in the ultraviolet region. First-principles calculations demonstrate that the very low thermal expansion originates mainly from the invariability of the solid [B24 O48 ] truncated octahedra that are fixed by the [Zn4 O13 ] clusters in the ZBO structure.

  7. Genetic determinants for cadmium and arsenic resistance among Listeria monocytogenes serotype 4b isolates from sporadic human listeriosis patients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In Listeria monocytogenes serotype 4b from sporadic listeriosis, heavy metal resistance was primarily encountered in certain clonal groups (ECI, ECII, ECIa). All arsenic-resistant isolates harbored the arsenic resistance cassette previously identified in pLI100; ECIa harbored additional arsenic resi...

  8. Increased expression of plasma membrane Ca(2+)ATPase 4b in platelets from hypertensives: a new sign of abnormal thrombopoiesis?

    PubMed

    Dally, Saoussen; Chaabane, Chiraz; Corvazier, Elisabeth; Bredoux, Raymonde; Bobe, Regis; Ftouhi, Bochra; Slimane, Hedia; Raies, Aly; Enouf, Jocelyne

    2007-11-01

    Platelet Ca(2+) homeostasis is controlled by a multi-Ca(2+)ATPase system including two PMCA (plasma membrane Ca(2+)ATPase) and seven SERCA (sarco/endoplasmic reticulum Ca(2+)ATPase) isoforms. Previous studies have shown similar platelet Ca(2+) abnormalities in diabetic and hypertensive patients, including an increase in intracellular [Ca(2+)](I), a possible modulation of PMCA activity and increased PMCA tyrosine phosphorylation. Very recently, we found that platelets from diabetic patients also exhibited increased PMCA4b expression. In the present study we looked for further similarities between diabetic and hypertensive patients. We first confirmed a decrease in Ca(2+)ATPase activity (mean 55 + 7%) in mixed platelet membranes isolated from 10 patients with hypertension compared with those from 10 healthy controls. In addition, the decreased Ca(2+)ATPase activity correlated with the DBP of the different patients, as expected for PMCA activity. Second, we performed a pilot study of six hypertensives to examine their expressions of PMCA and SERCA mRNA and proteins. Like the diabetic patients, 100% of hypertensives were found to present a major increase in PMCA4b expression (mean value of 218 +/- 21%). We thus determined that platelets from diabetic and hypertensive patients showed similar increased PMCA4b isoform. Since increased PMCA4b expression was recently found to be associated with a perturbation of megakaryocytopoiesis, these findings may also point to an abnormality in platelet maturation in hypertension.

  9. 75 FR 40843 - International Conference on Harmonisation; Draft Guidance on Q4B Evaluation and Recommendation of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-14

    ... Q4B Evaluation and Recommendation of Pharmacopoeial Texts for Use in the International Conference on... Pharmacopoeial Texts for Use in the ICH Regions; Annex 13: Bulk Density and Tapped Density of Powders General... General Chapter harmonized text from each of the three pharmacopoeias (United States, European,...

  10. The interaction between the Hepatitis C proteins NS4B and NS5A is involved in viral replication

    PubMed Central

    David, Naama; Yaffe, Yakey; Hagoel, Lior; Elazar, Menashe; Glenn, Jeffrey S.; Hirschberg, Koret; Sklan, Ella H.

    2015-01-01

    Hepatitis C virus (HCV) replicates in membrane associated, highly ordered replication complexes (RCs). These complexes include viral and host proteins necessary for viral RNA genome replication. The interaction network among viral and host proteins underlying the formation of these RCs is yet to be thoroughly characterized. Here, we investigated the association between NS4B and NS5A, two critical RC components. We characterized the interaction between these proteins using fluorescence resonance energy transfer and a mammalian two-hybrid system. Specific tryptophan residues within the C-terminal domain (CTD) of NS4B were shown to mediate this interaction. Domain I of NS5A, was sufficient to mediate its interaction with NS4B. Mutations in the NS4B CTD tryptophan residues abolished viral replication. Moreover, one of these mutations also affected NS5A hyperphosphorylation. These findings provide new insights into the importance of the NS4B–NS5A interaction and serve as a starting point for studying the complex interactions between the replicase subunits. PMID:25462354

  11. The Prediction of Success in Engineering Graphics Using the Group Embedded Figures Test and the Hidden Figures Test.

    ERIC Educational Resources Information Center

    Wilson, Russell C.; Davis, Paul D.

    1985-01-01

    A study was conducted to continue the assessment of the Group Embedded Figures Test (GEFT), to assess the value of the Hidden Figures Test (HFT), and to assess the usefulness of the two instruments used in combination as tools for predicting student success and early identification of students who may need special assistance in engineering…

  12. KDM4B histone demethylase and G9a regulate expression of vascular adhesion proteins in cerebral microvessels

    PubMed Central

    Choi, Ji-Young; Yoon, Sang-Sun; Kim, Sang-Eun; Ahn Jo, Sangmee

    2017-01-01

    Intercellular adhesion molecule 1 (ICAM1) mediates the adhesion and transmigration of leukocytes across the endothelium, promoting inflammation. We investigated the epigenetic mechanism regulating ICAM1 expression. The pro-inflammatory cytokine TNF-α dramatically increased ICAM1 mRNA and protein levels in human brain microvascular endothelial cells and mouse brain microvessels. Chromatin immunoprecipitation revealed that TNF-α reduced methylation of histone H3 at lysines 9 and 27 (H3K9 and H3K27), well-known residues involved in gene suppression. Inhibition of G9a and EZH2, histone methyltransferases responsible for methylation at H3K9 and H3K27, respectively as well as G9a overexpression demonstrated the involvement of G9a in TNF-α-induced ICAM1 expression and leukocyte adhesion and transmigration. A specific role for KDM4B, a histone demethylase targeting H3K9me2, in TNF-α-induced ICAM1 upregulation was validated with siRNA. Moreover, treating mice with a KDM4 inhibitor ML324 blocked TNF-α-mediated neutrophil adhesion. Similarly, TNF-α-induced VCAM1 expression was suppressed by G9a overexpression and KDM4B knockdown. Collectively, we demonstrated that modification of H3K9me2 by G9a and KDM4B regulates expression of vascular adhesion molecules, and that depletion of these proteins or KDM4B reduces inflammation-induced leukocyte extravasation. Thus, blocking ICAM1 or KDM4B could offer a novel therapeutic opportunity treating brain diseases. PMID:28327608

  13. Figure-ground segregation: A fully nonlocal approach.

    PubMed

    Dimiccoli, Mariella

    2016-09-01

    We present a computational model that computes and integrates in a nonlocal fashion several configural cues for automatic figure-ground segregation. Our working hypothesis is that the figural status of each pixel is a nonlocal function of several geometric shape properties and it can be estimated without explicitly relying on object boundaries. The methodology is grounded on two elements: multi-directional linear voting and nonlinear diffusion. A first estimation of the figural status of each pixel is obtained as a result of a voting process, in which several differently oriented line-shaped neighborhoods vote to express their belief about the figural status of the pixel. A nonlinear diffusion process is then applied to enforce the coherence of figural status estimates among perceptually homogeneous regions. Computer simulations fit human perception and match the experimental evidence that several cues cooperate in defining figure-ground segregation. The results of this work suggest that figure-ground segregation involves feedback from cells with larger receptive fields in higher visual cortical areas.

  14. Ion Figuring of Replicated X-Ray Optics

    NASA Technical Reports Server (NTRS)

    Cantey, Thomas M.; Gregory, Don A.

    1997-01-01

    This investigation included experiments to demonstrate ion beam figuring effects on electroless nickel with the expressed desire to figure X-ray optic mandrels. It was important to establish that ion beam figuring did not induce any adverse effects to the nickel surface. The ion beam has consistently been shown to be an excellent indicator of the quality of the subsurface. Polishing is not the only cause for failure in the ion beam final figuring process, the material composition is equally important. Only by careful consideration of both these factors can the ion beam final figuring process achieve its greatest potential. The secondary goal was to construct a model for representing the ion beam material removal rate. Representing the ion beam removal rate is only an approximation and has a number of limiting factors. The resolution of the metrology apparatus limits the modeling of the beam function as well. As the surface error corrections demand more precision in the final figuring, the model representing beam function must be equally precise. The precision to which the beam function can be represented is not only determined by the model but also by the measurements producing that model. The method developed for determining the beam function has broad application to any material destined to be ion beam figured.

  15. Figure-ground modulation in awake primate thalamus

    PubMed Central

    Jones, Helen E.; Andolina, Ian M.; Shipp, Stewart D.; Adams, Daniel L.; Cudeiro, Javier; Salt, Thomas E.; Sillito, Adam M.

    2015-01-01

    Figure-ground discrimination refers to the perception of an object, the figure, against a nondescript background. Neural mechanisms of figure-ground detection have been associated with feedback interactions between higher centers and primary visual cortex and have been held to index the effect of global analysis on local feature encoding. Here, in recordings from visual thalamus of alert primates, we demonstrate a robust enhancement of neuronal firing when the figure, as opposed to the ground, component of a motion-defined figure-ground stimulus is located over the receptive field. In this paradigm, visual stimulation of the receptive field and its near environs is identical across both conditions, suggesting the response enhancement reflects higher integrative mechanisms. It thus appears that cortical activity generating the higher-order percept of the figure is simultaneously reentered into the lowest level that is anatomically possible (the thalamus), so that the signature of the evolving representation of the figure is imprinted on the input driving it in an iterative process. PMID:25901330

  16. Figure-ground modulation in awake primate thalamus.

    PubMed

    Jones, Helen E; Andolina, Ian M; Shipp, Stewart D; Adams, Daniel L; Cudeiro, Javier; Salt, Thomas E; Sillito, Adam M

    2015-06-02

    Figure-ground discrimination refers to the perception of an object, the figure, against a nondescript background. Neural mechanisms of figure-ground detection have been associated with feedback interactions between higher centers and primary visual cortex and have been held to index the effect of global analysis on local feature encoding. Here, in recordings from visual thalamus of alert primates, we demonstrate a robust enhancement of neuronal firing when the figure, as opposed to the ground, component of a motion-defined figure-ground stimulus is located over the receptive field. In this paradigm, visual stimulation of the receptive field and its near environs is identical across both conditions, suggesting the response enhancement reflects higher integrative mechanisms. It thus appears that cortical activity generating the higher-order percept of the figure is simultaneously reentered into the lowest level that is anatomically possible (the thalamus), so that the signature of the evolving representation of the figure is imprinted on the input driving it in an iterative process.

  17. Fast figuring of large optics by reactive atom plasma

    NASA Astrophysics Data System (ADS)

    Castelli, Marco; Jourdain, Renaud; Morantz, Paul; Shore, Paul

    2012-09-01

    The next generation of ground-based astronomical observatories will require fabrication and maintenance of extremely large segmented mirrors tens of meters in diameter. At present, the large production of segments required by projects like E-ELT and TMT poses time frames and costs feasibility questions. This is principally due to a bottleneck stage in the optical fabrication chain: the final figuring step. State-of-the-art figure correction techniques, so far, have failed to meet the needs of the astronomical community for mass production of large, ultra-precise optical surfaces. In this context, Reactive Atom Plasma (RAP) is proposed as a candidate figuring process that combines nanometer level accuracy with high material removal rates. RAP is a form of plasma enhanced chemical etching at atmospheric pressure based on Inductively Coupled Plasma technology. The rapid figuring capability of the RAP process has already been proven on medium sized optical surfaces made of silicon based materials. In this paper, the figure correction of a 3 meters radius of curvature, 400 mm diameter spherical ULE mirror is presented. This work demonstrates the large scale figuring capability of the Reactive Atom Plasma process. The figuring is carried out by applying an in-house developed procedure that promotes rapid convergence. A 2.3 μm p-v initial figure error is removed within three iterations, for a total processing time of 2.5 hours. The same surface is then re-polished and the residual error corrected again down to λ/20 nm rms. These results highlight the possibility of figuring a metre-class mirror in about ten hours.

  18. Breath Figure Method for Construction of Honeycomb Films

    PubMed Central

    Dou, Yingying; Jin, Mingliang; Zhou, Guofu; Shui, Lingling

    2015-01-01

    Honeycomb films with various building units, showing potential applications in biological, medical, physicochemical, photoelectric, and many other areas, could be prepared by the breath figure method. The ordered hexagonal structures formed by the breath figure process are related to the building units, solvents, substrates, temperature, humidity, air flow, and other factors. Therefore, by adjusting these factors, the honeycomb structures could be tuned properly. In this review, we summarized the development of the breath figure method of fabricating honeycomb films and the factors of adjusting honeycomb structures. The organic-inorganic hybrid was taken as the example building unit to discuss the preparation, mechanism, properties, and applications of the honeycomb films. PMID:26343734

  19. Role of p70S6K1-mediated phosphorylation of eIF4B and PDCD4 proteins in the regulation of protein synthesis.

    PubMed

    Dennis, Michael D; Jefferson, Leonard S; Kimball, Scot R

    2012-12-14

    Modulation of mRNA binding to the 40 S ribosomal subunit during translation initiation controls not only global rates of protein synthesis but also regulates the pattern of protein expression by allowing for selective inclusion, or exclusion, of mRNAs encoding particular proteins from polysomes. The mRNA binding step is modulated by signaling through a protein kinase known as the mechanistic target of rapamycin complex 1 (mTORC1). mTORC1 directly phosphorylates the translational repressors eIF4E binding proteins (4E-BP) 1 and 2, releasing them from the mRNA cap binding protein eIF4E, thereby promoting assembly of the eIF4E·eIF4G complex. mTORC1 also phosphorylates the 70-kDa ribosomal protein S6 kinase 1 (p70S6K1), which subsequently phosphorylates eIF4B, and programmed cell death 4 (PDCD4), which sequesters eIF4A from the eIF4E·eIF4G complex, resulting in repressed translation of mRNAs with highly structured 5'-untranslated regions. In the present study, we compared the role of the 4E-BPs in the regulation of global rates of protein synthesis to that of eIF4B and PDCD4. We found that maintenance of eIF4E interaction with eIF4G was not by itself sufficient to sustain global rates of protein synthesis in the absence of mTORC1 signaling to p70S6K1; phosphorylation of both eIF4B and PDCD4 was additionally required. We also found that the interaction of eIF4E with eIF4G was maintained in the liver of fasted rats as well as in serum-deprived mouse embryo fibroblasts lacking both 4E-BP1 and 4E-BP2, suggesting that the interaction of eIF4G with eIF4E is controlled primarily through the 4E-BPs.

  20. CRL4B interacts with and coordinates the SIN3A-HDAC complex to repress CDKN1A and drive cell cycle progression.

    PubMed

    Ji, Qinghong; Hu, Huili; Yang, Fan; Yuan, Jupeng; Yang, Yang; Jiang, Liangqian; Qian, Yanyan; Jiang, Baichun; Zou, Yongxin; Wang, Yan; Shao, Changshun; Gong, Yaoqin

    2014-11-01

    CUL4B, a scaffold protein that assembles the CRL4B ubiquitin ligase complex, participates in the regulation of a broad spectrum of biological processes. Here, we demonstrate a crucial role of CUL4B in driving cell cycle progression. We show that loss of CUL4B results in a significant reduction in cell proliferation and causes G1 cell cycle arrest, accompanied by the upregulation of the cyclin-dependent kinase (CDK) inhibitors (CKIs) p21 and p57 (encoded by CDKN1A and CDKN1C, respectively). Strikingly, CUL4B was found to negatively regulate the function of p21 through transcriptional repression, but not through proteolysis. Furthermore, we demonstrate that CRL4B and SIN3A-HDAC complexes interact with each other and co-occupy the CDKN1A and CDKN1C promoters. Lack of CUL4B led to a decreased retention of SIN3A-HDAC components and increased levels of acetylated H3 and H4. Interestingly, the ubiquitylation function of CRL4B is not required for the stable retention of SIN3A-HDAC on the promoters of target genes. Thus, in addition to directly contributing to epigenetic silencing by catalyzing H2AK119 monoubiquitylation, CRL4B also facilitates the deacetylation function of SIN3A-HDAC. Our findings reveal a coordinated action between CRL4B and SIN3A-HDAC complexes in transcriptional repression.

  1. Surface Figure Measurement of Silicon Carbide Mirrors at Cryogenic Temperatures

    NASA Technical Reports Server (NTRS)

    Blake, Peter; Mink, Ronald G.; Chambers, John; Robinson, F. David; Content, David; Davila, Pamela

    2005-01-01

    The surface figure of a developmental silicon carbide mirror, cooled to 87 K and then 20 K within a cryostat, was measured with unusually high precision at the Goddard Space Flight Center (GSFC). The concave spherical mirror, with a radius of 600 mm and a clear aperture of 150 mm, was fabricated of sintered silicon carbide. The mirror was mounted to an interface plate representative of an optical bench, made of the material Cesic@, a composite of silicon, carbon, and silicon carbide. The change in optical surface figure as the mirror and interface plate cooled from room temperature to 20 K was 3.7 nm rms, with a standard uncertainty of 0.23 nm in the rms statistic. Both the cryo-change figure and the uncertainty are among the lowest such figures yet published. This report describes the facilities, experimental methods, and uncertainty analysis of the measurements.

  2. A new figure of merit for wideband vibration energy harvesters

    NASA Astrophysics Data System (ADS)

    Liu, W. Q.; Badel, A.; Formosa, F.; Wu, Y. P.

    2015-12-01

    The performance evaluation method is a very important part in the field of vibration energy harvesting. It provides the ability to compare and rate different vibration energy harvesters (VEHs). Considering the lack of a well-recognized tool, this article proposed a new systematic figure of merit for the appraisement of wideband VEHs. Extensive investigations are first performed for some classic figures for linear VEHs. With the common fundamental information obtained, the proposed figure integrates four essential factors: the revised energy harvester effectiveness, the mechanical quality factor, the normalized bandwidth and the effective mass density. Special considerations are devoted to the properties of wideband VEHs about the operation range and the average power in this domain which are related to the performance target of stable power output. Afterward, this new figure is applied to some literature VEHs and demonstrated to present good evaluations of wideband VEHs. Moreover, it exhibits the ability to point out the improvement information of the concerned VEHs further developments.

  3. [Effective English writing for tables and figures in andrological papers].

    PubMed

    Luo, Yong-He; Lu, Jin-Chun

    2012-08-01

    Tables and figures play a critical role in enhancing the quality of an andrological paper. As visual elements, well-presented tables and figures can reduce the length of the manuscript and meanwhile efficiently capture a large amount of information by clear and concise display of detailed results and complex relationships, patterns and trends, offer explicit statistical or graphical support to important ideas, and add to the value of the whole paper. The effectiveness of a table or figure lies not only in its well-crafted structural design, but even more in its language presentation. This article presents some essential and practical guidelines to effective English writing of the title, body and footnotes of tables and figures in andrological papers.

  4. High-precision Photogrammetric Surface Figure Measurements under Cryogenic Environment

    NASA Astrophysics Data System (ADS)

    Lou, Z.; Qian, Y.; Fan, S. H.; Liu, C. R.; Wang, H. R.; Zuo, Y. X.; Cheng, J. Q.; Yang, J.

    2016-01-01

    Limited by the working temperature of the measurement equipments, most of the high-precision surface figure measurement techniques cannot be applied under a cryogenic environment. This paper reports the first attempt to measure the surface figure of a high-precision terahertz reflector panel under low temperatures based on photogrammetry. The measurement employs a high resolution industrial camera sitting on an automatic experimental platform which enables photos been taken in an automatic fashion inside a climate chamber. A repeatable accuracy of 2.1 μm rms is achieved under the cryogenic environment. Furthermore, surface figure measured by a three-coordinate measuring machine under room temperature is used to calibrate the thickness variation of the paper targets. By this technique, the surface figure of an aluminum prototype panel of the 5 meter Dome A Terahertz Telescope (DATE5) is measured from room temperature down to -55°C.

  5. Figuring Large Mandrels for Forming X-Ray Mirrors Substrates

    NASA Technical Reports Server (NTRS)

    Wright, Geraldine; Fleetwood, Charles; Content, David; Saha, Timo; Kolos, Linette; Colella, David

    2004-01-01

    Constellation X mirrors are discussed in this presentation. Topics include:assemblies, mirror segments, optical assemble pathfinder mandrels, the figuring process, and a best quadrant,clear aperture, and full aperture.

  6. 16 CFR Figure 2 to Part 1610 - Flammability Apparatus Views

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Flammability Apparatus Views 2 Figure 2 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS... Apparatus Views ER25MR08.001...

  7. 16 CFR Figure 2 to Part 1610 - Flammability Apparatus Views

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Flammability Apparatus Views 2 Figure 2 to Part 1610 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FLAMMABLE FABRICS ACT REGULATIONS... Apparatus Views ER25MR08.001...

  8. Figuring out the Statistics of the ICC World Cup 2011

    ERIC Educational Resources Information Center

    Shiwalkar, Jyoti P.; Deshpande, M. N.

    2013-01-01

    This paper deals with the analysis of cricket match results from the ICC World Cup 2011. We believe that such data provide good material for interesting classroom exercises. (Contains 7 tables and 1 figure.)

  9. 13. WEST ELEVATION, POWERHOUSE, WITH FIGURES AND AUTOMOBILES Historic photograph ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    13. WEST ELEVATION, POWERHOUSE, WITH FIGURES AND AUTOMOBILES Historic photograph no. 1646, no date, held at Media Arts and Services Department, Pacific Gas & Electric Co., San Francisco, CA. - Centerville Hydroelectric System, Powerhouse, Butte Creek, Centerville, Butte County, CA

  10. 40 CFR 90.6 - Table and figure numbering; position.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    .... 90.6 Section 90.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... will indicate the topic. (b) Figures for each subpart appear in an appendix at the end of the subpart... the topic....

  11. 40 CFR 90.6 - Table and figure numbering; position.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    .... 90.6 Section 90.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... will indicate the topic. (b) Figures for each subpart appear in an appendix at the end of the subpart... the topic....

  12. 40 CFR 90.6 - Table and figure numbering; position.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    .... 90.6 Section 90.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... will indicate the topic. (b) Figures for each subpart appear in an appendix at the end of the subpart... the topic....

  13. 40 CFR 90.6 - Table and figure numbering; position.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    .... 90.6 Section 90.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... will indicate the topic. (b) Figures for each subpart appear in an appendix at the end of the subpart... the topic....

  14. 40 CFR 90.6 - Table and figure numbering; position.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    .... 90.6 Section 90.6 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS... will indicate the topic. (b) Figures for each subpart appear in an appendix at the end of the subpart... the topic....

  15. Significant Figures in Measurements with Uncertainty: A Working Criterion

    NASA Astrophysics Data System (ADS)

    Vilchis, Abraham

    2017-03-01

    Generally speaking, students have difficulty reporting out measurements and estimates of quantities used in the laboratory, and with handling the significant figures associated with them. When required to make calculation involving quantities with different numbers of significant figures, they have difficulty in assigning the corresponding digits to the final result. When in addition, the quantities have uncertainty, the operations entailed pose an even greater challenge. The article advocates for some working rules for students (and teachers) in an effort to combat this problem.

  16. 49 CFR Appendix - Figures to Subpart N of Part 572

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Figures to Subpart N of Part 572 Transportation... Version Test conditions and instrumentation. Pt. 572, Subpt. N, Fig. N1 Figures to Subpart N of Part 572 ER18JY02.000 Pt. 572, Subpt. N, Fig. N2 ER18JY02.001 Pt. 572, Subpt. N, Fig. N3 ER18JY02.002 Pt. 572,...

  17. Precise method for investigation of Lissajous generalized figures

    NASA Astrophysics Data System (ADS)

    Bednarek, Stanisław

    2014-07-01

    This article describes the Lissajous generalized figure and the original instrument for its investigation. Two specially prepared electrodynamic loudspeakers—a horizontal and a vertical—cause oscillations in two mirrors. It is possible to precisely control the motion of the mirrors, achieve a high frequency of oscillation and investigate anharmonic vibrations because loudspeakers are powered by electronic generators. Eccentric mounting, and rotation of a vertical loudspeaker, also allow composition of the oscillations in inclined directions, which generates Lissajous’ generalized figures.

  18. Constellation-X Cylinder Figuring and Polishing Studies

    NASA Technical Reports Server (NTRS)

    Waluschka, Eugene; Arsenovic, Petar; Content, David; Saha, Timo; Strojny, Carl; Wright, Geraldine; Fleetwood, Charles

    2001-01-01

    In support of Goddard's Constellation-X mandrel manufacturing effort a series of fabrication experiments are being performed to determine a best approach. Currently, polishing immediately after diamond turning, produces a RMS surface roughness of 0.31 nm, on a nickel plated aluminum mandrel. Studies currently under way will incorporate an abrasive figuring step followed by a polishing operation. The current diamond turning, figuring and polishing procedures will be described and the results presented.

  19. 49 CFR Appendix A to Subpart U of... - Figures

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Figures A Appendix A to Subpart U of Part 572... Dummy, 50th Percentile Adult Male Instrumentation and test conditions. Pt. 572, Subpt. U, App. A Appendix A to Subpart U of Part 572—Figures ER14DE06.000 ER16JN08.006 ER14DE06.002 ER14DE06.003...

  20. 40 CFR Appendix B to Subpart E of... - Figures

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 21 2013-07-01 2013-07-01 false Figures B Appendix B to Subpart E of Part 91 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED..., App. B Appendix B to Subpart E of Part 91—Figures ER04OC96.044 ER04OC96.045 ER04OC96.046...

  1. 49 CFR Appendix A to Subpart U of... - Figures

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Figures A Appendix A to Subpart U of Part 572... Dummy, 50th Percentile Adult Male Instrumentation and test conditions. Pt. 572, Subpt. U, App. A Appendix A to Subpart U of Part 572—Figures ER14DE06.000 ER16JN08.006 ER14DE06.002 ER14DE06.003...

  2. 49 CFR Appendix A to Subpart V of... - Figures

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 49 Transportation 7 2010-10-01 2010-10-01 false Figures A Appendix A to Subpart V of Part 572... Dummy, Small Adult Female Instrumentation and test conditions. Pt. 572, Subpt. V, App. A Appendix A to Subpart V of Part 572—Figures ER14DE06.009 ER14DE06.010 ER14DE06.011 ER14DE06.012 ER14DE06.013...

  3. 49 CFR Appendix A to Subpart V of... - Figures

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Figures A Appendix A to Subpart V of Part 572... Dummy, Small Adult Female Instrumentation and test conditions. Pt. 572, Subpt. V, App. A Appendix A to Subpart V of Part572—Figures ER14DE06.009 ER14DE06.010 ER14DE06.011 ER14DE06.012 ER14DE06.013...

  4. 49 CFR Appendix A to Subpart V of... - Figures

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Figures A Appendix A to Subpart V of Part 572... Dummy, Small Adult Female Instrumentation and test conditions. Pt. 572, Subpt. V, App. A Appendix A to Subpart V of Part 572—Figures ER14DE06.009 ER14DE06.010 ER14DE06.011 ER14DE06.012 ER14DE06.013...

  5. Noise destroys feedback enhanced figure-ground segmentation but not feedforward figure-ground segmentation.

    PubMed

    Romeo, August; Arall, Marina; Supèr, Hans

    2012-01-01

    Figure-ground (FG) segmentation is the separation of visual information into background and foreground objects. In the visual cortex, FG responses are observed in the late stimulus response period, when neurons fire in tonic mode, and are accompanied by a switch in cortical state. When such a switch does not occur, FG segmentation fails. Currently, it is not known what happens in the brain on such occasions. A biologically plausible feedforward spiking neuron model was previously devised that performed FG segmentation successfully. After incorporating feedback the FG signal was enhanced, which was accompanied by a change in spiking regime. In a feedforward model neurons respond in a bursting mode whereas in the feedback model neurons fired in tonic mode. It is known that bursts can overcome noise, while tonic firing appears to be much more sensitive to noise. In the present study, we try to elucidate how the presence of noise can impair FG segmentation, and to what extent the feedforward and feedback pathways can overcome noise. We show that noise specifically destroys the feedback enhanced FG segmentation and leaves the feedforward FG segmentation largely intact. Our results predict that noise produces failure in FG perception.

  6. Neutrons Flux Distributions of the Pu-Be Source and its Simulation by the MCNP-4B Code

    NASA Astrophysics Data System (ADS)

    Faghihi, F.; Mehdizadeh, S.; Hadad, K.

    Neutron Fluence rate of a low intense Pu-Be source is measured by Neutron Activation Analysis (NAA) of 197Au foils. Also, the neutron fluence rate distribution versus energy is calculated using the MCNP-4B code based on ENDF/B-V library. Theoretical simulation as well as our experimental performance are a new experience for Iranians to make reliability with the code for further researches. In our theoretical investigation, an isotropic Pu-Be source with cylindrical volume distribution is simulated and relative neutron fluence rate versus energy is calculated using MCNP-4B code. Variation of the fast and also thermal neutrons fluence rate, which are measured by NAA method and MCNP code, are compared.

  7. The calculated magnetic, electronic and thermodynamic properties of Ce3Co29Si4B10 compound

    NASA Astrophysics Data System (ADS)

    Huo, Jin-Rong; Wang, Xiao-Xu; Hu, Yao-Wen; Zhang, Guo-Hua; Cheng, Hai-Xia; Li, Lu; Qian, Ping

    2016-05-01

    The magnetic moment, lattice parameter and atom fraction coordinates for Ce3Co29Si4B10 are calculated by the first-principles GGA+U method, and the results indicate that the calculated and experimental values are basically accordant when U=2.6 eV. We study the interaction effect and orbital hybridization between Co and Ce atoms. The projected density of states at U=2.6 eV which provided by Co-2c, Ce-2b and Ce-4d sites are contrasted with else U values. Meanwhile the electron density of states for different sites and the distance between various atoms are exhibited. In addition, the thermodynamic properties of Ce3Co29Si4B10 are evaluated by using a series of interatomic pair potentials.

  8. Report on inspection of compliance with DOE Order 2030.4B at the Savannah River Site

    SciTech Connect

    1997-03-01

    The purpose of this inspection was to evaluate contractor compliance at the Savannah River Site (SRS) with Department of Energy (DOE) Order 2030.4B, {open_quotes}Reporting Fraud, Waste, And Abuse To The Office Of Inspector General.{close_quotes} The specific objective was to determine if the SRS management and operating (M&O) contractors were complying with the requirements in Paragraph 6.c. of DOE Order 2030.4B. These requirements are: (1) annual notification to employees of their duty to report allegations of fraud, waste, abuse, corruption, or mismanagement; (2) display and publish the DOE Office of Inspector General (OIG) Hotline telephone number in common areas of buildings; (3) display and publish the DOE OIG Hotline number in telephone books and newsletters; and (4) notify the OIG cases referred to other law enforcement entities.

  9. Algorithm for ion beam figuring of low-gradient mirrors.

    PubMed

    Jiao, Changjun; Li, Shengyi; Xie, Xuhui

    2009-07-20

    Ion beam figuring technology for low-gradient mirrors is discussed. Ion beam figuring is a noncontact machining technique in which a beam of high-energy ions is directed toward a target workpiece to remove material in a predetermined and controlled fashion. Owing to this noncontact mode of material removal, problems associated with tool wear and edge effects, which are common in conventional contact polishing processes, are avoided. Based on the Bayesian principle, an iterative dwell time algorithm for planar mirrors is deduced from the computer-controlled optical surfacing (CCOS) principle. With the properties of the removal function, the shaping process of low-gradient mirrors can be approximated by the linear model for planar mirrors. With these discussions, the error surface figuring technology for low-gradient mirrors with a linear path is set up. With the near-Gaussian property of the removal function, the figuring process with a spiral path can be described by the conventional linear CCOS principle, and a Bayesian-based iterative algorithm can be used to deconvolute the dwell time. Moreover, the selection criterion of the spiral parameter is given. Ion beam figuring technology with a spiral scan path based on these methods can be used to figure mirrors with non-axis-symmetrical errors. Experiments on SiC chemical vapor deposition planar and Zerodur paraboloid samples are made, and the final surface errors are all below 1/100 lambda.

  10. Figure-ground interaction in the human visual cortex.

    PubMed

    Appelbaum, Lawrence G; Wade, Alex R; Pettet, Mark W; Vildavski, Vladimir Y; Norcia, Anthony M

    2008-07-18

    Discontinuities in feature maps serve as important cues for the location of object boundaries. Here we used multi-input nonlinear analysis methods and EEG source imaging to assess the role of several different boundary cues in visual scene segmentation. Synthetic figure/ground displays portraying a circular figure region were defined solely by differences in the temporal frequency of the figure and background regions in the limiting case and by the addition of orientation or relative alignment cues in other cases. The use of distinct temporal frequencies made it possible to separately record responses arising from each region and to characterize the nature of nonlinear interactions between the two regions as measured in a set of retinotopically and functionally defined cortical areas. Figure/background interactions were prominent in retinotopic areas, and in an extra-striate region lying dorsal and anterior to area MT+. Figure/background interaction was greatly diminished by the elimination of orientation cues, the introduction of small gaps between the two regions, or by the presence of a constant second-order border between regions. Nonlinear figure/background interactions therefore carry spatially precise, time-locked information about the continuity/discontinuity of oriented texture fields. This information is widely distributed throughout occipital areas, including areas that do not display strong retinotopy.

  11. FBXO44-Mediated Degradation of RGS2 Protein Uniquely Depends on a Cullin 4B/DDB1 Complex

    PubMed Central

    Sjögren, Benita; Swaney, Steven; Neubig, Richard R.

    2015-01-01

    The ubiquitin-proteasome system for protein degradation plays a major role in regulating cell function and many signaling proteins are tightly controlled by this mechanism. Among these, Regulator of G Protein Signaling 2 (RGS2) is a target for rapid proteasomal degradation, however, the specific enzymes involved are not known. Using a genomic siRNA screening approach, we identified a novel E3 ligase complex containing cullin 4B (CUL4B), DNA damage binding protein 1 (DDB1) and F-box protein 44 (FBXO44) that mediates RGS2 protein degradation. While the more typical F-box partners CUL1 and Skp1 can bind FBXO44, that E3 ligase complex does not bind RGS2 and is not involved in RGS2 degradation. These observations define an unexpected DDB1/CUL4B-containing FBXO44 E3 ligase complex. Pharmacological targeting of this mechanism provides a novel therapeutic approach to hypertension, anxiety, and other diseases associated with RGS2 dysregulation. PMID:25970626

  12. An improved method for expression and purification of functional human Ca(2+) transporter PMCA4b in Saccharomyces cerevisiae.

    PubMed

    Corbacho, Isaac; García-Prieto, Francisco F; Hinojosa, Ara E; Berrocal, María; Mata, Ana M

    2016-04-01

    Human plasma membrane calcium ATPases (PMCAs) are highly regulated transporters responsible for the extrusion of calcium out of the cell. Since calcium homeostasis is implicated in several diseases and neurodegenerative disorders, understanding PMCAs activity is crucial. One of the major hindrances is the availability of these proteins for functional and structural analysis. Here, using the yeast Saccharomyces cerevisiae system, we show a new and enhanced method for the expression of the full-length human PMCA isoform 4b (hPMCA4b) and a truncated form lacking its auto-inhibitory domain. We have also improved a method for the purification of the native isoform by calmodulin-agarose affinity chromatography, and developed a new method to purify the truncated isoform by glutathione-Sepharose affinity chromatography. One of the most relevant features of this work is that, when compared to PMCAs purification from pig brain, our method provides a pure single isoform instead of a mixture of isoforms, essential for fine-tuning the activity of PMCA4b. Another relevant feature is that the method described in this work has a superior yield of protein than previously established methods to purify PMCA proteins expressed in yeasts.

  13. SCN4B acts as a metastasis-suppressor gene preventing hyperactivation of cell migration in breast cancer

    PubMed Central

    Bon, Emeline; Driffort, Virginie; Gradek, Frédéric; Martinez-Caceres, Carlos; Anchelin, Monique; Pelegrin, Pablo; Cayuela, Maria-Luisa; Marionneau-Lambot, Séverine; Oullier, Thibauld; Guibon, Roseline; Fromont, Gaëlle; Gutierrez-Pajares, Jorge L.; Domingo, Isabelle; Piver, Eric; Moreau, Alain; Burlaud-Gaillard, Julien; Frank, Philippe G.; Chevalier, Stéphan; Besson, Pierre; Roger, Sébastien

    2016-01-01

    The development of metastases largely relies on the capacity of cancer cells to invade extracellular matrices (ECM) using two invasion modes termed ‘mesenchymal' and ‘amoeboid', with possible transitions between these modes. Here we show that the SCN4B gene, encoding for the β4 protein, initially characterized as an auxiliary subunit of voltage-gated sodium channels (NaV) in excitable tissues, is expressed in normal epithelial cells and that reduced β4 protein levels in breast cancer biopsies correlate with high-grade primary and metastatic tumours. In cancer cells, reducing β4 expression increases RhoA activity, potentiates cell migration and invasiveness, primary tumour growth and metastatic spreading, by promoting the acquisition of an amoeboid–mesenchymal hybrid phenotype. This hyperactivated migration is independent of NaV and is prevented by overexpression of the intracellular C-terminus of β4. Conversely, SCN4B overexpression reduces cancer cell invasiveness and tumour progression, indicating that SCN4B/β4 represents a metastasis-suppressor gene. PMID:27917859

  14. Magnetic phase transformations and superconductivity in Dy0.8Y0.2Rh4B4

    NASA Astrophysics Data System (ADS)

    Dmitriev, V. M.; Zaleskiĭ, A.; Khlybov, E. P.; Rybal'Chenko, L. F.; Khristenko, E. V.; Ishchenko, L. A.; Terekhov, A. V.; Kostyleva, I. E.; Lachenkov, S. A.

    2008-11-01

    The results of experimental studies of the magnetic and the superconducting properties of the compound Dy0.8Y0.2Rh4B4 with tetragonal body-centered crystal structure of the perovskite type (LuRu4B4) are presented. It is shown that the compound undergoes a paramagnet-ferrimagnet phase transition at the Curie temperature TC≈30.5K and its magnetic compensation temperature Tcomp≈17K. According to resistance measurements, the compound becomes a ferrimagnetic superconductor at Tconset≈5.9K which undergoes a ferrimagnet-antiferromagnet phase transition at TN≈2.7K while still remaining a superconductor. The specific heat exhibits a sharp maximum at this temperature. Point-contact Andreev reflection spectroscopy is used to measure the temperature and field dependences of the order parameter Δ(T ,H) and the temperature dependence of the upper critical field Hc2(T ). The dependences obtained differ radically from those generally accepted for conventional superconductors. The results obtained are discussed in connection with the possibility of triplet pairing in Dy0.8Y0.2Rh4B4.

  15. Dithiazolo[5,4-b:4',5'-d]phosphole: a highly luminescent electron-accepting building block.

    PubMed

    He, Xiaoming; Woo, Alva Y Y; Borau-Garcia, Javier; Baumgartner, Thomas

    2013-06-03

    A family of highly emissive dithiazolo[5,4-b:4',5'-d]phospholes has been designed and synthesized. The structures of two trivalent P species, as well as their corresponding P oxides, have been confirmed by X-ray crystallography. The parent dithiazolo[5,4-b:4',5'-d]phosphole oxide exhibits strong blue photoluminescence at λem = 442 nm, with an excellent quantum yield efficiency of ϕPL = 0.81. The photophysical properties of these compounds can be easily tuned by extension of the conjugation and modification of the phosphorus center. Compared with the established dithieno[3,2-b:2',3'-d]phosphole system, the incorporation of electronegative nitrogen atoms leads to significantly lowered frontier orbital energy levels, as validated by both electrochemistry and theoretical calculations, thus suggesting that the dithiazolo[5,4-b:4',5'-d]phospholes are valuable, air-stable, n-type conjugated materials. These new building blocks have been further applied to the construction of an extended oligomer with fluorene. Extension of the dithiazolophosphole core with triazole units through click reactions also provides a suitable N,N-chelating moiety for metal binding and a representative molecular species was successfully used as a selective colorimetric and fluorescent sensor for Cu(II) ions.

  16. Association of PDE4B Polymorphisms with Susceptibility to Schizophrenia: A Meta-Analysis of Case-Control Studies

    PubMed Central

    Feng, Yanguo; Cheng, Dejun; Zhang, Chaofeng; Li, Yuchun; Zhang, Zhiying; Wang, Juan; Shi, Yuzhong

    2016-01-01

    Background The PDE4B single nucleotide polymorphisms (SNPs) have been reported to be associated with schizophrenia risk. However, current findings are ambiguous or even conflicting. To better facilitate the understanding the genetic role played by PDE4B in susceptibility to schizophrenia, we collected currently available data and conducted this meta-analysis. Methods A comprehensive electronic literature searching of PubMed, Embase, Web of Science and Cochrane Library was performed. The association between PDE4B SNPs and schizophrenia was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs) under allelic, dominant and recessive genetic models. The random effects model was utilized when high between-study heterogeneity (I2 > 50%) existed, otherwise the fixed effects model was used. Results Five studies comprising 2376 schizophrenia patients and 3093 controls were finally included for meta-analysis. The rs1040716 was statistically significantly associated with schizophrenia risk in Asian and Caucasian populations under dominant model (OR = 0.87, 95% CI: 0.76–0.99, P = 0.04). The rs2180335 was significantly related with schizophrenia risk in Asian populations under allelic (OR = 0.82, 95% CI: 0.72–0.93, P = 0.003) and dominant (OR = 0.75, 95% CI: 0.64–0.88, P < 0.001) models. A significant association was also observed between rs4320761 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.75–1.00, P = 0.048). In addition, a strong association tendency was found between rs6588190 and schizophrenia in Asian populations under allelic model (OR = 0.87, 95% CI: 0.76–1.00, P = 0.055). Conclusion This meta-analysis suggests that PDE4B SNPs are genetically associated with susceptibility to schizophrenia. However, due to limited sample size, more large-scale, multi-racial association studies are needed to further clarify the genetic association between various PDE4B variants and schizophrenia. PMID:26756575

  17. Two C-terminal variants of NBC4, a new member of the sodium bicarbonate cotransporter family: cloning, characterization, and localization.

    PubMed

    Pushkin, A; Abuladze, N; Newman, D; Lee, I; Xu, G; Kurtz, I

    2000-07-01

    We report the cloning, characterization, and chromosomal assignment of a new member of the sodium bicarbonate cotransporter (NBC) family, NBC4. The NBC4 gene was mapped to chromosome 2p13 and is a new candidate gene for Alstrom syndrome. Two variants of the transporter have been isolated from human testis and heart, which differ in their C termini. NBC4a encodes a 1137-residue polypeptide and is widely expressed in various tissues, including liver, testis, and spleen. NBC4b is identical to NBC4a except that it has a 16-nucleotide insert, creating a C-terminal frame shift. NBC4b encodes a 1074-residue polypeptide and is highly expressed in heart. Amino acids 1-1046 are common to both NBC4 variants. NBC4a has two protein-interacting domains that are lacking in NBC4b: a proline-rich sequence, PPPSVIKIP (amino acids 1102-1110), and a consensus PDZ-interacting domain, SYSL (1134-1137). NBC4b lacks the stretch of charged residues present in the C terminus of NBC4a and other members of the NBC family. Unlike other members of the NBC family, both NBC4a and NBC4b have a unique glycine-rich region (amino acids 440-469). In comparison with other members of the bicarbonate transport superfamily, NBC4a and NBC4b are most similar structurally to the electrogenic sodium bicarbonate cotransporters (NBC1).

  18. EEG signatures accompanying auditory figure-ground segregation.

    PubMed

    Tóth, Brigitta; Kocsis, Zsuzsanna; Háden, Gábor P; Szerafin, Ágnes; Shinn-Cunningham, Barbara G; Winkler, István

    2016-11-01

    In everyday acoustic scenes, figure-ground segregation typically requires one to group together sound elements over both time and frequency. Electroencephalogram was recorded while listeners detected repeating tonal complexes composed of a random set of pure tones within stimuli consisting of randomly varying tonal elements. The repeating pattern was perceived as a figure over the randomly changing background. It was found that detection performance improved both as the number of pure tones making up each repeated complex (figure coherence) increased, and as the number of repeated complexes (duration) increased - i.e., detection was easier when either the spectral or temporal structure of the figure was enhanced. Figure detection was accompanied by the elicitation of the object related negativity (ORN) and the P400 event-related potentials (ERPs), which have been previously shown to be evoked by the presence of two concurrent sounds. Both ERP components had generators within and outside of auditory cortex. The amplitudes of the ORN and the P400 increased with both figure coherence and figure duration. However, only the P400 amplitude correlated with detection performance. These results suggest that 1) the ORN and P400 reflect processes involved in detecting the emergence of a new auditory object in the presence of other concurrent auditory objects; 2) the ORN corresponds to the likelihood of the presence of two or more concurrent sound objects, whereas the P400 reflects the perceptual recognition of the presence of multiple auditory objects and/or preparation for reporting the detection of a target object.

  19. Full text and figure display improves bioscience literature search.

    PubMed

    Divoli, Anna; Wooldridge, Michael A; Hearst, Marti A

    2010-04-14

    When reading bioscience journal articles, many researchers focus attention on the figures and their captions. This observation led to the development of the BioText literature search engine, a freely available Web-based application that allows biologists to search over the contents of Open Access Journals, and see figures from the articles displayed directly in the search results. This article presents a qualitative assessment of this system in the form of a usability study with 20 biologist participants using and commenting on the system. 19 out of 20 participants expressed a desire to use a bioscience literature search engine that displays articles' figures alongside the full text search results. 15 out of 20 participants said they would use a caption search and figure display interface either frequently or sometimes, while 4 said rarely and 1 said undecided. 10 out of 20 participants said they would use a tool for searching the text of tables and their captions either frequently or sometimes, while 7 said they would use it rarely if at all, 2 said they would never use it, and 1 was undecided. This study found evidence, supporting results of an earlier study, that bioscience literature search systems such as PubMed should show figures from articles alongside search results. It also found evidence that full text and captions should be searched along with the article title, metadata, and abstract. Finally, for a subset of users and information needs, allowing for explicit search within captions for figures and tables is a useful function, but it is not entirely clear how to cleanly integrate this within a more general literature search interface. Such a facility supports Open Access publishing efforts, as it requires access to full text of documents and the lifting of restrictions in order to show figures in the search interface.

  20. Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease

    SciTech Connect

    Romano, Keith P.; Laine, Jennifer M.; Deveau, Laura M.; Cao, Hong; Massi, Francesca; Schiffer, Celia A.

    2011-08-16

    Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance.

  1. Molecular Mechanisms of Viral and Host Cell Substrate Recognition by Hepatitis C Virus NS3/4A Protease▿

    PubMed Central

    Romano, Keith P.; Laine, Jennifer M.; Deveau, Laura M.; Cao, Hong; Massi, Francesca; Schiffer, Celia A.

    2011-01-01

    Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance. PMID:21507982

  2. Learning to rank figures within a biomedical article.

    PubMed

    Liu, Feifan; Yu, Hong

    2014-01-01

    Hundreds of millions of figures are available in biomedical literature, representing important biomedical experimental evidence. This ever-increasing sheer volume has made it difficult for scientists to effectively and accurately access figures of their interest, the process of which is crucial for validating research facts and for formulating or testing novel research hypotheses. Current figure search applications can't fully meet this challenge as the "bag of figures" assumption doesn't take into account the relationship among figures. In our previous study, hundreds of biomedical researchers have annotated articles in which they serve as corresponding authors. They ranked each figure in their paper based on a figure's importance at their discretion, referred to as "figure ranking". Using this collection of annotated data, we investigated computational approaches to automatically rank figures. We exploited and extended the state-of-the-art listwise learning-to-rank algorithms and developed a new supervised-learning model BioFigRank. The cross-validation results show that BioFigRank yielded the best performance compared with other state-of-the-art computational models, and the greedy feature selection can further boost the ranking performance significantly. Furthermore, we carry out the evaluation by comparing BioFigRank with three-level competitive domain-specific human experts: (1) First Author, (2) Non-Author-In-Domain-Expert who is not the author nor co-author of an article but who works in the same field of the corresponding author of the article, and (3) Non-Author-Out-Domain-Expert who is not the author nor co-author of an article and who may or may not work in the same field of the corresponding author of an article. Our results show that BioFigRank outperforms Non-Author-Out-Domain-Expert and performs as well as Non-Author-In-Domain-Expert. Although BioFigRank underperforms First Author, since most biomedical researchers are either in- or out

  3. Weight-related words associated with figure silhouettes.

    PubMed

    Greenleaf, Christy; Starks, Misty; Gomez, Laura; Chambliss, Heather; Martin, Scott

    2004-12-01

    Antifat attitudes and obesity bias are prevalent in Western society; however, little is known about the social meanings and connotations of weight-related words such as fat, overweight, and obese (e.g., Robison & Erdman, 1998). The purpose of this study was to explore college students' perceptions of weight-related terminology. Participants (n=131) completed a modified figure rating scale in which they identified male and female figure silhouettes most associated with a variety of weight-related words and personal characteristics. Additionally, participants completed a word association task and provided definitions of five weight terms. Results indicated that participants grouped weight terms into two groupings (i.e., "slender" and "heavy" weight terms) both in the figure rating task and in the word association and definition tasks. Both male and female participants selected smaller female figure silhouettes for the weight terms overweight, large, fat, and normal weight than for the male figure silhouettes. Moreover, associations between weight-related words and personal characteristics, including normal weight -physically fit and overweight -lazy, were found. The results suggest that weight-related words carry with them social meanings and values that reflect an "ideology of blame."

  4. Three-part Oppel-Kundt illusory figure.

    PubMed

    Bertulis, Algis; Surkys, Tadas; Bulatov, Aleksandr; Gutauskas, Algirdas

    2009-01-01

    The Oppel-Kundt illusion was examined in the psychophysical experiments with the classical two-part stimuli and modified three-part figures. The modified versions comprised either one filled medial interval and two empty flanking intervals or one empty space situated in between two fillings. The illusion was measured as a function of the number of filling elements in the referential parts of the figures. The curves obtained by two modified figures and by the original two-part stimulus were quite similar in shape, but the magnitudes of the illusions differed significantly. The figure with two filled intervals yielded about twice-stronger illusory effect than the contrasting figure with a single filled and two empty intervals. The two-part stimulus showed the illusion magnitudes in the midst. Our assumption suggests the illusory effect being related particularly to over estimations of the filled interval when compared with the empty interval displayed side-to-side. The unfilled interval might not contribute to the illusion.

  5. Reduced cost and improved figure of sapphire optical components

    NASA Astrophysics Data System (ADS)

    Walters, Mark; Bartlett, Kevin; Brophy, Matthew R.; DeGroote Nelson, Jessica; Medicus, Kate

    2015-10-01

    Sapphire presents many challenges to optical manufacturers due to its high hardness and anisotropic properties. Long lead times and high prices are the typical result of such challenges. The cost of even a simple 'grind and shine' process can be prohibitive. The high precision surfaces required by optical sensor applications further exacerbate the challenge of processing sapphire thereby increasing cost further. Optimax has demonstrated a production process for such windows that delivers over 50% time reduction as compared to traditional manufacturing processes for sapphire, while producing windows with less than 1/5 wave rms figure error. Optimax's sapphire production process achieves significant improvement in cost by implementation of a controlled grinding process to present the best possible surface to the polishing equipment. Following the grinding process is a polishing process taking advantage of chemical interactions between slurry and substrate to deliver excellent removal rates and surface finish. Through experiments, the mechanics of the polishing process were also optimized to produce excellent optical figure. In addition to reducing the cost of producing large sapphire sensor windows, the grinding and polishing technology Optimax has developed aids in producing spherical sapphire components to better figure quality. In addition to reducing the cost of producing large sapphire sensor windows, the grinding and polishing technology Optimax has developed aids in producing spherical sapphire components to better figure quality. Through specially developed polishing slurries, the peak-to-valley figure error of spherical sapphire parts is reduced by over 80%.

  6. Inhibitory competition in figure-ground perception: context and convexity.

    PubMed

    Peterson, Mary A; Salvagio, Elizabeth

    2008-12-15

    Convexity has long been considered a potent cue as to which of two regions on opposite sides of an edge is the shaped figure. Experiment 1 shows that for a single edge, there is only a weak bias toward seeing the figure on the convex side. Experiments 1-3 show that the bias toward seeing the convex side as figure increases as the number of edges delimiting alternating convex and concave regions increases, provided that the concave regions are homogeneous in color. The results of Experiments 2 and 3 rule out a probability summation explanation for these context effects. Taken together, the results of Experiments 1-3 show that the homogeneity versus heterogeneity of the convex regions is irrelevant. Experiment 4 shows that homogeneity of alternating regions is not sufficient for context effects; a cue that favors the perception of the intervening regions as figures is necessary. Thus homogeneity alone does not alone operate as a background cue. We interpret our results within a model of figure-ground perception in which shape properties on opposite sides of an edge compete for representation and the competitive strength of weak competitors is further reduced when they are homogeneous.

  7. Determination of visual figure and ground in dynamically deforming shapes.

    PubMed

    Barenholtz, Elan; Feldman, Jacob

    2006-10-01

    Figure/ground assignment - determining which part of the visual image is foreground and which background - is a critical step in early visual analysis, upon which much later processing depends. Previous research on the assignment of figure and ground to opposing sides of a contour has almost exclusively involved static geometric factors - such as convexity, symmetry, and size - in non-moving images. Here, we introduce a new class of cue to figural assignment based on the motion of dynamically deforming contours. Subjects viewing an animated, deforming shape tended to assign figure and ground so that articulating curvature extrema - i.e., "hinging" vertices - had negative (concave) contour curvature. This articulating-concavity bias is present when all known static cues to figure/ground are absent or neutral in each of the individual frames of the animation, and even seems to override a number of well-known static cues when they are in opposition to the motion cue. We propose that the phenomenon reflects the visual system's inbuilt expectations about the way shapes will deform - specifically, that deformations tend to involve rigid parts articulating at concavities.

  8. Isolation and structure of ciguatoxin-4A, a new ciguatoxin precursor, from cultures of dinoflagellate Gambierdiscus toxicus and parrotfish Scarus gibbus.

    PubMed

    Satake, M; Ishibashi, Y; Legrand, A M; Yasumoto, T

    1996-12-01

    A new ciguatoxin congener, ciguatoxin-4A (CTX4A), was isolated from cultures of marine dinoflagellate Gambierdiscus toxicus, and its structure was elucidated to be 52-epiciguatoxin-4B on the basis of spectroscopic data. Chromatographic and spectral comparisons indicated that CTX4A was identical with a structurally unelucidated congener known as scaritoxin or SG1.

  9. Douglas OA-4A Dolphin

    NASA Technical Reports Server (NTRS)

    1938-01-01

    Douglas OA-4A Dolphin: This twin-engine Douglas OA-4A Dolphin was unusual in comparison with other OA-4s in that it employed a nose wheel instead of a tail wheel during its NACA testing at Langley. Here is is seen in the NACA hangar in September 1938.

  10. Pathognomonic symptom associated with lightning strike: Lichtenberg figure.

    PubMed

    Yigit, Mehmet; Tanrikulu, Nazmiye; Turkdogan, Kenan Ahmet; Yigit, Eda

    2015-02-01

    Lightning strikes especially occur during spring and summer months in the afternoons when there is heavy rain. In deaths resulting from lightning strike, there may either be no evidence on the dead person's clothes or body, or there may be burnt or torn patches on their clothes and lichtenberg figures specific to lightning strikes on their bodies. In such cases that also have a comorbid of cognitive dysfunction, since there is generally amnesia, having these figures during the physical examination has a valuable place in early diagnosis and quick treatment. This paper presents a case of lightning strike that was found to have Lichtenberg figures on the back and right leg after secondary examination.

  11. Figure of Merit for Carbon Nanotube Photothermoelectric Detectors.

    PubMed

    Erikson, Kristopher J; He, Xiaowei; Talin, A Alec; Mills, Bernice; Hauge, Robert H; Iguchi, Takashi; Fujimura, Naoki; Kawano, Yukio; Kono, Junichiro; Léonard, François

    2015-12-22

    Carbon nanotubes (CNTs) have emerged as promising materials for visible, infrared, and terahertz photodetectors. Further development of these photodetectors requires a fundamental understanding of the mechanisms that govern their behavior as well as the establishment of figures of merit for technology applications. Recently, a number of CNT detectors have been shown to operate based on the photothermoelectric effect. Here we present a figure of merit for these detectors, which includes the properties of the material and the device. In addition, we use a suite of experimental characterization methods for the thorough analysis of the electrical, thermoelectric, electrothermal, and photothermal properties of the CNT thin-film devices. Our measurements determine the quantities that enter the figure of merit and allow us to establish a path toward future performance improvements.

  12. Social dimensions of judgments of integrity in public figures.

    PubMed

    Sparks, Paul; Farsides, Tom

    2011-03-01

    The notion of 'integrity' remains relatively unexplored in the social psychological literature, despite it being central to some important theoretical perspectives (notably, self-affirmation theory). It is an eminently positive - and well-used - epithet in descriptions of public figures. The two studies reported here addressed laypeople's conceptions of integrity. The findings indicate that in relation to eight public figures, the best general predictor of judgments of integrity was perceptions of 'sincerity' (characterized by attributes such as genuine and honest). For three of the public figures strongly linked to civil rights issues, judgments of integrity were also predicted by perceptions of 'standing for something'. The findings suggest that the social character of integrity merits further psychological research attention.

  13. Brief report: human figure drawings by children with Asperger's syndrome.

    PubMed

    Lim, Hui Keow; Slaughter, Virginia

    2008-05-01

    Twenty-nine children with Asperger's syndrome and 28 typically developing children, matched on gender, chronological age and nonverbal IQ, were asked to produce a free drawing, then requested to draw a person, a house and a tree. The drawings were scored using standardized procedures for assessing accuracy, detail and complexity. There were no differences between the diagnostic groups on the tree or house drawing scores. The human figure drawing scores of children with Asperger's syndrome were significantly lower than those of the typically developing children, and there was a positive correlation between human figure drawing scores and communication sub-scores on the Vineland Adaptive Behaviour Scales, for the Asperger's group. These results suggest that the selective deficit in generating human figure representations may derive from a relative lack of interest in the social world, and/or limited practice in drawing people.

  14. Novel figurative phrases and idioms: phrase characteristics over multiple presentations.

    PubMed

    Schweigert, Wendy A; Cintron, Jennifer; Sullivan, Karin; Ilic, Emily; Ellis, Shannon; Dobrowits, Carrie; Roberts, Crystal

    2003-07-01

    In a series of three studies, characteristics of novel figurative phrases were compared with those of established idioms. Studies 1 and 2 found that certain correlations were found to be strong and in one direction for familiar idioms and comparably strong but in the opposite direction for novel figurative phrases, with the correlations for less familiar idioms usually falling partway between these extremes. Study 2 also noted that written or auditory presentation had minimal effects on characteristic ratings. In Study 3 the correlations among characteristics stayed relatively constant for familiar idioms after one, three, or six presentations, but for the novel figurative phrases, after multiple presentations the correlations changed in the direction of the established idioms.

  15. Kepler's Theory of Highly Symmetric Plane Figures and Solids

    NASA Astrophysics Data System (ADS)

    Betsch, Gerhard

    The main idea of Kepler's Mysterium Cosmographicum of 1596 involves the five regular "Platonic" polyhedra. Hence it seems appropriate to discuss Kepler's considerations on, or his "theory" of regular plane figures and solids. This is a key aspect of his "geometrical cosmology". In modern mathematics the regularity of figures and solids is normally expressed in terms of symmetries and symmetry groups. Although Kepler himself does not speak of symmetries, the author is applying at some points the modern, admittedly anachronistic terminology. This seems to be justified, because here is presented a mathematician's view rather than a historical discourse. The tradition of plane regular figures and regular solids, from antiquity to Kepler's time, and the sourses of Kepler's mathematics have been thoroughly investigated by Hofmann and Fields.

  16. Giant magnetic coercivity in YNi4B-type SmNi3TB (T=Mn-Cu) solid solutions

    NASA Astrophysics Data System (ADS)

    Yao, Jinlei; Yan, Chang; Yapaskurt, V. O.; Morozkin, A. V.

    2016-12-01

    The effects of transition metal substitution for Ni on the magnetic properties of the YNi4B-type SmNi4B via SmNi3TB (T=Mn, Fe, Co, Cu) solid solutions have been investigated. SmNi4B, SmNi3MnB, SmNi3FeB, SmNi3CoB and SmNi3CuB show ferromagnetic ordering at 40 K, 210 K, 322 K, 90 K and 57 K and field sensitive metamagnetic-like transitions at 15 K, 100 K, 185 K, 55 K and 15 K in a magnetic field of 10 kOe, respectively. The magnetocaloric effects of SmNi3TB (T=Mn-Cu) were calculated in terms of isothermal magnetic entropy change (ΔSm). The magnetic entropy ΔSm reaches value of -0.94 J/kg K at 40 K for SmNi4B, -1.5 J/kg K at 205 K for SmNi3MnB, -0.54 J/kg K at 320 K for SmNi3FeB, -0.49 J/kg K at 90 K for SmNi3CoB and -0.54 J/kg K at 60 K for SmNi3CuB in field change of 0-50 kOe around the Curie temperature. They show positive ΔSm of +0.71 J/kg K at ~10 K for SmNi4B, +1.69 J/kg K at 30 K for SmNi3MnB, +0.89 J/kg K at 110 K for SmNi3FeB, +1.08 J/kg K at 25 K for SmNi3CoB and +1.12 J/kg K at 10 K for SmNi3CuB in field change of 0-50 kOe around the low temperature metamagnetic-like transition. Below the field induced transition temperature (change of magnetic structure), SmNi3TB (T=Mn-Cu) exhibits giant magnetic coercivity of 74 kOe at 5 K for SmNi4B, 69 kOe at 20 K (90 kOe at 10 K) for SmNi3MnB, 77 kOe at 60 K for SmNi3FeB, 88 kOe at 20 K for SmNi3CoB and 52 kOe at 5 K for SmNi3CuB.

  17. Estrogen receptor alpha prevents bladder cancer via INPP4B inhibited akt pathway in vitro and in vivo.

    PubMed

    Hsu, Iawen; Yeh, Chiuan-Ren; Slavin, Spencer; Miyamoto, Hiroshi; Netto, George J; Tsai, Yu-Chieh; Muyan, Mesut; Wu, Xue-Ru; Messing, Edward M; Guancial, Elizabeth A; Yeh, Shuyuan

    2014-09-15

    Clinical reports show males have a higher bladder cancer (BCa) incidence than females. The sexual difference of BCa occurrence suggests that estrogen and its receptors may affect BCa development. Estrogen receptor alpha (ERα) is the classic receptor to convey estrogen signaling, however, the function of ERα in BCa development remains largely unknown. To understand the in vivo role of ERα in BCa development, we generated total and urothelial specific ERα knockout mice (ERαKO) and used the pre- carcinogen BBN to induce BCa. Earlier reports showed that ERα promotes breast and ovarian cancers in females. Surprisingly and of clinical importance, our results showed that ERα inhibits BCa development and loss of the ERα gene results in an earlier onset and higher incidence of BBN-induced in vivo mouse BCa. Supportively, carcinogen induced malignant transformation ability was reduced in ERα expressing urothelial cells as compared to ERα negative cells. Mechanism studies suggest that ERα could control the expression of INPP4B to reduce AKT activity and consequently reduce BCa cell growth. In addition, IHC staining of clinical sample analyses show that INPP4B expression, in correlation with reduced ERα, is significantly reduced in human BCa specimens. Together, this is the first report using the in vivo cre-loxP gene knockout mouse model to characterize ERα roles in BCa development. Our studies provide multiple in vitro cell studies and in vivo animal model data as well as human BCa tissue analyses to prove ERα plays a protective role in BCa initiation and growth at least partly via modulating the INPP4B/Akt pathway.

  18. First report of severe parainfluenza virus 4B and rhinovirus C coinfection in a liver transplant recipient treated with immunoglobulin.

    PubMed

    Sridhar, Siddharth; Luk, Hayes K H; Lau, Susanna K P; Woo, Patrick C Y

    2014-12-01

    We describe the first reported case of severe pneumonia due to coinfection by parainfluenza virus type 4B and rhinovirus C in a liver transplant recipient. The patient responded promptly to intravenous immunoglobulin and timely infection control measures prevented spreading of the infections. This report highlights respiratory viral coinfections as a possible cause of severe morbidity in transplant recipients and the importance of efficient molecular diagnostic technologies with major impact on clinical practice in a transplant center. It also describes a potential therapeutic strategy for such patients.

  19. Developing VUV spectroscopy for protein folding and material luminescence on beamline 4B8 at the Beijing Synchrotron Radiation Facility.

    PubMed

    Tao, Ye; Huang, Yan; Gao, Zhenghua; Zhuang, Hao; Zhou, Aiyu; Tan, Yinglei; Li, Daowu; Sun, Shuaishuai

    2009-11-01

    The new 4B8 beamline provides UV-VUV light in the wavelength range from 360 to 120 nm. It uniquely enables two kinds of spectroscopy measurements: synchrotron radiation circular dichroism spectroscopy and VUV excited fluorescence spectroscopy. The former is mainly used in protein secondary structure studies, and the latter in VUV excited luminescent materials research. Remote access to fluorescence measurement has been realised and users can collect data online. Besides steady-state measurements, fluorescence lifetime measurements have been established using the time domain method, while a laser-induced temperature jump is under development for protein folding dynamics using circular dichroism as a probe.

  20. Polarization preservation and control in a figure-8 ring

    SciTech Connect

    Derbenev, Yaroslav S.; Morozov, Vasiliy; Lin, Fanglei; Zhang, Yuhong; Kondratenko, A. M.; Kondratenko, M. A.; Filatov, Yuri

    2016-02-01

    We present a complete scheme for managing the polarization of ion beams in Jefferson Lab's proposed Medium-energy Electron-Ion Collider (MEIC). It provides preservation of the ion polarization during all stages of beam acceleration and polarization control in the collider's experimental straights. We discuss characteristic features of the spin motion in accelerators with Siberian snakes and in accelerators of figure-8 shape. We propose 3D spin rotators for polarization control in the MEIC ion collider ring. We provide polarization calculations in the collider with the 3D rotator for deuteron and proton beams. The main polarization control features of the figure-8 design are summarized.