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Sample records for proprotein convertase encoded

  1. The Proprotein Convertase Encoded by amontillado (amon) Is Required in Drosophila Corpora Cardiaca Endocrine Cells Producing the Glucose Regulatory Hormone AKH

    PubMed Central

    Rhea, Jeanne M.; Wegener, Christian; Bender, Michael

    2010-01-01

    Peptide hormones are potent signaling molecules that coordinate animal physiology, behavior, and development. A key step in activation of these peptide signals is their proteolytic processing from propeptide precursors by a family of proteases, the subtilisin-like proprotein convertases (PCs). Here, we report the functional dissection of amontillado (amon), which encodes the Drosophila homolog of the mammalian PC2 protein, using cell-type specific inactivation and rescue experiments, and we show that amon is required in the islet-like adipokinetic hormone (AKH)–producing cells that regulate sugar homeostasis. In Drosophila, AKH acts analogously to vertebrate glucagon to increase circulating sugar levels from energy stores, while insulin-like peptides (DILPs) act to decrease sugar levels. amon mutant larvae have significantly reduced hemolymph sugar levels, and thus phenocopy larvae where the AKH–producing cells in the corpora cardiaca have been ablated. Reduction of amon expression in these cells via cell-specific RNA inactivation also results in larvae with reduced sugar levels while expression of amon in AKH cells in an amon mutant background rescues hypoglycemia. Hypoglycemia in larvae resulting from amon RNA inactivation in the AKH cells can be rescued by global expression of the akh gene. Finally, mass spectrometric profiling shows that the production of mature AKH is inhibited in amon mutants. Our data indicate that amon function in the AKH cells is necessary to maintain normal sugar homeostasis, that amon functions upstream of akh, and that loss of mature AKH is correlated with loss of amon activity. These observations indicate that the AKH propeptide is a proteolytic target of the amon proprotein convertase and provide evidence for a conserved role of PC2 in processing metabolic peptide hormones. PMID:20523747

  2. The proprotein convertase encoded by amontillado (amon) is required in Drosophila corpora cardiaca endocrine cells producing the glucose regulatory hormone AKH.

    PubMed

    Rhea, Jeanne M; Wegener, Christian; Bender, Michael

    2010-05-01

    Peptide hormones are potent signaling molecules that coordinate animal physiology, behavior, and development. A key step in activation of these peptide signals is their proteolytic processing from propeptide precursors by a family of proteases, the subtilisin-like proprotein convertases (PCs). Here, we report the functional dissection of amontillado (amon), which encodes the Drosophila homolog of the mammalian PC2 protein, using cell-type specific inactivation and rescue experiments, and we show that amon is required in the islet-like adipokinetic hormone (AKH)-producing cells that regulate sugar homeostasis. In Drosophila, AKH acts analogously to vertebrate glucagon to increase circulating sugar levels from energy stores, while insulin-like peptides (DILPs) act to decrease sugar levels. amon mutant larvae have significantly reduced hemolymph sugar levels, and thus phenocopy larvae where the AKH-producing cells in the corpora cardiaca have been ablated. Reduction of amon expression in these cells via cell-specific RNA inactivation also results in larvae with reduced sugar levels while expression of amon in AKH cells in an amon mutant background rescues hypoglycemia. Hypoglycemia in larvae resulting from amon RNA inactivation in the AKH cells can be rescued by global expression of the akh gene. Finally, mass spectrometric profiling shows that the production of mature AKH is inhibited in amon mutants. Our data indicate that amon function in the AKH cells is necessary to maintain normal sugar homeostasis, that amon functions upstream of akh, and that loss of mature AKH is correlated with loss of amon activity. These observations indicate that the AKH propeptide is a proteolytic target of the amon proprotein convertase and provide evidence for a conserved role of PC2 in processing metabolic peptide hormones. PMID:20523747

  3. Proprotein Convertases in Tumor Progression and Malignancy

    PubMed Central

    Khatib, Abdel-Majid; Siegfried, Géraldine; Chrétien, Michel; Metrakos, Peter; Seidah, Nabil G.

    2002-01-01

    The mammalian subtilisin/kexin-like proprotein convertase (PC) family has been implicated in the activation of a wide spectrum of proteins. These proteins are usually synthesized as inactive precursors before their conversion to fully mature bioactive forms. A large majority of these active proteins such as matrix metalloproteases, growth factors, and adhesion molecules are crucial in the processes of cellular transformation, acquisition of the tumorigenic phenotype, and metastases formation. Inhibition of PCs significantly affects the malignant phenotype of various tumor cells. In addition to direct tumor cell proliferation and migration blockade, PC inhibitors can also be used to target tumor angiogenesis. In this Review article we discuss a number of recent findings on the clinical relevance of PCs in cancer patients, their implication in the regulation of multiple cellular functions that impact on the invasive/metastatic potential of cancer cells. Thus, PC inhibitors may constitute new promising agents for the treatment of multiple tumors and/or in adjuvant therapy to prevent recurrence. PMID:12057895

  4. Substrate Cleavage Analysis of Furin and Related Proprotein Convertases

    PubMed Central

    Remacle, Albert G.; Shiryaev, Sergey A.; Oh, Eok-Soo; Cieplak, Piotr; Srinivasan, Anupama; Wei, Ge; Liddington, Robert C.; Ratnikov, Boris I.; Parent, Amelie; Desjardins, Roxane; Day, Robert; Smith, Jeffrey W.; Lebl, Michal; Strongin, Alex Y.

    2008-01-01

    We present the data and the technology, a combination of which allows us to determine the identity of proprotein convertases (PCs) related to the processing of specific protein targets including viral and bacterial pathogens. Our results, which support and extend the data of other laboratories, are required for the design of effective inhibitors of PCs because, in general, an inhibitor design starts with a specific substrate. Seven proteinases of the human PC family cleave the multibasic motifs R-X-(R/K/X)-R↓ and, as a result, transform proproteins, including those from pathogens, into biologically active proteins and peptides. The precise cleavage preferences of PCs have not been known in sufficient detail; hence we were unable to determine the relative importance of the individual PCs in infectious diseases, thus making the design of specific inhibitors exceedingly difficult. To determine the cleavage preferences of PCs in more detail, we evaluated the relative efficiency of furin, PC2, PC4, PC5/6, PC7, and PACE4 in cleaving over 100 decapeptide sequences representing the R-X-(R/K/X)-R↓ motifs of human, bacterial, and viral proteins. Our computer analysis of the data and the follow-on cleavage analysis of the selected full-length proteins corroborated our initial results thus allowing us to determine the cleavage preferences of the PCs and to suggest which PCs are promising drug targets in infectious diseases. Our results also suggest that pathogens, including anthrax PA83 and the avian influenza A H5N1 (bird flu) hemagglutinin precursor, evolved to be as sensitive to PC proteolysis as the most sensitive normal human proteins. PMID:18505722

  5. Proprotein Convertases Process and Thereby Inactivate Formylglycine-generating Enzyme*

    PubMed Central

    Ennemann, Eva C.; Radhakrishnan, Karthikeyan; Mariappan, Malaiyalam; Wachs, Michaela; Pringle, Thomas H.; Schmidt, Bernhard; Dierks, Thomas

    2013-01-01

    Formylglycine-generating enzyme (FGE) post-translationally converts a specific cysteine in newly synthesized sulfatases to formylglycine (FGly). FGly is the key catalytic residue of the sulfatase family, comprising 17 nonredundant enzymes in human that play essential roles in development and homeostasis. FGE, a resident protein of the endoplasmic reticulum, is also secreted. A major fraction of secreted FGE is N-terminally truncated, lacking residues 34–72. Here we demonstrate that this truncated form is generated intracellularly by limited proteolysis mediated by proprotein convertase(s) (PCs) along the secretory pathway. The cleavage site is represented by the sequence RYSR72↓, a motif that is conserved in higher eukaryotic FGEs, implying important functionality. Residues Arg-69 and Arg-72 are critical because their mutation abolishes FGE processing. Furthermore, residues Tyr-70 and Ser-71 confer an unusual property to the cleavage motif such that endogenous as well as overexpressed FGE is only partially processed. FGE is cleaved by furin, PACE4, and PC5a. Processing is disabled in furin-deficient cells but fully restored upon transient furin expression, indicating that furin is the major protease cleaving FGE. Processing by endogenous furin occurs mostly intracellularly, although also extracellular processing is observed in HEK293 cells. Interestingly, the truncated form of secreted FGE no longer possesses FGly-generating activity, whereas the unprocessed form of secreted FGE is active. As always both forms are secreted, we postulate that furin-mediated processing of FGE during secretion is a physiological means of higher eukaryotic cells to regulate FGE activity upon exit from the endoplasmic reticulum. PMID:23288839

  6. Proprotein convertases process and thereby inactivate formylglycine-generating enzyme.

    PubMed

    Ennemann, Eva C; Radhakrishnan, Karthikeyan; Mariappan, Malaiyalam; Wachs, Michaela; Pringle, Thomas H; Schmidt, Bernhard; Dierks, Thomas

    2013-02-22

    Formylglycine-generating enzyme (FGE) post-translationally converts a specific cysteine in newly synthesized sulfatases to formylglycine (FGly). FGly is the key catalytic residue of the sulfatase family, comprising 17 nonredundant enzymes in human that play essential roles in development and homeostasis. FGE, a resident protein of the endoplasmic reticulum, is also secreted. A major fraction of secreted FGE is N-terminally truncated, lacking residues 34-72. Here we demonstrate that this truncated form is generated intracellularly by limited proteolysis mediated by proprotein convertase(s) (PCs) along the secretory pathway. The cleavage site is represented by the sequence RYSR(72)↓, a motif that is conserved in higher eukaryotic FGEs, implying important functionality. Residues Arg-69 and Arg-72 are critical because their mutation abolishes FGE processing. Furthermore, residues Tyr-70 and Ser-71 confer an unusual property to the cleavage motif such that endogenous as well as overexpressed FGE is only partially processed. FGE is cleaved by furin, PACE4, and PC5a. Processing is disabled in furin-deficient cells but fully restored upon transient furin expression, indicating that furin is the major protease cleaving FGE. Processing by endogenous furin occurs mostly intracellularly, although also extracellular processing is observed in HEK293 cells. Interestingly, the truncated form of secreted FGE no longer possesses FGly-generating activity, whereas the unprocessed form of secreted FGE is active. As always both forms are secreted, we postulate that furin-mediated processing of FGE during secretion is a physiological means of higher eukaryotic cells to regulate FGE activity upon exit from the endoplasmic reticulum. PMID:23288839

  7. The proprotein convertase furin is required for trophoblast syncytialization

    PubMed Central

    Zhou, Z; Zhang, Q; Lu, X; Wang, R; Wang, H; Wang, Y-L; Zhu, C; Lin, H-Y; Wang, H

    2013-01-01

    The multinucleated syncytial trophoblast, which forms the outermost layer of the placenta and serves multiple functions, is differentiated from and maintained by cytotrophoblast cell fusion. Deficiencies in syncytial trophoblast differentiation or maintenance likely contribute to intrauterine growth restriction and pre-eclampsia, two common gestational diseases. The cellular and molecular mechanisms governing trophoblast syncytialization are poorly understood. We report here that the proprotein convertase furin is highly expressed in syncytial trophoblast in the first trimester human placentas, and expression of furin in the syncytiotrophoblast is significantly lower in the placentas from pre-eclamptic patients as compared with their gestational age-matched control placentas. Using multiple experimental models including induced fusion of choriocarcinoma BeWo cells and spontaneous fusion of primary cultured cytotrophoblast cells or placental explants, we demonstrate that cytotrophoblast cell fusion and syncytialization are accompanied by furin expression. Furin-specific siRNAs or inhibitors inhibit cell fusion in BeWo cells, as well as trophoblast syncytialization in human placental explants. Furthermore, type 1 IGF receptor (IGF1R) is indicated in this study as a substrate of furin, and processing of IGF1R by furin is an essential mechanism for syncytialization. Finally, using lentivirus-mediated RNAi targeting to mouse trophectoderm, we demonstrate that furin function is required for the development of syncytiotrophoblast structure in the labyrinth layer, as well as for normal embryonic development. PMID:23598405

  8. Proprotein convertases in high-density lipoprotein metabolism.

    PubMed

    Choi, Seungbum; Korstanje, Ron

    2013-01-01

    The proprotein convertase subtilisin/kexins (PCSKs) are a serine endopeptidase family. PCSK members cleave amino acid residues and modulate the activity of precursor proteins. Evidence from patients and animal models carrying genetic alterations in PCSK members show that PCSK members are involved in various metabolic processes. These studies further revealed the molecular mechanism by which genetic alteration of some PCSK members impairs normal molecular and physiological functions, which in turn lead to cardiovascular disease. High-density lipoprotein (HDL) is anti-atherogenic as it removes excessive amount of cholesterol from blood and peripheral tissues. Several PCSK members are involved in HDL metabolism. PCSK3, PCSK5, and PCSK6 process two triglyceride lipase family members, endothelial lipase and lipoprotein lipase, which are important for HDL remodeling. Recent studies in our lab found evidence that PCSK1 and PCSK9 are also involved in HDL metabolism. A mouse model carrying an amino acid substitution in PCSK1 showed an increase in serum apolipoprotein A1 (APOA1) level. Another mouse model lacking PCSK9 showed a decrease in APOE-containing HDL. In this review, we summarize the role of the five PCSK members in lipid, glucose, and bile acid (BA) metabolism, each of which can influence HDL metabolism. We propose an integrative model in which PCSK members regulate HDL metabolism through various molecular mechanisms and metabolic processes and genetic variation in some PCSK members may affect the efficiency of reverse cholesterol transport. PCSK members are considered as attractive therapeutic targets. A greater understanding of the molecular and physiological functions of PCSK members will improve therapeutic strategies and drug efficacy for cardiovascular disease where PCSK members play critical role, with fewer adverse effects. PMID:24252756

  9. An Atypical Proprotein Convertase in Giardia lamblia Differentiation

    PubMed Central

    Davids, B. J.; Gilbert, M. A.; Liu, Q.; Reiner, D. S.; Smith, A. J.; Lauwaet, T.; Lee, C.; McArthur, A. G.; Gillin, F. D.

    2010-01-01

    Proteolytic activity is important in the lifecycles of parasites and their interactions with hosts. Cysteine proteases have been best studied in Giardia, but other protease classes have been implicated in growth and/or differentiation. In this study, we employed bioinformatics to reveal the complete set of putative proteases in the Giardia genome. We identified 73 peptidase homologues distributed over 5 catalytic classes in the genome. Serial analysis of gene expression of the G. lamblia lifecycle found thirteen protease genes with significant transcriptional variation over the lifecycle, with only one serine protease transcript upregulated late in encystation. The translated gene sequence of this encystation-specific transcript was most similar to eukaryotic subtilisin-like proprotein convertases (SPC), although the typical catalytic triad was not identified. Epitope-tagged gSPC protein expressed in Giardia under its own promoter was upregulated during encystation with highest expression in cysts and it localized to encystation-specific secretory vesicles (ESV). Total gSPC from encysting cells produced proteolysis in gelatin gels that co-migrated with the epitope-tagged protease in immunoblots. Immuno-purified gSPC also had gelatinase activity. To test whether endogenous gSPC activity is involved in differentiation, trophozoites and cysts were exposed to the specific serine proteinase inhibitor 4-(2-Aminoethyl)-benzenesulfonyl fluoride hydrochloride (AEBSF). After 21 h encystation, a significant decrease in ESV was observed with 1 mM AEBSF and by 42 h the number of cysts was significantly reduced, but trophozoite growth was not inhibited. Concurrently, levels of cyst wall proteins 1 and 2, and AU1-tagged gSPC protein itself were decreased. Excystation of G. muris cysts was also significantly reduced in the presence of AEBSF. These results support the idea that serine protease activity is essential for Giardia encystation and excystation. PMID:21075147

  10. Small Molecule Proprotein Convertase Inhibitors for Inhibition of Embryo Implantation

    PubMed Central

    Ho, Huiting; Singh, Harmeet; Heng, Sophea; Nero, Tracy L.; Paule, Sarah; Parker, Michael W.; Johnson, Alan T.; Jiao, Guan-Sheng; Nie, Guiying

    2013-01-01

    Uterine proprotein convertase (PC) 6 plays a critical role in embryo implantation and is pivotal for pregnancy establishment. Inhibition of PC6 may provide a novel approach for the development of non-hormonal and female-controlled contraceptives. We investigated a class of five synthetic non-peptidic small molecule compounds that were previously reported as potent inhibitors of furin, another PC member. We examined (i) the potency of these compounds in inhibiting PC6 activity in vitro; (ii) their binding modes in the PC6 active site in silico; (iii) their efficacy in inhibiting PC6-dependent cellular processes essential for embryo implantation using human cell-based models. All five compounds showed potent inhibition of PC6 activity in vitro, and in silico docking demonstrated that these inhibitors could adopt a similar binding mode in the PC6 active site. However, when these compounds were tested for their inhibition of decidualization of primary human endometrial stromal cells, a PC6-dependent cellular process critical for embryo implantation, only one (compound 1o) showed potent inhibition. The lack of activity in the cell-based assay may reflect the inability of the compounds to penetrate the cell membrane. Because compound's lipophilicity is linked to cell penetration, a measurement of lipophilicity (logP) was calculated for each compound. Compound 1o is unique as it appears the most lipophilic among the five compounds. Compound 1o also inhibited another crucial PC6-dependent process, the attachment of human trophoblast spheroids to endometrial epithelial cells (a model for human embryo attachment). We thus identified compound 1o as a potent small molecule PC6 inhibitor with pharmaceutical potential to inhibit embryo implantation. Our findings also highlight that human cell-based functional models are vital to complement the biochemical and in silico analyses in the selection of promising drug candidates. Further investigations for compound 1o are warranted in

  11. Genetics of the First Seven Proprotein Convertase Enzymes in Health and Disease

    PubMed Central

    Turpeinen, Hannu; Ortutay, Zsuzsanna; Pesu, Marko

    2013-01-01

    Members of the substilisin/kexin like proprotein convertase (PCSK) protease family cleave and convert immature pro-proteins into their biologically active forms. By cleaving for example prohormones, cytokines and cell membrane proteins, PCSKs participate in maintaining the homeostasis in a healthy human body. Conversely, erratic enzymatic function is thought to contribute to the pathogenesis of a wide variety of diseases, including obesity and hypercholestrolemia. The first characterized seven PCSK enzymes (PCSK1-2, FURIN, PCSK4-7) process their substrates at a motif made up of paired basic amino acid residues. This feature results in a variable degree of biochemical redundancy in vitro, and consequently, shared substrate molecules between the different PCSK enzymes. This redundancy has confounded our understanding of the specific biological functions of PCSKs. The physiological roles of these enzymes have been best illustrated by the phenotypes of genetically engineered mice and patients that carry mutations in the PCSK genes. Recent developments in genome-wide methodology have generated a large amount of novel information on the genetics of the first seven proprotein convertases. In this review we summarize the reported genetic alterations and their associated phenotypes. PMID:24396277

  12. Proprotein convertase subtilisin/kexin type 9 (PCSK9) in lipid metabolism, atherosclerosis and ischemic stroke.

    PubMed

    Zhang, Lingling; Song, Kangping; Zhu, Mengting; Shi, Jinling; Zhang, Huijuan; Xu, Liang; Chen, Yingzhu

    2016-08-01

    Proprotein convertase subtilisin/kexin 9 (PCSK9) is the ninth member of the proprotein convertase family. It is an important regulator of cholesterol metabolism. PCSK9 can bind to low-density lipoprotein receptors (LDLRs) and induce the degradation of these receptors through the endosome/lysosome pathway, thus decreasing the LDLR levels on the cell surface of hepatocytes, resulting in increased serum low-density lipoprotein cholesterol (LDL-C) concentrations. Recent studies have found that gene polymorphisms of PCSK9 are associated with hypercholesterolemia, risk of atherosclerosis, and ischemic stroke. Furthermore, monoclonal antibodies, peptide mimetics, small molecule inhibitors and gene silencing agents that are associated with PCSK9 are some of the newer pharmaceutical therapeutic strategies and approaches for lowering serum LDL-C levels. In this review, we will discuss recent advances in PCSK9 research, which show that PCSK9 is correlated with lipid metabolism, atherosclerosis, and, in particular, ischemic stroke. We will also discuss the current state of PCSK9 therapeutics and their potential in modulating these diseases. PMID:26040332

  13. Proprotein convertase FURIN constrains Th2 differentiation and is critical for host resistance against Toxoplasma gondii.

    PubMed

    Oksanen, Anna; Aittomäki, Saara; Jankovic, Dragana; Ortutay, Zsuzsanna; Pulkkinen, Kati; Hämäläinen, Sanna; Rokka, Anne; Corthals, Garry L; Watford, Wendy T; Junttila, Ilkka; O'Shea, John J; Pesu, Marko

    2014-12-01

    The proprotein convertase subtilisin/kexin enzymes proteolytically convert immature proproteins into bioactive molecules, and thereby they serve as key regulators of cellular homeostasis. The archetype proprotein convertase subtilisin/kexin, FURIN, is a direct target gene of the IL-12/STAT4 pathway and it is upregulated in Th1 cells. We have previously demonstrated that FURIN expression in T cells critically regulates the maintenance of peripheral immune tolerance and the functional maturation of pro-TGF-β1 in vivo, but FURIN's role in cell-mediated immunity and Th polarization has remained elusive. In this article, we show that T cell-expressed FURIN is essential for host resistance against a prototypic Th1 pathogen, Toxoplasma gondii, and for the generation of pathogen-specific Th1 lymphocytes, including Th1-IL-10 cells. FURIN-deficient Th cells instead show elevated expression of IL-4R subunit α on cell surface, sensitized IL-4/STAT6 signaling, and a propensity to polarize toward the Th2 phenotype. By exploring FURIN-interacting proteins in Jurkat T cells with Strep-Tag purification and mass spectrometry, we further identify an association with a cytoskeleton modifying Ras-related C3 botulinum toxin substrate/dedicator of cytokinesis 2 protein complex and unravel that FURIN promotes F-actin polymerization, which has previously been shown to downregulate IL-4R subunit α cell surface expression and promote Th1 responses. In conclusion, our results demonstrate that in addition to peripheral immune tolerance, T cell-expressed FURIN is also a central regulator of cell-mediated immunity and Th1/2 cell balance. PMID:25355923

  14. Hypercholesterolemia, low density lipoprotein receptor and proprotein convertase subtilisin/kexin-type 9

    PubMed Central

    Gu, Hong-mei; Zhang, Da-wei

    2015-01-01

    Abstract Atherosclerotic cardiovascular disease is the main cause of mortality and morbidity in the world. Plasma levels of low density lipoprotein cholesterol (LDL-C) are positively correlated with the risk of atherosclerosis. High plasma LDL concentrations in patients with hypercholesterolemia lead to build-up of LDL in the inner walls of the arteries, which becomes oxidized and promotes the formation of foam cells, consequently initiating atherosclerosis. Plasma LDL is mainly cleared through the LDL receptor (LDLR) pathway. Mutations in the LDLR cause familiar hypercholesterolemia and increase the risk of premature coronary heart disease. The expression of LDLR is regulated at the transcriptional level via the sterol regulatory element binding protein 2 (SREBP-2) and at the posttranslational levels mainly through proprotein convertase subtilisin/kexin-type 9 (PCSK9) and inducible degrader of the LDLR (IDOL). In this review, we summarize the latest advances in the studies of PCSK9. PMID:26445568

  15. The prohormone theory and the proprotein convertases: it is all about serendipity.

    PubMed

    Chrétien, Michel

    2011-01-01

    When I became a physician and an endocrinologist in the early 1960s, peptide hormone sequencing was still in its infancy; it was also far removed from my immediate interests. Through chance encounters with prominent teachers and mentors, I later became increasingly convinced that elucidation of the primary sequence of peptide hormones is key to understanding their production as well as their functions in human health and disease. My interest for pituitary hormones led me to discover that the sequence of β-melanocyte-stimulating hormone was contained within that γ and β-lipotropins and could be released from the latter by limited endoproteolysis. This prohormone theory became the leitmotiv of my career as a clinician/scientist. Through serendipity and the efforts of many laboratories including mine, this theory has now been widely confirmed, extended to various precursor proteins and implicated in many diseases. It has led to our discovery of the proprotein convertases. PMID:21805236

  16. Proprotein convertase FURIN constrains Th2 differentiation and is critical for host resistance against Toxoplasma gondii

    PubMed Central

    Oksanen, Anna; Aittomäki, Saara; Jankovic, Dragana; Ortutay, Zsuzsanna; Pulkkinen, Kati; Hämäläinen, Sanna; Rokka, Anne; Corthals, Garry L.; Watford, Wendy T.; Junttila, Ilkka; O’Shea, John J.; Pesu, Marko

    2014-01-01

    The proprotein convertase subtilisin/kexin (PCSK) enzymes proteolytically convert immature proproteins into bioactive molecules and thereby they serve as key regulators of cellular homeostasis. The archetype PCSK, FURIN is a direct target gene of the IL-12/STAT4 pathway and it is upregulated in T helper 1 type cells. We have previously demonstrated that FURIN expression in T cells critically regulates the maintenance of peripheral immune tolerance and the functional maturation of pro-TGFβ-1 in vivo, but FURIN’s role in cell-mediated immunity and Th polarization has remained elusive. Here, we show that T-cell-expressed FURIN is essential for host resistance against a prototypic Th1 pathogen, Toxoplasma gondii and for the generation of pathogen-specific Th1 lymphocytes, including Th1-IL-10 cells. FURIN-deficient Th cells instead show elevated expression of IL-4 receptor subunit alpha (IL-4Rα) on cell surface, sensitized IL-4/STAT6 signaling and a propensity to polarize towards the Th2 phenotype. By exploring FURIN-interacting proteins in Jurkat T cells with Strep-Tag purification and mass-spectrometry we further identify an association with a cytoskeleton modifying RAC/DOCK2 protein complex and unravel that FURIN promotes F-actin polymerization, which has previously been shown to down-regulate IL-4Rα cell surface expression and promote Th1 responses. In conclusion, our results demonstrate that in addition to peripheral immune tolerance, T-cell-expressed FURIN is also a central regulator of cell-mediated immunity and Th1/2 cell balance. PMID:25355923

  17. The proprotein convertase amontillado (amon) is required during Drosophila pupal development.

    PubMed

    Rayburn, Lowell Y M; Rhea, Jeanne; Jocoy, Steven R; Bender, Michael

    2009-09-01

    Peptide hormones governing many developmental processes are generated via endoproteolysis of inactive precursor molecules by a family of subtilisin-like proprotein convertases (SPCs). We previously identified mutations in the Drosophila amontillado (amon) gene, a homolog of the vertebrate neuroendocrine-specific Prohormone Convertase 2 (PC2) gene, and showed that amon is required during embryogenesis, early larval development, and larval molting. Here, we define amon requirements during later developmental stages using a conditional rescue system and find that amon is required during pupal development for head eversion, leg and wing disc extension, and abdominal differentiation. Immuno-localization experiments show that amon protein is expressed in a subset of central nervous system cells but does not co-localize with peptide hormones known to elicit molting behavior, suggesting the involvement of novel regulatory peptides in this process. The amon protein is expressed in neuronal cells that innervate the corpus allatum and corpora cardiaca of the ring gland, an endocrine organ which is the release site for many key hormonal signals. Expression of amon in a subset of these cell types using the GAL4/UAS system in an amon mutant background partially rescues larval molting and growth. Our results show that amon is required for pupal development and identify a subset of neuronal cell types in which amon function is sufficient to rescue developmental progression and growth defects shown by amon mutants. The results are consistent with a model that the amon protein acts to proteolytically process a diverse suite of peptide hormones that coordinate larval and pupal growth and development. PMID:19559693

  18. The proprotein convertase amontillado (amon) is required during Drosophila pupal development

    PubMed Central

    Rayburn, Lowell Y.M.; Rhea, Jeanne; Jocoy, Steven R.; Bender, Michael

    2009-01-01

    Peptide hormones governing many developmental processes are generated via endoproteolysis of inactive precursor molecules by a family of subtilisin-like proprotein convertases (SPCs). We previously identified mutations in the Drosophila amontillado (amon) gene, a homolog of the vertebrate neuroendocrine-specific Prohormone Convertase 2 (PC2) gene, and showed that amon is required during embryogenesis, early larval development, and larval molting. Here, we define amon requirements during later developmental stages using a conditional rescue system and find that amon is required during pupal development for head eversion, leg and wing disc extension, and abdominal differentiation. Immuno-localization experiments show that amon protein is expressed in a subset of central nervous system cells but does not co-localize with peptide hormones known to elicit molting behavior, suggesting the involvement of novel regulatory peptides in this process. The amon protein is expressed in neuronal cells that innervate the corpus allatum and corpora cardiaca of the ring gland, an endocrine organ which is the release site for many key hormonal signals. Expression of amon in a subset of these cell types using the GAL4/UAS system in an amon mutant background partially rescues larval molting and growth. Our results show that amon is required for pupal development and identify a subset of neuronal cell types in which amon function is sufficient to rescue developmental progression and growth defects shown by amon mutants. The results are consistent with a model that the amon protein acts to proteolytically process a diverse suite of peptide hormones that coordinate larval and pupal growth and development. PMID:19559693

  19. The Proprotein Convertase Furin Contributes to Rhabdomyosarcoma Malignancy by Promoting Vascularization, Migration and Invasion

    PubMed Central

    Jaaks, Patricia; D’Alessandro, Valentina; Grob, Nicole; Büel, Sina; Hajdin, Katarina; Schäfer, Beat W.; Bernasconi, Michele

    2016-01-01

    The proprotein convertase (PC) furin cleaves precursor proteins, an important step in the activation of many cancer-associated proteins. Substrates of furin and furin-like PCs play a role in proliferation, metastasis and invasion. Some of them are involved in the progression of the pediatric soft tissue sarcoma rhabdomyosarcoma (RMS). In this study, we show that PCs, and in particular furin, are expressed in RMS cell lines. To investigate the functional role of furin, we generated RMS cell lines with modulated furin activity. Silencing or stable inhibition of furin delayed tumor growth in Rh30 and RD xenografts in vivo, and was correlated with lower microvessel density. Reduced furin activity also decreased migration and invasion abilities in vitro, and inhibition of furin in RMS cells diminished processing of IGF1R, VEGF-C, PDGF-B and MT1-MMP, leading to lower levels of mature proteins. Furthermore, we found that furin activity is required for proper IGF signaling in RMS cells, as furin silencing resulted in reduced phosphorylation of Akt upon IGF1 stimulation. Taken together, our results suggest that furin plays an important role in the malignant phenotype of RMS cells by activating proteins involved in tumor growth and vascularization, metastasis and invasion. PMID:27548722

  20. Purification of the proprotein convertase furin by affinity chromatography based on PC-specific inhibitors

    PubMed Central

    Kuester, Miriam; Becker, Gero L.; Hardes, Kornelia; Lindberg, Iris; Steinmetzer, Torsten; Than, Manuel E.

    2013-01-01

    In eucaryotes, many secreted proteins and peptides are proteolytically excised from larger precursor proteins by a specific class of serine proteases, the proprotein/prohormone convertases (PCs). This cleavage is essential for substrate activation, making the PCs very interesting pharmacological targets in cancer and infectious disease research. Correspondingly, their structure, function and inhibition are intensely studied – studies that require the respective target proteins in large amounts and at high purity. Here we describe the development of a novel purification protocol of furin, the best-studied member of the PC family. We combined the heterologous expression of furin from CHO cells with a novel purification scheme employing an affinity step that efficiently extracts only active furin from the conditioned medium by using furin-specific inhibitor moieties as bait. Several potential affinity tags were synthesized and their binding to furin characterized. The best compound, Biotin-(Adoa)2-Arg-Pro-Arg-4-Amba coupled to streptavidin-Sepharose beads, was used in a three-step chromatographic protocol and routinely resulted in a high yield of a homogeneous furin preparation with a specific activity of ~60 units/mg protein. This purification and the general strategy can easily be adapted to the efficient purification of other PC family members. PMID:21875402

  1. Small-intestinal dysfunction accompanies the complex endocrinopathy of human proprotein convertase 1 deficiency

    PubMed Central

    Jackson, Robert S.; Creemers, John W.M.; Farooqi, I. Sadaf; Raffin-Sanson, Marie-Laure; Varro, Andrea; Dockray, Graham J.; Holst, Jens J.; Brubaker, Patricia L.; Corvol, Pierre; Polonsky, Kenneth S.; Ostrega, Diane; Becker, Kenneth L.; Bertagna, Xavier; Hutton, John C.; White, Anne; Dattani, Mehul T.; Hussain, Khalid; Middleton, Stephen J.; Nicole, Thomasina M.; Milla, Peter J.; Lindley, Keith J.; O’Rahilly, Stephen

    2003-01-01

    We have previously described the only reported case of human proprotein convertase 1 (PC1) deficiency, in a female (Subject A) with obesity, hypogonadism, hypoadrenalism, and reactive hypoglycemia. We now report the second case of human PC1 deficiency (Subject B), also due to compound heterozygosity for novel missense and nonsense mutations. While both subjects shared the phenotypes of obesity, hypoadrenalism, reactive hypoglycemia, and elevated circulating levels of certain prohormones, the clinical presentation of Subject B was dominated by severe refractory neonatal diarrhea, malabsorptive in type. Subsequent investigation of Subject A revealed marked small-intestinal absorptive dysfunction, which was not previously clinically suspected. We postulate that PC1, presumably in the enteroendocrine cells, is essential for the normal absorptive function of the human small intestine. The differences in the nature and severity of presentation between the two cases cannot readily be explained on the basis of allelic heterogeneity, as the nonsense and missense mutations from both subjects had comparably severe effects on the catalytic activity of PC1. Despite Subject A’s negligible PC1 activity, some mature ACTH and glucagon-like peptide 17-36amide were detectable in her plasma, suggesting that the production of these hormones, at least in humans, does not have an absolute dependence on PC1. The presence of severe obesity and the absence of growth retardation in both subjects contrast markedly with the phenotype of mice lacking PC1 and suggest that the precise physiological repertoire of this enzyme may vary between mammalian species. PMID:14617756

  2. The proprotein convertase PC1/3 regulates TLR9 trafficking and the associated signaling pathways

    PubMed Central

    Duhamel, M.; Rodet, F.; Murgoci, A. N.; Desjardins, R.; Gagnon, H.; Wisztorski, M.; Fournier, I.; Day, R.; Salzet, M.

    2016-01-01

    Endosomal TLR9 is considered as a potent anti-tumoral therapeutic target. Therefore, it is crucial to decipher the mechanisms controlling its trafficking since it determines TLR9 activation and signalling. At present, the scarcity of molecular information regarding the control of this trafficking and signalling is noticeable. We have recently demonstrated that in macrophages, proprotein convertase 1/3 (PC1/3) is a key regulator of TLR4 Myd88-dependent signalling. In the present study, we established that PC1/3 also regulates the endosomal TLR9. Under CpG-ODN challenge, we found that PC1/3 traffics rapidly to co-localize with TLR9 in CpG-ODN-containing endosomes with acidic pH. In PC1/3 knockdown macrophages, compartmentalization of TLR9 was altered and TLR9 clustered in multivesicular bodies (MVB) as demonstrated by co-localization with Rab7. This demonstrates that PC1/3 controls TLR9 trafficking. This clustering of TLR9 in MVB dampened the anti-inflammatory STAT3 signalling pathway while it promoted the pro-inflammatory NF-kB pathway. As a result, macrophages from PC1/3 KO mice and rat PC1/3-KD NR8383 macrophages secreted more pro-inflammatory cytokines such as TNF-α, IL6, IL1α and CXCL2. This is indicative of a M1 pro-inflammatory phenotype. Therefore, PC1/3 KD macrophages represent a relevant mean for cell therapy as “Trojan” macrophages. PMID:26778167

  3. Enhanced UV-Induced Skin Carcinogenesis in Transgenic Mice Overexpressing Proprotein Convertases1

    PubMed Central

    Fu, Jian; Bassi, Daniel E; Zhang, Jirong; Li, Tianyu; Cai, Kathy Q; Testa, Courtney Lyons; Nicolas, Emmanuelle; Klein-Szanto, Andres J

    2013-01-01

    The proprotein convertases (PCs) furin and PACE4 process numerous substrates involved in tumor growth, invasion, and metastasis. We have previously shown that PCs increase the susceptibility to chemical skin carcinogenesis. Because of the human relevancy of UV radiation in the etiopathogenesis of human skin cancer, we investigated whether or not transgenic mice overexpressing either furin alone or both furin and PACE4 show increased susceptibility to UV carcinogenesis. After backcrossing our previously described furin and PACE4 transgenic lines, targeted to the epidermis, into a SKH-1 background, we exposed both single and double transgenic mice to UV radiation for 34 weeks. The results showed an increase in squamous cell carcinoma (SCC) multiplicity of approximately 70% in the single furin transgenic mouse line SF47 (P < .002) and a 30% increase in the other single transgenic line SF49 when compared to wild-type (WT) SKH-1 mice. Interestingly, there was also an increase in the percentage of high histologic grade SCCs in the transgenic lines compared to the WT mice, i.e., WT = 9%, SF47 = 15%, and SF49 = 26% (P < .02). Targeting both furin and PACE4 to the epidermis in double transgenic mice did not have an additive effect on tumor incidence/multiplicity but did enhance the tumor histopathologic grade, i.e., a significant increase in higher grade SCCs was seen in the bigenic mouse line SPF47 (P < .02). Thus, we observed an increased susceptibility to UV in single furin transgenic mice that was not substantially enhanced in the double furin/PACE4 transgenic mice. PMID:23441131

  4. Proprotein convertase subtilisin kexin type 9 and high-density lipoprotein metabolism: experimental animal models and clinical evidence.

    PubMed

    Ferri, Nicola; Corsini, Alberto; Macchi, Chiara; Magni, Paolo; Ruscica, Massimiliano

    2016-07-01

    Proprotein convertase subtilisin kexin type 9 (PCSK9) belongs to the proprotein convertase family. Several studies have demonstrated its involvement in the regulation of low-density lipoprotein (LDL) cholesterol levels by inducing the degradation of the LDL receptor (LDLR). However, experimental, epidemiologic, and pharmacologic data provide important evidence on the role of PCSK9 also on high-density lipoproteins (HDLs). In mice, PCSK9 regulates the HDL cholesterol (HDL-C) levels by the degradation of hepatic LDLR, thus inhibiting the uptake of apolipoprotein (Apo)E-containing HDLs. Several epidemiologic and genetic studies reported positive relationship between PCSK9 and HDL-C levels, likely by reducing the uptake of the ApoE-containing HDL particles. PCSK9 enhances also the degradation of LDLR's closest family members, ApoE receptor 2, very low-density lipoprotein receptor, and LDLR-related protein 1. This feature provides a molecular mechanism by which PCSK9 may affect HDL metabolism. Experimental studies demonstrated that PCSK9 directly interacts with HDL by modulating PCSK9 self-assembly and its binding to the LDLR. Finally, the inhibition of PCSK9 by means of monoclonal antibodies directed to PCSK9 (ie, evolocumab and alirocumab) determines an increase of HDL-C fraction by 7% and 4.2%, respectively. Thus, the understanding of the role of PCSK9 on HDL metabolism needs to be elucidated with a particular focus on the effect of PCSK9 on HDL-mediated reverse cholesterol transport. PMID:26548330

  5. The Central Role of Proprotein Convertase Subtilisin/Kexin Type 9 in Septic Pathogen Lipid Transport and Clearance.

    PubMed

    Walley, Keith R; Francis, Gordon A; Opal, Steven M; Stein, Evan A; Russell, James A; Boyd, John H

    2015-12-01

    Microbial cell walls contain pathogenic lipids, including LPS in gram-negative bacteria, lipoteichoic acid in gram-positive bacteria, and phospholipomannan in fungi. These pathogen lipids are major ligands for innate immune receptors and figure prominently in triggering the septic inflammatory response. Alternatively, pathogen lipids can be cleared and inactivated, thus limiting the inflammatory response. Accordingly, biological mechanisms for sequestering and clearing pathogen lipids from the circulation have evolved. Pathogen lipids released into the circulation are initially bound by transfer proteins, notably LPS binding protein and phospholipid transfer protein, and incorporated into high-density lipoprotein particles. Next, LPS binding protein, phospholipid transfer protein, and other transfer proteins transfer these lipids to ApoB-containing lipoproteins, including low-density (LDL) and very-low-density lipoproteins and chylomicrons. Pathogen lipids within these lipoproteins and their remnants are then cleared from the circulation by the liver. Hepatic clearance involves the LDL receptor (LDLR) and possibly other receptors. Once absorbed by the liver, these lipids are then excreted in the bile. Recent evidence suggests pathogen lipid clearance can be modulated. Importantly, reduced proprotein convertase subtilisin/kexin type 9 activity increases recycling of the LDLR and thereby increases LDLR on the surface of hepatocytes, which increases clearance by the liver of pathogen lipids transported in LDL. Increased pathogen lipid clearance, which can be achieved by inhibiting proprotein convertase subtilisin/kexin type 9, may decrease the systemic inflammatory response to sepsis and improve clinical outcomes. PMID:26252194

  6. VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5

    PubMed Central

    Szumska, Dorota; Pieles, Guido; Essalmani, Rachid; Bilski, Michal; Mesnard, Daniel; Kaur, Kulvinder; Franklyn, Angela; El Omari, Kamel; Jefferis, Joanna; Bentham, Jamie; Taylor, Jennifer M.; Schneider, Jurgen E.; Arnold, Sebastian J.; Johnson, Paul; Tymowska-Lalanne, Zuzanna; Stammers, Dave; Clarke, Kieran; Neubauer, Stefan; Morris, Andrew; Brown, Steve D.; Shaw-Smith, Charles; Cama, Armando; Capra, Valeria; Ragoussis, Jiannis; Constam, Daniel; Seidah, Nabil G.; Prat, Annik; Bhattacharya, Shoumo

    2008-01-01

    We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, a presacral mass, renal and palatal agenesis, and pulmonary hypoplasia. It results from a C470R mutation in the proprotein convertase PCSK5 (PC5/6). Compound mutants (Pcsk5Vcc/null) completely recapitulate the Pcsk5Vcc/Vcc phenotype, as does an epiblast-specific conditional deletion of Pcsk5. The C470R mutation ablates a disulfide bond in the P domain, and blocks export from the endoplasmic reticulum and proprotein convertase activity. We show that GDF11 is cleaved and activated by PCSK5A, but not by PCSK5A-C470R, and that Gdf11-deficient embryos, in addition to having anteroposterior patterning defects and renal and palatal agenesis, also have a presacral mass, anorectal malformation, and exomphalos. Pcsk5 mutation results in abnormal expression of several paralogous Hox genes (Hoxa, Hoxc, and Hoxd), and of Mnx1 (Hlxb9). These include known Gdf11 targets, and are necessary for caudal embryo development. We identified nonsynonymous mutations in PCSK5 in patients with VACTERL (vertebral, anorectal, cardiac, tracheoesophageal, renal, limb malformation OMIM 192350) and caudal regression syndrome, the phenotypic features of which resemble the mouse mutation. We propose that Pcsk5, at least in part via GDF11, coordinately regulates caudal Hox paralogs, to control anteroposterior patterning, nephrogenesis, skeletal, and anorectal development. PMID:18519639

  7. A Homolog of Subtilisin-Like Proprotein Convertase 7 Is Essential to Anterior Neural Development in Xenopus

    PubMed Central

    Senturker, Sema; Thomas, John Terrig; Mateshaytis, Jennifer; Moos, Malcolm

    2012-01-01

    Background Subtilisin-like Proprotein Convertase 7 (SPC7) is a member of the subtilisin/kexin family of pro-protein convertases. It cleaves many pro-proteins to release their active proteins, including members of the bone morphogenetic protein (BMP) family of signaling molecules. Other SPCs are known to be required during embryonic development but corresponding data regarding SPC7 have not been reported previously. Methodology/Principal Findings We demonstrated that Xenopus SPC7 (SPC7) was expressed predominantly in the developing brain and eye, throughout the neural plate initially, then more specifically in the lens and retina primordia as development progressed. Since no prior functional information has been reported for SPC7, we used gain- and loss-of-function experiments to investigate the possibility that it may also convey patterning or tissue specification information similarly to Furin, SPC4, and SPC6. Overexpression of SPC7 was without effect. In contrast, injection of SPC7 antisense morpholino oligonucleotides (MO) into a single blastomere at the 2- or 4-cell stage produced marked disruption of head structures; anophthalmia was salient. Bilateral injections suppressed head and eye formation completely. In parallel with suppression of eye and brain development by SPC7 knockdown, expression of early anterior neural markers (Sox2, Otx2, Rx2, and Pax6) and late eye-specific markers (β-Crystallin and Opsin), and of BMP target genes such as Tbx2 and Tbx3, was reduced or eliminated. Taken together, these findings suggest a critical role for SPC7–perhaps, at least in part, due to activation of one or more BMPs–in early patterning of the anterior neural plate and its derivatives. Conclusion/Significance SPC7 is required for normal development of the eye and brain, possibly through processing BMPs, though other potential substrates cannot be excluded. PMID:22761776

  8. Synthetic peptides derived from the prosegments of proprotein convertase 1/3 and furin are potent inhibitors of both enzymes.

    PubMed Central

    Basak, Ajoy; Lazure, Claude

    2003-01-01

    Proprotein convertases (PCs) are Ca(2+)-dependent serine proteases of the subtilisin/kexin family which are known specifically to cleave propeptide and proprotein substrates at the C-terminal of R-X-(K/R)-R/ to generate the relevant biologically active peptides. PCs are initially synthesized as enzymically inactive proenzyme forms where the prosegments play an important inhibitory role to the respective enzymes. Here we investigated whether synthetic peptides derived from the pro-region could also represent specific and potent inhibitors. Based upon sequence alignment, secondary structure analysis and hydrophilicity plot, a number of peptides ranging from 8 to 33 residues were selected. These included segments encompassing residues 55-62, 50-62, 39-62, 50-83, 55-83, 64-83 and 74-83 in the pro-mouse PC1/3 sequence and residues 54-62, 48-62 and 39-62 of the pro-human furin sequence. All peptides were prepared by solid-phase FastMoc chemistry, purified by reversed-phase HPLC and characterized by MS and amino acid analysis. These peptides were tested in vitro for inhibitory activity towards recombinant mouse PC1/3 and human furin. Progress-curve and end-time kinetic analysis demonstrated that a number of these peptides, particularly those containing both the primary and the secondary processing sites, displayed strong inhibition of both enzymes with inhibition constants (K (i)) in the high nanomolar range. Unlike the whole propeptide, these small synthetic peptide inhibitors exhibited either true competitive or mixed competitive inhibition, depending on the sequence. Our data revealed further the critical role of the last two basic amino acid residues (e.g. Lys(82)-Arg(83) for the mouse PC1/3 sequence) of the prodomain in imparting a strong anti-convertase activity. The study also establishes the inhibitory potential of certain regions contained within the prosegment of the two convertases. PMID:12662153

  9. From proprotein convertase subtilisin/kexin type 9 to its inhibition: state-of-the-art and clinical implications.

    PubMed

    Navarese, Eliano P; Kołodziejczak, Michalina; Dimitroulis, Dimitrios; Wolff, Georg; Busch, Hans L; Devito, Fiorella; Sionis, Alessandro; Ciccone, Marco Matteo

    2016-01-01

    Statins are recommended as first-line therapy for patients with hypercholesterolaemia. A sizable proportion of patients, however, does not reach therapeutic goals, is statin intolerant, or, despite optimal statin therapy, is at high risk of ischaemic events. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in lipid metabolism and several comorbidities. Monoclonal antibodies targeting PCSK9 are a new lipid-lowering approach with the potential to improve clinical outcomes in patients with dyslipidaemia. In this review, we discuss current experimental and clinical evidence of the role of PCSK9 and its inhibition on lipid metabolism and several pathologic conditions with a focus on clinical outcomes. A state-of-the-art analysis of current clinical evidence and future directions on PCSK9 and its inhibition is provided. PMID:27533061

  10. Chromosomal assignment of the genes for proprotein convertases PC4, PC5, and PACE 4 in mouse and human

    SciTech Connect

    Mbikay, M.; Seidah, N.G.; Chretien, M.

    1995-03-01

    The genes for three subtilisin/kexin-like proprotein convertases, PC4, PC5, and PACE4, were mapped in the mouse by RFLP analysis of a DNA panel from a (C57BL/6JEi x SPRET/Ei) F{sub 1} x SPRET/Ei backcross. The chromosomal locations of the human homologs were determined by Southern blot analysis of a DNA panel from human-rodent somatic cell hybrids, most of which contained a single human chromosome each. The gene for PC4 (Pcsk4 locus) mapped to mouse chromosome 10, close to the Adn (adipsin, a serine protease) locus and near the Amh (anti-Mullerian hormone) locus; in a human, the gene was localized to chromosome 19. The gene for PC5 (Pcsk5 locus) mapped to mouse chromosome 19 close to the Lpc1 (lipoacortin-1) locus and, in human, was localized to chromosome 9. The gene for PACE4 (Pcsk6 locus) mapped to mouse chromosome 7, at a distance of 13 cM from the Pcsk3 locus, which specifies furin, another member of this family of enzymes previoulsy mapped to this chromosome. This is in concordance with the known close proximity of these two loci in the homologous region on human chromosome 15q25-qter. Pcsk3 and Pcsk6 mapped to a region of mouse chromosome 7 that has been associated cytogenetically with postnatal lethality in maternal disomy, suggesting that these genes might be candidates for imprinting. 43 refs., 3 figs., 2 tabs.

  11. A proprotein convertase-inhibiting serpin with an endoplasmic reticulum targeting signal from Branchiostoma lanceolatum, a close relative of vertebrates

    PubMed Central

    Bentele, Caterina; Krüger, Olaf; Tödtmann, Ulf; Oley, Mareke; Ragg, Hermann

    2006-01-01

    Lancelets are considered to take a key position in the evolution of lineages leading to vertebrates. Herein, a serpin from the lancelet Branchiostoma lanceolatum, Bl-Spn1, was identified that inhibits the PCs (proprotein convertases) PC1/3 and furin. The inhibitor forms SDS-stable complexes with either of its targets. Analysis of the inhibitor/furin reaction products by mass spectroscopy assigns the enzyme's cleavage position C-terminally to Met-Met-Lys-Arg↓ in the reactive site loop of Spn1, in concordance with the classical recognition/cleavage site of the principal vertebrate PCs. The inhibitor is equipped with a canonical ER (endoplasmic reticulum) retrieval signal, Lys-Asp-Glu-Leu (KDEL), marking the inhibitor as a guardian of the cellular secretory routes. Deletion of the ER retrieval signal results in the export of the inhibitor into the medium of transfected COS-7 cells, consistent with the assigned intracellular location. These results identify Bl-Spn1 as the first serpin that may inhibit PC1/3-like subtilases at their natural sites of action. Phylogenetic comparisons support a concept implying a general role for ER-residing serpins in the surveillance of subtilase-like enzymes along the constitutive and regulated secretory pathways of metazoans including a role in the defence of intruders that turn PCs to their propagation. PMID:16445382

  12. Enhanced aggressiveness of benzopyrene-induced squamous carcinomas in transgenic mice overexpressing the proprotein convertase PACE4 (PCSK6).

    PubMed

    Bassi, Daniel E; Cenna, Jonathan; Zhang, Jirong; Cukierman, Edna; Klein-Szanto, Andres J

    2015-10-01

    PACE4 (PCSK6) is a proprotein convertase (PC) capable of processing numerous substrates involved in tumor growth, invasion, and metastasis. Because of the human relevancy of the tobacco-associated carcinogen benzo[a]pyrene (B(a)P) we investigated whether transgenic mice in which this PC is targeted to the epidermis (K5-PACE4) may be more susceptible to B(a)P complete carcinogenesis than wild type (WT) mice. In an in vitro experiment, using cell lines derived from skin tumors obtained after B(a)P treatment, we observed that PACE4 overexpression and activity accounts for an increased proliferation rate, exaggerated sensitivity to the PC inhibitor CMK, and interference with IGF-1R autophosphorylation. Squamous cell carcinomas, obtained from K5-PACE4 mice subjected to complete chemical carcinogenesis, were characterized by a 50% increase in cell proliferation, when compared with similar tumors from WT mice. In addition, tumors from K5-PACE4 mice showed deeper invasion into the underlying dermis. Thus, mice overexpressing PACE4 exhibited tumors of increased growth rate and invasive potential when exposed to the human carcinogen B(a)P, further supporting the significance of PCs in tumor growth and progression. PMID:24845697

  13. The Plasma Level of Proprotein Convertase FURIN in Patients with Suspected Infection in the Emergency Room: A Prospective Cohort Study.

    PubMed

    Ranta, N; Turpeinen, H; Oksanen, A; Hämäläinen, S; Huttunen, R; Uusitalo-Seppälä, R; Rintala, E; Aittoniemi, J; Pesu, M

    2015-12-01

    There is an increasing need for novel biomarkers that enable better diagnostic and prognostic stratification of patients with suspected infection. A proprotein convertase enzyme FURIN is upregulated upon immune cell activation, and it promotes infectivity by cleaving and activating pathogens. In this study, we determined FURIN levels in plasma using ELISA from 537 patients that were admitted to emergency room with suspected infection. Patients were sorted to high- and low-level FURIN groups with a cut-off level of 370 pg/ml. The study cohort included five diagnostic groups: Group 1, no systemic inflammatory response syndrome (SIRS, n = 59 patients); Group 2, bacterial infection without SIRS (n = 67); Group 3, SIRS, but no bacterial infection (n = 308); Group 4, sepsis without organ failure (n = 308); and Group 5, severe sepsis (n = 49). Statistically significant associations were not found between the plasma level of FURIN and the prevalence of sepsis (P = 0.957), diagnostic group of a patient (P = 0.737) or the bacteria in blood culture (P = 0.499). Additionally, the concentration of FURIN did not predict the severity or case fatality of the infectious disease. However, statistically significant associations were found between high plasma level of FURIN and diagnosed rheumatic disease (P < 0.001) as well as with the prevalence of non-smokers (P = 0.034). Thus, albeit the plasma level of FURIN does not predict the severity of infectious disease, it may be of use in the diagnostics of autoimmune diseases. PMID:26346780

  14. Dynamic palmitoylation of lymphoma proprotein convertase prolongs its half-life, but is not essential for trans-Golgi network localization.

    PubMed Central

    van de Loo, J W; Teuchert, M; Pauli, I; Plets, E; Van de Ven, W J; Creemers, J W

    2000-01-01

    Proprotein convertases are responsible for the endoproteolytic activation of proproteins in the secretory pathway. The most recently discovered member of this family, lymphoma proprotein convertase (LPC), is a type-I transmembrane protein. Previously, we have demonstrated that its cytoplasmic tail is palmitoylated. In this study, we have identified the two most proximal cysteine residues in the cytoplasmic tail as palmitoylation sites. Substitution of either cysteine residue by alanine interfered with palmitoylation of the other. Palmitoylation of LPC was found to be sensitive to the protein palmitoyltransferase inhibitor tunicamycin but not cerulenin. It was also insensitive to the drugs brefeldin A, monensin and cycloheximide, indicating that the modification occurs in a late exocytic or endocytic compartment. Turnover of palmitoylated LPC is significantly faster (t(1/2) approximately 50 min) than that of the LPC polypeptide backbone (t(1/2) approximately 3 h), suggesting that palmitoylation is reversible. Abrogation of palmitoylation reduced the half-life of the LPC protein, but did not affect steady-state localization of LPC in the trans-Golgi network. Finally, LPC could not be detected in detergent-resistant membrane rafts. Taken together, these results suggest that dynamic palmitoylation of LPC is important for stability, but does not function as a dominant trafficking signal. PMID:11104692

  15. Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder.

    PubMed

    Kim, WooJin; Zekas, Erin; Lodge, Robert; Susan-Resiga, Delia; Marcinkiewicz, Edwidge; Essalmani, Rachid; Mihara, Koichiro; Ramachandran, Rithwik; Asahchop, Eugene; Gelman, Benjamin; Cohen, Éric A; Power, Christopher; Hollenberg, Morley D; Seidah, Nabil G

    2015-11-01

    The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND. PMID:26283733

  16. Neuroinflammation-Induced Interactions between Protease-Activated Receptor 1 and Proprotein Convertases in HIV-Associated Neurocognitive Disorder

    PubMed Central

    Kim, WooJin; Zekas, Erin; Lodge, Robert; Susan-Resiga, Delia; Marcinkiewicz, Edwidge; Essalmani, Rachid; Mihara, Koichiro; Ramachandran, Rithwik; Asahchop, Eugene; Gelman, Benjamin; Cohen, Éric A.; Power, Christopher; Hollenberg, Morley D.

    2015-01-01

    The proprotein convertases (PCs) furin, PC5, PACE4, and PC7 cleave secretory proteins after basic residues, including the HIV envelope glycoprotein (gp160) and Vpr. We evaluated the abundance of PC mRNAs in postmortem brains of individuals exhibiting HIV-associated neurocognitive disorder (HAND), likely driven by neuroinflammation and neurotoxic HIV proteins (e.g., envelope and Vpr). Concomitant with increased inflammation-related gene expression (interleukin-1β [IL-1β]), the mRNA levels of the above PCs are significantly increased, together with those of the proteinase-activated receptor 1 (PAR1), an inflammation-associated receptor that is cleaved by thrombin at ProArg41↓ (where the down arrow indicates the cleavage location), and potentially by PCs at Arg41XXXXArg46↓. The latter motif in PAR1, but not its R46A mutant, drives its interactions with PCs. Indeed, PAR1 upregulation leads to the inhibition of membrane-bound furin, PC5B, and PC7 and inhibits gp160 processing and HIV infectivity. Additionally, a proximity ligation assay revealed that furin and PC7 interact with PAR1. Reciprocally, increased furin expression reduces the plasma membrane abundance of PAR1 by trapping it in the trans-Golgi network. Furthermore, soluble PC5A/PACE4 can target/disarm cell surface PAR1 through cleavage at Arg46↓. PACE4/PC5A decreased calcium mobilization induced by thrombin stimulation. Our data reveal a new PC-PAR1-interaction pathway, which offsets the effects of HIV-induced neuroinflammation, viral infection, and potentially the development of HAND. PMID:26283733

  17. Regulation of HIF-1 alpha by the proprotein convertases furin and PC7 in human squamous carcinoma cells.

    PubMed

    Fu, Jian; Zhang, Jirong; Gong, Yulan; Testa, Courtney Lyons; Klein-Szanto, Andres J

    2015-09-01

    Proprotein convertases (PC), a family of serine proteases, process cancer-related substrates such as growth factors, growth factor receptors, cell adhesion molecules, metalloproteinases, etc. HIF-1α is a major transcription factor involved in tumorigenesis by sensing intratumoral hypoxia. Furin (PCSK3) is one of the numerous target genes regulated by HIF-1α transactivation and its distribution into endosomal compartments and onto the cell surface can be triggered by hypoxia via HIF-1α. siRNAs to knockdown PCs were transfected into cells alone or in combination with different drug treatments. Protein and RNA expression levels were analyzed by Western blotting or RT-PCR, respectively. PC7 (PCSK7) and furin siRNAs upregulated HIF-1α protein under normoxic condition to a level similar to that obtained by cobalt chloride treatment, eventually leading to activation of VEGF-A synthesis in two human head and neck squamous cell carcinoma cell lines. The unchanged levels of HIF-1α mRNA expression under siRNA treatment and the additive HIF-1α induction of PC siRNAs and either cobalt chloride or the 26S ribosome inhibitor, MG-132, suggested a post-transcriptional PC-mediated regulation. Furthermore, cycloheximide chase showed that PC7/furin siRNA regulation occurred at the level of HIF-1α translation. A specific IGF-1R signaling inhibitor was able to attenuate the PC siRNA induction of HIF-1α, suggesting the involvement of the IGF-1R pathway. Thus, the data show that PCs regulate HIF-1α. Furin and PC7 siRNAs induced HIF-1α protein by increasing its translation, resulting in upregulation of VEGF-A. This finding may provide insight into intricate PC functions that seem to be independent from their substrate-processing activity. PMID:24436242

  18. Effects of niacin, statin, and fenofibrate on circulating proprotein convertase subtilisin/kexin type 9 levels in patients with dyslipidemia.

    PubMed

    Khera, Amit V; Qamar, Arman; Reilly, Muredach P; Dunbar, Richard L; Rader, Daniel J

    2015-01-15

    Recent trials demonstrated substantial improvement in lipid parameters with inhibition of proprotein convertase subtilisin-like/kexin type 9 (PCSK9). Although statins and fibrates have been reported to increase plasma PCSK9 levels, the effect of niacin on PCSK9 is unknown. We investigated the impact of niacin, atorvastatin, and fenofibrate on PCSK9 levels in 3 distinct studies. A statin-only study randomized 74 hypercholesterolemic patients to placebo, atorvastatin 10 mg/day, or atorvastatin 80 mg/day for 16 weeks. A dose-related increase in PCSK9 was noted such that atorvastatin 80 mg increased PCSK9 by a mean +27% (95% confidence interval [CI] +12 to +42), confirming the effect of statin therapy on raising PCSK9. A second study randomized 70 patients with carotid atherosclerosis to simvastatin 20 mg/day, simvastatin 80 mg/day, or simvastatin 20 mg/extended-release (ER) niacin 2 g/day. PCSK9 levels were increased with statin therapy, but decreased with the simvastatin 20 mg/ER niacin combination (mean -13%, CI -3 to -23). A final study involved 19 dyslipidemic participants on atorvastatin 10 mg with serial addition of fenofibric acid 135 mg followed by ER niacin 2 g/day. Fenofibric acid led to a +23% (CI +10 to +36, p = 0.001) increase in PCSK9; the addition of niacin resulted in a subsequent -17% decrease (CI -19 to -5, p = 0.004). A positive association was noted between change in PCSK9 and low-density lipoprotein cholesterol levels (r = 0.62, p = 0.006) with the addition of niacin. In conclusion, niacin therapy offsets the increase in PCSK9 levels noted with statin and fibrate therapy. A portion of the low-density lipoprotein cholesterol reduction seen with niacin therapy may be due to reduction in PCSK9. PMID:25432415

  19. Inflammatory Proprotein Convertase-Matrix Metalloproteinase Proteolytic Pathway in Antigen-presenting Cells as a Step to Autoimmune Multiple Sclerosis*

    PubMed Central

    Shiryaev, Sergey A.; Remacle, Albert G.; Savinov, Alexei Y.; Chernov, Andrei V.; Cieplak, Piotr; Radichev, Ilian A.; Williams, Roy; Shiryaeva, Tatiana N.; Gawlik, Katarzyna; Postnova, Tatiana I.; Ratnikov, Boris I.; Eroshkin, Alexei M.; Motamedchaboki, Khatereh; Smith, Jeffrey W.; Strongin, Alex Y.

    2009-01-01

    Multiple sclerosis (MS) is a disease of the central nervous system with autoimmune etiology. Susceptibility to MS is linked to viral and bacterial infections. Matrix metalloproteinases (MMPs) play a significant role in the fragmentation of myelin basic protein (MBP) and demyelination. The splice variants of the single MBP gene are expressed in the oligodendrocytes of the central nervous system (classic MBP) and in the immune cells (Golli-MBPs). Our data suggest that persistent inflammation caused by environmental risk factors is a step to MS. We have discovered biochemical evidence suggesting the presence of the inflammatory proteolytic pathway leading to MS. The pathway involves the self-activated furin and PC2 proprotein convertases and membrane type-6 MMP (MT6-MMP/MMP-25) that is activated by furin/PC2. These events are followed by MMP-25 proteolysis of the Golli-MBP isoforms in the immune system cells and stimulation of the specific autoimmune T cell clones. It is likely that the passage of these autoimmune T cell clones through the disrupted blood-brain barrier to the brain and the recognition of neuronal, classic MBP causes inflammation leading to the further up-regulation of the activity of the multiple individual MMPs, the massive cleavage of MBP in the brain, demyelination, and MS. In addition to the cleavage of Golli-MBPs, MMP-25 proteolysis readily inactivates crystallin αB that is a suppressor of MS. These data suggest that MMP-25 plays an important role in MS pathology and that MMP-25, especially because of its restricted cell/tissue expression pattern and cell surface/lipid raft localization, is a promising drug target in MS. PMID:19726693

  20. Inflammatory proprotein convertase-matrix metalloproteinase proteolytic pathway in antigen-presenting cells as a step to autoimmune multiple sclerosis.

    PubMed

    Shiryaev, Sergey A; Remacle, Albert G; Savinov, Alexei Y; Chernov, Andrei V; Cieplak, Piotr; Radichev, Ilian A; Williams, Roy; Shiryaeva, Tatiana N; Gawlik, Katarzyna; Postnova, Tatiana I; Ratnikov, Boris I; Eroshkin, Alexei M; Motamedchaboki, Khatereh; Smith, Jeffrey W; Strongin, Alex Y

    2009-10-30

    Multiple sclerosis (MS) is a disease of the central nervous system with autoimmune etiology. Susceptibility to MS is linked to viral and bacterial infections. Matrix metalloproteinases (MMPs) play a significant role in the fragmentation of myelin basic protein (MBP) and demyelination. The splice variants of the single MBP gene are expressed in the oligodendrocytes of the central nervous system (classic MBP) and in the immune cells (Golli-MBPs). Our data suggest that persistent inflammation caused by environmental risk factors is a step to MS. We have discovered biochemical evidence suggesting the presence of the inflammatory proteolytic pathway leading to MS. The pathway involves the self-activated furin and PC2 proprotein convertases and membrane type-6 MMP (MT6-MMP/MMP-25) that is activated by furin/PC2. These events are followed by MMP-25 proteolysis of the Golli-MBP isoforms in the immune system cells and stimulation of the specific autoimmune T cell clones. It is likely that the passage of these autoimmune T cell clones through the disrupted blood-brain barrier to the brain and the recognition of neuronal, classic MBP causes inflammation leading to the further up-regulation of the activity of the multiple individual MMPs, the massive cleavage of MBP in the brain, demyelination, and MS. In addition to the cleavage of Golli-MBPs, MMP-25 proteolysis readily inactivates crystallin alphaB that is a suppressor of MS. These data suggest that MMP-25 plays an important role in MS pathology and that MMP-25, especially because of its restricted cell/tissue expression pattern and cell surface/lipid raft localization, is a promising drug target in MS. PMID:19726693

  1. Lipoprotein(a) Catabolism Is Regulated by Proprotein Convertase Subtilisin/Kexin Type 9 through the Low Density Lipoprotein Receptor*

    PubMed Central

    Romagnuolo, Rocco; Scipione, Corey A.; Boffa, Michael B.; Marcovina, Santica M.; Seidah, Nabil G.; Koschinsky, Marlys L.

    2015-01-01

    Elevated levels of lipoprotein(a) (Lp(a)) have been identified as an independent risk factor for coronary heart disease. Plasma Lp(a) levels are reduced by monoclonal antibodies targeting proprotein convertase subtilisin/kexin type 9 (PCSK9). However, the mechanism of Lp(a) catabolism in vivo and the role of PCSK9 in this process are unknown. We report that Lp(a) internalization by hepatic HepG2 cells and primary human fibroblasts was effectively reduced by PCSK9. Overexpression of the low density lipoprotein (LDL) receptor (LDLR) in HepG2 cells dramatically increased the internalization of Lp(a). Internalization of Lp(a) was markedly reduced following treatment of HepG2 cells with a function-blocking monoclonal antibody against the LDLR or the use of primary human fibroblasts from an individual with familial hypercholesterolemia; in both cases, Lp(a) internalization was not affected by PCSK9. Optimal Lp(a) internalization in both hepatic and primary human fibroblasts was dependent on the LDL rather than the apolipoprotein(a) component of Lp(a). Lp(a) internalization was also dependent on clathrin-coated pits, and Lp(a) was targeted for lysosomal and not proteasomal degradation. Our data provide strong evidence that the LDLR plays a role in Lp(a) catabolism and that this process can be modulated by PCSK9. These results provide a direct mechanism underlying the therapeutic potential of PCSK9 in effectively lowering Lp(a) levels. PMID:25778403

  2. Proprotein convertase subtilisin/kexin type 9 inhibition: a new therapeutic mechanism for reducing cardiovascular disease risk.

    PubMed

    Bergeron, Nathalie; Phan, Binh An P; Ding, Yunchen; Fong, Aleyna; Krauss, Ronald M

    2015-10-27

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays an important role in the regulation of cholesterol homeostasis. By binding to hepatic low-density lipoprotein (LDL) receptors and promoting their lysosomal degradation, PCSK9 reduces LDL uptake, leading to an increase in LDL cholesterol concentrations. Gain-of-function mutations in PCSK9 associated with high LDL cholesterol and premature cardiovascular disease have been causally implicated in the pathophysiology of autosomal-dominant familial hypercholesterolemia. In contrast, the more commonly expressed loss-of-function mutations in PCSK9 are associated with reduced LDL cholesterol and cardiovascular disease risk. The development of therapeutic approaches that inhibit PCSK9 function has therefore attracted considerable attention from clinicians and the pharmaceutical industry for the management of hypercholesterolemia and its associated cardiovascular disease risk. This review summarizes the effects of PCSK9 on hepatic and intestinal lipid metabolism and the more recently explored functions of PCSK9 in extrahepatic tissues. Therapeutic approaches that prevent interaction of PCSK9 with hepatic LDL receptors (monoclonal antibodies, mimetic peptides), inhibit PCSK9 synthesis in the endoplasmic reticulum (antisense oligonucleotides, siRNAs), and interfere with PCSK9 function (small molecules) are also described. Finally, clinical trials testing the safety and efficacy of monoclonal antibodies to PCSK9 are reviewed. These have shown dose-dependent decreases in LDL cholesterol (44%-65%), apolipoprotein B (48%-59%), and lipoprotein(a) (27%-50%) without major adverse effects in various high-risk patient categories, including those with statin intolerance. Initial reports from 2 of these trials have indicated the expected reduction in cardiovascular events. Hence, inhibition of PCSK9 holds considerable promise as a therapeutic option for decreasing cardiovascular disease risk. PMID:26503748

  3. Furin and proprotein convertase 7 (PC7)/lymphoma PC endogenously expressed in rat liver can be resolved into distinct post-Golgi compartments.

    PubMed Central

    Wouters, S; Leruth, M; Decroly, E; Vandenbranden, M; Creemers, J W; van de Loo, J W; Ruysschaert, J M; Courtoy, P J

    1998-01-01

    The intracellular compartmentalization in rat liver of the membrane-associated convertases furin and proprotein convertase 7 (PC7)/lymphoma PC (LPC) was investigated by analytical subcellular fractionation. In control animals, both enzymes were found to localize in fractions depleted of endoplasmic reticulum, cis-Golgi and lysosomal markers, but to co-distribute with the Golgi marker galactosyltransferase and the trans-Golgi network (TGN) marker TGN38. After overloading Golgi-derived vesicles with very-low-density lipoproteins (VLDL) by feeding rats with ethanol, the distribution of PC7/LPC was shifted markedly towards lower densities, in contrast with those of furin and the TGN marker. This provides support for the TGN localization of endogenously expressed furin and indicates that, at steady state, a considerable proportion of PC7/LPC may be associated with vesicles derived from the TGN. PMID:9820806

  4. In vitro elucidation of substrate specificity and bioassay of proprotein convertase 4 using intramolecularly quenched fluorogenic peptides.

    PubMed Central

    Basak, Sarmistha; Chrétien, Michel; Mbikay, Majambu; Basak, Ajoy

    2004-01-01

    The fourth member of Ca2+-dependent mammalian secretory subtilase, PC4 (proprotein convertase 4), is primarily expressed in testicular germ cell and ovarian macrophage. Its role in sperm fertilization and in early embryonic development has been demonstrated earlier through several studies, including those with PC4 null mice. A number of physiological substrates found in reproductive tissues have been postulated or identified for PC4 by various biochemical studies. These include growth factors IGF-1 (insulin-like growth factor-1) and IGF-2, hormonal polypeptide proPACAP (where PACAP stands for pituitary adenylate cyclase-activating polypeptide) and a number of surface proteins of ADAM (ADisintegrin And Metalloproteinase-like) family such as ADAM-1 (fertilin a), ADAM-2 (fertilin b), ADAM-3 (procyritestin) and ADAM-5. To provide further evidence in support of this notion and also to study the substrate specificity and bioassay of PC4, a series of intramolecularly quenched fluorogenic peptides containing the cleavage sites and several mutants were prepared. A comparative kinetic analysis and measurement of Vmax (app)/Km (app) ratio of these fluorogenic substrates against PC4 and PC7 revealed that the mutant variants of h (human) proPACAP and m (mouse) ADAM-5 derived peptides Q-PACAP141-151-mutant [Abz-141RVKNKGRRI150P151SY(NO2)-A-CONH2] (150A151Y replaced by PS) and Q-ADAM-5380-388-mutant [Abz-380E381PKPARRP388RY(NO2)A-CONH2] (381R replaced by P) are most efficiently and selectively cleaved by PC4. Using these two and Q-IGF-263-71 peptides, we showed that the sperm extract of normal adult mice is much higher when compared with that of PC4-null mice. This suggests that these fluorogenic peptides are useful for specific bioassay of PC4 activity. In addition, kinetic studies with various peptidyl-MCA indicate that the hexapeptide Ac-KTKQLR-MCA (where MCA stands for 4-methyl coumaryl-7-amide) is most efficiently and selectively cleaved by PC4 at RMCA, making it another

  5. Expert consensus on the rational clinical use of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.

    PubMed

    Achimastos, Apostolos; Alexandrides, Theodoros; Alexopoulos, Dimitrios; Athyros, Vasilios; Bargiota, Alexandra; Bilianou, Eleni; Chrysochoou, Christina; Drogari, Evridiki; Elisaf, Moses; Ganotakis, Emanouel; Goudevenos, Ioannis; Ioannidis, Ioannis; Kolovou, Genovefa; Kotsis, Vasilios; Lekakis, Ioannis; Liberopoulos, Evangelos; Melidonis, Andreas; Nikolaou, Vasilios; Ntaios, George; Papanas, Nikolaos; Pappas, Stavros; Pitsavos, Christos; Rallidis, Loukianos; Richter, Dimitrios; Skoumas, Ioannis; Tentolouris, Nicolaos; Tousoulis, Dimitrios; Tselepis, Alexandros; Tsioufis, Konstantinos; Tziakas, Dimitrios; Tziomalos, Konstantinos; Vardas, Panagiotis; Vlachopoulos, Charalabos; Vlahakos, Dimitrios

    2016-01-01

    Two proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, evolocumab and alirocumab, have recently been approved by both the Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for the treatment of hypercholesterolemia. These fully human monoclonal antibodies selectively block PCSK9, thus permitting the low-density lipoprotein (LDL) receptor to effectively recycle to the surface of liver cells. The administration of these antibodies leads to robust LDL cholesterol (LDL-C) lowering by 50-60% on top of maximum hypolipidemic treatment. At least 4 randomized, placebo-controlled studies are under way and will address the question of whether the administration of these PCSK9 inhibitors is associated with a significant reduction of cardiovascular events. Because of the high cost associated with the use of these medications it is very important to consider which patients may gain the most benefit, at least until the results of outcome studies are available. In this Consensus paper, 34 clinicians/scientists define 3 groups of patients that should be currently considered as candidates for the use of these novel drugs. These include: 1a. Adults with established cardiovascular disease and LDL-C≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 1b. Adults with diabetes and established cardiovascular disease or chronic kidney disease or target organ damage and LDL-C ≥100 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe, 2. Adults with familial hypercholesterolemia (FH) without established cardiovascular disease and LDL-C ≥130 mg/dL while on lifestyle modifications and maximally tolerated hypolipidemic treatment, i.e. high-intensity statin + ezetimibe (evolocumab is also indicated in children above 12 years with homozygous FH), and 3. Adults at high or very high cardiovascular risk

  6. Two proprotein convertase subtilisin/kexin type 9 (PCSK9) paralogs from the tropical sea cucumber (Stichopus monotuberculatus): Molecular characterization and inducible expression with immune challenge.

    PubMed

    Ren, Chunhua; Chen, Ting; Jiang, Xiao; Sun, Hongyan; Qian, Jing; Hu, Chaoqun; Wang, Yanhong

    2016-09-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a multifunctional protein that widely exists in eukaryotic species. In this study, two PCSK9 paralogs, named StmPCSK9-1 and StmPCSK9-2, were identified from the tropical sea cucumber (Stichopus monotuberculatus). The cDNAs of StmPCSK9-1 and StmPCSK9-2 are 1330 kb and 1508 kb in size, respectively. The open reading frames (ORF) for StmPCSK9-1 and StmPCSK9-2 cDNAs are 1128 and 1167 bp in length, encoding the proteins of 375 and 388 amino acids with the deduced molecular weights of 38.76 and 41.07 kDa, respectively. In accord with other members in PCSK9 family, the two StmPCSK9 paralogs possessed the inhibitor_I9 and peptidase_S8 functional domains, seven active sites, a catalytic triad and two calcium binding sites. For the gene structure, the splicing of the two StmPCSK9 paralogs was relatively conserved. In addition, the mRNA expression of StmPCSK9-1 and StmPCSK9-2 was only detected in the sea cucumber intestine and coelomocytes, and the expression levels of both the two StmPCSK9 paralogs were higher in intestine. Moreover, StmPCSK9-2 was found to be a cytoplasm protein without signal peptide, and show no response to the immune challenge. On the contrary, StmPCSK9-1 was a secreted protein and the transcriptional expression of StmPCSK9-1 was significantly up-regulated by lipopolysaccharides (LPS) treatment and slightly down-regulated by polyriboinosinic polyribocytidylic acid [Poly (I:C)] challenge in in vitro experiments performed in the cultural primary coelomocytes, suggesting that the StmPCSK9-1 may play critical roles in the innate immune defense of sea cucumber, S. monotuberculatus, against bacterial and/or viral infections. PMID:27426522

  7. Proprotein convertase 5/6 cleaves platelet-derived growth factor A in the human endometrium in preparation for embryo implantation.

    PubMed

    Paule, Sarah; Nebl, Thomas; Webb, Andrew I; Vollenhoven, Beverley; Rombauts, Luk J F; Nie, Guiying

    2015-03-01

    Establishment of endometrial receptivity is vital for successful embryo implantation. Proprotein convertase 5/6 (referred to as PC6) is up-regulated in the human endometrium specifically at the time of epithelial receptivity. PC6, a serine protease of the proprotein convertase family, plays an important role in converting precursor proteins into their active forms through specific proteolysis. The proform of platelet-derived growth factor A (pro-PDGFA) requires PC cleavage to convert to the active-PDGFA. We investigated the PC6-mediated activation of PDGFA in the human endometrium during the establishment of receptivity. Proteomic analysis identified that the pro-PDGFA was increased in the conditioned medium of HEC1A cells in which PC6 was stably knocked down by small interfering RNA (PC6-siRNA). Western blot analysis demonstrated an accumulation of the pro-PDGFA but a reduction in the active-PDGFA in PC6-siRNA cell lysates and medium compared with control. PC6 cleavage of pro-PDGFA was further confirmed in vitro by incubation of recombinant pro-PDGFA with PC6. Immunohistochemistry revealed cycle-stage-specific localization of the active-PDGFA in the human endometrium. During the non-receptive phase, the active-PDGFA was barely detectable. In contrast, it was localized specifically to the apical surface of the luminal and glandular epithelium in the receptive phase. Furthermore, the active-PDGFA was detected in uterine lavage with levels being significantly higher in the receptive than the non-receptive phase. We thus identified that the secreted PDGFA may serve as a biomarker for endometrial receptivity. This is also the first study demonstrating that the active-PDGFA localizes to the apical surface of the endometrium during receptivity. PMID:25429785

  8. Furin-cleaved Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Is Active and Modulates Low Density Lipoprotein Receptor and Serum Cholesterol Levels

    PubMed Central

    Lipari, Michael T.; Li, Wei; Moran, Paul; Kong-Beltran, Monica; Sai, Tao; Lai, Joyce; Lin, S. Jack; Kolumam, Ganesh; Zavala-Solorio, Jose; Izrael-Tomasevic, Anita; Arnott, David; Wang, Jianyong; Peterson, Andrew S.; Kirchhofer, Daniel

    2012-01-01

    Proprotein convertase subtilisin/kexin 9 (PCSK9) regulates plasma LDL cholesterol levels by regulating the degradation of LDL receptors. Another proprotein convertase, furin, cleaves PCSK9 at Arg218-Gln219 in the surface-exposed “218 loop.” This cleaved form circulates in blood along with the intact form, albeit at lower concentrations. To gain a better understanding of how cleavage affects PCSK9 function, we produced recombinant furin-cleaved PCSK9 using antibody Ab-3D5, which binds the intact but not the cleaved 218 loop. Using Ab-3D5, we also produced highly purified hepsin-cleaved PCSK9. Hepsin cleaves PCSK9 at Arg218-Gln219 more efficiently than furin but also cleaves at Arg215-Phe216. Further analysis by size exclusion chromatography and mass spectrometry indicated that furin and hepsin produced an internal cleavage in the 218 loop without the loss of the N-terminal segment (Ser153–Arg218), which remained attached to the catalytic domain. Both furin- and hepsin-cleaved PCSK9 bound to LDL receptor with only 2-fold reduced affinity compared with intact PCSK9. Moreover, they reduced LDL receptor levels in HepG2 cells and in mouse liver with only moderately lower activity than intact PCSK9, consistent with the binding data. Single injection into mice of furin-cleaved PCSK9 resulted in significantly increased serum cholesterol levels, approaching the increase by intact PCSK9. These findings indicate that circulating furin-cleaved PCSK9 is able to regulate LDL receptor and serum cholesterol levels, although somewhat less efficiently than intact PCSK9. Therapeutic anti-PCSK9 approaches that neutralize both forms should be the most effective in preserving LDL receptors and in lowering plasma LDL cholesterol. PMID:23135270

  9. Proprotein Convertase Subtilisin/Kexin Type 7 (PCSK7) Is Essential for the Zebrafish Development and Bioavailability of Transforming Growth Factor β1a (TGFβ1a)*

    PubMed Central

    Turpeinen, Hannu; Oksanen, Anna; Kivinen, Virpi; Kukkurainen, Sampo; Uusimäki, Annemari; Rämet, Mika; Parikka, Mataleena; Hytönen, Vesa P.; Nykter, Matti; Pesu, Marko

    2013-01-01

    Proprotein convertase subtilisin/kexin (PCSK) enzymes convert proproteins into bioactive end products. Although other PCSK enzymes are known to be essential for biological processes ranging from cholesterol metabolism to host defense, the in vivo importance of the evolutionarily ancient PCSK7 has remained enigmatic. Here, we quantified the expressions of all pcsk genes during the 1st week of fish development and in several tissues. pcsk7 expression was ubiquitous and evident already during the early development. To compare mammalian and zebrafish PCSK7, we prepared homology models, which demonstrated remarkable structural conservation. When the PCSK7 function in developing larvae was inhibited, we found that PCSK7-deficient fish have defects in various organs, including the brain, eye, and otic vesicle, and these result in mortality within 7 days postfertilization. A genome-wide analysis of PCSK7-dependent gene expression showed that, in addition to developmental processes, several immune system-related pathways are also regulated by PCSK7. Specifically, the PCSK7 contributed to the mRNA expression and proteolytic cleavage of the cytokine TGFβ1a. Consequently, tgfβ1a morphant fish displayed phenotypical similarities with pcsk7 morphants, underscoring the importance of this cytokine in the zebrafish development. Targeting PCSK activity has emerged as a strategy for treating human diseases. Our results suggest that inhibiting PCSK7 might interfere with normal vertebrate development. PMID:24178295

  10. A proteomic approach reveals transient association of reticulocalbin-3, a novel member of the CREC family, with the precursor of subtilisin-like proprotein convertase, PACE4

    PubMed Central

    Tsuji, Akihiko; Kikuchi, Yayoi; Sato, Yukimi; Koide, Shizuyo; Yuasa, Keizo; Nagahama, Masami; Matsuda, Yoshiko

    2006-01-01

    SPCs (subtilisin-like proprotein convertases) are a family of seven structurally related serine endoproteases that are involved in the proteolytic activation of proproteins. In an effort to examine the substrate protein for PACE4 (paired basic amino-acid-cleaving enzyme-4), an SPC, a potent protein inhibitor of PACE4, an α1-antitrypsin RVRR (Arg-Val-Arg-Arg) variant, was expressed in GH4C1 cells. Ectopic expression of the RVRR variant caused accumulation of the 48 kDa protein in cells. Sequence analysis indicates that the 48 kDa protein is a putative Ca2+-binding protein, RCN-3 (reticulocalbin-3), which had previously been predicted by bioinformatic analysis of cDNA from the human hypothalamus. RCN-3 is a member of the CREC (Cab45/reticulocalbin/ERC45/calumenin) family of multiple EF-hand Ca2+-binding proteins localized to the secretory pathway. The most interesting feature of the RCN-3 sequence is the presence of five Arg-Xaa-Xaa-Arg motifs, which represents the target sequence of SPCs. Biosynthetic studies showed that RCN-3 is transiently associated with proPACE4, but not with mature PACE4. Inhibition of PACE4 maturation by a Ca2+ ionophore resulted in accumulation of the proPACE4–RCN-3 complex in cells. Furthermore, autoactivation and secretion of PACE4 was increased upon co-expression with RCN-3. Our findings suggest that selective and transient association of RCN-3 with the precursor of PACE4 plays an important role in the biosynthesis of PACE4. PMID:16433634

  11. Repression of liver colorectal metastasis by the serpin Spn4A a naturally occurring inhibitor of the constitutive secretory proprotein convertases

    PubMed Central

    Sfaxi, Fatma; Scamuffa, Nathalie; Lalou, Claude; Ma, Jia; Metrakos, Peter; Siegfried, Géraldine; Ragg, Hermann; Bikfalvi, Andreas; Calvo, Fabien; Khatib, Abdel-Majid

    2014-01-01

    Liver is the most common site of metastasis from colorectal cancers, and liver of patients with liver colorectal metastasis have abnormal levels of the proprotein convertases (PCs). These proteases are involved in the activation and/or expression of various colon cancer-related mediators, making them promising targets in colorectal liver metastasis therapy. Here, we revealed that the serpin Spn4 from Drosophila melanogaster inhibits the activity of all the PCs found in the constitutive secretory pathway and represses the metastatic potential of the colon cancer cells HT-29 and CT-26. In these cells, Spn4A inhibited the processing of the PCs substrates IGF-1R and PDGF-A that associated their reduced anchorage-independent growth, invasiveness and survival in response to apoptotic agents. In vivo, Spn4A-expressing tumor cells showed repressed subcutaneous tumor development and liver metastases formation in response to their intrasplenic inoculation. In these cells Spn4A induced the expression of molecules with anti-metastatic functions and inhibited expression of pro-tumorigenic molecules. Taken together, our findings identify Spn4A as the only endogenous inhibitor of all the constitutive secretory pathway PCs, which is able to repress the metastatic potential of colon cancer cells. These results suggest the potential use of Spn4A and/or derivates as a useful adduct colorectal liver metastasis prevention. PMID:24961901

  12. Characterization of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Trafficking Reveals a Novel Lysosomal Targeting Mechanism via Amyloid Precursor-like Protein 2 (APLP2)

    PubMed Central

    DeVay, Rachel M.; Shelton, David L.; Liang, Hong

    2013-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low density lipoprotein receptor protein levels by diverting it to lysosomes. Monoclonal antibody therapeutics aimed to neutralize PCSK9 have been shown to successfully lower serum LDL levels; however, we previously found that such therapeutic antibodies are subject to PCSK9-mediated clearance. In this study, we discovered that PCSK9 interacts via its C-terminal domain directly and in a pH-dependent manner with amyloid precursor protein as well as its closely related family member, amyloid precursor protein-like protein 2. Furthermore, we determined that amyloid precursor protein-like protein-2, but not amyloid precursor protein, is involved in mediating postendocytic delivery of PCSK9 to lysosomes and is therefore important for PCSK9 function. Based on our data, we propose a model for a lysosomal transport complex by which a soluble protein can target another protein for degradation from the luminal side of the membrane by bridging it to a lysosomally targeted transmembrane protein. PMID:23430252

  13. The New Face of Hyperlipidemia Management: Proprotein Convertase Subtilisin/Kexin Inhibitors (PCSK-9) and Their Emergent Role As An Alternative To Statin Therapy.

    PubMed

    Smith, Lillian; Mosley, Juan; Yates, Jarah; Caswell, Luke

    2016-01-01

    This review analyzes Proprotein Convertase Subtilisin/Kexin 9 inhibitors (PCSK-9), a new medication class that has arisen in the last year to combat hypercholesterolemia. They are targeted towards patients who are unable to achieve acceptable low density lipoprotein (LDL) levels despite maximum statin therapy, as well as those who are unable to tolerate maximum statin therapy due to side effects such as myopathy or myalgia. Two of these medications have been released in the last year: alirocumab (Praluent) and evolocumab (Repatha). This article will overview this medication class, describe their pathophysiology, and analyze the clinical data from the numerous studies and trials done on both of these medications for their efficacy and safety outcomes. Data compiled on this new class of medications support the research that PCSK-9 inhibitors are both a safe and effective means of lowering the LDL levels of resistant or otherwise currently unmanaged hypercholesterolemia patients.This article is open to POST-PUBLICATION REVIEW. Registered readers (see "For Readers") may comment by clicking on ABSTRACT on the issue's contents page. PMID:27096698

  14. Recent advances in the understanding and care of familial hypercholesterolaemia: significance of the biology and therapeutic regulation of proprotein convertase subtilisin/kexin type 9.

    PubMed

    Page, Michael M; Stefanutti, Claudia; Sniderman, Allan; Watts, Gerald F

    2015-07-01

    Familial hypercholesterolaemia (FH) is an autosomal co-dominant disorder that markedly raises plasma low-density lipoprotein-cholesterol (LDL-C) concentration, causing premature atherosclerotic coronary artery disease (CAD). FH has recently come under intense focus and, although there is general consensus in recent international guidelines regarding diagnosis and treatment, there is debate about the value of genetic studies. Genetic testing can be cost-effective as part of cascade screening in dedicated centres, but the full mutation spectrum responsible for FH has not been established in many populations, and its use in primary care is not at present logistically feasible. Whether using genetic testing or not, cholesterol screening of family members of index patients with an abnormally raised LDL-C must be used to determine the need for early treatment to prevent the development of CAD. The metabolic defects in FH extend beyond LDL, and may affect triacylglycerol-rich and high-density lipoproteins, lipoprotein(a) and oxidative stress. Achievement of the recommended targets for LDL-C with current treatments is difficult, but this may be resolved by new drug therapies. Lipoprotein apheresis remains an effective treatment for severe FH and, although expensive, it costs less than the two recently introduced orphan drugs (lomitapide and mipomersen) for homozygous FH. Recent advances in understanding of the biology of proprotein convertase subtilisin/kexin type 9 (PCSK9) have further elucidated the regulation of lipoprotein metabolism and led to new drugs for effectively treating hypercholesterolaemia in FH and related conditions, as well as for treating many patients with statin intolerance. The mechanisms of action of PCSK9 inhibitors on lipoprotein metabolism and atherosclerosis, as well as their impact on cardiovascular outcomes and cost-effectiveness, remain to be established. PMID:25881720

  15. 60 YEARS OF POMC: From the prohormone theory to pro-opiomelanocortin and to proprotein convertases (PCSK1 to PCSK9).

    PubMed

    Chrétien, Michel; Mbikay, Majambu

    2016-05-01

    Pro-opiomelanocortin (POMC), is a polyprotein expressed in the pituitary and the brain where it is proteolytically processed into peptide hormones and neuropeptides with distinct biological activities. It is the prototype of multipotent prohormones. The prohormone theory was first suggested in 1967 when Chrétien and Li discovered γ-lipotropin and observed that (i) it was part of β-lipotropin (β-LPH), a larger polypeptide characterized 2 years earlier and (ii) its C-terminus was β-melanocyte-stimulating hormone (β-MSH). This discovery led them to propose that the lipotropins might be related biosynthetically to the biologically active β-MSH in a precursor to end product relationship. The theory was widely confirmed in subsequent years. As we celebrate the 50th anniversary of the sequencing of β-LPH, we reflect over the lessons learned from the sequencing of those proteins; we explain their extension to the larger POMC precursor; we examine how the theory of precursor endoproteolysis they inspired became relevant for vast fields in biology; and how it led, after a long and arduous search, to the novel proteolytic enzymes called proprotein convertases. This family of nine enzymes plays multifaceted functions in growth, development, metabolism, endocrine, and brain functions. Their genetics has provided many insights into health and disease. Their therapeutic targeting is foreseeable in the near future. Thus, what started five decades ago as a theory based on POMC fragments, has opened up novel and productive avenues of biological and medical research, including, for our own current interest, a highly intriguing hypocholesterolemic Gln152His PCSK9 mutation in French-Canadian families. PMID:26762158

  16. Docosahexaenoic Acid Attenuates Cardiovascular Risk Factors via a Decline in Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Plasma Levels.

    PubMed

    Rodríguez-Pérez, Celia; Ramprasath, Vanu Ramkumar; Pu, Shuaihua; Sabra, Ali; Quirantes-Piné, Rosa; Segura-Carretero, Antonio; Jones, Peter J H

    2016-01-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a circulating protein that regulates cholesterol metabolism by promoting LDL receptor degradation in the liver and has recently been proposed as a therapeutic target in the management of hyperlipidaemia. We investigated the impact of dietary fat on the metabolism of sterols and on plasma PCSK9 concentrations to explore likely clinical usefulness. In a post hoc analysis of a double-blind randomised crossover controlled feeding trial, the Canola Oil Multicenter Intervention Trial (COMIT), volunteers (n = 54) with at least one condition related to metabolic syndrome consumed diets with one of the following treatment oils in beverages: (1) conventional canola oil (Canola); (2) canola oil rich in docosahexanoic acid (DHA) (CanolaDHA); and (3) high-oleic acid canola oil (CanolaOleic). The enrichment in oleic acid resulted in lower plasma cholesterol concentration compared with diets enriched in DHA. Contrarily, DHA-enriched oil significantly decreased plasma PCSK9 and triacylglycerols levels, but increased circulating levels of sterols. The variations in lathosterol, sitosterol, and campesterol indicate that plasma PCSK9 levels are sensitive to changes in cholesterol synthesis and/or absorption. There was a significant correlation between plasma PCSK9 levels and plasma triacylglicerol and apolipoprotein B levels, which was not affected by dietary fat. Therefore, our results suggest that the impact of dietary fats should not be discarded as complementary treatment in the management of patients with hyperlipidaemia. These findings should be considered in the analysis of ongoing studies and may represent a cautionary note in the treatment of patients with cardiovascular risk. PMID:26620373

  17. Independent Link Between Levels of Proprotein Convertase Subtilisin/Kexin Type 9 and FABP4 in a General Population Without Medication.

    PubMed

    Furuhashi, Masato; Omori, Akina; Matsumoto, Megumi; Kataoka, Yu; Tanaka, Marenao; Moniwa, Norihito; Ohnishi, Hirofumi; Yoshida, Hideaki; Saitoh, Shigeyuki; Shimamoto, Kazuaki; Miura, Tetsuji

    2016-07-15

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to and degrades the low-density lipoprotein (LDL) receptor, leading to hypercholesterolemia and cardiovascular risk. Fatty acid binding protein 4 (FABP4/adipocyte FABP/aP2) is secreted from adipocytes in association with lipolysis, and circulating FABP4 has been reported to act as an adipokine for the development of insulin resistance and atherosclerosis. Elevated serum FABP4 level is associated with obesity, insulin resistance, dyslipidemia, and atherosclerosis. In this study, we examined the association between circulating levels of FABP4 and PCSK9 in a general population. A total of 265 subjects (male/female: 98/167) who were not on medication were recruited from subjects of the Tanno-Sobetsu Study, and concentrations of FABP4 and PCSK9 were measured. The level of FABP4, but not that of PCSK9, showed a gender difference, being higher in women than in men. FABP4 level was independently associated with gender, adiposity, renal dysfunction, and levels of cholesterol and PCSK9. There was a significant and gender-different correlation between PCSK9 level and age: negatively in men (r = -0.250, p = 0.013) and positively in women (r = 0.183, p = 0.018). After adjustment of age, gender, and LDL cholesterol level, PCSK9 level was positively and independently correlated with FABP4 concentration. In conclusion, PCSK9 level is differentially regulated by gender during aging. Circulating FABP4 is independently associated with the PCSK9 level, suggesting that elevation of FABP4 level as an adipokine leads to dyslipidemia through increased PCSK9 level and subsequent degradation of the LDL receptor. PMID:27241838

  18. Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Single Domain Antibodies Are Potent Inhibitors of Low Density Lipoprotein Receptor Degradation.

    PubMed

    Weider, Elodie; Susan-Resiga, Delia; Essalmani, Rachid; Hamelin, Josée; Asselin, Marie-Claude; Nimesh, Surendra; Ashraf, Yahya; Wycoff, Keith L; Zhang, Jianbing; Prat, Annik; Seidah, Nabil G

    2016-08-01

    Single domain antibodies (sdAbs) correspond to the antigen-binding domains of camelid antibodies. They have the same antigen-binding properties and specificity as monoclonal antibodies (mAbs) but are easier and cheaper to produce. We report here the development of sdAbs targeting human PCSK9 (proprotein convertase subtilisin/kexin type 9) as an alternative to anti-PCSK9 mAbs. After immunizing a llama with human PCSK9, we selected four sdAbs that bind PCSK9 with a high affinity and produced them as fusion proteins with a mouse Fc. All four sdAb-Fcs recognize the C-terminal Cys-His-rich domain of PCSK9. We performed multiple cellular assays and demonstrated that the selected sdAbs efficiently blocked PCSK9-mediated low density lipoprotein receptor (LDLR) degradation in cell lines, in human hepatocytes, and in mouse primary hepatocytes. We further showed that the sdAb-Fcs do not affect binding of PCSK9 to the LDLR but rather block its induced cellular LDLR degradation. Pcsk9 knock-out mice expressing a human bacterial artificial chromosome (BAC) transgene were generated, resulting in plasma levels of ∼300 ng/ml human PCSK9. Mice were singly or doubly injected with the best sdAb-Fc and analyzed at day 4 or 11, respectively. After 4 days, mice exhibited a 32 and 44% decrease in the levels of total cholesterol and apolipoprotein B and ∼1.8-fold higher liver LDLR protein levels. At 11 days, the equivalent values were 24 and 46% and ∼2.3-fold higher LDLR proteins. These data constitute a proof-of-principle for the future usage of sdAbs as PCSK9-targeting drugs that can efficiently reduce LDL-cholesterol, and as tools to study the Cys-His-rich domain-dependent sorting the PCSK9-LDLR complex to lysosomes. PMID:27284008

  19. Proprotein Convertase 1/3 (PC1/3) in the Rat Alveolar Macrophage Cell Line NR8383: Localization, Trafficking and Effects on Cytokine Secretion

    PubMed Central

    Gagnon, Hugo; Refaie, Sarah; Gagnon, Sandra; Desjardins, Roxane; Salzet, Michel; Day, Robert

    2013-01-01

    The proprotein convertase 1/3 (PC1/3) is an important post-translational processing enzyme for the activation of precursor proteins within the regulated secretory pathway. Well characterized for its role in the neural and endocrine systems, we recently reported an unconventional role of PC1/3 as a modulator of the Toll-like receptor innate immune response. There are only a few reports that have studied PC1/3 expression in macrophages, and more investigation is needed to better characterize its function. These studies would greatly benefit from model cell lines. Our study aims to identify and characterize PC1/3 in a relevant model macrophage cell line and to determine the links between PC1/3 and innate immune cellular responses. We describe the rat alveolar cell line, NR8383, as expressing PC1/3 and the most common Toll-like receptors. In NR8383 cells, PC1/3 is localized at the Trans-Golgi network and traffics to lysosome related vesicles upon lipopolysaccharide stimulation. Moreover, we report the co-localization of PC1/3 and Toll-like receptor 4 upon lipopolysaccharide stimulation. Down regulation of PC1/3 by shRNA produce a similar phenotype in NR8383 to what we previously reported in isolated peritoneal macrophages. PC1/3 shRNA induced changes in the cellular organization and expression of the specific trafficking regulator RAB GTPase. As a consequence, NR8383 down-regulated for PC1/3, present an abnormal cytokine secretion profile. We conclude that the NR8383 cell line represents a good model to study PC1/3 in macrophages and we present PC1/3 as an important regulator of vesicle trafficking and secretion in macrophages. PMID:23637853

  20. Safety and efficacy of LY3015014, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9): a randomized, placebo-controlled Phase 2 study

    PubMed Central

    Kastelein, John J.P.; Nissen, Steven E.; Rader, Daniel J.; Hovingh, G. Kees; Wang, Ming-Dauh; Shen, Tong; Krueger, Kathryn A.

    2016-01-01

    Aims The objective of this study was to evaluate the efficacy, safety, and tolerability of LY3015014 (LY), a neutralizing antibody of proprotein convertase subtilisin/kexin type 9 (PCSK9), administered every 4 or 8 weeks in patients with primary hypercholesterolaemia, when added to a background of standard-of-care lipid-lowering therapy, including statins. Methods and results Double-blind, placebo-controlled trial randomized 527 patients with primary hypercholesterolaemia from June 2013 to January 2014 at 61 community and academic centres in North America, Europe, and Japan. Patients were randomized to subcutaneous injections of LY 20, 120, or 300 mg every 4 weeks (Q4W); 100 or 300 mg every 8 weeks (Q8W) alternating with placebo Q4W; or placebo Q4W. The primary endpoint was percentage change from baseline in low-density lipoprotein cholesterol (LDL-C) by beta quantification at Week 16. The mean baseline LDL-C by beta quantification was 136.3 (SD, 45.0)mg/dL. LY3015014 dose-dependently decreased LDL-C, with a maximal reduction of 50.5% with 300 mg LY Q4W and 37.1% with 300 mg LY Q8W compared with a 7.6% increase with placebo maintained at the end of the dosing interval. There were no treatment-related serious adverse events (AEs). The most common AE terms (>10% of any treatment group) reported more frequently with LY compared with placebo were injection site (IS) pain and IS erythema. No liver or muscle safety issues emerged. Conclusions LY3015014 dosed every 4 or 8 weeks, resulted in robust and durable reductions in LDL-C. No clinically relevant safety issues emerged with the administration of LY. The long-term effects on cardiovascular outcomes require further investigation. PMID:26757788

  1. Efficiency and Safety of Proprotein Convertase Subtilisin/Kexin 9 Monoclonal Antibody on Hypercholesterolemia: A Meta-Analysis of 20 Randomized Controlled Trials

    PubMed Central

    Li, Chuanwei; Lin, Ling; Zhang, Wen; Zhou, Liang; Wang, Hongyong; Luo, Xiaoli; Luo, Hao; Cai, Yue; Zeng, Chunyu

    2015-01-01

    Background Proprotein convertase subtilisin/kexin9 (PCSK9) monoclonal antibody significantly reduces low-density lipoprotein cholesterol level in patients with hypercholesterolemia. The goal of this study was to review recently reported randomized controlled trials to investigate the therapeutic effects and safety of PCSK9 inhibitors. Methods and Results The clinical randomized controlled trials published from inception to March 19, 2015 were identified from The Cochrane Library databases, PUBMED, and EBASE. Randomized controlled trials of at least 8 weeks duration using PCSK9 inhibitors in treating patients with hypercholesterolemia were included. Mean difference (MD) with a 95% CI was used to calculate the continuous data, the standardized mean difference with a 95% CI was used when the unit was not unified, and risk ratio with a 95% CI was used for dichotomous data. After screening, 20 trials fulfilled the inclusion criteria. PCSK9 inhibitors significantly decreased the levels of low-density lipoprotein cholesterol (MD=−65.29 mg/dL, 95% CI: −72.08 to −58.49), total cholesterol (MD=−60.04 mg/dL, 95% CI: −69.95 to −50.13), triglycerides (MD=−12.21 mg/dL, 95% CI: −16.21 to −8.22) and apolipoprotein-B (MD=−41.01 mg/dL, 95% CI: −46.07 to −35.94), lipoprotein(a) (standardized mean difference=−0.94, 95% CI: −1.12 to −0.77) and increased the levels of high-density lipoprotein cholesterol (MD=3.40 mg/dL, 95% CI: 3.12 to 3.68) and apolipoprotein-A1 (MD=6.75 mg/dL, 95% CI: 4.64 to 8.86). There was no significant difference in the incidence of treatment-emergent adverse events (risk ratio=1.01, 95% CI: 0.98 to 1.04), serious treatment-emergent adverse events (risk ratio=1.01, 95% CI: 0.88 to 1.17), and the discontinuation of treatment between the 2 groups (risk ratio=1.07, 95% CI: 0.86 to 1.34). Conclusions The meta-analysis indicated that PCSK9 inhibitors had a strong effect in lowering low-density lipoprotein cholesterol and other

  2. Suppressor of Cytokine Signaling-3 (SOCS-3) Induces Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) Expression in Hepatic HepG2 Cell Line.

    PubMed

    Ruscica, Massimiliano; Ricci, Chiara; Macchi, Chiara; Magni, Paolo; Cristofani, Riccardo; Liu, Jingwen; Corsini, Alberto; Ferri, Nicola

    2016-02-12

    The suppressor of cytokine signaling (SOCS) proteins are negative regulators of the JAK/STAT pathway activated by proinflammatory cytokines, including the tumor necrosis factor-α (TNF-α). SOCS3 is also implicated in hypertriglyceridemia associated to insulin resistance. Proprotein convertase subtilisin kexin type 9 (PCSK9) levels are frequently found to be positively correlated to insulin resistance and plasma very low density lipoprotein (VLDL) triglycerides concentrations. The present study aimed to investigate the possible role of TNF-α and JAK/STAT pathway on de novo lipogenesis and PCSK9 expression in HepG2 cells. TNF-α induced both SOCS3 and PCSK9 in a concentration-dependent manner. This effect was inhibited by transfection with siRNA anti-STAT3, suggesting the involvement of the JAK/STAT pathway. Retroviral overexpression of SOCS3 in HepG2 cells (HepG2(SOCS3)) strongly inhibited STAT3 phosphorylation and induced PCSK9 mRNA and protein, with no effect on its promoter activity and mRNA stability. Consistently, siRNA anti-SOCS3 reduced PCSK9 mRNA levels, whereas an opposite effect was observed with siRNA anti-STAT3. In addition, HepG2(SOCS3) express higher mRNA levels of key enzymes involved in the de novo lipogenesis, such as fatty-acid synthase, stearoyl-CoA desaturase (SCD)-1, and apoB. These responses were associated with a significant increase of SCD-1 protein, activation of sterol regulatory element-binding protein-1c (SREBP-1), accumulation of cellular triglycerides, and secretion of apoB. HepG2(SOCS3) show lower phosphorylation levels of insulin receptor substrate 1 (IRS-1) Tyr(896) and Akt Ser(473) in response to insulin. Finally, insulin stimulation produced an additive effect with SOCS3 overexpression, further inducing PCSK9, SREBP-1, fatty acid synthase, and apoB mRNA. In conclusion, our data candidate PCSK9 as a gene involved in lipid metabolism regulated by proinflammatory cytokine TNF-α in a SOCS3-dependent manner. PMID:26668321

  3. The proprotein convertase subtilisin/kexin type 9 gene E670G polymorphism and serum lipid levels in the Guangxi Bai Ku Yao and Han populations

    PubMed Central

    2011-01-01

    Background Proprotein convertase subtilisin-like kexin type 9 (PCSK9) plays a key role in regulating plasma low-density lipoprotein cholesterol (LDL-C) levels. However, the association of E670G (rs505151) polymorphism in the PCSK9 gene and serum lipid levels is inconsistent in several previous studies. The present study was undertaken to detect the association of PCSK9 E670G polymorphism and several environmental factors with serum lipid levels in the Guangxi Bai Ku Yao and Han populations. Methods A total of 649 subjects of Bai Ku Yao and 646 participants of Han were randomly selected from our previous samples. Genotypes of the PCSK9 E670G polymorphism were determined via polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis, and then confirmed by direct sequencing. Results Serum levels of total cholesterol, high-density lipoprotein cholesterol (HDL-C), LDL-C, and apolipoprotein (Apo) AI were lower in Bai Ku Yao than in Han (P < 0.01 for all). The frequency of G allele was 2.00% in Bai Ku Yao and 4.80% in Han (P < 0.01). There was significant difference in the genotypic and allelic frequencies between Bai Ku Yao and Han (P < 0.01); between normal LDL-C (≤ 3.20 mmol/L) and high LDL-C subgroups (> 3.20 mmol/L, P < 0.01) in Bai Ku Yao; and between normal HDL-C (≥ 0.91 mmol/L) and low HDL-C (< 0.91 mmol/L, P < 0.05), between normal ApoAI (≥ 1.00 g/L) and low ApoAI (< 1.00 g/L, P < 0.05), or between normal ApoAI/ApoB ratio (≥ 1.00) and low ApoAI/ApoB ratio (< 1.00, P < 0.01) subgroups in Han. The G allele carriers in Han had higher serum HDL-C levels and the ratio of ApoAI to ApoB than the G allele noncarriers. The G allele carriers in Han had higher serum HDL-C and ApoAI levels than the G allele noncarriers in males (P < 0.05 for each), whereas the G allele carriers had lower serum ApoB levels and higher the ratio of ApoAI to ApoB than the G allele noncarriers in females (P < 0.05 for all). Serum HDL-C and Apo

  4. Enediynyl peptides and iso-coumarinyl methyl sulfones as inhibitors of proprotein convertases PCSK8/SKI-1/S1P and PCSK4/PC4: Design, synthesis and biological evaluations.

    PubMed

    Basak, Ajoy; Goswami, Mukunda; Rajkumar, Abishankari; Mitra, Tapobrata; Majumdar, Swapan; O'Reilly, Paul; Bdour, Hussam M; Trudeau, Vance L; Basak, Amit

    2015-01-01

    The proprotein convertases PCSK8 and PCSK4 are, respectively, the 8th and 4th members of Ca(+2)-dependent serine endoprotease of Proprotein Convertase Subtilisin Kexin (PCSK) super family structurally related to the bacterial subtilisin and yeast kexin. The membrane bound PCSK8 (also called SKI-1 or S1P) is implicated in sterol regulation and lipid synthesis via its role in the maturation of human (h) SREBP-2. It also plays role in cartilage formation, bone mineralization, as well as viral pathogenesis. On the other hand, PCSK4 has been linked to mammalian fertilization and placenta growth. Owing to these findings, interest has grown to develop specific inhibitors against these enzymes for potential biochemical and therapeutic applications. In this study we developed two types of small molecule inhibitors of PCSK8 and PCSK4 and demonstrated their anti-proteolytic activities in vitro cell-free and in vitro cell culture systems. These are isocoumarinyl methyl sulfone derivatives and enediyne amino acid containing peptides. Our in vitro data suggested that one of the 7 sulfone derivatives (methyl phenyl sulfone) inhibited PCSK8 with inhibition constant Ki ∼255μM. It also blocked PCSK8-mediated processing of hSREBP-2 in HepG2 cell in a concentration-dependent manner. However all 7 iso-coumarinyl methyl sulfones inhibited htrypsin with IC50 ranging from 2 to 165μM. In contrast, all our designed enediynyl peptides inhibited PCSK8 and PCSK4 activity with Ki and IC50 in low μM or high nM ranges. All compounds exhibited competitive inhibition as indicated by their enzyme kinetic plots and observed dependence of IC50 value on substrate concentration. Our study confirmed that incorporation at the substrate cleavage site of 'Enediyne amino acid' generates potent inhibitors of PCSK8 and PCSK4. This represents a novel approach for future development of inhibitors of PCSK or other enzymes. PMID:25881830

  5. Implication of the proprotein convertases furin, PC5 and PC7 in the cleavage of surface glycoproteins of Hong Kong, Ebola and respiratory syncytial viruses: a comparative analysis with fluorogenic peptides.

    PubMed Central

    Basak, A; Zhong, M; Munzer, J S; Chrétien, M; Seidah, N G

    2001-01-01

    Fluorogenic peptides encompassing the processing sites of envelope glycoproteins of the infectious influenza A Hong Kong virus (HKV), Ebola virus (EBOV) and respiratory syncytial virus (RSV) were tested for cleavage by soluble recombinants of the proprotein convertases furin, PC5 and PC7. Kinetic studies with these intramolecularly quenched fluorogenic peptides revealed selective cleavages at the physiological dibasic sites. The HKV peptide is cleaved by both furin and PC5 with similar efficacy; in comparison, PC7 cleaves this substrate poorly. In contrast with the basic tetrapeptide insertion within the haemagglutinin sequence of HKV, two other dipeptide insertions revealed a poorer cleavage with a similar rank order of potency. These results demonstrate that the N-terminal RERR insertion to the wild-type avian RKKR downward arrow sequence is functionally significant, and suggest that the approx. 5-fold increase in cleavage efficacy contributes to the high infectivity of the H5N1 virus subtype. With regard to RSV peptide processing, PC7 is twice as effective as PC5 and furin. The EBOV peptide was processed with similar efficiency by the three enzymes. Our observations that all of these cleavages can be effectively inhibited by a plant andrographolide derivative at 250 microM or less might aid in the design of potent convertase inhibitors as alternative antiviral therapies. PMID:11171050

  6. cDNA structure, tissue distribution, and chromosomal localization of rat PC7, a novel mammalian proprotein convertase closest to yeast kexin-like proteinases.

    PubMed Central

    Seidah, N G; Hamelin, J; Mamarbachi, M; Dong, W; Tardos, H; Mbikay, M; Chretien, M; Day, R

    1996-01-01

    By using reverse transcription-coupled PCR on rat anterior pituitary RNA, we isolated a 285-bp cDNA coding for a novel subtilisin/kexin-like protein convertase (PC), called rat (r) PC7. By screening rat spleen and PC12 cell lambda gt11 cDNA libraries, we obtained a composite 3.5-kb full-length cDNA sequence of rPC7. The open reading frame codes for a prepro-PC with a 36-amino acid signal peptide, a 104-amino acid prosegment ending with a cleavable RAKR sequence, and a 747-amino acid type I membrane-bound glycoprotein, representing the mature form of this serine proteinase. Phylogenetic analysis suggests that PC7 represents the most divergent enzyme of the mammalian convertase family and that it is the closest member to the yeast convertases krp and kexin. Northern blot analyses demonstrated a widespread expression with the richest source of rPC7 mRNA being the colon and lymphoid-associated tissues. In situ hybridization revealed a distinctive tissue distribution that sometimes overlaps with that of furin, suggesting that PC7 has widespread proteolytic functions. The gene for PC7 (Pcsk7) was mapped to mouse chromosome 9 by linkage analysis of an interspecific backcross DNA panel. Images Fig. 3 Fig. 4 Fig. 5 PMID:8622945

  7. A visible light induced photoelectrochemical aptsensor constructed by aligned ZnO@CdTe core shell nanocable arrays/carboxylated g-C3N4 for the detection of Proprotein convertase subtilisin/kexin type 6 gene.

    PubMed

    Pang, Xuehui; Pan, Jihong; Gao, Picheng; Wang, Youying; Wang, Liguo; Du, Bin; Wei, Qin

    2015-12-15

    It was reported that Proprotein convertase subtilisin/kexin type 6 (PCSK6) can promote the progression of rheumatoid arthritis to a higher aggressive status. In this work, a novel visible light induced photoelectrochemical (PEC) platform was designed to detect PCSK6 gene. ZnO@CdTe nanocable arrays/carboxylated g-C3N4 used as the PEC signal generator. Hexagonal ZnO nanorods grew on ITO electrode firstly. CdTe were then electrodeposited on the ZnO nanorods surface to enhance the photogenerated h(+)/e(-) separation efficiency. Carboxylated g-C3N4 was utilized to improve h(+)/e(-) separation efficiency and anchor the capture probes of PCSK6 gene by the covalent bonding effect. The 5' and 3' primers captured PCSK6 ssDNA by the specific recognition. The linear range was 10 pg/mL to 20.0 ng/mL with a detection limit of 2 pg/mL. PMID:26119758

  8. Serum proprotein convertase subtilisin/kexin type 9 concentration is not increased by plant stanol ester consumption in normo- to moderately hypercholesterolaemic non-obese subjects. The BLOOD FLOW intervention study.

    PubMed

    Simonen, Piia; Stenman, Ulf-Håkan; Gylling, Helena

    2015-09-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates low-density lipoprotein (LDL) cholesterol (LDL-C) metabolism by targeting LDL receptors for degradation. Statins increase serum PCSK9 concentration limiting the potential of statins to reduce LDL-C, whereas ezetimibe, inhibitor of cholesterol absorption, has ambiguous effects on circulating PCSK9 levels. Plant stanols also reduce cholesterol absorption, but their effect on serum PCSK9 concentration is not known. Therefore, we performed a controlled, randomized, double-blind study, in which 92 normo- to moderately hypercholesterolaemic subjects (35 males and 57 females) consumed vegetable-oil spread 20 g/day enriched (plant stanol group, n=46) or not (control group, n=46) with plant stanols 3 g/day as ester for 6 months. Fasting blood samples were drawn at baseline and at the end of the study. Serum PCSK9 concentration was analysed with Quantikine Elisa Immunoassay, serum and lipoprotein lipids enzymatically and serum non-cholesterol sterols with GLC. At baseline, PCSK9 concentration varied from 91 to 716 ng/ml with a mean value of 278±11 (S.E.M.) ng/ml with no gender difference. It correlated with serum and LDL-C, serum triglycerides, age, body mass index (BMI) and plasma glucose concentration, but not with variables of cholesterol metabolism when adjusted to serum cholesterol. Plant stanols reduced LDL-C by 10% from controls (P<0.05), but PCSK9 levels were unchanged and did not differ between the groups. In conclusion, the present study demonstrated for the first time that inhibition of cholesterol absorption with plant stanol esters did not affect serum PCSK9 concentration. Thus, plant stanol esters provide an efficient dietary means to lower LDL-C without interfering with the PCSK9 metabolism and in this regard the LDL receptor-mediated cellular cholesterol uptake and removal. PMID:25857271

  9. CdSe quantum dot-functionalized TiO2 nanohybrids as a visible light induced photoelectrochemical platform for the detection of proprotein convertase subtilisin/kexin type 6.

    PubMed

    Pang, Xuehui; Pan, Jihong; Wang, Lin; Ren, Wei; Gao, Picheng; Wei, Qin; Du, Bin

    2015-09-15

    Proprotein convertase subtilisin/kexin type 6 (PCSK6) plays a major role in promoting the progression of rheumatoid arthritis to a higher aggressive status. A novel highly sensitive photoelectrochemical platform was developed for the detection of PCSK6 by using CdSe quantum dots (QDs)-functionalized TiO2 nanoparticles (NPs) nanohybrids (TiO2@CdSe) as the photo-to-electron conversion medium. TiO2@CdSe showed excellent visible-light absorbency, and much higher photoelectrochemical activity than both CdSe QDs and TiO2 NPs. The 5' and 3' primers of PCSK6 ssDNA acted as capture probes to realize the detection of PCSK6 ssDNA by the specific recognition. The capture probes can be fixed by poly-l-lysine (PLL) through positively strong electrostatic attraction and the carboxyl group of TiO2@CdSe nanohybrids. PLL was electropolymerized on ITO electrode by cyclic voltammetry (CV). Simultaneously, the amino group of PLL can interact with the carboxyl group of TiO2@CdSe nanohybrids to enhance the stability of the photoelectrochemical signal. The fabricated aptsensor exhibited excellent performance towards PCSK6 with a wide linear range (0.5 pg/mL to 80.0 ng/mL) and a detection limit of 0.1 fg/mL. This work opens up a new detection platform for PCSK6 with good sensitivity, reproducibility and stability. PMID:25889349

  10. Ectopically expressed pro-group X secretory phospholipase A2 is proteolytically activated in mouse adrenal cells by furin-like proprotein convertases: implications for the regulation of adrenal steroidogenesis.

    PubMed

    Layne, Joseph D; Shridas, Preetha; Webb, Nancy R

    2015-03-20

    Group X secretory phospholipase A2 (GX sPLA2) hydrolyzes mammalian cell membranes, liberating free fatty acids and lysophospholipids. GX sPLA2 is produced as a pro-enzyme (pro-GX sPLA2) that contains an N-terminal 11-amino acid propeptide ending in a dibasic motif, suggesting cleavage by a furin-like proprotein convertase (PC). Although propeptide cleavage is clearly required for enzymatic activity, the protease(s) responsible for pro-GX sPLA2 activation have not been identified. We previously reported that GX sPLA2 negatively regulates adrenal glucocorticoid production, likely by suppressing liver X receptor-mediated activation of steroidogenic acute regulatory protein expression. In this study, using a FLAG epitope-tagged pro-GX sPLA2 expression construct (FLAG-pro-GX sPLA2), we determined that adrenocorticotropic hormone (ACTH) enhanced FLAG-pro-GX sPLA2 processing and phospholipase activity secreted by Y1 adrenal cells. ACTH increased the expression of furin and PCSK6, but not other members of the PC family, in Y1 cells. Overexpression of furin and PCSK6 in HEK 293 cells significantly enhanced FLAG-pro-GX sPLA2 processing, whereas siRNA-mediated knockdown of both PCs almost completely abolished FLAG-pro-GX sPLA2 processing in Y1 cells. Expression of either furin or PCSK6 enhanced the ability of GX sPLA2 to suppress liver X receptor reporter activity. The PC inhibitor decanoyl-Arg-Val-Lys-Arg-chloromethyl ketone significantly suppressed FLAG-pro-GX sPLA2 processing and sPLA2 activity in Y1 cells, and it significantly attenuated GX sPLA2-dependent inhibition of steroidogenic acute regulatory protein expression and progesterone production. These findings provide strong evidence that pro-GX sPLA2 is a substrate for furin and PCSK6 proteolytic processing and define a novel mechanism for regulating corticosteroid production in adrenal cells. PMID:25623068

  11. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial

    PubMed Central

    Fitzgerald, Kevin; Frank-Kamenetsky, Maria; Shulga-Morskaya, Svetlana; Liebow, Abigail; Bettencourt, Brian R; Sutherland, Jessica E; Hutabarat, Renta M; Clausen, Valerie A; Karsten, Verena; Cehelsky, Jeffrey; Nochur, Saraswathy V; Kotelianski, Victor; Horton, Jay; Mant, Timothy; Chiesa, Joseph; Ritter, James; Munisamy, Malathy; Vaishnaw, Akshay K; Gollob, Jared A; Simon, Amy

    2015-01-01

    Summary Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds to LDL receptors, leading to their degradation. Genetics studies have shown that loss-of-function mutations in PCSK9 result in reduced plasma LDL cholesterol and decreased risk of coronary heart disease. We aimed to investigate the safety and efficacy of ALN-PCS, a small interfering RNA that inhibits PCSK9 synthesis, in healthy volunteers with raised cholesterol who were not on lipid-lowering treatment. Methods We did a randomised, single-blind, placebo-controlled, phase 1 dose-escalation study in healthy adult volunteers with serum LDL cholesterol of 3·00 mmol/L or higher. Participants were randomly assigned in a 3:1 ratio by computer algorithm to receive one dose of intravenous ALN-PCS (with doses ranging from 0·015 to 0·400 mg/kg) or placebo. The primary endpoint was safety and tolerability of ALN-PCS. Secondary endpoints were the pharmacokinetic characteristics of ALN-PCS and its pharmacodynamic effects on PCSK9 and LDL cholesterol. Study participants were masked to treatment assignment. Analysis was per protocol and we used ANCOVA to analyse pharmacodynamic endpoint data. This trial is registered with ClinicalTrials.gov, number NCT01437059. Findings Of 32 participants, 24 were randomly allocated to receive a single dose of ALN-PCS (0·015 mg/kg [n=3], 0·045 mg/kg [n=3], 0·090 mg/kg [n=3], 0·150 mg/kg [n=3], 0·250 mg/kg [n=6], or 0·400 mg/kg [n=6]) and eight to placebo. The proportions of patients affected by treatment-emergent adverse events were similar in the ALN-PCS and placebo groups (19 [79%] vs seven [88%]). ALN-PCS was rapidly distributed, with peak concentration and area under the curve (0 to last measurement) increasing in a roughly dose-proportional way across the dose range tested. In the group given 0·400 mg/kg of ALN-PCS, treatment resulted in a mean 70% reduction in circulating PCSK9 plasma protein (p<0·0001) and a mean 40% reduction in LDL cholesterol from

  12. Synthetic Small-Molecule Prohormone Convertase 2 Inhibitors

    PubMed Central

    Kowalska, Dorota; Liu, Jin; Appel, Jon R.; Ozawa, Akihiko; Nefzi, Adel; Mackin, Robert B.; Houghten, Richard A.; Lindberg, Iris

    2009-01-01

    The proprotein convertases are believed to be responsible for the proteolytic maturation of a large number of peptide hormone precursors. Although potent furin inhibitors have been identified, thus far, no small-molecule prohormone convertase 1/3 or prohormone convertase 2 (PC2) inhibitors have been described. After screening 38 small-molecule positional scanning libraries against recombinant mouse PC2, two promising chemical scaffolds were identified: bicyclic guanidines, and pyrrolidine bis-piperazines. A set of individual compounds was designed from each library and tested against PC2. Pyrrolidine bis-piperazines were irreversible, time-dependent inhibitors of PC2, exhibiting noncompetitive inhibition kinetics; the most potent inhibitor exhibited a Ki value for PC2 of 0.54 μM. In contrast, the most potent bicyclic guanidine inhibitor exhibited a Ki value of 3.3 μM. Cross-reactivity with other convertases was limited: pyrrolidine bis-piperazines exhibited Ki values greater than 25 μM for PC1/3 or furin, whereas the Ki values of bicyclic guanidines for these other convertases were more than 15 μM. We conclude that pyrrolidine bis-piperazines and bicyclic guanidines represent promising initial leads for the optimization of therapeutically active PC2 inhibitors. PC2-specific inhibitors may be useful in the pharmacological blockade of PC2-dependent cleavage events, such as glucagon production in the pancreas and ectopic peptide production in small-cell carcinoma, and to study PC2-dependent proteolytic events, such as opioid peptide production. PMID:19074544

  13. A model for the structure of the P domains in the subtilisin-like prohormone convertases

    PubMed Central

    Lipkind, Gregory M.; Zhou, An; Steiner, Donald F.

    1998-01-01

    The proprotein convertases are a family of at least seven calcium-dependent endoproteases that process a wide variety of precursor proteins in the secretory pathway. All members of this family possess an N-terminal proregion, a subtilisin-like catalytic module, and an additional downstream well-conserved region of ≈150 amino acid residues, the P domain, which is not found in any other subtilase. The pro and catalytic domains cannot be expressed in the absence of the P domains; their thermodynamic instability may be attributable to the presence of large numbers of negatively charged Glu and Asp side chains in the substrate binding region for recognition of multibasic residue cleavage sites. Based on secondary structure predictions, we here propose that the P domains consist of 8-stranded β-barrels with well-organized inner hydrophobic cores, and therefore are independently folded components of the proprotein convertases. We hypothesize further that the P domains are integrated through strong hydrophobic interactions with the catalytic domains, conferring structural stability and regulating the properties and activity of the convertases. A molecular model of these interdomain interactions is proposed in this report. PMID:9636145

  14. Potential role of proprotein convertase SKI-1 in the mineralization of primary bone.

    PubMed

    Gorski, Jeff P; Huffman, Nichole T; Cui, Chaoying; Henderson, Ellen P; Midura, Ronald J; Seidah, Nabil G

    2009-01-01

    The biochemical mechanism controlling nucleation of mineral crystals in developing bone, along with the growth and propagation of these crystals once formed, remains poorly understood. To define the nucleation mechanism, a proteomics analysis was begun on isolated biomineralization foci (BMF), sites of initial crystal nucleation in osteoblastic cell cultures and in primary bone. Comparative analyses of the protein profile for mineralized BMF with that for total osteoblast cultures revealed the latter were enriched in several proteins including BAG-75 and BSP, as well as fragments of each. When 12 protease inhibitors were added separately to UMR 106-01 osteoblastic cultures, only the serine protease inhibitor 4-(2-aminoethyl) benzenesulfonyl fluoride hydrochloride (AEBSF) blocked cleavage of BAG-75 and BSP, and prevented mineral crystal nucleation within BMF. Consideration of the specificities of the inhibitors tested and the fact that AEBSF inhibition was not dependent upon inclusion of FBS in the culture media indicated that mineral nucleation does not require serine protease plasmin, thrombin, kallikrein, urokinase, C1s or furin. In contrast, SKI-1 (S1P or site-1) is a membrane-bound serine protease inhibitable by AEBSF. We show here for the first time that mineralizing UMR 106 cells express a 98-kDa active, soluble form of SKI-1 within BMF. In contrast, nonmineralizing UMR cells appear to differentially process SKI-1 into smaller immunoreactive fragments (<35 kDa). These findings suggest that SKI-1 plays a direct or indirect role in assembly of functional nucleation complexes containing BAG-75 and BSP and their fragments, thus facilitating initial mineral nucleation within these biomineralization foci. PMID:18728345

  15. Differential expression of the pro-natriuretic peptide convertases corin and furin in experimental heart failure and atrial fibrosis

    PubMed Central

    Boerrigter, Guido; Huntley, Brenda K.; Sangaralingham, S. Jeson; McKie, Paul M.; Harty, Gail J.; Harders, Gerald E.; Burnett, John C.

    2013-01-01

    In heart failure (HF), the cardiac hormone natriuretic peptides (NPs) atrial (ANP), B-type (BNP), and C-type (CNP) play a key role to protect cardiac remodeling. The proprotein convertases corin and furin process their respective pro-NPs into active NPs. Here we define in a canine model of HF furin and corin gene and protein expression in normal and failing left atrium (LA) or ventricle (LV) testing the hypothesis that the NP proproteins convertases production is altered in experimental HF. Experimental canine HF was produced by rapid right ventricular pacing for 10 days. NPs, furin, and corin mRNA expression were determined by quantitative RT-PCR. Protein concentration or expression was determined by immunostaining, radioimmunoassay, or Western blot. Furin and corin proteins were present in normal canine LA and LV myocardium and vasculature and in smooth muscle cells. In normal canines, expression of NPs was dominant in the atrium compared with the ventricle. In experimental early stage HF characterized with marked atrial fibrosis, ANP, BNP, and CNP mRNA, and protein concentrations were higher in HF LA but not HF LV compared with normals. In LA, corin mRNA and protein expressions in HF were lower, whereas furin mRNA and protein expressions were higher than normals. NPs and furin expressions were augmented in the atrium in experimental early stage HF and, conversely, corin mRNA and protein expressions were decreased with atrial remodeling. Selective changes of these NP convertases may have significance in the regulation of pro-NP processing and atrial remodeling in early stage HF. PMID:23152112

  16. Nucleobindin-1 encodes a nesfatin-1-like peptide that stimulates insulin secretion.

    PubMed

    Ramesh, Naresh; Mohan, Haneesha; Unniappan, Suraj

    2015-05-15

    Nesfatin-1 (82 amino acid) is an anorexigenic and insulinotropic peptide encoded in a secreted precursor, nucleobindin-2 (NUCB2). Nucleobindin-1 (NUCB1) is a protein with very high sequence similarity to NUCB2. We hypothesized that a nesfatin-1 like peptide (NLP) is encoded in NUCB1, and this peptide is biologically active. In silico analysis found a signal peptide cleavage site at position 25 (Arginine) and 26 (Valine) preceding the NLP region in NUCB1 sequence, and potential proprotein convertase cleavage sites at Lys-Arg (KR), forming a 77 amino acid NLP. RT-PCR studies found NUCB1 mRNA in both pancreas and MIN6 cells. NUCB1-like immunoreactivity was detected in mouse insulinoma (MIN6) cells, and pancreatic islet beta cells of mice. In order to determine the biological activity of NLP, MIN6 cells were incubated with synthetic rat NLP. NLP (10nM and 100nM) upregulated preproinsulin mRNA expression and insulin secretion at 1h post-incubation. In identical experiments using MIN6 cells, a scrambled peptide based on the NLP sequence did not elicit any effects on preproinsulin mRNA expression or insulin secretion. From this result, it is clear that an intact NLP sequence is required for its biological activity. NLP appears as another endogenous insulinotropic peptide encoded in NUCB1. PMID:25907657

  17. Differential localization of prohormone convertases PC1 and PC2 in two distinct types of secretory granules in rat pituitary gonadotrophs.

    PubMed

    Uehara, M; Yaoi, Y; Suzuki, M; Takata, K; Tanaka, S

    2001-04-01

    Prohormone convertases PC1 and PC2 are endoproteases involved in prohormone cleavage at pairs of basic amino acids. There is a report that prohormone convertase exists in the rat anterior pituitary gonadotrophs, where it had previously been considered that proprotein processing does not take place. In addition to luteinizing hormone and follicle-stimulating hormone, rat pituitary gonadotrophs contain chromogranin A (CgA) and secretogranin II (SgII), two members of the family of granin proteins, which have proteolytic sites in their molecules. In the present study we examined whether there is a close correlation between subcellular localization of prohormone convertases and granin proteins. Ultrathin sections of rat anterior pituitary were immunolabeled with anti-PC1 or -PC2 antisera and then stained with immunogold. Immunogold particles for PC1 were exclusively found in large, lucent secretory granules, whereas those for PC2 were seen in both large, lucent and small, dense granules. The double-immunolabeling also demonstrated colocalization of PC2 and SgII in small, dense granules and of PC1, PC2, and CgA in large, lucent granules. These immunocytochemical results suggest that PC2 may be involved in the proteolytic processing of SgII and that both PC1 and PC2 may be necessary to process CgA. PMID:11383885

  18. The mouse matrix metalloproteinase, epilysin (MMP-28), is alternatively spliced and processed by a furin-like proprotein convertase.

    PubMed Central

    Illman, Sara A; Keski-Oja, Jorma; Parks, William C; Lohi, Jouko

    2003-01-01

    Epilysin (MMP-28) is a recently identified member of the matrix metalloproteinase (MMP) family. To explore the expression of epilysin in vivo and to gain insight into its biological functions, we have cloned the mouse epilysin cDNA and determined its expression. The amino acid sequence of the mouse protein is 85% identical with the human sequence and contains conserved features such as an RKKR furin-activation sequence following the prodomain. Unexpectedly, we found two alternatively spliced forms of the epilysin mRNA lacking 30 and 72 nt at the beginning of the seventh exon coding for part of the haemopexin domain. Expression of recombinant epilysin in HT-1080 fibrosarcoma cells indicated that epilysin was secreted as a major 48 kDa form and a minor 58 kDa form. Expression of the 58 kDa form was increased by a synthetic furin inhibitor at the expense of the 48 kDa form, suggesting that furin cleaves and activates epilysin. Epilysin mRNA was detected in a number of mouse tissues, with the highest expression in the lung, placenta, heart and uterus, and lower levels in the testis and gastrointestinal tract. The wide expression of epilysin in intact, healthy tissues suggests that this MMP functions in physiological tissue homoeostasis and turnover. PMID:12803542

  19. Mammalian subtilisin/kexin isozyme SKI-1: A widely expressed proprotein convertase with a unique cleavage specificity and cellular localization

    PubMed Central

    Seidah, Nabil G.; Mowla, Seyed J.; Hamelin, Josée; Mamarbachi, Aida M.; Benjannet, Suzanne; Touré, Barry B.; Basak, Ajoy; Munzer, Jon Scott; Marcinkiewicz, Jadwiga; Zhong, Mei; Barale, Jean-Christophe; Lazure, Claude; Murphy, Richard A.; Chrétien, Michel; Marcinkiewicz, Mieczyslaw

    1999-01-01

    Using reverse transcriptase–PCR and degenerate oligonucleotides derived from the active-site residues of subtilisin/kexin-like serine proteinases, we have identified a highly conserved and phylogenetically ancestral human, rat, and mouse type I membrane-bound proteinase called subtilisin/kexin-isozyme-1 (SKI-1). Computer databank searches reveal that human SKI-1 was cloned previously but with no identified function. In situ hybridization demonstrates that SKI-1 mRNA is present in most tissues and cells. Cleavage specificity studies show that SKI-1 generates a 28-kDa product from the 32-kDa brain-derived neurotrophic factor precursor, cleaving at an RGLT↓SL bond. In the endoplasmic reticulum of either LoVo or HK293 cells, proSKI-1 is processed into two membrane-bound forms of SKI-1 (120 and 106 kDa) differing by the nature of their N-glycosylation. Late along the secretory pathway some of the membrane-bound enzyme is shed into the medium as a 98-kDa form. Immunocytochemical analysis of stably transfected HK293 cells shows that SKI-1 is present in the Golgi apparatus and within small punctate structures reminiscent of endosomes. In vitro studies suggest that SKI-1 is a Ca2+-dependent serine proteinase exhibiting a wide pH optimum for cleavage of pro-brain-derived neurotrophic factor. PMID:9990022

  20. The Drosophila DPP signal is produced by cleavage of its proprotein at evolutionary diversified furin-recognition sites

    PubMed Central

    Künnapuu, Jaana; Björkgren, Ida; Shimmi, Osamu

    2009-01-01

    Maturation of bone morphogenetic proteins (BMPs) requires cleavage of their precursor proteins by furin-type proprotein convertases. Here, we find that cleavage sites of the BMP2/4/decapentaplegic (DPP) subfamily have been evolutionary diversified and can be categorized into 4 different types. Cnidaria BMP2/4/DPP is considered to be a prototype containing only 1 furin site. Bilateria BMP2/4/DPP acquired an additional cleavage site with either the combination of minimal–optimal or optimal–optimal furin sites. DPPs belonging to Diptera, such as Drosophila and mosquito, and Lepidoptera of silkworm contain a third cleavage site between the 2 optimal furin sites. We studied how the 3 furin sites (FSI–III) of Drosophila DPP coordinate maturation of ligands and contribute to signals in vivo. Combining mutational analysis of furin-recognition sites and RNAi experiments, we found that the Drosophila DPP precursor is initially cleaved at an upstream furin-recognition site (FSII), with consequent cleavages at 2 furin sites (FSI and FSIII). Both Dfurin1 and Dfurin2 are involved in the processing of DPP proproteins. Biochemical and genetic analyses using cleavage mutants of DPP suggest the first cleavage at FSII to be critical and sufficient for long-range DPP signaling. Our data suggest that the Drosophila DPP precursor is cleaved in a different manner from vertebrate BMP4 even though they are functional orthologs. This indicates that the furin-cleavage sites in BMP2/4/DPP precursors are tolerant to mutations acquired through evolution and have adapted to different systems in diversified species. PMID:19433798

  1. Furin is the primary in vivo convertase of angiopoietin-like 3 and endothelial lipase in hepatocytes.

    PubMed

    Essalmani, Rachid; Susan-Resiga, Delia; Chamberland, Ann; Asselin, Marie-Claude; Canuel, Maryssa; Constam, Daniel; Creemers, John W; Day, Robert; Gauthier, Dany; Prat, Annik; Seidah, Nabil G

    2013-09-13

    The proprotein convertases (PCs) furin, PC5/6, and PACE4 exhibit unique and/or complementary functions. Their knock-out (KO) in mice resulted in strong and specific phenotypes demonstrating that, in vivo, these PCs are unique and essential during development. However, they also exhibit redundant functions. Liver angiopoietin-like 3 (ANGPTL3) inhibits lipolysis by binding to lipoprotein lipases. It is found in the plasma as full length and truncated forms. The latter is more active and generated by cleavage at a furin-like site. Endothelial lipase (EL) binds heparin sulfate proteoglycans on cell surfaces and catalyzes the hydrolysis of HDL phospholipids. EL activity is regulated by two endogenous inhibitors, ANGPTL3 and ANGPTL4, and by PCs that inactivate EL through cleavage releasing the N-terminal catalytic and C-terminal lipid-binding domains. Herein, because furin and PC5/6 complete KOs are lethal, we used mice lacking furin or PC5/6 specifically in hepatocytes (hKO) or mice completely lacking PACE4. In primary hepatocytes, ANGPTL3 was processed into a shorter form of ANGPTL3 intracellularly by furin only, and extracellularly mainly by PACE4. In vivo, the absence of furin in hepatocytes reduced by ∼50% the circulating levels of cleaved ANGPTL3, while the lack of PACE4 had only a minor effect. Analysis of the EL processing in primary hepatocytes and in vivo revealed that it is mostly cleaved by furin. However, the lack of furin or PC5/6 in hepatocytes and complete PACE4 KO did not appreciably modify plasma HDL levels or EL activity. Thus, inhibition of furin in liver would not be expected to modify the plasma lipid profiles. PMID:23918928

  2. Cleavage of a Neuroinvasive Human Respiratory Virus Spike Glycoprotein by Proprotein Convertases Modulates Neurovirulence and Virus Spread within the Central Nervous System

    PubMed Central

    Meessen-Pinard, Mathieu; Dubé, Mathieu; Day, Robert; Seidah, Nabil G.; Talbot, Pierre J.

    2015-01-01

    Human coronaviruses (HCoV) are respiratory pathogens that may be associated with the development of neurological diseases, in view of their neuroinvasive and neurotropic properties. The viral spike (S) glycoprotein is a major virulence factor for several coronavirus species, including the OC43 strain of HCoV (HCoV-OC43). In an attempt to study the role of this protein in virus spread within the central nervous system (CNS) and neurovirulence, as well as to identify amino acid residues important for such functions, we compared the sequence of the S gene found in the laboratory reference strain HCoV-OC43 ATCC VR-759 to S sequences of viruses detected in clinical isolates from the human respiratory tract. We identified one predominant mutation at amino acid 758 (from RRSR↓ G758 to RRSR↓R758), which introduces a putative furin-like cleavage (↓) site. Using a molecular cDNA infectious clone to generate a corresponding recombinant virus, we show for the first time that such point mutation in the HCoV-OC43 S glycoprotein creates a functional cleavage site between the S1 and S2 portions of the S protein. While the corresponding recombinant virus retained its neuroinvasive properties, this mutation led to decreased neurovirulence while potentially modifying the mode of virus spread, likely leading to a limited dissemination within the CNS. Taken together, these results are consistent with the adaptation of HCoV-OC43 to the CNS environment, resulting from the selection of quasi-species harboring mutations that lead to amino acid changes in viral genes, like the S gene in HCoV-OC43, which may contribute to a more efficient establishment of a less pathogenic but persistent CNS infection. This adaptative mechanism could potentially be associated with human encephalitis or other neurological degenerative pathologies. PMID:26545254

  3. MBTPS1/SKI-1/S1P proprotein convertase is required for ECM signaling and axial elongation during somitogenesis and vertebral development†

    PubMed Central

    Achilleos, Annita; Huffman, Nichole T.; Marcinkiewicyz, Edwidge; Seidah, Nabil G.; Chen, Qian; Dallas, Sarah L.; Trainor, Paul A.; Gorski, Jeff P.

    2015-01-01

    Caudal regression syndrome (sacral agenesis), which impairs development of the caudal region of the body, occurs with a frequency of about 2 live births per 100 000 newborns although this incidence rises to 1 in 350 infants born to mothers with gestational diabetes. The lower back and limbs can be affected as well as the genitourinary and gastrointestinal tracts. The axial skeleton is formed during embryogenesis through the process of somitogenesis in which the paraxial mesoderm periodically segments into bilateral tissue blocks, called somites. Somites are the precursors of vertebrae and associated muscle, tendons and dorsal dermis. Vertebral anomalies in caudal regression syndrome may arise through perturbation of somitogenesis or, alternatively, could result from defective bone formation and patterning. We discovered that MBTPS1/SKI-1/S1P, which proteolytically activates a class of transmembrane transcription factors, plays a critical role in somitogenesis and the pathogenesis of lumbar/sacral vertebral anomalies. Conditional deletion of Mbtps1 yields a viable mouse with misshapen, fused and reduced number of lumbar and sacral vertebrae, under-developed hind limb bones and a kinky, shortened tail. We show that Mbtps1 is required to (i) maintain the Fgf8 ‘wavefront’ in the presomitic mesoderm that underpins axial elongation, (ii) sustain the Lfng oscillatory ‘clock’ activity that governs the periodicity of somite formation and (iii) preserve the composition and character of the somitic extracellular matrix containing fibronectin, fibrillin2 and laminin. Based on this spinal phenotype and known functions of MBTPS1, we reason that loss-of-function mutations in Mbtps1 may cause the etiology of caudal regression syndrome. PMID:25652402

  4. [Severe hypercholesterolaemia - when to use the proprotein convertase subtilisin-kexin type 9 protease inhibitors (PCSK9 inhibitors)? Polish Society of Cardiology experts' group statement].

    PubMed

    Cybulska, Barbara; Pająk, Andrzej; Ponikowski, Piotr; Rynkiewicz, Andrzej; Stępińska, Janina; Średniawa, Beata; Kalarus, Zbigniew; Gaciong, Zbigniew; Hoffman, Piotr; Jankowski, Piotr; Kłosiewicz-Latoszek, Longina; Kaźmierczak, Jarosław; Mitręga, Katarzyna; Opolski, Grzegorz

    2016-01-01

    The severe hypercholesterolaemia can be recognised when low density lipoprotein cholesterol (LDL-C) serum levels are equal to or above 5 mmol/L (≥ 190 mg/dL). The prevalence of LDL-C ≥ 5 mmol/L is 3.8% in Polish population aged 18-79 years. Among these adults there are patients with familial hypercholesterolaemia (FH). According to meta-analysis of 6 Polish population surveys prevalence of heterozygous FH (HeFH) diagnosed using Dutch Lipid Clinic criteria is 0.4% (95% Cl 0.28-0.53%) in men and women aged 20-74 years, i.e. one in every 250 people. As HeFH is a wellknown cause of premature coronary heart disease the rigorous treatment targets for LDL-C have been established in clinical guidelines. Their achivements, even with a high dose of high efficacy statin therapy is difficult or even imposible. New strong hypolipidaemic drugs i.e. PCSK9 inhibitors have been initiated against this chalange. Both drugs, evolocumab and alirocumab, have been extensively studied in numerous phase 2 and phase 3 trials. Fewer studies with bococizumab are available until now. The PCSK9 inhibitors, as monotherapy as well in combination with statins were associated with mean LDL-C reduction about 60%. It means that the majority of patients (70-90%) with severe hypercholesterolaemia (including HeFH), treated with statins, after addition of PCSK9 inhibitors were able to achive an LDL-C < 2.5 mmol/L (< 100 mg/dL) or < 1.8 mmol/L (< 70 mg/dL) level. Another group of patients who may benefit from PCSK9 inhibitors include those who need lipid lowering therapy, but who are statin intolerant, especially because of statin-associated muscle symptoms (SAMS). In our statement we have accepted the diagnosis of SAMS proposed recently by European Atherosclerosis Society. Today the longest clinical trial with evolocumab (11 months) was the open OSLER study, and with alirocumab ODYSSEY LONG TERM (78 weeks). In the first one the reduction of cardiovascular events by 53% (95% Cl 22-72%) was observed, and in the second one by 48% (10-69%). Neurocognitive events were reported more frequently with both drugs than with placebo. This adverse effect will be the subject of observation in ongoing studies. We still await the results of 4 ongoing large placebo controlled phase 3 trials investigating whether PCSK9 inhibitors on background of statin therapy reduce cardiovascular events. Meanwhile evolocumab, as well as alirocumab have been accepted to use in clinical practice by European Medicine Agency. In this situation the experts of Polish Society of Cardiology have prepared the statement on the use PCSK9 inhibitors with indication in the first place for HeFH patients, statin intolerant and those at high risk who are not able to reach LDL-C target level with a high potent high dose statin. PMID:27098076

  5. Two independent targeting signals in the cytoplasmic domain determine trans-Golgi network localization and endosomal trafficking of the proprotein convertase furin.

    PubMed Central

    Schäfer, W; Stroh, A; Berghöfer, S; Seiler, J; Vey, M; Kruse, M L; Kern, H F; Klenk, H D; Garten, W

    1995-01-01

    Furin, a subtilisin-like eukaryotic endoprotease, is responsible for proteolytic cleavage of cellular and viral proteins transported via the constitutive secretory pathway. Cleavage occurs at the C-terminus of basic amino acid sequences, such as R-X-K/R-R and R-X-X-R. Furin was found predominantly in the trans-Golgi network (TGN), but also in clathrin-coated vesicles dispatched from the TGN, on the plasma membrane as an integral membrane protein and in the medium as an anchorless enzyme. When furin was vectorially expressed in normal rat kidney (NRK) cells it accumulated in the TGN similarly to the endogenous glycoprotein TGN38, often used as a TGN marker protein. The signals determining TGN targeting of furin were investigated by mutational analysis of the cytoplasmic tail of furin and by using the hemagglutinin (HA) of fowl plague virus, a protein with cell surface destination, as a reporter molecule, in which membrane anchor and cytoplasmic tail were replaced by the respective domains of furin. The membrane-spanning domain of furin grafted to HA does not localize the chimeric molecule to the TGN, whereas the cytoplasmic domain does. Results obtained on furin mutants with substitutions and deletions of amino acids in the cytoplasmic tail indicate that wild-type furin is concentrated in the TGN by a mechanism involving two independent targeting signals, which consist of the acidic peptide CPSDSEEDEG783 and the tetrapeptide YKGL765. The acidic signal in the cytoplasmic domain of a HA-furin chimera is necessary and sufficient to localize the reporter molecule to the TGN, whereas YKGL is a determinant for targeting to the endosomes. The data support the concept that the acidic signal, which is the dominant one, retains furin in the TGN, whereas the YKGL motif acts as a retrieval signal for furin that has escaped to the cell surface. Images PMID:7781597

  6. A novel method for direct measurement of complement convertases activity in human serum.

    PubMed

    Blom, A M; Volokhina, E B; Fransson, V; Strömberg, P; Berghard, L; Viktorelius, M; Mollnes, T E; López-Trascasa, M; van den Heuvel, L P; Goodship, T H; Marchbank, K J; Okroj, M

    2014-10-01

    Complement convertases are enzymatic complexes that play a central role in sustaining and amplification of the complement cascade. Impairment of complement function leads directly or indirectly to pathological conditions, including higher infection rate, kidney diseases, autoimmune- or neurodegenerative diseases and ischaemia-reperfusion injury. An assay for direct measurement of activity of the convertases in patient sera is not available. Existing assays testing convertase function are based on purified complement components and, thus, convertase formation occurs under non-physiological conditions. We designed a new assay, in which C5 blocking compounds enabled separation of the complement cascade into two phases: the first ending at the stage of C5 convertases and the second ending with membrane attack complex formation. The use of rabbit erythrocytes or antibody-sensitized sheep erythrocytes as the platforms for convertase formation enabled easy readout based on measurement of haemolysis. Thus, properties of patient sera could be studied directly regarding convertase activity and membrane attack complex formation. Another advantage of this assay was the possibility to screen for host factors such as C3 nephritic factor and other anti-complement autoantibodies, or gain-of-function mutations, which prolong the half-life of complement convertases. Herein, we present proof of concept, detailed description and validation of this novel assay. PMID:24853370

  7. PC8 [corrected], a new member of the convertase family.

    PubMed

    Bruzzaniti, A; Goodge, K; Jay, P; Taviaux, S A; Lam, M H; Berta, P; Martin, T J; Moseley, J M; Gillespie, M T

    1996-03-15

    A novel subtilisin-like protein, PC8, was identified by PCR using degenerate primers to conserved amino acid residues in the catalytic region of members of the prohormone convertase family. PC8 was predicted to be 785 residues long and was structurally related to the mammalian convertases furin, PACE4, PC1 and PC2, sharing more than 50% amino acid identity over the catalytic region with these family members. PC8 possessed the catalytically important Asp, His, Asn and Ser amino acids, the homo B domain of this family of enzymes and a C-terminal hydrophobic sequence indicative of a transmembrane domain. Structurally, PC8 is more related to furin and PACE4 than to PC1 or PC2. Like furin and PACE4, PC8 mRNA was found to be widely expressed; this is in contrast with PC1 and PC2, which have a restricted distribution. Two transcripts, of 4.5 and 3.5 kb, were detected in both human cell lines and rat tissues. Unlike furin and PACE4, both of which map to chromosome 15, PC8 maps to chromosome 11q23-11q24, suggesting that this gene may have resulted from an ancient gene duplication event from either furin or PACE4, or conversely that these genes arose from PC8. PMID:8615762

  8. C8, a new member of the convertase family.

    PubMed Central

    Bruzzaniti, A; Goodge, K; Jay, P; Taviaux, S A; Lam, M H; Berta, P; Martin, T J; Moseley, J M; Gillespie, M T

    1996-01-01

    A novel subtilisin-like protein, PC8, was identified by PCR using degenerate primers to conserved amino acid residues in the catalytic region of members of the prohormone convertase family. PC8 was predicted to be 785 residues long and was structurally related to the mammalian convertases furin, PACE4, PC1 and PC2, sharing more than 50% amino acid identity over the catalytic region with these family members. PC8 possessed the catalytically important Asp, His, Asn and Ser amino acids, the homo B domain of this family of enzymes and a C-terminal hydrophobic sequence indicative of a transmembrane domain. Structurally, PC8 is more related to furin and PACE4 than to PC1 or PC2. Like furin and PACE4, PC8 mRNA was found to be widely expressed; this is in contrast with PC1 and PC2, which have a restricted distribution. Two transcripts, of 4.5 and 3.5 kb, were detected in both human cell lines and rat tissues. Unlike furin and PACE4, both of which map to chromosome 15, PC8 maps to chromosome 11q23-11q24, suggesting that this gene may have resulted from an ancient gene duplication event from either furin or PACE4, or conversely that these genes arose from PC8. PMID:8615762

  9. Biochemical and Cell Biological Properties of the Human Prohormone Convertase 1/3 Ser357Gly Mutation: A PC1/3 Hypermorph

    PubMed Central

    Blanco, Elias H.; Peinado, Juan R.; Martín, Martín G.

    2014-01-01

    Satiety and appetite signaling are accomplished by circulating peptide hormones. These peptide hormones require processing from larger precursors to become bioactive, often by the proprotein convertase 1/3 (PC1/3). Several subcellular maturation steps are necessary for PC1/3 to achieve its optimal enzymatic activity. Certain PC1/3 variants found in the general population slightly attenuate its enzymatic activity and are associated with obesity and diabetes. However, mutations that increase PC1/3 activity and/or affect its specificity could also have physiological consequences. We here present data showing that the known human Ser357Gly PC1/3 mutant (PC1/3S357G) represents a PC1/3 hypermorph. Conditioned media from human embryonic kidney-293 cells transfected with PC1/3WT and PC1/3S357G were collected and enzymatic activity characterized. PC1/3S357G exhibited a lower calcium dependence; a higher pH optimum (neutral); and a higher resistance to peptide inhibitors than the wild-type enzyme. PC1/3S357G exhibited increased cleavage to the C-terminally truncated form, and kinetic parameters of the full-length and truncated mutant enzymes were also altered. Lastly, the S357G mutation broadened the specificity of the enzyme; we detected PC2-like specificity on the substrate proCART, the precursor of the cocaine- and amphetamine regulated transcript neuropeptide known to be associated with obesity. The production of another anorexigenic peptide normally synthesized only by PC2, αMSH, was increased when proopiomelanocortin was coexpressed with PC1/3S357G. Considering the aberrant enzymatic profile of PC1/3S357G, we hypothesize that this enzyme possesses unusual processing activity that may significantly change the profile of circulating peptide hormones. PMID:24932808

  10. Specificity of prohormone convertase endoproteolysis of progastrin in AtT-20 cells.

    PubMed Central

    Dickinson, C J; Sawada, M; Guo, Y J; Finniss, S; Yamada, T

    1995-01-01

    Biologically active peptide hormones are synthesized from larger precursor proteins by a variety of posttranslational processing reactions. Endoproteolytic cleavage at the Lys74-Lys75 dibasic processing site of progastrin is the major determinant for the relative distribution of gastrin heptadecapeptide and tetratriacontapeptide in tissues. Thus, we explored the ability of two prohormone convertases, PC1/PC3 and PC2, to cleave this important site within progastrin. We expressed wild-type human gastrin cDNA and mutant cDNAs in which the Lys74Lys75 site was changed to Lys74Arg75, Arg74Arg75, and Arg74Lys75 residues in AtT-20 cells. Because AtT-20 cells express Pc1/PC3 but not PC2, we also coexpressed a cDNA encoding PC2 in both wild-type and mutant gastrin-producing AtT-20 cells. Wild-type Lys74Lys75 and mutant Arg74Arg75 progastrin processing sites were efficiently cleaved in AtT-20 cells only after coexpression of PC2. Mutant Lys74Arg75 progastrin was readily processed in cells in the presence or absence of PC2 coexpression, but, in contrast, mutant Arg74Lys75 progastrin was inefficiently cleaved regardless of PC2 coexpression. Northern analysis revealed the presence of PC2 but not PC1/ PC3 in canine antral gastrin-producing G cells. These data suggest that PC2 but not PC1/PC3 is responsible for the cleavage of the Lys74Lys75 site in wild-type progastrin. Images PMID:7657815

  11. Isolation and Characterization of a Thionin Proprotein-processing Enzyme from Barley.

    PubMed

    Plattner, Stephan; Gruber, Clemens; Stadlmann, Johannes; Widmann, Stefan; Gruber, Christian W; Altmann, Friedrich; Bohlmann, Holger

    2015-07-17

    Thionins are plant-specific antimicrobial peptides that have been isolated from the endosperm and leaves of cereals, from the leaves of mistletoes, and from several other plant species. They are generally basic peptides with three or four disulfide bridges and a molecular mass of ~5 kDa. Thionins are produced as preproproteins consisting of a signal peptide, the thionin domain, and an acidic domain. Previously, only mature thionin peptides have been isolated from plants, and in addition to removal of the signal peptide, at least one cleavage processing step between the thionin and the acidic domain is necessary to release the mature thionin. In this work, we identified a thionin proprotein-processing enzyme (TPPE) from barley. Purification of the enzyme was guided by an assay that used a quenched fluorogenic peptide comprising the amino acid sequence between the thionin and the acidic domain of barley leaf-specific thionin. The barley TPPE was identified as a serine protease (BAJ93208) and expressed in Escherichia coli as a strep tag-labeled protein. The barley BTH6 thionin proprotein was produced in E. coli using the vector pETtrx1a and used as a substrate. We isolated and sequenced the BTH6 thionin from barley to confirm the N and C terminus of the peptide in planta. Using an in vitro enzymatic assay, the recombinant TPPE was able to process the quenched fluorogenic peptide and to cleave the acidic domain at least at six sites releasing the mature thionin from the proprotein. Moreover, it was found that the intrinsic three-dimensional structure of the BTH6 thionin domain prevents cleavage of the mature BTH6 thionin by the TPPE. PMID:26013828

  12. Isolation and Characterization of a Thionin Proprotein-processing Enzyme from Barley*

    PubMed Central

    Plattner, Stephan; Gruber, Clemens; Stadlmann, Johannes; Widmann, Stefan; Gruber, Christian W.; Altmann, Friedrich; Bohlmann, Holger

    2015-01-01

    Thionins are plant-specific antimicrobial peptides that have been isolated from the endosperm and leaves of cereals, from the leaves of mistletoes, and from several other plant species. They are generally basic peptides with three or four disulfide bridges and a molecular mass of ∼5 kDa. Thionins are produced as preproproteins consisting of a signal peptide, the thionin domain, and an acidic domain. Previously, only mature thionin peptides have been isolated from plants, and in addition to removal of the signal peptide, at least one cleavage processing step between the thionin and the acidic domain is necessary to release the mature thionin. In this work, we identified a thionin proprotein-processing enzyme (TPPE) from barley. Purification of the enzyme was guided by an assay that used a quenched fluorogenic peptide comprising the amino acid sequence between the thionin and the acidic domain of barley leaf-specific thionin. The barley TPPE was identified as a serine protease (BAJ93208) and expressed in Escherichia coli as a strep tag-labeled protein. The barley BTH6 thionin proprotein was produced in E. coli using the vector pETtrx1a and used as a substrate. We isolated and sequenced the BTH6 thionin from barley to confirm the N and C terminus of the peptide in planta. Using an in vitro enzymatic assay, the recombinant TPPE was able to process the quenched fluorogenic peptide and to cleave the acidic domain at least at six sites releasing the mature thionin from the proprotein. Moreover, it was found that the intrinsic three-dimensional structure of the BTH6 thionin domain prevents cleavage of the mature BTH6 thionin by the TPPE. PMID:26013828

  13. Role of Endoproteolytic Dibasic Proprotein Processing in Maturation of Secretory Proteins in Trichoderma reesei

    PubMed Central

    Goller, Sabine P.; Schoisswohl, Doris; Baron, Michel; Parriche, Martine; Kubicek, Christian P.

    1998-01-01

    Cell extracts of Trichoderma reesei exhibited dibasic endopeptidase activity toward the carboxylic side of KR, RR, and PR sequences. This activity was stimulated by the presence of Ca2+ ions and localized in vesicles of low bouyant density; it therefore exhibited some similarity to yeast Kex2. Analytical chromatofocusing revealed a single peak of activity. The dibasic endopeptidase activity was strongly and irreversibly inhibited in vitro as well as in vivo by 1 mM p-amidinophenylmethylsulfonyl fluoride (pAPMSF) but not by PMSF at concentrations up to 5 mM. We therefore used pAPMSF to study the role of the dibasic endopeptidase in the secretion of protein by T. reesei. Secretion of xylanase I (proprotein processing sequence -R-R-↓-R-↓-A-) and xylanase II (-K-R-↓-Q-) was strongly inhibited by 1 mM pAPMSF, and a larger, unprocessed enzyme form was detected intracellularly under these conditions. Secretion of cellobiohydrolase II (CBH II; -E-R-↓-Q-) was only slightly inhibited by pAPMSF, and no accumulation of unprocessed precursors was detected. In contrast, secretion of CBH I (-R-A-↓-Q-) was stimulated by pAPMSF addition, and a simultaneous decrease in the concentration of intracellular CBH I was detected. Similar experiments were also carried out with a single heterologous protein, ShBLE, the phleomycin-binding protein from Streptoalloteichus hindustanus, fused to a series of model proprotein-processing sequences downstream of the expression signals of the Aspergillus nidulans gpdA promoter. Consistent with the results obtained with homologous proteins, pAPMSF inhibited the secretion of ShBLE with fusions containing dibasic (RK and KR) target sequences, but it even stimulated secretion in fusions to LR, NHA, and EHA target sequences. Addition of 5 mM PMSF, a nonspecific inhibitor of serine protease, nonspecifically inhibited the secretion of heterologous proteins from fusions bearing the NHA and LR targets. These data point to the existence of different

  14. A circulating inhibitor of fluid-phase amplification. C3 convertase formation in systemic lupus erythematosus.

    PubMed Central

    Waldo, F B; Forristal, J; Beischel, L; West, C D

    1985-01-01

    C3 nephritic factor (C3NeF) was used to assess the formation of the fluid-phase amplification convertase, C3b,Bb, in 37 serum specimens from 24 patients with systemic lupus erythematosus (SLE). C3b,Bb formation was measured by the concentration of Ba, released when C3b,B is activated. Incubation of normal human serum (NHS) with C3NeF accelerates C3b amplification loop turnover with the formation of large quantities of C3b,Bb. In contrast, sera from 22 of 24 patients with SLE formed little or no convertase when incubated with C3NeF. C3 conversion to C3b was commensurately reduced. The inhibition could not be attributed to depressed serum concentrations of C3, factor B, or classical pathway components. Inhibitor present in excess could be demonstrated in 23 of 34 specimens of SLE serum by mixing experiments. The spontaneous convertase formation that occurs when a portion of the serum H is inactivated with F(ab')2 anti-H was also shown to be inhibited in SLE serum. The inhibition was found, however, to be H dependent in that convertase formation was normal in SLE serum depleted of H. It is concluded that the C3b in most SLE sera is unusually susceptible to inactivation by H, but a functional abnormality was not demonstrable in either C3 or H isolated from SLE serum. The inhibition could be simulated in NHS by addition of heparin, 100 micrograms/ml. In vivo, inhibition of convertase formation could interfere with the solubilization and disposal of immune complexes by reducing the deposition of C3b on the immune complex lattice. PMID:3159752

  15. Deficiency of prohormone convertase dPC2 (AMONTILLADO) results in impaired production of bioactive neuropeptide hormones in Drosophila.

    PubMed

    Wegener, Christian; Herbert, Henrik; Kahnt, Jörg; Bender, Michael; Rhea, Jeanne M

    2011-08-01

    Peptide hormones synthesized by secretory neurons in the CNS are important regulators of physiology, behavior, and development. Like other neuropeptides, they are synthesized from larger precursor molecules by a specific set of enzymes. Using a combination of neurogenetics, immunostainings, and direct mass spectrometric profiling, we show that the presence of Drosophila prohormone convertase 2 encoded by the gene amontillado (amon) is a prerequisite for the proper processing of neuropeptide hormones from the major neurohemal organs of the CNS. A loss of amon correlates with a loss of neuropeptide hormone signals from the larval ring gland and perisympathetic organs. Neuropeptide hormone signals were still detectable in the adult corpora cardiaca of older amon-deficient flies which were amon heat-shock-rescued until eclosion. A semiquantification by direct peptide profiling using stable isotopic standards showed, however, that their neuropeptide hormone levels are strongly reduced. Targeted expression of GFP under the control of amon regulatory regions revealed a co-localization with the investigated peptide hormones in secretory neurons of the brain and ventral nerve cord. The lack of AMON activity resulted in a deficiency of L3 larva to enter the wandering phase. In conclusion, our findings provide the first direct evidence that AMON is a key enzyme in the production of neuropeptides in the fruitfly. PMID:21138435

  16. Interaction of Drosophila melanogaster prohormone convertase 2 and 7B2. Insect cell-specific processing and secretion.

    PubMed

    Hwang, J R; Siekhaus, D E; Fuller, R S; Taghert, P H; Lindberg, I

    2000-06-01

    The prohormone convertases (PCs) are an evolutionarily ancient group of proteases required for the maturation of neuropeptide and peptide hormone precursors. In Drosophila melanogaster, the homolog of prohormone convertase 2, dPC2 (amontillado), is required for normal hatching behavior, and immunoblotting data indicate that flies express 80- and 75-kDa forms of this protein. Because mouse PC2 (mPC2) requires 7B2, a helper protein for productive maturation, we searched the fly data base for the 7B2 signature motif PPNPCP and identified an expressed sequence tag clone encoding the entire open reading frame for this protein. dPC2 and d7B2 cDNAs were subcloned into expression vectors for transfection into HEK-293 cells; mPC2 and rat 7B2 were used as controls. Although active mPC2 was detected in medium in the presence of either d7B2 or r7B2, dPC2 showed no proteolytic activity upon coexpression of either d7B2 or r7B2. Labeling experiments showed that dPC2 was synthesized but not secreted from HEK-293 cells. However, when dPC2 and either d7B2 or r7B2 were coexpressed in Drosophila S2 cells, abundant immunoreactive dPC2 was secreted into the medium, coincident with the appearance of PC2 activity. Expression and secretion of dPC2 enzyme activity thus appears to require insect cell-specific posttranslational processing events. The significant differences in the cell biology of the insect and mammalian enzymes, with 7B2 absolutely required for secretion of dPC2 and zymogen conversion occurring intracellularly in the case of dPC2 but not mPC2, support the idea that the Drosophila enzyme has specific requirements for maturation and secretion that can be met only in insect cells. PMID:10749852

  17. An aspartyl cathepsin, CTH3, is essential for proprotein processing during secretory granule maturation in Tetrahymena thermophila

    PubMed Central

    Kumar, Santosh; Briguglio, Joseph S.; Turkewitz, Aaron P.

    2014-01-01

    In Tetrahymena thermophila, peptides secreted via dense-core granules, called mucocysts, are generated by proprotein processing. We used expression profiling to identify candidate processing enzymes, which localized as cyan fluorescent protein fusions to mucocysts. Of note, the aspartyl cathepsin Cth3p plays a key role in mucocyst-based secretion, since knockdown of this gene blocked proteolytic maturation of the entire set of mucocyst proproteins and dramatically reduced mucocyst accumulation. The activity of Cth3p was eliminated by mutation of two predicted active-site mutations, and overexpression of the wild-type gene, but not the catalytic-site mutant, partially rescued a Mendelian mutant defective in mucocyst proprotein processing. Our results provide the first direct evidence for the role of proprotein processing in this system. Of interest, both localization and the CTH3 disruption phenotype suggest that the enzyme provides non–mucocyst-related functions. Phylogenetic analysis of the T. thermophila cathepsins, combined with prior work on the role of sortilin receptors in mucocyst biogenesis, suggests that repurposing of lysosomal enzymes was an important step in the evolution of secretory granules in ciliates. PMID:24943840

  18. Insights into complement convertase formation based on the structure of the factor B-cobra venom factor complex

    PubMed Central

    Janssen, Bert J C; Gomes, Lucio; Koning, Roman I; Svergun, Dmitri I; Koster, Abraham J; Fritzinger, David C; Vogel, Carl-Wilhelm; Gros, Piet

    2009-01-01

    Immune protection by the complement system critically depends on assembly of C3 convertases on the surface of pathogens and altered host cells. These short-lived protease complexes are formed through pro-convertases, which for the alternative pathway consist of the complement component C3b and the pro-enzyme factor B (FB). Here, we present the crystal structure at 2.2-Å resolution, small-angle X-ray scattering and electron microscopy (EM) data of the pro-convertase formed by human FB and cobra venom factor (CVF), a potent homologue of C3b that generates more stable convertases. FB is loaded onto CVF through its pro-peptide Ba segment by specific contacts, which explain the specificity for the homologous C3b over the native C3 and inactive products iC3b and C3c. The protease segment Bb binds the carboxy terminus of CVF through the metal-ion dependent adhesion site of the Von Willebrand factor A-type domain. A possible dynamic equilibrium between a ‘loading' and ‘activation' state of the pro-convertase may explain the observed difference between the crystal structure of CVFB and the EM structure of C3bB. These insights into formation of convertases provide a basis for further development of complement therapeutics. PMID:19574954

  19. A humanised antibody that regulates the alternative pathway convertase: potential for therapy of renal disease associated with nephritic factors1

    PubMed Central

    Paixão-Cavalcante, Danielle; Torreira, Eva; Lindorfer, Margaret A.; de Cordoba, Santiago Rodriguez; Morgan, B. Paul; Taylor, Ronald P.; Llorca, Oscar; Harris, Claire L.

    2014-01-01

    Dysregulation of the complement alternative pathway (AP) can cause disease in various organs that may be life-threatening. Severe AP dysregulation can be triggered by autoantibodies to the C3 convertase, termed nephritic factors, which cause pathological stabilisation of the convertase enzyme and confer resistance to innate control mechanisms; unregulated complement consumption followed by deposition of C3 fragments in tissues ensues. The monoclonal antibody, 3E7, and its humanised derivative, H17, have been shown previously to specifically bind activated C3 and prevent binding of both the activating protein, factor B, and the inhibitor, factor H, opposite effects that complicate its potential for therapy. Using ligand binding assays, functional assays and electron microscopy, we show that these antibodies bind C3b via a site which overlaps the binding site on C3 for the Ba domain within factor B, thereby blocking an interaction essential for convertase formation. Both antibodies also bind the preformed convertase, C3bBb, and provide powerful inhibition of complement activation by preventing cleavage of C3. Critically, the antibodies also bound and inhibited C3 cleavage by the nephritic factor-stabilised convertase. We suggest that by preventing enzyme formation and/or cleavage of C3 to its active downstream fragments, H17 may be an effective therapy for conditions caused by severe dysregulation of the C3 convertase, and in particular those involving nephritic factors, such as dense deposit disease. PMID:24729617

  20. Activation of bean (Phaseolus vulgaris) [alpha]-amylase inhibitor requires proteolytic processing of the proprotein

    SciTech Connect

    Pueyo, J.J.; Hunt, D.C.; Chrispeels, M.J. )

    1993-04-01

    Seeds of the common bean (Phaseolus vulgaris) contain a plant defense protein that inhibits the [alpha]-amylases of mammals and insects. This [alpha]-amylase inhibitor ([alpha]Al) is synthesized as a proprotein on the endoplasmic reticulum and is proteolytically processed after arrival in the protein storage vacuoles to polypeptides of relative molecular weight (M[sub r]) 15,000 to 18,000. The authors report two types of evidence that proteolytic processing is linked to activation of the inhibitory activity. First, by surveying seed extracts of wild accessions of P. vulgaris and other species in the genus Phaseolus, they found that antibodies to [alpha]Al recognize large (M[sub r] 30,000-35,000) polypeptides as well as typical [alpha]Al processing products (M[sub r] 15,000-18,000). [alpha]Al activity was found in all extracts that had the typical [alpha]Al processed polypeptides, but was absent from seed extracts that lacked such polypeptides. Second, they made a mutant [alpha]Al in which asparagine-77 is changed to aspartic acid-77. This mutation slows down the proteolytic processing of pro-[alpha]Al when the gene is expressed in tobacco. When pro-[alpha]Al was separated from mature [alpha]Al by gel filtration, pro-[alpha]Al was found not to have [alpha]-amylase inhibitory activity. The authors interpret these results to mean that formation of the active inhibitor is causally related to proteolytic processing of the proprotein. They suggest that the polypeptide cleavage removes a conformation constraint on the precursor to produce the biochemically active molecule. 43 refs., 5 figs., 1 tab.

  1. Activation of bean (Phaseolus vulgaris) alpha-amylase inhibitor requires proteolytic processing of the proprotein.

    PubMed Central

    Pueyo, J J; Hunt, D C; Chrispeels, M J

    1993-01-01

    Seeds of the common bean (Phaseolus vulgaris) contain a plant defense protein that inhibits the alpha-amylases of mammals and insects. This alpha-amylase inhibitor (alpha AI) is synthesized as a proprotein on the endoplasmic reticulum and is proteolytically processed after arrival in the protein storage vacuoles to polypeptides of relative molecular weight (M(r)) 15,000 to 18,000. We report two types of evidence that proteolytic processing is linked to activation of the inhibitory activity. First, by surveying seed extracts of wild accessions of P. vulgaris and other species in the genus Phaseolus, we found that antibodies to alpha AI recognize large (M(r) 30,000-35,000) polypeptides as well as typical alpha AI processing products (M(r) 15,000-18,000). Alpha AI activity was found in all extracts that had the typical alpha AI processed polypeptides, but was absent from seed extracts that lacked such polypeptides. Second, we made a mutant alpha AI in which asparagine-77 is changed to aspartic acid-77. This mutation slows down the proteolytic processing of pro-alpha AI when the gene is expressed in tobacco. When pro-alpha AI was separated from mature alpha AI by gel filtration, pro-alpha AI was found not to have alpha-amylase inhibitory activity. We interpret these results to mean that formation of the active inhibitor is causally related to proteolytic processing of the proprotein. We suggest that the polypeptide cleavage removes a conformational constraint on the precursor to produce the biochemically active molecule. PMID:8310064

  2. Mutant PAX6 downregulates prohormone convertase 2 expression in mouse islets.

    PubMed

    Chen, Yuanyuan; Cao, Wenwan; Zhou, Shixin; Shen, Liang; Wen, Jinhua

    2013-11-01

    Transcriptional factor paired box 6 (PAX6) is very important for the development of the eyes, central nervous system, and pancreas. PAX6 mutations are associated with a diabetic phenotype and abnormal glucose metabolism. Our previous study showed that PAX6 directly bound to and activated the prohormone convertase 1/3 (Pc1/3) gene promoter and subsequently regulated proinsulin processing. Prohormone convertase 2 (PC2) is the essential enzyme for pancreatic proinsulin processing. To study the regulation of PAX6 in Pc2 expression, we did research on the pancreas of Pax6 R266Stop mutant mice, where truncated mutations happened in the C-terminal of the PAX6 protein. Our studies showed that the mutant PAX6 protein was stable and regulated the activity of Pc2 promoter as shown by luciferase activity assays. We found that the wild-type PAX6 protein imparts a transcriptional effect, and the mutant PAX6 can also regulate the downstream molecules. The results provide new insights into the mechanism of truncated PAX6 in regulating the functions of the pancreas and endocrine system. PMID:24047795

  3. Gene organization and alternative splicing of human prohormone convertase PC8.

    PubMed Central

    Goodge, K A; Thomas, R J; Martin, T J; Gillespie, M T

    1998-01-01

    The mammalian Ca2+-dependent serine protease prohormone convertase PC8 is expressed ubiquitously, being transcribed as 3.5, 4.3 and 6.0 kb mRNA isoforms in various tissues. To determine the origin of these various mRNA isoforms we report the characterization of the human PC8 gene, which has been previously localized to chromosome 11q23-24. Consisting of 16 exons, the human PC8 gene spans approx. 27 kb. A comparison of the position of intron-exon junctions of the human PC8 gene with the gene structures of previously reported prohormone convertase genes demonstrated a divergence of the human PC8 from the highly conserved nature of the gene organization of this enzyme family. The nucleotide sequence of the 5'-flanking region of the human PC8 is reported and possesses putative promoter elements characteristic of a GC-rich promoter. Further supporting the potential role of a GC-rich promoter element, multiple transcriptional initiation sites within a 200 bp region were demonstrated. We propose that the various mRNA isoforms of PC8 result from the inclusion of intronic sequences within transcripts. PMID:9820811

  4. Encoding Dictionaries.

    ERIC Educational Resources Information Center

    Ide, Nancy

    1995-01-01

    Describes problems in devising a Text Encoding Initiative (TEI) encoding format for dictionaries. Asserts that the high degree of structuring and compression of information are among the most complex text types treated in the TEI. Concludes that the source of some TEI problems lies in the design of Standard Generalized Markup Language (SGML). (CFR)

  5. The neuroendocrine polypeptide 7B2 is an endogenous inhibitor of prohormone convertase PC2.

    PubMed Central

    Martens, G J; Braks, J A; Eib, D W; Zhou, Y; Lindberg, I

    1994-01-01

    The subtilisin-like prohormone convertase PC2 and the polypeptide 7B2 (an intracellularly cleaved protein of unknown function) are both selectively present in the regulated secretory pathway of neurons and endocrine cells. Here we demonstrate that intact recombinant 7B2 is a potent inhibitor of PC2 and prevents proPC2 cleavage in vitro, whereas the 7B2 cleavage product is virtually inactive. The PC2-related proteinase PC1/PC3 is not inhibited by 7B2. Furthermore, the carboxyl-terminal half of the 7B2 protein sequence is distantly related to the so-called potato inhibitor I family (which includes subtilisin inhibitors). Our findings indicate that 7B2 is a physiological inhibitor of PC2 and may provide alternative avenues for the manipulation of peptide hormone levels. Images PMID:8016065

  6. Enzymatic activity of soluble and membrane tethered peptide pro-hormone convertase 1.

    PubMed

    Bruzzaniti, Angela; Mains, Richard E

    2002-05-01

    Pro-hormone convertases PC1 and PC2 perform endoproteolytic cleavages of precursors in peptide-containing secretory granules. PC1 and PC2 are soluble, secreted with bioactive peptides. Evolutionarily related PCs have membrane tethers, not secreted. We tethered PC1 to the transmembrane-cytoplasmic domains (CD) of a granule enzyme (peptidylglycine-alpha-amidating monooxygenase; PAM) and Golgi-localized PC8. The tethered PC1 is far more stable to elevated temperature and denaturants than soluble PC1, and more active. Both tethers allow PC1 to visit the cell surface transiently, cleaving soluble molecules outside the cell. Both membrane-bound PC1 chimeras cleave membrane PAM into soluble active fragments when PAM is expressed on adjacent cells. PMID:12084516

  7. Deciphering ENCODE.

    PubMed

    Diehl, Adam G; Boyle, Alan P

    2016-04-01

    The ENCODE project represents a major leap from merely describing and comparing genomic sequences to surveying them for direct indicators of function. The astounding quantity of data produced by the ENCODE consortium can serve as a map to locate specific landmarks, guide hypothesis generation, and lead us to principles and mechanisms underlying genome biology. Despite its broad appeal, the size and complexity of the repository can be intimidating to prospective users. We present here some background about the ENCODE data, survey the resources available for accessing them, and describe a few simple principles to help prospective users choose the data type(s) that best suit their needs, where to get them, and how to use them to their best advantage. PMID:26962025

  8. The Crystal Structure of Cobra Venom Factor, a Cofactor for C3- and C5-Convertase CVFBb

    SciTech Connect

    Krishnan, Vengadesan; Ponnuraj, Karthe; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V.L.

    2009-05-26

    Cobra venom factor (CVF) is a functional analog of human complement component C3b, the active fragment of C3. Similar to C3b, in human and mammalian serum, CVF binds factor B, which is then cleaved by factor D, giving rise to the CVFBb complex that targets the same scissile bond in C3 as the authentic complement convertases C4bC2a and C3bBb. Unlike the latter, CVFBb is a stable complex and an efficient C5 convertase. We solved the crystal structure of CVF, isolated from Naja naja kouthia venom, at 2.6 {angstrom} resolution. The CVF crystal structure, an intermediate between C3b and C3c, lacks the TED domain and has the CUB domain in an identical position to that seen in C3b. The similarly positioned CUB and slightly displaced C345c domains of CVF could play a vital role in the formation of C3 convertases by providing important primary binding sites for factor B.

  9. Biologically active APRIL is secreted following intracellular processing in the Golgi apparatus by furin convertase

    PubMed Central

    López-Fraga, M.; Fernández, R.; Albar, J.P.; Hahne, M.

    2001-01-01

    Tumor necrosis factor (TNF) ligand family members are synthesized as transmembrane proteins, and cleavage of the membrane-anchored proteins from the cell surface is frequently observed. The TNF-related ligands APRIL and BLyS and their cognate receptors BCMA/TACI form a two ligand/two receptor system that has been shown to participate in B- and T-cell stimulation. In contrast to BLyS, which is known to be cleaved from the cell surface, we found that APRIL is processed intracellularly by furin convertase. Blockage of protein transport from the endoplasmic reticulum to the Golgi apparatus by Brefeldin A treatment abrogated APRIL processing, whereas monensin, an inhibitor of post-Golgi transport, did not interfere with cleavage of APRIL, but blocked secretion of processed APRIL. Thus, APRIL shows a unique maturation pathway among the TNF ligand family members, as it not detectable as a membrane-anchored protein at the cell surface, but is processed in the Golgi apparatus prior to its secretion. PMID:11571266

  10. Enkephalin convertase: Characterization and localization with ( sup 3 H)-guanidinoethylmercap-tosuccinic acid

    SciTech Connect

    Lynch, D.R.

    1988-01-01

    Enkephalin convertase (EC) has been characterized by the binding of its selective inhibitor ({sup 3}H)-guanidinoethylmercaptosuccinic acid (GEMSA). The pharmacology and affinity of ({sup 3}H)-GEMSA binding match the pharmacology of EC activity and the inhibition of EC activity by GEMSA. EC activity and ({sup 3}H)-GEMSA binding activity copurify to homogeneity demonstrating that ({sup 3}H)-GEMSA binds selectively to EC. The selective association of ({sup 3}H)-GEMSA for EC allows localization of membrane bound EC by in vitro autoradiography. EC is heterogeneously distributed in the rat brain with the highest levels in the outer zone of the median eminence and in the hypothalamic magnocellular nuclei. In the pituitary gland, autoradiography localizes EC to all three lobes with the highest levels in the intermediate lobe. In the adrenal EC is found exclusively in the medulla. In the gastrointestinal tract, EC is localized to epithelial surfaces where its function cannot be that of propeptide processing. In the heart EC is localized to atrium where it likely processes precursors of atrial natriuretic factor.

  11. Activation and routing of membrane-tethered prohormone convertases 1 and 2.

    PubMed

    Bruzzaniti, A; Marx, R; Mains, R E

    1999-08-27

    Many peptide hormones and neuropeptides are processed by members of the subtilisin-like family of prohormone convertases (PCs), which are either soluble or integral membrane proteins. PC1 and PC2 are soluble PCs that are primarily localized to large dense core vesicles in neurons and endocrine cells. We examined whether PC1 and PC2 were active when expressed as membrane-tethered proteins, and how tethering to membranes alters the biosynthesis, enzymatic activity, and intracellular routing of these PCs. PC1 and PC2 chimeras were constructed using the transmembrane domain and cytoplasmic domain of the amidating enzyme, peptidylglycine alpha-amidating monooxygenase (PAM). The membrane-tethered PCs were rerouted from large dense core vesicles to the Golgi region. In addition, the chimeras were transiently expressed at the cell surface and rapidly internalized to the Golgi region in a fashion similar to PAM. Membrane-tethered PC1 and PC2 exhibited changes in pro-domain maturation rates, N-glycosylation, and in the pH and calcium optima required for maximal enzymatic activity against a fluorogenic substrate. In addition, the PC chimeras efficiently cleaved endogenous pro-opiomelanocortin to the correct bioactive peptides. The PAM transmembrane domain/cytoplasmic domain also prevented stimulated secretion of pro-opiomelanocortin products in AtT-20 cells. PMID:10455138

  12. The structure of C2b, a fragment of complement component C2 produced during C3 convertase formation

    SciTech Connect

    Krishnan, Vengadesan; Xu, Yuanyuan; Macon, Kevin; Volanakis, John E.; Narayana, Sthanam V. L.

    2009-03-01

    The crystal structure of C2b has been determined at 1.8 Å resolution, which reveals the arrangement of its three complement control protein (CCP) modules. A model for complement component C2 is presented and its conformational changes during the C3-convertase formation are also discussed. The second component of complement (C2) is a multi-domain serine protease that provides catalytic activity for the C3 and C5 convertases of the classical and lectin pathways of human complement. The formation of these convertases requires the Mg{sup 2+}-dependent binding of C2 to C4b and the subsequent cleavage of C2 by C1s or MASP2, respectively. The crystal structure of full-length C2 is not yet available, although the structure of its C-terminal catalytic segment C2a has been determined. The crystal structure of the N-terminal segment C2b of C2 determined to 1.8 Å resolution presented here reveals the arrangement of its three CCP domains. The domains are arranged differently compared with most other CCP-domain assemblies, but their arrangement is similar to that found in the Ba part of the full-length factor B structure. The crystal structures of C2a, C2b and full-length factor B are used to generate a model for C2 and a discussion of the domain association and possible interactions with C4b during formation of the C4b–C2 complex is presented. The results of this study also suggest that upon cleavage by C1s, C2a domains undergo conformational rotation while bound to C4b and the released C2b domains may remain folded together similar to as observed in the intact protein.

  13. Lymphoma chemovirotherapy: CD20-targeted and convertase-armed measles virus can synergize with fludarabine.

    PubMed

    Ungerechts, Guy; Springfeld, Christoph; Frenzke, Marie E; Lampe, Johanna; Johnston, Patrick B; Parker, William B; Sorscher, Eric J; Cattaneo, Roberto

    2007-11-15

    Combination chemotherapy regimen incorporating CD20 antibodies are commonly used in the treatment of CD20-positive non-Hodgkin's lymphoma (NHL). Fludarabine phosphate (F-araAMP), cyclophosphamide, and CD20 antibodies (Rituximab) constitute the FCR regimen for treating selected NHL, including aggressive mantle cell lymphoma (MCL). As an alternative to the CD20 antibody, we generated a CD20-targeted measles virus (MV)-based vector. This vector was also armed with the prodrug convertase purine nucleoside phosphorylase (PNP) that locally converts the active metabolite of F-araAMP to a highly diffusible substance capable of efficiently killing bystander cells. We showed in infected cells that early prodrug administration controls vector spread, whereas late administration enhances cell killing. Control of spread by early prodrug administration was also shown in an animal model: F-araAMP protected genetically modified mice susceptible to MV infection from a potentially lethal intracerebral challenge. Enhanced oncolytic potency after extensive infection was shown in a Burkitt's lymphoma xenograft model (Raji cells): After systemic vector inoculation, prodrug administration enhanced the therapeutic effect synergistically. In a MCL xenograft model (Granta 519 cells), intratumoral (i.t.) vector administration alone had high oncolytic efficacy: All mice experienced complete but temporary tumor regression, and survival was two to four times longer than that of untreated mice. Cells from MCL patients were shown to be sensitive to infection. Thus, synergy of F-araAMP with a PNP-armed and CD20-targeted MV was shown in one lymphoma therapy model after systemic vector inoculation. PMID:18006839

  14. Stringent Regulation of Complement Lectin Pathway C3/C5 Convertase By C4b-Binding Protein (C4bp)

    PubMed Central

    Rawal, Nenoo; Rajagopalan, Rema; Salvi, Veena P.

    2009-01-01

    The complement lectin pathway, an essential component of the innate immune system, is geared for rapid recognition of infections as each C4b deposited via this pathway is capable of forming a C3/C5 convertase. In the present study, role of C4b-binding protein (C4BP) in regulating the lectin pathway C3/C5 convertase assembled on zymosan and sheep erythrocytes coated with mannan (EMan) was examined. While the C4BP concentration for inhibiting 50% (IC50) formation of surface-bound C3 convertase on the two surfaces was similar to that obtained for the soluble C3 convertase (1.05 nM), ∼3- and 41-fold more was required to inhibit assembly of the C5 convertase on zymosan (2.81 nM) and EMan (42.66 nM). No difference in binding interactions between C4BP and surface-bound C4b alone or in complex with C3b was observed. Increasing the C4b density on zymosan (14,000-431,000 C4b/Zym) increased the number of C4b bound per C4BP from 2.87 to 8.23 indicating that at high C4b density all seven α-chains of C4BP are engaged in C4b-binding. In contrast, the number of C4b bound per C4BP remained constant (3.79 ± 0.60) when the C4b density on EMan was increased. The data also show that C4BP regulates assembly and decay of the lectin pathway C3/C5 convertase more stringently than the classical pathway C3/C5 convertase because of a ∼7 to 13-fold greater affinity for C4b deposited via the lectin pathway than the classical pathway. C4BP thus regulates efficiently the four times greater potential of the lectin pathway than the classical pathway in generating the C3/C5 convertase and hence production of pro-inflammatory products, which are required to fight infections but occasionally cause pathological inflammatory reactions. PMID:19660812

  15. The Spn4 gene of Drosophila encodes a potent furin-directed secretory pathway serpin

    PubMed Central

    Richer, Martin J.; Keays, Clairessa A.; Waterhouse, Jennifer; Minhas, Jessey; Hashimoto, Carl; Jean, François

    2004-01-01

    Proprotein convertases (PCs) are an important class of host-cell serine endoproteases implicated in many physiological and pathological processes. Owing to their expanding roles in the proteolytic events required for generating infectious microbial pathogens and for tumor growth and invasiveness, there is increasing interest in identifying endogenous PC inhibitors. Here we report the identification of Spn4A, a previously uncharacterized secretory pathway serine protease inhibitor (serpin) from Drosophila melanogaster that contains a consensus furin cleavage site, -ArgP4-Arg-Lys-ArgP1↓-, in its reactive site loop (RSL). Our biochemical and kinetics analysis revealed that recombinant Spn4A inhibits human furin (Ki, 13 pM; kass, 3.2 × 107 M–1·s–1) and Drosophila PC2 (Ki, 3.5 nM; kass, 9.2 × 104 M–1·s–1) by a slow-binding mechanism characteristic of serpin molecules and forms a kinetically trapped SDS-stable complex with each enzyme. For both PCs, the stoichiometry of inhibition by Spn4A is nearly 1, which is characteristic of known physiological serpin–protease interactions. Mass analysis of furin–Spn4A reaction products identified the actual reactive site center of Spn4A to be -ArgP4-Arg-Lys-ArgP1↓-. Moreover, we demonstrate that Spn4A's highly effective PC inhibition properties are critically dependent on the unusual length of its RSL, which is composed of 18 aa instead of the typical 17-residue RSL found in most other inhibitory serpins. The identification of Spn4A, the most potent and effective natural serpin of PCs identified to date, suggests that Spn4A could be a prototype of endogenous serpins involved in the precise regulation of PC-dependent proteolytic cleavage events in the secretory pathway of eukaryotic cells. PMID:15247425

  16. Developmentally regulated expression by Trypanosoma cruzi of molecules that accelerate the decay of complement C3 convertases

    SciTech Connect

    Rimoldi, M.T.; Sher, A.; Heiny, A.; Lituchy, A.; Hammer, C.H.; Joiner, K.

    1988-01-01

    The authors recently showed that culture-derived metacyclic trypomastigotes (CMT), but not epimastigotes (Epi), of the Miranda 99 strain of Trypanosoma cruzi evade lysis by the human alternative complement pathway because of inefficient binding of factor B to complement component C3b on the parasite surface. These results suggested that CMT and tissue-culture-derived trypomastigotes (TCT), which also activate the alternative pathway poorly, might produce a molecule capable of interfering with factor B binding to C3b. They now demonstrate that CMT and TCT lysates, as well as molecules spontaneously shed from CMT and TCT but not Epi, accelerate decay of /sup 125/I-labeled factor Bb from the alternative-pathway C3 convertase (C3bBb) assembled on zymosan or Epi and also accelerate decay of the classical-pathway C3 convertase (C4b2a) on sheep erythrocytes. Parasites metabolically labeled with (/sup 35/S)methionine spontaneously shed a limited number of radioactive components, ranging in molecular mass from 86 to 155 kDa for trypomastigotes and 25 to 80 kDa for Epi. Decay-accelerating activity within supernatants is inactivated by papain and is coeluted with /sup 35/S-containing polypeptides on FPLC anion-exchange chromatography, suggesting that the active constituents are protein molecules. Molecules with decay-accelerating activity may explain the developmentally regulated resistance to complement-mediated lysis in infective and vertebrate stages for T. cruzi life cycle.

  17. Expression and localization of prohormone convertase PC1 in the calcitonin-producing cells of the bullfrog ultimobranchial gland.

    PubMed

    Yaoi, Yuichi; Suzuki, Masakazu; Tomura, Hideaki; Kurabuchi, Shingo; Sasayama, Yuichi; Tanaka, Shigeyasu

    2003-11-01

    We examined the expression and localization of the prohormone convertases, PC1 and PC2, in the ultimobranchial gland of the adult bullfrog using immunohistochemical (IHC) and in situ hybridization (ISH) techniques. In the ultimobranchial gland, PC1-immunoreactive cells were columnar, and were present in the follicular epithelium. When serial sections were immunostained with anti-calcitonin, anti-CGRP, anti-PC1, and anti-PC2 sera, PC1 was found only in the calcitonin/CGRP-producing cells. No PC2-immunopositive cells were detected. In the ISH, PC1 mRNA-positive cells were detected in the follicle cells in the ultimobranchial gland. No PC2 mRNA-positive cells were detected. RT-PCR revealed expression of the mRNAs of PC1 and the PC2 in the ultimobranchial gland. However, very little of the PC2 mRNA is probably translated because no PC2 protein was detected either by IHC staining or by Western blotting analysis. We conclude that the main prohormone convertase that is involved in the proteolytic cleavage of procalcitonin in the bullfrog is PC1. PMID:14566018

  18. Expression and Localization of Prohormone Convertase PC1 in the Calcitonin-producing Cells of the Bullfrog Ultimobranchial Gland

    PubMed Central

    Yaoi, Yuichi; Suzuki, Masakazu; Tomura, Hideaki; Kurabuchi, Shingo; Sasayama, Yuichi; Tanaka, Shigeyasu

    2003-01-01

    We examined the expression and localization of the prohormone convertases, PC1 and PC2, in the ultimobranchial gland of the adult bullfrog using immunohistochemical (IHC) and in situ hybridization (ISH) techniques. In the ultimobranchial gland, PC1-immunoreactive cells were columnar, and were present in the follicular epithelium. When serial sections were immunostained with anti-calcitonin, anti-CGRP, anti-PC1, and anti-PC2 sera, PC1 was found only in the calcitonin/CGRP-producing cells. No PC2-immunopositive cells were detected. In the ISH, PC1 mRNA-positive cells were detected in the follicle cells in the ultimobranchial gland. No PC2 mRNA-positive cells were detected. RT-PCR revealed expression of the mRNAs of PC1 and the PC2 in the ultimobranchial gland. However, very little of the PC2 mRNA is probably translated because no PC2 protein was detected either by IHC staining or by Western blotting analysis. We conclude that the main prohormone convertase that is involved in the proteolytic cleavage of procalcitonin in the bullfrog is PC1. PMID:14566018

  19. Isolation of the human PC6 gene encoding the putative host protease for HIV-1 gp160 processing in CD4+ T lymphocytes.

    PubMed Central

    Miranda, L; Wolf, J; Pichuantes, S; Duke, R; Franzusoff, A

    1996-01-01

    Production of infectious HIV-1 virions is dependent on the processing of envelope glycoprotein gp160 by a host cell protease. The protease in human CD4+ T lymphocytes has not been unequivocally identified, yet members of the family of mammalian subtilisin-like protein convertases (SPCs), which are soluble or membrane-bound proteases of the secretory pathway, best fulfill the criteria. These proteases are required for proprotein maturation and cleave at paired basic amino acid motifs in numerous cellular and viral glycoprotein precursors, both in vivo and in vitro. To identify the gp160 processing protease, we have used reverse transcription-PCR and Northern blot analyses to ascertain the spectrum of SPC proteases in human CD4+ T cells. We have cloned novel members of the SPC family, known as the human PC6 genes. Two isoforms of the hPC6 protease are expressed in human T cells, hPC6A and the larger hPC6B. The patterns of SPC gene expression in human T cells has been compared with the furin-defective LoVo cell line, both of which are competent in the production of infectious HIV virions. This comparison led to the conclusion that the hPC6 gene products are the most likely candidates for the host cell protease responsible for HIV-1 gp160 processing in human CD4+ T cells. Images Fig. 1 Fig. 3 PMID:8755538

  20. Prohormone convertase 2 activity is increased in the hippocampus of Wfs1 knockout mice

    PubMed Central

    Tein, Karin; Kasvandik, Sergo; Kõks, Sulev; Vasar, Eero; Terasmaa, Anton

    2015-01-01

    Background: Mutations in WFS1 gene cause Wolfram syndrome, which is a rare autosomal recessive disorder, characterized by diabetes insipidus, diabetes mellitus, optic nerve atrophy, and deafness. The WFS1 gene product wolframin is located in the endoplasmic reticulum. Mice lacking this gene exhibit disturbances in the processing and secretion of peptides, such as vasopressin and insulin. In the brain, high levels of the wolframin protein have been observed in the hippocampus, amygdala, and limbic structures. The aim of this study was to investigate the effect of Wfs1 knockout (KO) on peptide processing in mouse hippocampus. A peptidomic approach was used to characterize individual peptides in the hippocampus of wild-type and Wfs1 KO mice. Results: We identified 126 peptides in hippocampal extracts and the levels of 10 peptides differed between Wfs1 KO and wild-type mice at P < 0.05. The peptide with the largest alteration was little-LEN, which level was 25 times higher in the hippocampus of Wfs1 KO mice compared to wild-type mice. Processing (cleavage) of little-LEN from the Pcsk1n gene product proSAAS involves prohormone convertase 2 (PC2). Thus, PC2 activity was measured in extracts prepared from the hippocampus of Wfs1 KO mice. The activity of PC2 in Wfs1 mutant mice was significantly higher (149.9 ± 2.3%, p < 0.0001, n = 8) than in wild-type mice (100.0 ± 7.0%, n = 8). However, Western blot analysis showed that protein levels of 7B2, proPC2 and PC2 were same in both groups, and so were gene expression levels. Conclusion: Processing of proSAAS is altered in the hippocampus of Wfs1-KO mice, which is caused by increased activity of PC2. Increased activity of PC2 in Wfs1 KO mice is not caused by alteration in the levels of PC2 protein. Our results suggest a functional link between Wfs1 and PC2. Thus, the detailed molecular mechanism of the role of Wfs1 in the regulation of PC2 activity needs further investigation. PMID:26379490

  1. Testing the Activity of Complement Convertases in Serum/Plasma for Diagnosis of C4NeF-Mediated C3 Glomerulonephritis.

    PubMed

    Blom, Anna M; Corvillo, Fernando; Magda, Michal; Stasiłojć, Grzegorz; Nozal, Pilar; Pérez-Valdivia, Miguel Ángel; Cabello-Chaves, Virginia; Rodríguez de Córdoba, Santiago; López-Trascasa, Margarita; Okrój, Marcin

    2016-07-01

    Autoantibodies termed C3-nephritic factor (C3NeF), which stabilize convertases of the alternative complement pathway, often stimulate autoinflammatory diseases. However, knowledge about analogous autoantibodies acting on the classical pathway (C4NeF) is limited to a few reports, which indicate association with kidney dysfunction, systemic lupus erythematous, and infections. C4NeF may appear independently from C3NeF, but the lack of a routine diagnostic method predisposes C4NeF for being an underestimated player in autoinflammatory episodes. We tested the activity of classical convertases directly in serum/plasma to screen samples from 13 patients with C3 glomerulopathies and identified one patient showing significantly prolonged half-life of these enzymes. Observed effect was reproduced by immunoglobulins purified from patient's plasma and additionally confirmed on classical convertase built from purified components. Isolated immunoglobulins protected classical convertases from both spontaneous and inhibitor-driven decay but not from C4b proteolysis. The patient had a decreased serum level of C3, elevated sC5b-9, and normal concentrations of factor B and C4. Neither C3NeF nor other autoantibodies directed against alternative pathway proteins (factor H, factor B, factor I, C3, and properdin) were found. Genetic analysis showed no mutations in C3, CFB, CFH, CFI, MCP, THBD, and DGKE genes. Renal biopsy revealed a membranoproliferative pattern with intense C3 deposits. Our results underline the importance of C4NeF as an independent pathogenic factor and a need for the implementation of routine examination of classical convertase activity. Proposed method may enable robust inspection of such atypical cases. PMID:27146825

  2. Inhibition of Prohormone Convertases PC1/3 and PC2 by 2,5-Dideoxystreptamine Derivatives

    PubMed Central

    Vivoli, Mirella; Caulfield, Thomas R.; Martínez-Mayorga, Karina; Johnson, Alan T.; Jiao, Guan-Sheng

    2012-01-01

    The prohormone convertases PC1/3 and PC2 are eukaryotic serine proteases involved in the proteolytic maturation of peptide hormone precursors and are implicated in a variety of pathological conditions, including obesity, diabetes, and neurodegenerative diseases. In this work, we screened 45 compounds obtained by derivatization of a 2,5-dideoxystreptamine scaffold with guanidinyl and aryl substitutions for convertase inhibition. We identified four promising PC1/3 competitive inhibitors and three PC2 inhibitors that exhibited various inhibition mechanisms (competitive, noncompetitive, and mixed), with sub- and low micromolar inhibitory potency against a fluorogenic substrate. Low micromolar concentrations of certain compounds blocked the processing of the physiological substrate proglucagon. The best PC2 inhibitor effectively inhibited glucagon synthesis, a known PC2-mediated process, in a pancreatic cell line; no cytotoxicity was observed. We also identified compounds that were able to stimulate both 87 kDa PC1/3 and PC2 activity, behavior related to the presence of aryl groups on the dideoxystreptamine scaffold. By contrast, inhibitory activity was associated with the presence of guanidinyl groups. Molecular modeling revealed interactions of the PC1/3 inhibitors with the active site that suggest structural modifications to further enhance potency. In support of kinetic data suggesting that PC2 inhibition probably occurs via an allosteric mechanism, we identified several possible allosteric binding sites using computational searches. It is noteworthy that one compound was found to both inhibit PC2 and stimulate PC1/3. Because glucagon acts in functional opposition to insulin in blood glucose homeostasis, blocking glucagon formation and enhancing proinsulin cleavage with a single compound could represent an attractive therapeutic approach in diabetes. PMID:22169851

  3. Mutational analysis of predicted interactions between the catalytic and P domains of prohormone convertase 3 (PC3/PC1)

    PubMed Central

    Ueda, Kazuya; Lipkind, Gregory M.; Zhou, An; Zhu, Xiaorong; Kuznetsov, Andrey; Philipson, Louis; Gardner, Paul; Zhang, Chunling; Steiner, Donald F.

    2003-01-01

    The subtilisin-like prohormone convertases (PCs) contain an essential downstream domain (P domain), which has been predicted to have a β-barrel structure that interacts with and stabilizes the catalytic domain (CAT). To assess possible sites of hydrophobic interaction, a series of mutant PC3–enhanced GFP constructs were prepared in which selected nonpolar residues on the surface of CAT were substituted by the corresponding polar residues in subtilisin Carlsberg. To investigate the folding potential of the isolated P domain, signal peptide–P domain–enhanced GFP constructs with mutated and/or truncated P domains were also made. All mutants were expressed in βTC3 cells, and their subcellular localization and secretion were determined. The mutants fell into three main groups: (i) Golgi/secreted, (ii) ER/nonsecreted, and (iii) apoptosis inducing. The destabilizing CAT mutations indicate that the side chains of V292, T328, L351, Q408, H409, V412, and F441 and nonpolar fragments of the side chains of R405 and W413 form a hydrophobic patch on CAT that interacts with the P domain. We also have found that the P domain can fold independently, as indicated by its secretion. Interestingly, T594, which is near the P domain C terminus, was not essential for P domain secretion but is crucial for the stability of intact PC3. T594V produced a stable enzyme, but T594D did not, which suggests that T594 participates in important hydrophobic interactions within PC3. These findings support our conclusion that the catalytic and P domains contribute to the folding and thermodynamic stability of the convertases through reciprocal hydrophobic interactions. PMID:12721373

  4. Chloroplast Elongation Factor Ts Pro-Protein Is an Evolutionarily Conserved Fusion with the S1 Domain-Containing Plastid-Specific Ribosomal Protein-7

    PubMed Central

    Beligni, María Verónica; Yamaguchi, Kenichi; Mayfield, Stephen P.

    2004-01-01

    The components of chloroplast translation are similar to those of prokaryotic translation but contain some additional unique features. Proteomic analysis of the Chlamydomonas reinhardtii chloroplast ribosome identified an S1-like protein, plastid-specific ribosomal protein-7 (PSRP-7), as a stoichiometric component of the 30S subunit. Here, we report that PSRP-7 is part of a polyprotein that contains PSRP-7 on its amino end and two translation elongation factor Ts (EF-Ts) domains at the carboxy end. We named this polyprotein PETs (for polyprotein of EF-Ts). Pets is a single-copy gene containing the only chloroplast PSRP-7 and EF-Ts sequences found in the C. reinhardtii genome. The pets precursor transcript undergoes alternative splicing to generate three mRNAs with open reading frames (ORFs) of 1.68, 1.8, and 3 kb. A 110-kD pro-protein is translated from the 3-kb ORF, and the majority of this protein is likely posttranslationally processed into the 65-kD protein PSRP-7 and a 55-kD EF-Ts. PETs homologs are found in Arabidopsis thaliana and rice (Oryza sativa). The conservation of the 110-kD PETs polyprotein in the plant kingdom suggests that PSRP-7 and EF-Ts function together in some aspects of chloroplast translation and that the PETs pro-protein may have a novel function as a whole. PMID:15548736

  5. Autoantibody stabilization of the classical pathway C3 convertase leading to C3 deficiency and Neisserial sepsis: C4 nephritic factor revisited

    PubMed Central

    Miller, Elizabeth C.; Chase, Nicole M.; Densen, Peter; Hintermeyer, Mary K.; Casper, James T.; Atkinson, John P.

    2012-01-01

    C3 deficiency is a rare disorder that leads to recurrent pyogenic infections. Here we describe a previously healthy 18 y/o Caucasian male with severe meningococcal disease. Total hemolytic activity was zero secondary to an undetectable C3. The C3 gene was normal by sequencing. Mixing the patient’s serum with normal human serum led to C3 consumption. An IgG autoantibody in the patient’s serum was identified that stabilized the classical pathway C3 and C5 convertases, thus preventing decay of these enzyme complexes. This autoantibody is an example of a C4 nephritic factor, with an additional feature of stabilizing the C5 convertase. Previous patients with C4 nephritic factor had membranoproliferative glomerulonephritis. Two years after presentation, this patient’s C3 remains undetectable with no evidence of renal disease. We revisit the role of autoantibodies to classical pathway convertases in disease, reviews the literature on C4-NeF and we comment on its detection in the clinical laboratory. PMID:23117396

  6. The fsr Quorum-Sensing System and Cognate Gelatinase Orchestrate the Expression and Processing of Proprotein EF_1097 into the Mature Antimicrobial Peptide Enterocin O16

    PubMed Central

    Dundar, Halil; Brede, Dag A.; La Rosa, Sabina Leanti; El-Gendy, Ahmed Osama; Diep, Dzung B.

    2015-01-01

    ABSTRACT A novel antimicrobial peptide designated enterocin O16 was purified from Enterococcus faecalis. Mass spectrometry showed a monoisotopic mass of 7,231 Da, and N-terminal Edman degradation identified a 29-amino-acid sequence corresponding to residues 90 to 119 of the EF_1097 protein. Bioinformatic analysis showed that enterocin O16 is composed of the 68 most C-terminal residues of the EF_1097 protein. Introduction of an in-frame isogenic deletion in the ef1097 gene abolished the production of enterocin O16. Enterocin O16 has a narrow inhibitory spectrum, as it inhibits mostly lactobacilli. Apparently, E. faecalis is intrinsically resistant to the antimicrobial peptide, as no immunity connected to the production of enterocin O16 could be identified. ef1097 has previously been identified as one of three loci regulated by the fsr quorum-sensing system. The introduction of a nonsense mutation into fsrB consistently impaired enterocin O16 production, but externally added gelatinase biosynthesis-activating pheromone restored the antimicrobial activity. Functional genetic analysis showed that the EF_1097 proprotein is processed extracellularly into enterocin O16 by the metalloprotease GelE. Thus, it is evident that the fsr quorum-sensing system constitutes the regulatory unit that controls the expression of the EF_1097 precursor protein and the protease GelE and that the latter is required for the formation of enterocin O16. On the basis of these results, this study identified antibacterial antagonism as a novel aspect related to the function of fsr and provides a rationale for why ef1097 is part of the fsr regulon. IMPORTANCE The fsr quorum-sensing system modulates important physiological functions in E. faecalis via the activity of GelE. The present study presents a new facet of fsr signaling. The system controls the expression of three primary target operons (fsrABCD, gelE-sprE, and ef1097-ef1097b). We demonstrate that the concerted expression of these operons

  7. Properdin can initiate complement activation by binding specific target surfaces and providing a platform for de novo convertase assembly.

    PubMed

    Spitzer, Dirk; Mitchell, Lynne M; Atkinson, John P; Hourcade, Dennis E

    2007-08-15

    Complement promotes the rapid recognition and elimination of pathogens, infected cells, and immune complexes. The biochemical basis for its target specificity is incompletely understood. In this report, we demonstrate that properdin can directly bind to microbial targets and provide a platform for the in situ assembly and function of the alternative pathway C3 convertases. This mechanism differs from the standard model wherein nascent C3b generated in the fluid phase attaches nonspecifically to its targets. Properdin-directed complement activation occurred on yeast cell walls (zymosan) and Neisseria gonorrhoeae. Properdin did not bind wild-type Escherichia coli, but it readily bound E. coli LPS mutants, and the properdin-binding capacity of each strain correlated with its respective serum-dependent AP activation rate. Moreover, properdin:single-chain Ab constructs were used to direct serum-dependent complement activation to novel targets. We conclude properdin participates in two distinct complement activation pathways: one that occurs by the standard model and one that proceeds by the properdin-directed model. The properdin-directed model is consistent with a proposal made by Pillemer and his colleagues >50 years ago. PMID:17675523

  8. Morphine treatment selectively regulates expression of rat pituitary POMC and the prohormone convertases PC1/3 and PC2

    PubMed Central

    Anghel, Adrian; Paez Espinosa, Enma V.; Stuart, Ronald C.; Lutfy, Kabirullah; Nillni, Eduardo A.; Friedman, Theodore C.

    2013-01-01

    The prohormone convertases, PC1/3 and PC2 are thought to be responsible for the activation of many prohormones through processing including the endogenous opioid peptides. We propose that maintenance of hormonal homeostasis can be achieved, in part, via alterations in levels of these enzymes that control the ratio of active hormone to prohormone. In order to test the hypothesis that exogenous opioids regulate the endogenous opioid system and the enzymes responsible for their biosynthesis, we studied the effect of short-term morphine or naltrexone treatment on pituitary PC1/3 and PC2 as well as on the level of pro-opiomelanocortin (POMC), the precursor gene for the biosynthesis of the endogenous opioid peptide, beta-endorphin. Using ribonuclease protection assays, we observed that morphine down-regulated and naltrexone up-regulated rat pituitary PC1/3 and PC2 mRNA. Immunofluorescence and Western blot analysis confirmed that the protein levels changed in parallel with the changes in mRNA levels and were accompanied by changes in the levels of phosphorylated cyclic-AMP response element binding protein. We propose that the alterations of the prohormone processing system may be a compensatory mechanism in response to an exogenous opioid ligand whereby the organism tries to restore its homeostatic hormonal milieu following exposure to the opioid, possibly by regulating the levels of multiple endogenous opioid peptides and other neuropeptides in concert. PMID:23891651

  9. ENCODE data at the ENCODE portal.

    PubMed

    Sloan, Cricket A; Chan, Esther T; Davidson, Jean M; Malladi, Venkat S; Strattan, J Seth; Hitz, Benjamin C; Gabdank, Idan; Narayanan, Aditi K; Ho, Marcus; Lee, Brian T; Rowe, Laurence D; Dreszer, Timothy R; Roe, Greg; Podduturi, Nikhil R; Tanaka, Forrest; Hong, Eurie L; Cherry, J Michael

    2016-01-01

    The Encyclopedia of DNA Elements (ENCODE) Project is in its third phase of creating a comprehensive catalog of functional elements in the human genome. This phase of the project includes an expansion of assays that measure diverse RNA populations, identify proteins that interact with RNA and DNA, probe regions of DNA hypersensitivity, and measure levels of DNA methylation in a wide range of cell and tissue types to identify putative regulatory elements. To date, results for almost 5000 experiments have been released for use by the scientific community. These data are available for searching, visualization and download at the new ENCODE Portal (www.encodeproject.org). The revamped ENCODE Portal provides new ways to browse and search the ENCODE data based on the metadata that describe the assays as well as summaries of the assays that focus on data provenance. In addition, it is a flexible platform that allows integration of genomic data from multiple projects. The portal experience was designed to improve access to ENCODE data by relying on metadata that allow reusability and reproducibility of the experiments. PMID:26527727

  10. ENCODE data at the ENCODE portal

    PubMed Central

    Sloan, Cricket A.; Chan, Esther T.; Davidson, Jean M.; Malladi, Venkat S.; Strattan, J. Seth; Hitz, Benjamin C.; Gabdank, Idan; Narayanan, Aditi K.; Ho, Marcus; Lee, Brian T.; Rowe, Laurence D.; Dreszer, Timothy R.; Roe, Greg; Podduturi, Nikhil R.; Tanaka, Forrest; Hong, Eurie L.; Cherry, J. Michael

    2016-01-01

    The Encyclopedia of DNA Elements (ENCODE) Project is in its third phase of creating a comprehensive catalog of functional elements in the human genome. This phase of the project includes an expansion of assays that measure diverse RNA populations, identify proteins that interact with RNA and DNA, probe regions of DNA hypersensitivity, and measure levels of DNA methylation in a wide range of cell and tissue types to identify putative regulatory elements. To date, results for almost 5000 experiments have been released for use by the scientific community. These data are available for searching, visualization and download at the new ENCODE Portal (www.encodeproject.org). The revamped ENCODE Portal provides new ways to browse and search the ENCODE data based on the metadata that describe the assays as well as summaries of the assays that focus on data provenance. In addition, it is a flexible platform that allows integration of genomic data from multiple projects. The portal experience was designed to improve access to ENCODE data by relying on metadata that allow reusability and reproducibility of the experiments. PMID:26527727

  11. amontillado, the Drosophila homolog of the prohormone processing protease PC2, is required during embryogenesis and early larval development.

    PubMed Central

    Rayburn, Lowell Y M; Gooding, Holly C; Choksi, Semil P; Maloney, Dhea; Kidd, Ambrose R; Siekhaus, Daria E; Bender, Michael

    2003-01-01

    Biosynthesis of most peptide hormones and neuropeptides requires proteolytic excision of the active peptide from inactive proprotein precursors, an activity carried out by subtilisin-like proprotein convertases (SPCs) in constitutive or regulated secretory pathways. The Drosophila amontillado (amon) gene encodes a homolog of the mammalian PC2 protein, an SPC that functions in the regulated secretory pathway in neuroendocrine tissues. We have identified amon mutants by isolating ethylmethanesulfonate (EMS)-induced lethal and visible mutations that define two complementation groups in the amon interval at 97D1 of the third chromosome. DNA sequencing identified the amon complementation group and the DNA sequence change for each of the nine amon alleles isolated. amon mutants display partial embryonic lethality, are defective in larval growth, and arrest during the first to second instar larval molt. Mutant larvae can be rescued by heat-shock-induced expression of the amon protein. Rescued larvae arrest at the subsequent larval molt, suggesting that amon is also required for the second to third instar larval molt. Our data indicate that the amon proprotein convertase is required during embryogenesis and larval development in Drosophila and support the hypothesis that AMON acts to proteolytically process peptide hormones that regulate hatching, larval growth, and larval ecdysis. PMID:12586710

  12. Isolation of C4-binding protein from guinea pig plasma and demonstration of its function as a control protein of the classical complement pathway C3 convertase.

    PubMed

    Burge, J; Nicholson-Weller, A; Austen, K F

    1981-01-01

    A decay-accelerating factor of the classical complement pathway C3 convertase, C4b,2a, has been purified to homogeneity from guinea pig plasma by a 5-step procedure that includes 5% polyethyleneglycol-4000 (PEG-4000) precipitation, Sepharose 6B gel filtration, heparin-Sepharose chromatography, DE-52 anion exchange chromatography, and Sepharose-C4gp affinity chromatography. The protein elicited a monospecific antiserum in a rabbit and was found with the Mancini technique in both normal and C4-deficient guinea pig plasma at a concentration of 60 microgram/ml. The purified protein gave a single stained band of 550,000 m.w. on SDS-PAGE under nonreducing conditions and a single band of 72,000 m.w. with reduction and alkylation. On the basis of its m.w. and subunit structure, ability to bind to a C4 affinity column, and ability to regulate the classical C system by accelerating the decay of the classical C3 convertase this protein represents the guinea pig analog of the human C4-binding protein. PMID:6778916

  13. Localization of the gene encoding peptidylglycine [alpha]-amidating monooxygenase (PAM) to human chromosome 5q14-5q21

    SciTech Connect

    Ouafik, L.H.; Giraud, P.; Oliver, C. ); Mattei, M.G. ); Eipper, B.A.; Mains, R.E. )

    1993-11-01

    Peptidylglycine [alpha]-amidating monooxygenase (PAM; EC 1.14.17.3) is a multifunctional protein containing two enzymes that act sequentially to catalyze the [alpha]-amidation of neuroendocrine peptides. Southern blot analysis of human placental DNA demonstrated that PAM is encoded by a single gene. The chromosomal localization of the PAM gene was established using in situ hybridization. A 2.2-kb human PAM cDNA hybridized to human metaphase chromosomes revealed a significant clustering of silver grains over chromosome 5 bands q14-q21. The gene encoding another enzyme important in the post-translational processing of neuroendocrine precursors, prohormone convertase 1 (PC1), is localized in the same region (5q15-q21). 14 refs., 2 figs.

  14. SPINK5, the defective gene in netherton syndrome, encodes multiple LEKTI isoforms derived from alternative pre-mRNA processing.

    PubMed

    Tartaglia-Polcini, Alessandro; Bonnart, Chrystelle; Micheloni, Alessia; Cianfarani, Francesca; Andrè, Alessandra; Zambruno, Giovanna; Hovnanian, Alain; D'Alessio, Marina

    2006-02-01

    The multidomain serine protease inhibitor lymphoepithelial Kazal-type related inhibitor (LEKTI) represents a key regulator of the proteolytic events occurring during epidermal barrier formation and hair development, as attested by the severe autosomal recessive ichthyosiform skin condition Netherton syndrome (NS) caused by mutations in its encoding gene, serine protease inhibitor Kazal-type 5 (SPINK5). Synthesized as a proprotein, LEKTI is rapidly cleaved intracellularly, thus generating a number of potentially bioactive fragments that are secreted. Here, we show that SPINK5 generates three classes of transcripts encoding three different LEKTI isoforms, which differ in their C-terminal portion. In addition to the previously described 15 domain isoform, SPINK5 encodes a shorter LEKTI isoform composed of only the first 13 domains, as well as a longer isoform carrying a 30-amino-acid residue insertion between the 13th and 14th inhibitory domains. We demonstrate that variable amounts of SPINK5 alternative transcripts are detected in all SPINK5 transcriptionally active tissues. Finally, we show that in differentiated cultured human keratinocytes all SPINK5 alternative transcripts are translated into protein and that the LEKTI precursors generate distinct secreted C-terminal proteolytic fragments from a similar cleavage site. Since several data indicate a biological role for the pro-LEKTI-cleaved polypeptides, we hypothesize that the alternative processing of the SPINK5 pre-messenger RNA represents an additional mechanism to further increase the structural and functional diversity of the LEKTI bioactive fragments. PMID:16374478

  15. Alignment system for encoders

    NASA Technical Reports Server (NTRS)

    Villani, Daniel D. (Inventor)

    1988-01-01

    An improved encoder alignment system is disclosed which provides an indication of the extent of misalignment and a measure of the rate at which the misalignment may be changing. The invention is adapted for use with a conventional encoder which provides a digital coarse word having at least significant bit and a digital fine word having a least significant bit and a most significant bit. The invention generates the exclusive or of the least significant bit of the coarse digital signal and the least significant bit of the fine digital signal to provide a first signal. The invention then generates the exclusive or of the first signal and the complement of the most significant bit of the fine digital signal to provide an output signal which represents the misalignment of the encoder.

  16. Polarization encoded color camera.

    PubMed

    Schonbrun, Ethan; Möller, Guðfríður; Di Caprio, Giuseppe

    2014-03-15

    Digital cameras would be colorblind if they did not have pixelated color filters integrated into their image sensors. Integration of conventional fixed filters, however, comes at the expense of an inability to modify the camera's spectral properties. Instead, we demonstrate a micropolarizer-based camera that can reconfigure its spectral response. Color is encoded into a linear polarization state by a chiral dispersive element and then read out in a single exposure. The polarization encoded color camera is capable of capturing three-color images at wavelengths spanning the visible to the near infrared. PMID:24690806

  17. [Effectiveness and tolerance of the C3 convertase inhibitor, N-acetyl-aspartyl-magnesium glutamate in perennial rhinitis. Results of a double-blind, placebo-controlled study].

    PubMed

    Harnest, U; Kiehn, R; Sieger, C; Weibel, M A

    1989-02-01

    N-Acetyl-aspartyl magnesium glutamate (Rhinaaxia, NAAGA) is a new antiallergic substance for topical use. The compound covers a bilateral way of action. There is inhibition of the mast cell-degranulation and blocking of the C3-convertase, subsequently followed by a blocked cleavage of the fragments C3a and C5a, respectively. 20 patients suffering from perennial allergic rhinitis were treated according to a randomized double blind placebo-controlled study design. Apart from a nominal documentation of subjective complaints the degree of nasal obstruction was objectively rated via rhinomanometria. The nasal flow rate improved significantly in patients treated with NAAGA and subjective complaints decreased markedly. NAAGA showed to be well tolerated although 6 of 10 patients observed transient "nasal burning". PMID:2659003

  18. Ghrelin, ghrelin-O-acyl transferase, nucleobindin-2/nesfatin-1 and prohormone convertases in the pancreatic islets of Sprague Dawley rats during development.

    PubMed

    Mohan, Haneesha; Gasner, Michaela; Ramesh, Naresh; Unniappan, Suraj

    2016-06-01

    Ghrelin and nesfatin-1 are regulators of blood glucose and energy balance. Prohormone convertases (PCs) enable processing of ghrelin and nesfatin-1 from its precursors. An acylation, enabled by ghrelin O-acyl transferase (GOAT) is critical for many of the biological actions of ghrelin. To date, there is no research on the developmental expression of GOAT, and the co-expression of both NUCB2/nesfatin-1 and prohormone convertases in the pancreas. The objective of this research was to immunolocalize ghrelin, GOAT, NUCB2/nesfatin-1, PC1/3 and PC2 in the pancreas during fetal and postnatal periods of Sprague Dawley (SD) rats using immunohistochemical analysis. GOAT mRNA in the rat pancreas during development was also determined. In the pancreas, not all islet cells immunopositive for GOAT are immunoreactive for ghrelin on postnatal (P) days 20, 27 and adult. GOAT mRNA expression in the pancreas at P27 was higher than the expression levels in rest of the developmental stages tested. Both PC1/3 and PC2 are co-expressed with NUCB2/nesfatin-1 on embryonic (E) day E21, P13, P20. While similar co-localization was also found in P27 for NUCB2/nesfatin-1 and PC1/3, NUCB2/nesfatin-1 and PC2 were found in distinct populations of cells in P27. Some ghrelin and GOAT positive cells stained for nesfatin-1 as well. Meanwhile, no co-localization of somatostatin and glucaon with nesfatin-1 was found in the pancreas of SD rats. Our findings suggest that the endocrine pancreas can produce and process precursors of ghrelin and nesfatin-1 to make bioactive forms of both peptides. PMID:27071923

  19. Time-Encoded Imagers.

    SciTech Connect

    Marleau, Peter; Brubaker, Erik

    2014-11-01

    This report provides a short overview of the DNN R&D funded project, Time-Encoded Imagers. The project began in FY11 and concluded in FY14. The Project Description below provides the overall motivation and objectives for the project as well as a summary of programmatic direction. It is followed by a short description of each task and the resulting deliverables.

  20. Video Time Encoding Machines

    PubMed Central

    Lazar, Aurel A.; Pnevmatikakis, Eftychios A.

    2013-01-01

    We investigate architectures for time encoding and time decoding of visual stimuli such as natural and synthetic video streams (movies, animation). The architecture for time encoding is akin to models of the early visual system. It consists of a bank of filters in cascade with single-input multi-output neural circuits. Neuron firing is based on either a threshold-and-fire or an integrate-and-fire spiking mechanism with feedback. We show that analog information is represented by the neural circuits as projections on a set of band-limited functions determined by the spike sequence. Under Nyquist-type and frame conditions, the encoded signal can be recovered from these projections with arbitrary precision. For the video time encoding machine architecture, we demonstrate that band-limited video streams of finite energy can be faithfully recovered from the spike trains and provide a stable algorithm for perfect recovery. The key condition for recovery calls for the number of neurons in the population to be above a threshold value. PMID:21296708

  1. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  2. Reed-Solomon Encoder

    NASA Technical Reports Server (NTRS)

    Troung, T. K.; Reed, I. S.; Deutsch, L. J.; Hsu, I. S.; Wang, K.; Yeh, C. S.

    1985-01-01

    Report presents mathematical principles of Berlekamp bit serial multiplier algorithm and its application to design of very-large-scale integrated (VLSI) encoders for Reed-Solomon error-correcting codes. Structure made readily on single chip of negatively doped channel metal oxide semiconductor.

  3. The Text Encoding Initiative: Flexible and Extensible Document Encoding.

    ERIC Educational Resources Information Center

    Barnard, David T.; Ide, Nancy M.

    1997-01-01

    The Text Encoding Initiative (TEI), an international collaboration aimed at producing a common encoding scheme for complex texts, examines the requirement for generality versus the requirement to handle specialized text types. Discusses how documents and users tax the limits of fixed schemes requiring flexible extensible encoding to support…

  4. VLSI Reed-Solomon Encoder

    NASA Technical Reports Server (NTRS)

    Liu, K. Y.

    1983-01-01

    Modular Reed-solomon encoder uses identical custom VLSI chips called "symbol slices." By cascading and properly interconnecting group of these chips, encoder is made for any desired error-correcting capability and interleaving level. VLSI encoder requires only one-tenth the number of chips required by conventional Reed-Solomon Circuit implemented with discrete IC's.

  5. Time encoded radiation imaging

    DOEpatents

    Marleau, Peter; Brubaker, Erik; Kiff, Scott

    2014-10-21

    The various technologies presented herein relate to detecting nuclear material at a large stand-off distance. An imaging system is presented which can detect nuclear material by utilizing time encoded imaging relating to maximum and minimum radiation particle counts rates. The imaging system is integrated with a data acquisition system that can utilize variations in photon pulse shape to discriminate between neutron and gamma-ray interactions. Modulation in the detected neutron count rates as a function of the angular orientation of the detector due to attenuation of neighboring detectors is utilized to reconstruct the neutron source distribution over 360 degrees around the imaging system. Neutrons (e.g., fast neutrons) and/or gamma-rays are incident upon scintillation material in the imager, the photons generated by the scintillation material are converted to electrical energy from which the respective neutrons/gamma rays can be determined and, accordingly, a direction to, and the location of, a radiation source identified.

  6. Rotary encoding device

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B. (Inventor)

    1993-01-01

    A device for position encoding of a rotating shaft in which a polygonal mirror having a number of facets is mounted to the shaft and a light beam is directed towards the facets is presented. The facets of the polygonal mirror reflect the light beam such that a light spot is created on a linear array detector. An analog-to-digital converter is connected to the linear array detector for reading the position of the spot on the linear array detector. A microprocessor with memory is connected to the analog-to-digital converter to hold and manipulate the data provided by the analog-to-digital converter on the position of the spot and to compute the position of the shaft based upon the data from the analog-to-digital converter.

  7. Linear encoding device

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B. (Inventor)

    1993-01-01

    A Linear Motion Encoding device for measuring the linear motion of a moving object is disclosed in which a light source is mounted on the moving object and a position sensitive detector such as an array photodetector is mounted on a nearby stationary object. The light source emits a light beam directed towards the array photodetector such that a light spot is created on the array. An analog-to-digital converter, connected to the array photodetector is used for reading the position of the spot on the array photodetector. A microprocessor and memory is connected to the analog-to-digital converter to hold and manipulate data provided by the analog-to-digital converter on the position of the spot and to compute the linear displacement of the moving object based upon the data from the analog-to-digital converter.

  8. Intestinal Bile Acid Composition Modulates Prohormone Convertase 1/3 (PC1/3) Expression and Consequent GLP-1 Production in Male Mice.

    PubMed

    Morimoto, Kohkichi; Watanabe, Mitsuhiro; Sugizaki, Taichi; Irie, Jun-ichiro; Itoh, Hiroshi

    2016-03-01

    Besides an established medication for hypercholesterolemia, bile acid binding resins (BABRs) present antidiabetic effects. Although the mechanisms underlying these effects are still enigmatic, glucagon-like peptide-1 (GLP-1) appears to be involved. In addition to a few reported mechanisms, we propose prohormone convertase 1/3 (PC1/3), an essential enzyme of GLP-1 production, as a potent molecule in the GLP-1 release induced by BABRs. In our study, the BABR colestimide leads to a bile acid-specific G protein-coupled receptor TGR5-dependent induction of PC1/3 gene expression. Here, we focused on the alteration of intestinal bile acid composition and consequent increase of total TGR5 agonistic activity to explain the TGR5 activation. Furthermore, we demonstrate that nuclear factor of activated T cells mediates the TGR5-triggered PC1/3 gene expression. Altogether, our data indicate that the TGR5-dependent intestinal PC1/3 gene expression supports the BABR-stimulated GLP-1 release. We also propose a combination of BABR and dipeptidyl peptidase-4 inhibitor in the context of GLP-1-based antidiabetic therapy. PMID:26789236

  9. [Effectiveness and tolerance of the C3 convertase inhibitor, N-acetyl-aspartyl-magnesium glutamate with anti-allergic action. Results of a double-blind study].

    PubMed

    Gastpar, H; Kiehn, R; Sieger, C; Weibel, M A

    1989-02-01

    N-Acetyl-aspartyl magnesium glutamate (Rhinaaxia, NAAGA) is a topically active antiallergic dipeptide. The compound acts in two different ways. On the one hand NAAGA inhibits the mast cell-degranulation, on the other hand this compound blocks the activation of the C3-convertase, subsequently followed by a blocked cleavage of the fragments C3a and C5a, respectively. 20 patients suffering from pollinosis were treated for 2 weeks according to a randomized double-blind placebo-controlled study. Besides subjective complaints nasal obstruction was objectively documented via rhinomanometria. 9 out of 10 patients under placebo had to use the rescue drug tritoqualine, a histidine decarboxylase inhibitor, compared to none in the verum group (p less than 0.01). After 14 days of treatment with NAAGA the nasal peak flow rate increased by 21.5 l/min and 21.8 l/min in the tritoqualine/placebo group, respectively (not significant). Nasal obstruction improved statistically significantly after 7 and 14 days of treatment in both groups. Tolerance was reported to be good in either group. PMID:2659002

  10. Space vehicle onboard command encoder

    NASA Technical Reports Server (NTRS)

    1975-01-01

    A flexible onboard encoder system was designed for the space shuttle. The following areas were covered: (1) implementation of the encoder design into hardware to demonstrate the various encoding algorithms/code formats, (2) modulation techniques in a single hardware package to maintain comparable reliability and link integrity of the existing link systems and to integrate the various techniques into a single design using current technology. The primary function of the command encoder is to accept input commands, generated either locally onboard the space shuttle or remotely from the ground, format and encode the commands in accordance with the payload input requirements and appropriately modulate a subcarrier for transmission by the baseband RF modulator. The following information was provided: command encoder system design, brassboard hardware design, test set hardware and system packaging, and software.

  11. N-Consecutive-Phase Encoder

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush; Lee, Ho-Kyoung; Weber, Charles

    1995-01-01

    N-consecutive-phase encoder (NCPE) is conceptual encoder for generating alphabet of N consecutive full-response continuous-phase-modulation (CPM) signals. Enables use of binary preencoder of higher rate than used with simple continuous-phase encoder (CPE). NCPE makes possible to achieve power efficiencies and bandwidth efficiencies greater than conventional trellis coders with continuous-phase frequency-shift keying (CPFSK).

  12. Prosodic Encoding in Silent Reading.

    ERIC Educational Resources Information Center

    Wilkenfeld, Deborah

    In silent reading, short-memory tasks, such as semantic and syntactic processing, require a stage of phonetic encoding between visual representation and the actual extraction of meaning, and this encoding includes prosodic as well as segmental features. To test for this suprasegmental coding, an experiment was conducted in which subjects were…

  13. Peri-encoding predictors of memory encoding and consolidation.

    PubMed

    Cohen, Noga; Pell, Liat; Edelson, Micah G; Ben-Yakov, Aya; Pine, Alex; Dudai, Yadin

    2015-03-01

    We review reports of brain activations that occur immediately prior to the onset or following the offset of to-be-remembered information and can predict subsequent mnemonic success. Memory-predictive pre-encoding processes, occurring from fractions of a second to minutes prior to event onset, are mainly associated with activations in the medial temporal lobe (MTL), amygdala and midbrain, and with enhanced theta oscillations. These activations may be considered as the neural correlates of one or more cognitive operations, including contextual processing, attention, and the engagement of distinct computational modes associated with prior encoding or retrieval. Post-encoding activations that correlate with subsequent memory performance are mainly observed in the MTL, sensory cortices and frontal regions. These activations may reflect binding of elements of the encoded information and initiation of memory consolidation. In all, the findings reviewed here illustrate the importance of brain states in the immediate peri-encoding time windows in determining encoding success. Understanding these brain states and their specific effects on memory may lead to optimization of the encoding of desired memories and mitigation of undesired ones. PMID:25446944

  14. Information encoder/decoder using chaotic systems

    DOEpatents

    Miller, Samuel Lee; Miller, William Michael; McWhorter, Paul Jackson

    1997-01-01

    The present invention discloses a chaotic system-based information encoder and decoder that operates according to a relationship defining a chaotic system. Encoder input signals modify the dynamics of the chaotic system comprising the encoder. The modifications result in chaotic, encoder output signals that contain the encoder input signals encoded within them. The encoder output signals are then capable of secure transmissions using conventional transmission techniques. A decoder receives the encoder output signals (i.e., decoder input signals) and inverts the dynamics of the encoding system to directly reconstruct the original encoder input signals.

  15. Information encoder/decoder using chaotic systems

    DOEpatents

    Miller, S.L.; Miller, W.M.; McWhorter, P.J.

    1997-10-21

    The present invention discloses a chaotic system-based information encoder and decoder that operates according to a relationship defining a chaotic system. Encoder input signals modify the dynamics of the chaotic system comprising the encoder. The modifications result in chaotic, encoder output signals that contain the encoder input signals encoded within them. The encoder output signals are then capable of secure transmissions using conventional transmission techniques. A decoder receives the encoder output signals (i.e., decoder input signals) and inverts the dynamics of the encoding system to directly reconstruct the original encoder input signals. 32 figs.

  16. Implication of TNF-alpha convertase (TACE/ADAM17) in inducible nitric oxide synthase expression and inflammation in an experimental model of colitis.

    PubMed

    Colón, A L; Menchén, L A; Hurtado, O; De Cristóbal, J; Lizasoain, I; Leza, J C; Lorenzo, P; Moro, M A

    2001-12-21

    Tumour necrosis factor-alpha (TNF-alpha) is a pro-inflammatory cytokine which is shed in its soluble form by a disintegrin and metalloproteinase (ADAM) called TNF-alpha convertase (TACE; ADAM17). TNF-alpha plays a role in inflammatory bowel disease (IBD) and is involved in the expression of inducible nitric oxide synthase (iNOS) which has also been implicated in IBD. The study was designed to investigate whether colitis induced by trinitrobenzene sulphonic acid (TNBS) in rats produces an increase in TACE activity and/or expression and whether its pharmacological inhibition reduces TNF-alpha levels, iNOS expression and colonic damage in this model. TNBS (30 mg in 0.4 ml of 50% ethanol) was instilled into the colon of female Wistar rats. Saline or TACE inhibitor BB1101 (10 mg/kg/day) was administered intraperitoneally 5 days after TNBS instillation. On day 10, colons were removed and assessed for pathological score, myeloperoxidase (MPO), NO synthase (NOS), TACE enzymatic activity and protein levels, colonic TNF-alpha and NOx- levels. Instillation of TNBS caused an increase in TACE activity and expression and the release of TNF-alpha. TNBS also resulted in iNOS expression and colonic damage. BB1101 blocked TNBS-induced increase in TACE activity, TNF-alpha release and iNOS expression. Concomitantly, BB1101 ameliorated TNBS-induced colonic damage and inflammation. TNBS causes TNF-alpha release by an increase in TACE activity and expression and this results in the expression of iNOS and subsequent inflammation, suggesting that TACE inhibition may prove useful as a therapeutic means in IBD. PMID:11884025

  17. Islets of Langerhans from prohormone convertase-2 knockout mice show α-cell hyperplasia and tumorigenesis with elevated α-cell neogenesis

    PubMed Central

    Jones, Huw B; Reens, Jaimini; Brocklehurst, Simon R; Betts, Catherine J; Bickerton, Sue; Bigley, Alison L; Jenkins, Richard P; Whalley, Nicky M; Morgan, Derrick; Smith, David M

    2014-01-01

    Antagonism of the effects of glucagon as an adjunct therapy with other glucose-lowering drugs in the chronic treatment of diabetes has been suggested to aggressively control blood glucose levels. Antagonism of glucagon effects, by targeting glucagon secretion or disabling the glucagon receptor, is associated with α-cell hyperplasia. We evaluated the influence of total glucagon withdrawal on islets of Langerhans using prohormone convertase-2 knockout mice (PC2-ko), in which α-cell hyperplasia is present from a young age and persists throughout life, in order to understand whether or not sustained glucagon deficit would lead to islet tumorigenesis. PC2-ko and wild-type (WT) mice were maintained drug-free, and cohorts of these groups sampled at 3, 12 and 18 months for plasma biochemical and morphological (histological, immunohistochemical, electron microscopical and image analytical) assessments. WT mice showed no islet tumours up to termination of the study, but PC2-ko animals displayed marked changes in islet morphology from α-cell hypertrophy/hyperplasia/atypical hyperplasia, to adenomas and carcinomas, these latter being first encountered at 6–8 months. Islet hyperplasias and tumours primarily consisted of α-cells associated to varying degrees with other islet endocrine cell types. In addition to substantial increases in islet neoplasia, increased α-cell neogenesis associated primarily with pancreatic duct(ule)s was present. We conclude that absolute blockade of the glucagon signal results in tumorigenesis and that the PC2-ko mouse represents a valuable model for investigation of islet tumours and pancreatic ductal neogenesis. PMID:24456331

  18. C3b inactivator in the rheumatic diseases. Measurement by radial immunodiffusion and by inhibition of formation of properdin pathway C3 convertase.

    PubMed Central

    Whaley, K; Schur, P H; Ruddy, S

    1976-01-01

    C3b inactivator (C3bINA) has been measured in biologic fluids by radial immunodiffusion using a monospecific antiserum prepared in rabbits, and by a hemolytic assay which measures the reduction in the capacity of EAC43 cells bearing limited C3b sites to form C3B, the alternative pathway C3 convertase. The radial immunodiffusion and hemolytic assays show a good correlation (r = 0.86 P less than 0.001). Measurement of C3bINA concentrations in the sera of patients with systemic lupus erythematosus showed that during exacerbations of disease activity C3bINA concentrations tended to be lower, usually in association with reductions in C4, C3, factor B, and properdin, and sometimes with reductions of the alternative pathway proteins, factor B, and properdin alone. Supranormal values for C3bINA were found in the sera of 14 of 20 patients with seropositive rheumatoid arthritis and 3 of 9 seronegative patients, but none of 7 patients with degenerative joint disease. Synovial fluid concentrations of C3bINA, after correction for total synovial fluid protein and serum concentration of the enzyme, were significantly reduced in patients with rheumatoid arthritis compared to patients with degenerative joint disease (P less than 0.05). In both serum and synovial fluid from patients with rheumatoid arthritis, there was a good correlation between the concentrations of C3bINA and those of C3, factor B, and properdin, but not that of C4, suggesting that levels of C3bINA may serve to modulate recruitment of the properdin amplification loop in this disease. PMID:819459

  19. Two digital video encoder circuits

    NASA Astrophysics Data System (ADS)

    Eldon, John A.

    1992-11-01

    Central to `multimedia' image processing is the desire to encode computer graphics data into a standard television signal, complete with line, field, and color subcarrier synchronizing information. The numerous incompatibilities between television and computer display standards render this operation far less trivial than it sounds to anyone who hasn't worked with both types of signals. To simplify the task of encoding computer graphics signals into standard NTSC (North America and Japan) or PAL (most of Europe) television format for display, broadcast, or recording, TRW LSI Products Inc. has introduced the two newest members of it multimedia integrated circuit family, the TMC22090 and TMC22190 digital video encoders.

  20. Expression of a human proprotein processing enzyme: correct cleavage of the von Willebrand factor precursor at a paired basic amino acid site.

    PubMed Central

    Wise, R J; Barr, P J; Wong, P A; Kiefer, M C; Brake, A J; Kaufman, R J

    1990-01-01

    Intracellular proteolytic processing of precursor polypeptides is an essential step in the maturation of many proteins, including plasma proteins, hormones, neuropeptides, and growth factors. Most frequently, propeptide cleavage occurs after paired basic amino acid residues. To date, no mammalian propeptide processing enzyme with such specificity has been purified or cloned and functionally characterized. We report the isolation and functional expression of a cDNA encoding a propeptide-cleaving enzyme from a human liver cell line. The encoded protein, called PACE (paired basic amino acid cleaving enzyme), has structural homology to the well-characterized subtilisin-like protease Kex2 from yeast. The functional specificity of PACE for mediating propeptide cleavage at paired basic amino acid residues was demonstrated by the enhancement of propeptide processing of human von Willebrand factor when coexpressed with PACE in COS-1 cells. Images PMID:2251280

  1. Serial position encoding of signs.

    PubMed

    Miozzo, Michele; Petrova, Anna; Fischer-Baum, Simon; Peressotti, Francesca

    2016-09-01

    Reduced short-term memory (STM) capacity has been reported for sign as compared to speech when items have to be recalled in a specific order. This difference has been attributed to a more precise and efficient serial position encoding in verbal STM (used for speech) than visuo-spatial STM (used for sign). We tested in the present investigation whether the reduced STM capacity with signs stems from a lack of positional encoding available in verbal STM. Error analyses reported in prior studies have revealed that positions are defined in verbal STM by distance from both the start and the end of the sequence (both-edges positional encoding scheme). Our analyses of the errors made by deaf participants with finger-spelled letters revealed that the both-edges positional encoding scheme underlies the STM representation of signs. These results indicate that the cause of the STM disadvantage is not the type of positional encoding but rather the difficulties in binding an item in visuo-spatial STM to its specific position in the sequence. Both-edges positional encoding scheme could be specific of sign, since it has not been found in visuo-spatial STM tasks conducted with hearing participants. PMID:27244095

  2. Prohormone convertase 2 (PC2) null mice have increased mu opioid receptor levels accompanied by altered morphine-induced antinociception, tolerance and dependence.

    PubMed

    Lutfy, K; Parikh, D; Lee, D L; Liu, Y; Ferrini, M G; Hamid, A; Friedman, T C

    2016-08-01

    Chronic morphine treatment increases the levels of prohormone convertase 2 (PC2) in brain regions involved in nociception, tolerance and dependence. Thus, we tested if PC2 null mice exhibit altered morphine-induced antinociception, tolerance and dependence. PC2 null mice and their wild-type controls were tested for baseline hot plate latency, injected with morphine (1.25-10mg/kg) and tested for antinociception 30min later. For tolerance studies, mice were tested in the hot plate test before and 30min following morphine (5mg/kg) on day 1. Mice then received an additional dose so that the final dose of morphine was 10mg/kg on this day. On days 2-4, mice received additional doses of morphine (20, 40 and 80mg/kg on days 1, 2, 3, and 4, respectively). On day 5, mice were tested in the hot plate test before and 30min following morphine (5mg/kg). For withdrawal studies, mice were treated with the escalating doses of morphine (10, 20, 40 and 80mg/kg) for 4days, implanted with a morphine pellet on day 5 and 3 days later injected with naloxone (1mg/kg) and signs of withdrawal were recorded. Morphine dose-dependently induced antinociception and the magnitude of this response was greater in PC2 null mice. Tolerance to morphine was observed in wild-type mice and this phenomenon was blunted in PC2 null mice. Withdrawal signs were also reduced in PC2 null mice. Immunohistochemical studies showed up-regulation of the mu opioid receptor (MOP) protein expression in the periaqueductal gray area, ventral tegmental area, lateral hypothalamus, medial hypothalamus, nucleus accumbens, and somatosensory cortex in PC2 null mice. Likewise, naloxone specific binding was increased in the brains of these mice compared to their wild-type controls. The results suggest that the PC2-derived peptides may play a functional role in morphine-induced antinociception, tolerance and dependence. Alternatively, lack of opioid peptides led to up-regulation of the MOP and altered morphine

  3. Gravity referenced elevation encoder development

    NASA Astrophysics Data System (ADS)

    Goddard, R. E.

    1993-05-01

    Recent progress in the development of a gravity-sensor-based instrument for determining the elevation angle of DSN antennas is described. The benefits of such a system include the capability to locate the Gravity Referenced Elevation Encoder (GREE) directly on the primary reflector (thus bypassing structural flexure and deformation error sources), anticipated lower maintenance costs compared to the present gimbal encoders, direct replaceability, or supplementation of the present gimbal encoders and the utilization of off-the-shelf components to construct the GREE. This article includes a description of the nominal GREE design. Test results on a laboratory breadboard model are given. Rigid-body dynamics of the GREE are derived and the simulated performance in response to measured antenna vibrations is given.

  4. Gravity referenced elevation encoder development

    NASA Technical Reports Server (NTRS)

    Goddard, R. E.

    1993-01-01

    Recent progress in the development of a gravity-sensor-based instrument for determining the elevation angle of DSN antennas is described. The benefits of such a system include the capability to locate the Gravity Referenced Elevation Encoder (GREE) directly on the primary reflector (thus bypassing structural flexure and deformation error sources), anticipated lower maintenance costs compared to the present gimbal encoders, direct replaceability, or supplementation of the present gimbal encoders and the utilization of off-the-shelf components to construct the GREE. This article includes a description of the nominal GREE design. Test results on a laboratory breadboard model are given. Rigid-body dynamics of the GREE are derived and the simulated performance in response to measured antenna vibrations is given.

  5. Fly Photoreceptors Encode Phase Congruency

    PubMed Central

    Friederich, Uwe; Billings, Stephen A.; Hardie, Roger C.; Juusola, Mikko; Coca, Daniel

    2016-01-01

    More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli. PMID:27336733

  6. Fly Photoreceptors Encode Phase Congruency.

    PubMed

    Friederich, Uwe; Billings, Stephen A; Hardie, Roger C; Juusola, Mikko; Coca, Daniel

    2016-01-01

    More than five decades ago it was postulated that sensory neurons detect and selectively enhance behaviourally relevant features of natural signals. Although we now know that sensory neurons are tuned to efficiently encode natural stimuli, until now it was not clear what statistical features of the stimuli they encode and how. Here we reverse-engineer the neural code of Drosophila photoreceptors and show for the first time that photoreceptors exploit nonlinear dynamics to selectively enhance and encode phase-related features of temporal stimuli, such as local phase congruency, which are invariant to changes in illumination and contrast. We demonstrate that to mitigate for the inherent sensitivity to noise of the local phase congruency measure, the nonlinear coding mechanisms of the fly photoreceptors are tuned to suppress random phase signals, which explains why photoreceptor responses to naturalistic stimuli are significantly different from their responses to white noise stimuli. PMID:27336733

  7. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 47 Telecommunication 1 2012-10-01 2012-10-01 false EAS Encoder. 11.32 Section 11.32 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11.32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol described in § 11.31 and providing the EAS...

  8. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 47 Telecommunication 1 2014-10-01 2014-10-01 false EAS Encoder. 11.32 Section 11.32 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11.32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol described in § 11.31 and providing the EAS...

  9. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false EAS Encoder. 11.32 Section 11.32 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL EMERGENCY ALERT SYSTEM (EAS) Equipment Requirements § 11.32 EAS Encoder. (a) EAS Encoders must at a minimum be capable of encoding the EAS protocol described in § 11.31 and providing the EAS...

  10. How Infants Encode Spatial Extent

    ERIC Educational Resources Information Center

    Duffy, Sean; Huttenlocher, Janellen; Levine, Susan; Duffy, Renee

    2005-01-01

    This study explores how infants encode an object's spatial extent. We habituated 6.5-month-old infants to a dowel inside a container and then tested whether they dishabituate to a change in absolute size when the relation between dowel and container is held constant (by altering the size of both container and dowel) and when the relation changes…

  11. Shaft encoder presents digital output

    NASA Technical Reports Server (NTRS)

    Hillis, D. A.

    1966-01-01

    Circuits that include compensation circuitry time a capacitance relative to a reference voltage so that a digital presentation occurs that is representative of the positional condition of the mechanical shaft being monitored. This circuitry may be employed in multiples to furnish binary encoding of a number of rotating devices simultaneously.

  12. Encoding Standards for Linguistic Corpora.

    ERIC Educational Resources Information Center

    Ide, Nancy

    The demand for extensive reusability of large language text collections for natural languages processing research requires development of standardized encoding formats. Such formats must be capable of representing different kinds of information across the spectrum of text types and languages, capable of representing different levels of…

  13. Monolithic-integrated microlaser encoder.

    PubMed

    Sawada, R; Higurashi, E; Ito, T; Ohguchi, O; Tsubamoto, M

    1999-11-20

    We have developed an extremely small integrated microencoder whose sides are less than 1 mm long. It is 1/100 the size of conventional encoders. This microencoder consists of a laser diode, monolithic photodiodes, and fluorinated polyimide waveguides with total internal reflection mirrors. The instrument can measure the relative displacement between a grating scale and the encoder with a resolution of the order of 0.01 microm; it can also determine the direction in which the scale is moving. By using the two beams that were emitted from the two etched mirrors of the laser diode, by monolithic integration of the waveguide and photodiodes, and by fabrication of a step at the edge of the waveguide, we were able to eliminate conventional bulky optical components such as the beam splitter, the quarter-wavelength plate, bulky mirrors, and bulky photodetectors. PMID:18324228

  14. The PsychENCODE project

    PubMed Central

    Akbarian, Schahram; Liu, Chunyu; Knowles, James A; Vaccarino, Flora M; Farnham, Peggy J; Crawford, Gregory E; Jaffe, Andrew E; Pinto, Dalila; Dracheva, Stella; Geschwind, Daniel H; Mill, Jonathan; Nairn, Angus C; Abyzov, Alexej; Pochareddy, Sirisha; Prabhakar, Shyam; Weissman, Sherman; Sullivan, Patrick F; State, Matthew W; Weng, Zhiping; Peters, Mette A; White, Kevin P; Gerstein, Mark B; Senthil, Geetha; Lehner, Thomas; Sklar, Pamela; Sestan, Nenad

    2015-01-01

    Recent research on disparate psychiatric disorders has implicated rare variants in genes involved in global gene regulation and chromatin modification, as well as many common variants located primarily in regulatory regions of the genome. Understanding precisely how these variants contribute to disease will require a deeper appreciation for the mechanisms of gene regulation in the developing and adult human brain. The PsychENCODE project aims to produce a public resource of multidimensional genomic data using tissue- and cell type–specific samples from approximately 1,000 phenotypically well-characterized, high-quality healthy and disease-affected human post-mortem brains, as well as functionally characterize disease-associated regulatory elements and variants in model systems. We are beginning with a focus on autism spectrum disorder, bipolar disorder and schizophrenia, and expect that this knowledge will apply to a wide variety of psychiatric disorders. This paper outlines the motivation and design of PsychENCODE. PMID:26605881

  15. Nonconjugative Plasmids Encoding Sulfanilamide Resistance

    PubMed Central

    Mitsuhashi, Susumu; Inoue, Kunio; Inoue, Matsuhisa

    1977-01-01

    Nonconjugative plasmids encoding sulfanilamide (Sa) resistance were demonstrated at a high frequency in Shigella and Escherichia coli strains resistant to sulfanilamide. These Sa plasmids were all compatible with the standard plasmids used in compatibility testing. The sizes of seven Sa plasmids were measured by electron microscopy and ranged from 1.79 to 2.08 μm, corresponding to 3.5 to 3.9 megadaltons. Images PMID:334067

  16. Lessons from modENCODE.

    PubMed

    Brown, James B; Celniker, Susan E

    2015-01-01

    The modENCODE (Model Organism Encyclopedia of DNA Elements) Consortium aimed to map functional elements-including transcripts, chromatin marks, regulatory factor binding sites, and origins of DNA replication-in the model organisms Drosophila melanogaster and Caenorhabditis elegans. During its five-year span, the consortium conducted more than 2,000 genome-wide assays in developmentally staged animals, dissected tissues, and homogeneous cell lines. Analysis of these data sets provided foundational insights into genome, epigenome, and transcriptome structure and the evolutionary turnover of regulatory pathways. These studies facilitated a comparative analysis with similar data types produced by the ENCODE Consortium for human cells. Genome organization differs drastically in these distant species, and yet quantitative relationships among chromatin state, transcription, and cotranscriptional RNA processing are deeply conserved. Of the many biological discoveries of the modENCODE Consortium, we highlight insights that emerged from integrative studies. We focus on operational and scientific lessons that may aid future projects of similar scale or aims in other, emerging model systems. PMID:26133010

  17. Vector Encoding in Biochemical Networks

    NASA Astrophysics Data System (ADS)

    Potter, Garrett; Sun, Bo

    Encoding of environmental cues via biochemical signaling pathways is of vital importance in the transmission of information for cells in a network. The current literature assumes a single cell state is used to encode information, however, recent research suggests the optimal strategy utilizes a vector of cell states sampled at various time points. To elucidate the optimal sampling strategy for vector encoding, we take an information theoretic approach and determine the mutual information of the calcium signaling dynamics obtained from fibroblast cells perturbed with different concentrations of ATP. Specifically, we analyze the sampling strategies under the cases of fixed and non-fixed vector dimension as well as the efficiency of these strategies. Our results show that sampling with greater frequency is optimal in the case of non-fixed vector dimension but that, in general, a lower sampling frequency is best from both a fixed vector dimension and efficiency standpoint. Further, we find the use of a simple modified Ornstein-Uhlenbeck process as a model qualitatively captures many of our experimental results suggesting that sampling in biochemical networks is based on a few basic components.

  18. Hall effect encoding of brushless dc motors

    NASA Technical Reports Server (NTRS)

    Berard, C. A.; Furia, T. J.; Goldberg, E. A.; Greene, R. C.

    1970-01-01

    Encoding mechanism integral to the motor and using the permanent magnets embedded in the rotor eliminates the need for external devices to encode information relating the position and velocity of the rotating member.

  19. Novel optical encoder for harsh environments

    NASA Astrophysics Data System (ADS)

    Kress, Bernard; Mueller, Ulrich; Brac-de-la-Perriere, Vincent

    2014-09-01

    We are presenting a new optical encoder architecture for shaft encoding, both in incremental and absolute modes. This encoder is based on a diffractive optics technology platform. We have developed various disk based rotary diffractive encoders previously. This encoder is different in the way it is not a disk composed of successive gratings or computer generated holograms, but rather composed of a single element placed on the shaft. It is thus best suited for hollow shaft or end of shaft applications such as in encoder controlled electrical motors. This new architecture aims at solving some of the problems encountered with previous implementations of diffractive encoders such as disk wobble, disk to shaft centering and also encoding in harsh environments.

  20. Jam-resistant speech encoding

    NASA Astrophysics Data System (ADS)

    Poole, M. A.; Rifkin, R.

    1983-06-01

    This report describes techniques that provide increased jam resistance for digitized speech. Methods for increasing the jam resistance of pulse code modulated data are analyzed and evaluated in listener tests. Special emphasis is placed on new voice encoding approaches that take advantage of a spread spectrum system with a variable (or multiple)-data-rate/variable (or multiple)-AJ capability. Methods for matching a source to a channel in a jamming environment are investigated. Several techniques that provide about a 4 dB increase in jam resistance have been identified.

  1. Time Course of Grammatical Encoding in Agrammatism

    ERIC Educational Resources Information Center

    Lee, Jiyeon

    2011-01-01

    Producing a sentence involves encoding a preverbal message into a grammatical structure by retrieving lexical items and integrating them into a functional (semantic-to-grammatical) structure. Individuals with agrammatism are impaired in this grammatical encoding process. However, it is unclear what aspect of grammatical encoding is impaired and…

  2. Schematic driven layout of Reed Solomon encoders

    NASA Technical Reports Server (NTRS)

    Arave, Kari; Canaris, John; Miles, Lowell; Whitaker, Sterling

    1992-01-01

    Two Reed Solomon error correcting encoders are presented. Schematic driven layout tools were used to create the encoder layouts. Special consideration had to be given to the architecture and logic to provide scalability of the encoder designs. Knowledge gained from these projects was used to create a more flexible schematic driven layout system.

  3. Angular encoding in attosecond recollision

    NASA Astrophysics Data System (ADS)

    Kitzler, Markus; Xie, Xinhua; Roither, Stefan; Scrinzi, Armin; Baltuska, Andrius

    2008-02-01

    We describe a general concept of using the spatial information encoded in the time-dependent polarization of high harmonic radiation generated by orthogonally polarized two-color laser fields. The main properties of recolliding electron wave packets driven by such fields are reviewed. It is shown that in addition to the recollision energy the angle of recollision of such wave packets, which is directly mapped onto the polarization direction of the emitted high harmonic radiation, varies on a sub-laser-cycle time-scale. Thus, a mapping between the polarization angle and the frequency of the emitted radiation is established on an attosecond time scale. While the polarization angle encodes the spatial properties of the recollision process, the frequency is linked to time via the well-known dispersion relations of high harmonic generation. Based on these principles, we show that in combination with polarization selective detection the use of orthogonally polarized drive pulses for high harmonic generation permit one to construct spatially resolved attosecond measurements. Here, we present two examples of possible applications: (i) a method for isolating a single attosecond pulse from an attosecond pulse train which is more efficient than the cut-off selection method, and (ii) a technique for orbital tomography of molecules with attosecond resolution.

  4. Reconstruction of turbo-code encoders

    NASA Astrophysics Data System (ADS)

    Barbier, Johann

    2005-06-01

    Turbo-code encoders are one of the spreadest family of error correcting codes used in the communication's world, especially in space transmissions. This paper presents an efficient technique to reconstruct turbo-code encoders which allows a passive adversary, with only few bits of an intercepted message encoded by the target turbocode encoder, to determine the parameters of the turbo-code encoder used, and therefore to decode online the communications. Thereby, our results confirm that keeping secret the parameters of turbo-code encoders can not be considered as a cryptographically way to ensure confidentiality. The starting point of our work is algorithms due to Filiol which enable to find the parameters of each convolutional encoder in the turbo-code encoder. Then, we recover the interleaver with two new algorithms, the first one based on the dynamic trie structure and the second one on a first order statistical test. The first algorithm is dedicated to noiseless channels. The asymptotic complexity of the complete process is O(n4) when a n2-bit message is available to attack a n-bit turbo-code encoder. The second algorithm works for every kind of channel and the noise does not matter much. Additionally, we present experimental results which underline the right detection threshold to use to recover the interleaver with a high probability. Furthermore, this method also works for turbo-code encoders composed of punctured convolutional encoders.

  5. Molecular mechanisms for protein-encoded inheritance

    SciTech Connect

    Wiltzius, Jed J.W.; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R.; Apostol, Marcin I.; Goldschmidt, Lukasz; Soriaga, Angela B.; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

    2009-12-01

    In prion inheritance and transmission, strains are phenotypic variants encoded by protein 'conformations'. However, it is unclear how a protein conformation can be stable enough to endure transmission between cells or organisms. Here we describe new polymorphic crystal structures of segments of prion and other amyloid proteins, which offer two structural mechanisms for the encoding of prion strains. In packing polymorphism, prion strains are encoded by alternative packing arrangements (polymorphs) of {beta}-sheets formed by the same segment of a protein; in segmental polymorphism, prion strains are encoded by distinct {beta}-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring conformations capable of encoding strains. These molecular mechanisms for transfer of protein-encoded information into prion strains share features with the familiar mechanism for transfer of nucleic acid-encoded information into microbial strains, including sequence specificity and recognition by noncovalent bonds.

  6. Novelty's effect on memory encoding.

    PubMed

    Rangel-Gomez, Mauricio; Janenaite, Sigita; Meeter, Martijn

    2015-07-01

    It is often thought that novelty benefits memory formation. However, support for this idea mostly comes from paradigms that are open to alternative explanations. In the present study we manipulated novelty in a word-learning task through task-irrelevant background images. These background images were either standard (presented repeatedly), or novel (presented only once). Two types of background images were used: Landscape pictures and fractals. EEG was also recorded during encoding. Contrary to the idea that novelty aids memory formation, memory performance was not affected by the novelty of the background. In the evoked response potentials, we found evidence of distracting effects of novelty: both the N1 and P3b components were smaller to words studied with novel backgrounds, and the amplitude of the N2b component correlated negatively with subsequent retrieval. We conclude that although evidence from other studies does suggest benefits on a longer time scale, novelty has no instantaneous benefits for learning. PMID:26005196

  7. Digital plus analog output encoder

    NASA Technical Reports Server (NTRS)

    Hafle, R. S. (Inventor)

    1976-01-01

    The disclosed encoder is adapted to produce both digital and analog output signals corresponding to the angular position of a rotary shaft, or the position of any other movable member. The digital signals comprise a series of binary signals constituting a multidigit code word which defines the angular position of the shaft with a degree of resolution which depends upon the number of digits in the code word. The basic binary signals are produced by photocells actuated by a series of binary tracks on a code disc or member. The analog signals are in the form of a series of ramp signals which are related in length to the least significant bit of the digital code word. The analog signals are derived from sine and cosine tracks on the code disc.

  8. Engineering Genetically Encoded FRET Sensors

    PubMed Central

    Lindenburg, Laurens; Merkx, Maarten

    2014-01-01

    Förster Resonance Energy Transfer (FRET) between two fluorescent proteins can be exploited to create fully genetically encoded and thus subcellularly targetable sensors. FRET sensors report changes in energy transfer between a donor and an acceptor fluorescent protein that occur when an attached sensor domain undergoes a change in conformation in response to ligand binding. The design of sensitive FRET sensors remains challenging as there are few generally applicable design rules and each sensor must be optimized anew. In this review we discuss various strategies that address this shortcoming, including rational design approaches that exploit self-associating fluorescent domains and the directed evolution of FRET sensors using high-throughput screening. PMID:24991940

  9. Molecular cloning and expression of prohormone convertases PC1 and PC2 in the pituitary gland of the bullfrog, Rana catesbeiana.

    PubMed

    Yaoi, Yuichi; Suzuki, Masakazu; Tomura, Hideaki; Kikuyama, Sakae; Tanaka, Shigeyasu

    2003-09-01

    We cloned cDNAs encoding PC1 and PC2 from a cDNA library constructed for the anterior pituitary gland of the bullfrog (Rana catesbeiana) and sequenced them. The bullfrog PC1 cDNA consisted of 2972 base pairs (bp) with an open reading frame of 2208 bp and encoded a protein of 736 amino acids, including a putative signal peptide of 26 amino acids. The protein showed a high homology to R. ridibunda PC1 (95.1%) and mammalian PC1 (72.6%). The bullfrog PC2 cDNA consisted of 2242 bp with an open reading frame of 1914 bp and encoded a protein of 638 amino acids, including a putative signal peptide of 23 amino acids. This protein showed a high homology to R. ridibunda PC2 (95.5%) and mammalian PC2 (84.8%). The catalytic triad of serine proteinases of the subtilisin family was found at Asp-168, His-209, and Ser-383 in the PC1 protein and at Asp-167, His-208, and Ser-384 in the PC2 protein. In situ hybridization staining revealed that PC2 mRNA was detected in corticotrope cells of the tadpoles, but not in those of the adults. In the adult, only PC1 mRNA was detected in the pars distalis but both PC1 and PC2 mRNAs were detected in the pars intermedia. The data also showed that PC1 mRNA was expressed in gonadotrope cells. PMID:14578575

  10. Control Circuit For Reed-Solomon Encoder

    NASA Technical Reports Server (NTRS)

    Ross, Douglas

    1992-01-01

    Control circuit designed for use with commercially available AHA4610 Reed-Solomon encoder. Needed to select depth of interleaving and to synchronize input and output blocks of data and parity bits with suitable clock signals. Circuit provides synchronizing and control signals for Reed-Solomon encoder. Encoder can operate with asynchronous input and output data streams at rates up to 80 Mb/s. Interleaving depth selectable, and accommodation to input data rate automatic.

  11. NMDA receptors and memory encoding.

    PubMed

    Morris, Richard G M

    2013-11-01

    It is humbling to think that 30 years have passed since the paper by Collingridge, Kehl and McLennan showing that one of Jeff Watkins most interesting compounds, R-2-amino-5-phosphonopentanoate (d-AP5), blocked the induction of long-term potentiation in vitro at synapses from area CA3 of the hippocampus to CA1 without apparent effect on baseline synaptic transmission (Collingridge et al., 1983). This dissociation was one of the key triggers for an explosion of interest in glutamate receptors, and much has been discovered since that collectively contributes to our contemporary understanding of glutamatergic synapses - their biophysics and subunit composition, of the agonists and antagonists acting on them, and their diverse functions in different networks of the brain and spinal cord. It can be fairly said that Collingridge et al.'s (1983) observation was the stimulus that has led, on the one hand, to structural biological work at the atomic scale describing the key features of NMDA receptors that enables their coincidence function to happen; and, on the other, to work with whole animals investigating the contributions that calcium signalling via this receptor can have on rhythmical activities controlled by spinal circuits, memory encoding in the hippocampus (the topic of this article), visual cortical plasticity, sensitization in pain, and other functions. In this article, I lay out how my then interest in long-term potentiation (LTP) as a model of memory enabled me to recognise the importance of Collingridge et al.'s discovery - and how I and my colleagues endeavoured to take things forward in the area of learning and memory. This is in some respects a personal story, and I tell it as such. The idea that NMDA receptor activation is essential for memory encoding, though not for storage, took time to develop and to be accepted. Along the way, there have been confusions, challenges, and surprises surrounding the idea that activation of NMDA receptors can

  12. Encoders for block-circulant LDPC codes

    NASA Technical Reports Server (NTRS)

    Andrews, Kenneth; Dolinar, Sam; Thorpe, Jeremy

    2005-01-01

    In this paper, we present two encoding methods for block-circulant LDPC codes. The first is an iterative encoding method based on the erasure decoding algorithm, and the computations required are well organized due to the block-circulant structure of the parity check matrix. The second method uses block-circulant generator matrices, and the encoders are very similar to those for recursive convolutional codes. Some encoders of the second type have been implemented in a small Field Programmable Gate Array (FPGA) and operate at 100 Msymbols/second.

  13. Unconscious relational encoding depends on hippocampus

    PubMed Central

    Duss, Simone B.; Reber, Thomas P.; Hänggi, Jürgen; Schwab, Simon; Wiest, Roland; Müri, René M.; Brugger, Peter; Gutbrod, Klemens

    2014-01-01

    Textbooks divide between human memory systems based on consciousness. Hippocampus is thought to support only conscious encoding, while neocortex supports both conscious and unconscious encoding. We tested whether processing modes, not consciousness, divide between memory systems in three neuroimaging experiments with 11 amnesic patients (mean age = 45.55 years, standard deviation = 8.74, range = 23–60) and 11 matched healthy control subjects. Examined processing modes were single item versus relational encoding with only relational encoding hypothesized to depend on hippocampus. Participants encoded and later retrieved either single words or new relations between words. Consciousness of encoding was excluded by subliminal (invisible) word presentation. Amnesic patients and controls performed equally well on the single item task activating prefrontal cortex. But only the controls succeeded on the relational task activating the hippocampus, while amnesic patients failed as a group. Hence, unconscious relational encoding, but not unconscious single item encoding, depended on hippocampus. Yet, three patients performed normally on unconscious relational encoding in spite of amnesia capitalizing on spared hippocampal tissue and connections to language cortex. This pattern of results suggests that processing modes divide between memory systems, while consciousness divides between levels of function within a memory system. PMID:25273998

  14. Perceptually adapted MPEG video encoding

    NASA Astrophysics Data System (ADS)

    Bordes, Philippe; Guillotel, Philippe

    2000-06-01

    In picture quality assessment, the amount of distortion perceived by a human observer differs from one region to another according to its particular local content. This subjective perception can be explained/predicted by considering some simple psychovisual properties (masking) of the Human Visual System (HVS). We have implemented a HVS model based on a pyramid decomposition for extracting the spatial frequencies, associated with a multi-resolution motion representation. Then the visibility of the decoded errors is computed by exploiting the Kelly's contrast sensitivity spatio-velocity model. The resulting data is called a 'Quality-map.' Special attention has been paid to temporal/moving effects since, in the case of video sequences, motion strongly influences the subjective quality assessment. The quality of the motion information is thus preponderant. In the second part, two possible uses of these psychovisual properties for improving MPEG video encoding performances are depicted: (1) The pre-processing of the pictures to remove non-visible information using a motion adapted filtering. This process is efficient in term of bits saved and degradation is not significant especially on consumer electronic TV sets. (2) A perceptual quantizer based on a local adaptation scheme in order to obtain Quality-maps as uniform as possible (homogeneous perceived distortion), at constant bit-rate. Further improvements have been considered, especially when the viewer is tracking a moving object in the scene.

  15. Evaluation of GOES encoder lamps

    NASA Technical Reports Server (NTRS)

    Viehmann, W.; Helmold, N.

    1983-01-01

    Aging characteristics and life expectancies of flight quality, tungsten filament, encoder lamps are similar to those of 'commercial' grade gas filled lamps of similar construction, filament material and filament temperature. The aging and final failure by filament burnout are caused by single crystal growth over large portions of the filament with the concomitant development of facets and notches resulting in reduction of cross section and mechanical weakening of the filament. The life expectancy of presently produced lamps is about one year at their nominal operating voltage of five volts dc. At 4.5 volts, it is about two years. These life times are considerably shorter, and the degradation rates of lamp current and light flux are considerably higher, than were observed in the laboratory and in orbit on lamps of the same type manufactured more than a decade ago. It is speculated that the filaments of these earlier lamps contained a crystallization retarding dopant, possibly thorium oxide. To obtain the desired life expectancy of or = to four years in present lamps, operating voltages of or = to four volts dc would be required.

  16. Evidence for an interaction of the metalloprotease-disintegrin tumour necrosis factor alpha convertase (TACE) with mitotic arrest deficient 2 (MAD2), and of the metalloprotease-disintegrin MDC9 with a novel MAD2-related protein, MAD2beta.

    PubMed Central

    Nelson, K K; Schlöndorff, J; Blobel, C P

    1999-01-01

    Metalloprotease-disintegrins are a family of transmembrane glycoproteins that have a role in fertilization, sperm migration, myoblast fusion, neural development and ectodomain shedding. In the present study we used the yeast two-hybrid system to search for proteins that interact with the cytoplasmic domain of two metalloprotease-disintegrins, tumour necrosis factor alpha convertase (TACE; ADAM17) and MDC9 (ADAM9; meltrin gamma). We have identified mitotic arrest deficient 2 (MAD2) as a binding partner of the TACE cytoplasmic domain, and a novel MAD2-related protein, MAD2beta, as a binding partner of the MDC9 cytoplasmic domain. MAD2beta has 23% sequence identity with MAD2, which is a component of the spindle assembly (or mitotic) checkpoint mechanism. Northern blot analysis of human tissues indicates that MAD2beta mRNA is expressed ubiquitously. The interaction of the TACE and MDC9 cytoplasmic domains with their binding partners has been confirmed biochemically. The independent identification of MAD2 and MAD2beta as potential interacting partners of distinct metalloprotease-disintegrins raises the possibility of a link between metalloprotease-disintegrins and the cell cycle, or of functions for MAD2 and MAD2beta that are not related to cell cycle control. PMID:10527948

  17. Encoding and decoding in fMRI

    PubMed Central

    Naselaris, Thomas; Kay, Kendrick N.; Nishimoto, Shinji; Gallant, Jack L.

    2010-01-01

    Over the past decade fMRI researchers have developed increasingly sensitive techniques for analyzing the information represented in BOLD activity. The most popular of these techniques is linear classification, a simple technique for decoding information about experimental stimuli or tasks from patterns of activity across an array of voxels. A more recent development is the voxel-based encoding model, which describes the information about the stimulus or task that is represented in the activity of single voxels. Encoding and decoding are complementary operations: encoding uses stimuli to predict activity while decoding uses activity to predict information about stimuli. However, in practice these two operations are often confused, and their respective strengths and weaknesses have not been made clear. Here we use the concept of a linearizing feature space to clarify the relationship between encoding and decoding. We show that encoding and decoding operations can both be used to investigate some of the most common questions about how information is represented in the brain. However, focusing on encoding models offers two important advantages over decoding. First, an encoding model can in principle provide a complete functional description of a region of interest, while a decoding model can provide only a partial description. Second, while it is straightforward to derive an optimal decoding model from an encoding model it is much more difficult to derive an encoding model from a decoding model. We propose a systematic modeling approach that begins by estimating an encoding model for every voxel in a scan and ends by using the estimated encoding models to perform decoding. PMID:20691790

  18. Genetic variation at the PCSK9 locus, low density lipoproteins, response to pravastatin and coronary heart disease: results from PROSPER

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Caucasian carriers of the T allele at R46L in the proprotein convertase subtilisin/kexin type 9 (PCSK9) locus have been reported to have 15% lower low-density lipoprotein (LDL) cholesterol (C) levels and 47% lower coronary heart disease (CHD) risk. Our objective was to examine two PCSK9 single nucle...

  19. Association of low-frequency and rare coding-sequence variants with blood lipids and Coronary Heart Disease in 56,000 whites and blacks

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Low-frequency coding DNA sequence variants in the proprotein convertase subtilisin/kexin type 9 gene (PCSK9) lower plasma low-density lipoprotein cholesterol (LDL-C), protect against risk of coronary heart disease (CHD), and have prompted the development of a new class of therapeutics. It is uncerta...

  20. PCSK9 Inhibitors.

    PubMed

    Natarajan, Pradeep; Kathiresan, Sekar

    2016-05-19

    Alirocumab and evolocumab are monoclonal antibodies that block proprotein convertase subtilisin/kexin type 9 (PCSK9), a circulating protein that degrades low-density lipoprotein (LDL) receptors. These therapies increase LDL receptors on the cell surface and reduce plasma LDL cholesterol. Both therapies are approved to lower LDL cholesterol, a causative agent for atherosclerotic cardiovascular disease. PMID:27203103

  1. Congruity of Encoding in Children's Redintegrative Memory.

    ERIC Educational Resources Information Center

    Hall, Donald M.; Geis, Mary Fulcher

    The mnemonic consequences of semantic, acoustic, and orthographic encoding and the relationships between encoding and retrieval cues were investigated in an incidental-learning experiment involving 24 first-, third-, and fifth-grade pupils. Each child was asked one orienting question for each of 18 words; the questions differed in the type of…

  2. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... for either manual or automatic operation. (2) Inputs. The encoder shall have two inputs, one for audio... encoder shall have two outputs, one audio port and one data port (RS-232C with standard protocol and 1200... frequency components outside 200 to 4000 Hz shall be attenuated by 40 dB or more with respect to the...

  3. Experiments in encoding multilevel images as quadtrees

    NASA Technical Reports Server (NTRS)

    Lansing, Donald L.

    1987-01-01

    Image storage requirements for several encoding methods are investigated and the use of quadtrees with multigray level or multicolor images are explored. The results of encoding a variety of images having up to 256 gray levels using three schemes (full raster, runlength and quadtree) are presented. Although there is considerable literature on the use of quadtrees to store and manipulate binary images, their application to multilevel images is relatively undeveloped. The potential advantage of quadtree encoding is that an entire area with a uniform gray level may be encoded as a unit. A pointerless quadtree encoding scheme is described. Data are presented on the size of the quadtree required to encode selected images and on the relative storage requirements of the three encoding schemes. A segmentation scheme based on the statistical variation of gray levels within a quadtree quadrant is described. This parametric scheme may be used to control the storage required by an encoded image and to preprocess a scene for feature identification. Several sets of black and white and pseudocolor images obtained by varying the segmentation parameter are shown.

  4. Encoding information using Laguerre Gaussian modes

    NASA Astrophysics Data System (ADS)

    Trichili, Abderrahmen; Dudley, Angela; Ben Salem, Amine; Ndagano, Bienvenu; Zghal, Mourad; Forbes, Andrew

    2015-08-01

    We experimentally demonstrate an information encoding protocol using the two degrees of freedom of Laguerre Gaussian modes having different radial and azimuthal components. A novel method, based on digital holography, for information encoding and decoding using different data transmission scenarios is presented. The effects of the atmospheric turbulence introduced in free space communication is discussed as well.

  5. The Acquisition of Syntactically Encoded Evidentiality

    ERIC Educational Resources Information Center

    Rett, Jessica; Hyams, Nina

    2014-01-01

    This article presents several empirical studies of syntactically encoded evidentiality in English. The first part of our study consists of an adult online experiment that confirms claims in Asudeh & Toivonen (2012) that raised Perception Verb Similatives (PVSs; e.g. "John looks like he is sick") encode direct evidentiality. We then…

  6. DNA encoding a DNA repair protein

    DOEpatents

    Petrini, John H.; Morgan, William Francis; Maser, Richard Scott; Carney, James Patrick

    2006-08-15

    An isolated and purified DNA molecule encoding a DNA repair protein, p95, is provided, as is isolated and purified p95. Also provided are methods of detecting p95 and DNA encoding p95. The invention further provides p95 knock-out mice.

  7. Industrial Applications Of Optical Shaft Encoders

    NASA Astrophysics Data System (ADS)

    Edmister, Brian W.

    1980-11-01

    The development of the microprocessor and mini-computer for industrial process control has made the optical shaft angle encoder a natural choice for a position feedback transducer. Many of these applications, however, require the encoder to operate reliably in extremely hostile environments. In response to this, the encoder manufacturer has been faced with reliability problems which fall into the following general categories: 1. Exposure to weather 2. Wide operating and storage temperature range 3. Exposure to corrosive chemicals 4. Severe shock and vibration 5. High electrical noise levels 6. Severe blows to encoder housing 7. Operation in explosive atmospheres Three of these applications expose the encoder to most of these environmental conditions: 1. A jack-up control position feedback for an offshore oil well drilling rig 2. A depth measurement system for oil well logging instrumentation 3. Elevation and azimuth feedback for a solar power plant heliostat

  8. Source encoding for orbiter communications links

    NASA Technical Reports Server (NTRS)

    1975-01-01

    The feasibility of using data compression to improve link efficiency as an alternative to increased transmitter power, reducing receiver noise figures, increasing antenna gain through more stringent orbiter attitude constraints, etc. is studied. A method of encoding digital data is developed which permits low band-width encoding as well as a unique system of adaptive run length encoding. The effectiveness of these techniques for the air-to-ground link and for the bandwidth-limited ground-to-ground data link used for the orbiter downlink data is evaluated. Results are presented.

  9. Pulse Vector-Excitation Speech Encoder

    NASA Technical Reports Server (NTRS)

    Davidson, Grant; Gersho, Allen

    1989-01-01

    Proposed pulse vector-excitation speech encoder (PVXC) encodes analog speech signals into digital representation for transmission or storage at rates below 5 kilobits per second. Produces high quality of reconstructed speech, but with less computation than required by comparable speech-encoding systems. Has some characteristics of multipulse linear predictive coding (MPLPC) and of code-excited linear prediction (CELP). System uses mathematical model of vocal tract in conjunction with set of excitation vectors and perceptually-based error criterion to synthesize natural-sounding speech.

  10. Programmable Pulse-Position-Modulation Encoder

    NASA Technical Reports Server (NTRS)

    Zhu, David; Farr, William

    2006-01-01

    A programmable pulse-position-modulation (PPM) encoder has been designed for use in testing an optical communication link. The encoder includes a programmable state machine and an electronic code book that can be updated to accommodate different PPM coding schemes. The encoder includes a field-programmable gate array (FPGA) that is programmed to step through the stored state machine and code book and that drives a custom high-speed serializer circuit board that is capable of generating subnanosecond pulses. The stored state machine and code book can be updated by means of a simple text interface through the serial port of a personal computer.

  11. VLSI Reed-Solomon Encoder With Interleaver

    NASA Technical Reports Server (NTRS)

    Hsu, In-Shek; Deutsch, L. J.; Truong, Trieu-Kie; Reed, I. S.

    1990-01-01

    Size, weight, and susceptibility to burst errors reduced. Encoding system built on single very-large-scale integrated (VLSI) circuit chip produces (255,223) Reed-Solomon (RS) code with programmable interleaving up to depth of 5. (225,223) RS encoder includes new remainder-and-interleaver unit providing programmable interleaving of code words. Remainder-and-interleaver unit contains shift registers and modulo-2 adders. Signals on "turn" and "no-turn" lines control depth of interleaving. Based on E. R. Berlekamp's bit-serial multiplication algorithm for (225,223) RS encoder over Galois Field (2 to the 8th power).

  12. Cellobiohydrolase variants and polynucleotides encoding same

    SciTech Connect

    Wogulis, Mark

    2014-10-14

    The present invention relates to variants of a parent cellobiohydrolase II. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

  13. Phase function encoding of diffractive structures.

    PubMed

    Schilling, A; Herzig, H P

    2000-10-10

    We analyzed the direct sampling (DS) method for diffractive lens encoding, using exact electromagnetic diffraction theory. In addition to previously published research [Pure Appl. Opt. 7, 565 (1998)] we present what we believe to be new results for TM polarization. We found that the validity of the scalar-based DS method is even more extended for TM than for TE polarization. Additionally, we fabricated and characterized DS-encoded blazed gratings and found good agreement between the experimental and theoretical diffraction efficiencies. We analyzed quantitatively the influence of the encoding schemes DS and analytic quantization (AQ) on the quality of the focal spot. We also investigated the focal spot sizes (FWHM) and the Strehl ratios of the DS- and the AQ-encoded cylindrical lenses. PMID:18354523

  14. Cellobiohydrolase variants and polynucleotides encoding same

    DOEpatents

    Wogulis, Mark

    2013-09-24

    The present invention relates to variants of a parent cellobiohydrolase II. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

  15. Cellobiohydrolase variants and polynucleotides encoding the same

    DOEpatents

    Wogulis, Mark

    2014-09-09

    The present invention relates to variants of a parent cellobiohydrolase. The present invention also relates to polynucleotides encoding the cellobiohydrolase variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the cellobiohydrolase variants.

  16. Nucleotide sequences encoding a thermostable alkaline protease

    DOEpatents

    Wilson, David B.; Lao, Guifang

    1998-01-01

    Nucleotide sequences, derived from a thermophilic actinomycete microorganism, which encode a thermostable alkaline protease are disclosed. Also disclosed are variants of the nucleotide sequences which encode a polypeptide having thermostable alkaline proteolytic activity. Recombinant thermostable alkaline protease or recombinant polypeptide may be obtained by culturing in a medium a host cell genetically engineered to contain and express a nucleotide sequence according to the present invention, and recovering the recombinant thermostable alkaline protease or recombinant polypeptide from the culture medium.

  17. Nucleotide sequences encoding a thermostable alkaline protease

    DOEpatents

    Wilson, D.B.; Lao, G.

    1998-01-06

    Nucleotide sequences, derived from a thermophilic actinomycete microorganism, which encode a thermostable alkaline protease are disclosed. Also disclosed are variants of the nucleotide sequences which encode a polypeptide having thermostable alkaline proteolytic activity. Recombinant thermostable alkaline protease or recombinant polypeptide may be obtained by culturing in a medium a host cell genetically engineered to contain and express a nucleotide sequence according to the present invention, and recovering the recombinant thermostable alkaline protease or recombinant polypeptide from the culture medium. 3 figs.

  18. Encoding and decoding of femtosecond pulses.

    PubMed

    Weiner, A M; Heritage, J P; Salehi, J A

    1988-04-01

    We demonstrate the spreading of femtosecond optical pulses into picosecond-duration pseudonoise bursts. Spreading is accomplished by encoding pseudorandom binary phase codes onto the optical frequency spectrum. Subsequent decoding of the spectral phases restores the original pulse. We propose that frequency-domain encoding and decoding of coherent ultrashort pulses could form the basis for a rapidly reconfigurable, code-division multiple-access optical telecommunications network. PMID:19745879

  19. Navigating and Mining modENCODE Data

    PubMed Central

    Boley, Nathan; Wan, Kenneth H.; Bickel, Peter J.; Celniker, Susan E.

    2014-01-01

    modENCODE was a 5 yr NHGRI funded project (2007– 2012) to map the function of every base in the genomes of worms and flies characterizing positions of modified histones and other chromatin marks, origins of DNA replication, RNA transcripts and the transcription factor binding sites that control gene expression. Here we describe the Drosophila modENCODE datasets and how best to access and use them for genome wide and individual gene studies. PMID:24636835

  20. With blood in the joint - what happens next? Could activation of a pro-inflammatory signalling axis leading to iRhom2/TNFα-convertase-dependent release of TNFα contribute to haemophilic arthropathy?

    PubMed

    Haxaire, C; Blobel, C P

    2014-05-01

    One of the main complications of haemophilia A is haemophilic arthropathy (HA), a debilitating disease with a significant negative impact on motility and quality of life. Despite major advances in the treatment of haemophilia A, many patients still suffer from HA. We wish to develop new treatments for HA, but must first better understand its causes. Our laboratory studies molecular scissors that release the pro-inflammatory cytokine tumour necrosis factor alpha (TNFα) from cells. TNFα is considered the 'fire alarm' of the body - it helps to fight infections, but can also cause diseases such as inflammatory arthritis. We know that the molecular scissors, called TNFα convertase (TACE), and its newly discovered regulator termed iRhom2 can be rapidly activated by small amounts of cytokines, growth factors, and pro-inflammatory mediators present in the blood. We hypothesize that the rapid activation of TACE could help explain one of the unsolved mysteries regarding the development of HA, which is how even small amounts of blood can provoke a persistent inflammatory response. We propose that once blood enters the joint, iRhom2 and TACE are activated to release TNFα and that this could promote the development of HA in a similar manner to that in which it promotes rheumatoid arthritis (RA). We are currently using immune cells stimulated with blood degradation products, and mouse models of HA, to test this hypothesis. If successful, our study could provide the rationale for testing anti-TNF antibodies, which are already used to treat RA, for the treatment of HA. In addition, they might uncover iRhom2 and TACE as attractive new candidate targets for the treatment of HA. PMID:24762269

  1. Neurally Encoding Time for Olfactory Navigation

    PubMed Central

    Park, In Jun; Hein, Andrew M.; Bobkov, Yuriy V.; Reidenbach, Matthew A.; Ache, Barry W.; Principe, Jose C.

    2016-01-01

    Accurately encoding time is one of the fundamental challenges faced by the nervous system in mediating behavior. We recently reported that some animals have a specialized population of rhythmically active neurons in their olfactory organs with the potential to peripherally encode temporal information about odor encounters. If these neurons do indeed encode the timing of odor arrivals, it should be possible to demonstrate that this capacity has some functional significance. Here we show how this sensory input can profoundly influence an animal’s ability to locate the source of odor cues in realistic turbulent environments—a common task faced by species that rely on olfactory cues for navigation. Using detailed data from a turbulent plume created in the laboratory, we reconstruct the spatiotemporal behavior of a real odor field. We use recurrence theory to show that information about position relative to the source of the odor plume is embedded in the timing between odor pulses. Then, using a parameterized computational model, we show how an animal can use populations of rhythmically active neurons to capture and encode this temporal information in real time, and use it to efficiently navigate to an odor source. Our results demonstrate that the capacity to accurately encode temporal information about sensory cues may be crucial for efficient olfactory navigation. More generally, our results suggest a mechanism for extracting and encoding temporal information from the sensory environment that could have broad utility for neural information processing. PMID:26730727

  2. Neurally Encoding Time for Olfactory Navigation.

    PubMed

    Park, In Jun; Hein, Andrew M; Bobkov, Yuriy V; Reidenbach, Matthew A; Ache, Barry W; Principe, Jose C

    2016-01-01

    Accurately encoding time is one of the fundamental challenges faced by the nervous system in mediating behavior. We recently reported that some animals have a specialized population of rhythmically active neurons in their olfactory organs with the potential to peripherally encode temporal information about odor encounters. If these neurons do indeed encode the timing of odor arrivals, it should be possible to demonstrate that this capacity has some functional significance. Here we show how this sensory input can profoundly influence an animal's ability to locate the source of odor cues in realistic turbulent environments-a common task faced by species that rely on olfactory cues for navigation. Using detailed data from a turbulent plume created in the laboratory, we reconstruct the spatiotemporal behavior of a real odor field. We use recurrence theory to show that information about position relative to the source of the odor plume is embedded in the timing between odor pulses. Then, using a parameterized computational model, we show how an animal can use populations of rhythmically active neurons to capture and encode this temporal information in real time, and use it to efficiently navigate to an odor source. Our results demonstrate that the capacity to accurately encode temporal information about sensory cues may be crucial for efficient olfactory navigation. More generally, our results suggest a mechanism for extracting and encoding temporal information from the sensory environment that could have broad utility for neural information processing. PMID:26730727

  3. Multichannel Compressive Sensing MRI Using Noiselet Encoding

    PubMed Central

    Pawar, Kamlesh; Egan, Gary; Zhang, Jingxin

    2015-01-01

    The incoherence between measurement and sparsifying transform matrices and the restricted isometry property (RIP) of measurement matrix are two of the key factors in determining the performance of compressive sensing (CS). In CS-MRI, the randomly under-sampled Fourier matrix is used as the measurement matrix and the wavelet transform is usually used as sparsifying transform matrix. However, the incoherence between the randomly under-sampled Fourier matrix and the wavelet matrix is not optimal, which can deteriorate the performance of CS-MRI. Using the mathematical result that noiselets are maximally incoherent with wavelets, this paper introduces the noiselet unitary bases as the measurement matrix to improve the incoherence and RIP in CS-MRI. Based on an empirical RIP analysis that compares the multichannel noiselet and multichannel Fourier measurement matrices in CS-MRI, we propose a multichannel compressive sensing (MCS) framework to take the advantage of multichannel data acquisition used in MRI scanners. Simulations are presented in the MCS framework to compare the performance of noiselet encoding reconstructions and Fourier encoding reconstructions at different acceleration factors. The comparisons indicate that multichannel noiselet measurement matrix has better RIP than that of its Fourier counterpart, and that noiselet encoded MCS-MRI outperforms Fourier encoded MCS-MRI in preserving image resolution and can achieve higher acceleration factors. To demonstrate the feasibility of the proposed noiselet encoding scheme, a pulse sequences with tailored spatially selective RF excitation pulses was designed and implemented on a 3T scanner to acquire the data in the noiselet domain from a phantom and a human brain. The results indicate that noislet encoding preserves image resolution better than Fouirer encoding. PMID:25965548

  4. Multi-dimensionally encoded magnetic resonance imaging

    PubMed Central

    Lin, Fa-Hsuan

    2013-01-01

    Magnetic resonance imaging typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here we propose the multi-dimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel RF coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled. PMID:22926830

  5. Glutamine Flux Imaging Using Genetically Encoded Sensors

    PubMed Central

    Besnard, Julien; Okumoto, Sakiko

    2014-01-01

    Genetically encoded sensors allow real-time monitoring of biological molecules at a subcellular resolution. A tremendous variety of such sensors for biological molecules became available in the past 15 years, some of which became indispensable tools that are used routinely in many laboratories. One of the exciting applications of genetically encoded sensors is the use of these sensors in investigating cellular transport processes. Properties of transporters such as kinetics and substrate specificities can be investigated at a cellular level, providing possibilities for cell-type specific analyses of transport activities. In this article, we will demonstrate how transporter dynamics can be observed using genetically encoded glutamine sensor as an example. Experimental design, technical details of the experimental settings, and considerations for post-experimental analyses will be discussed. PMID:25146898

  6. Galileo high-resolution encoder system

    NASA Astrophysics Data System (ADS)

    Mancini, Dario; Cascone, Enrico; Schipani, Pietro

    1997-09-01

    The Galileo National Telescope (TNG) is a 3.6 meter Alt-Az telescope installed at the Astronomical Observatory of the Roque de Los Muchachos in La Palma, Canary Islands (Spain). The TNG motion control system, designed and realized by the Technology Working Group (TWG), is completely digital because of the versatility of this system topology. In a digital control system using an encoder as transducer means to have a digital feedback signal, therefore directly comparable with the reference without any conversion that is essential with other kinds of transducers. In the following the Galileo telescope (TNG) encoder system with its control electronics and the management software are described. It has been realized by a collaboration between the Heidenhain Company and the TWG. The TNG encoder system, at the state of the art, has one of the highest performances in the telescopes field, in terms of resolution, accuracy, readout time, reliability.

  7. Interoperability in encoded quantum repeater networks

    NASA Astrophysics Data System (ADS)

    Nagayama, Shota; Choi, Byung-Soo; Devitt, Simon; Suzuki, Shigeya; Van Meter, Rodney

    2016-04-01

    The future of quantum repeater networking will require interoperability between various error-correcting codes. A few specific code conversions and even a generalized method are known, however, no detailed analysis of these techniques in the context of quantum networking has been performed. In this paper we analyze a generalized procedure to create Bell pairs encoded heterogeneously between two separate codes used often in error-corrected quantum repeater network designs. We begin with a physical Bell pair and then encode each qubit in a different error-correcting code, using entanglement purification to increase the fidelity. We investigate three separate protocols for preparing the purified encoded Bell pair. We calculate the error probability of those schemes between the Steane [[7,1,3

  8. Quantum repeater with continuous variable encoding

    NASA Astrophysics Data System (ADS)

    Li, Linshu; Albert, Victor V.; Michael, Marios; Muralidharan, Sreraman; Zou, Changling; Jiang, Liang

    2016-05-01

    Quantum communication enables faithful quantum state transfer between different parties and protocols for cryptographic purposes. However, quantum communication over long distances (>1000km) remains challenging due to optical channel attenuation. This calls for investigation on developing novel encoding schemes that correct photon loss errors efficiently. In this talk, we introduce the generalization of multi-component Schrödinger cat states and propose to encode quantum information in these cat states for ultrafast quantum repeaters. We detail the quantum error correction procedures at each repeater station and characterize the performance of this novel encoding scheme given practical imperfections, such as coupling loss. A comparison with other quantum error correcting codes for bosonic modes will be discussed.

  9. Structure and strategy in encoding simplified graphs

    NASA Technical Reports Server (NTRS)

    Schiano, Diane J.; Tversky, Barbara

    1992-01-01

    Tversky and Schiano (1989) found a systematic bias toward the 45-deg line in memory for the slopes of identical lines when embedded in graphs, but not in maps, suggesting the use of a cognitive reference frame specifically for encoding meaningful graphs. The present experiments explore this issue further using the linear configurations alone as stimuli. Experiments 1 and 2 demonstrate that perception and immediate memory for the slope of a test line within orthogonal 'axes' are predictable from purely structural considerations. In Experiments 3 and 4, subjects were instructed to use a diagonal-reference strategy in viewing the stimuli, which were described as 'graphs' only in Experiment 3. Results for both studies showed the diagonal bias previously found only for graphs. This pattern provides converging evidence for the diagonal as a cognitive reference frame in encoding linear graphs, and demonstrates that even in highly simplified displays, strategic factors can produce encoding biases not predictable solely from stimulus structure alone.

  10. A Metric Encoding for Bounded Model Checking

    NASA Astrophysics Data System (ADS)

    Pradella, Matteo; Morzenti, Angelo; San Pietro, Pierluigi

    In Bounded Model Checking, both the system model and the checked property are translated into a Boolean formula to be analyzed by a SAT-solver. We introduce a new encoding technique which is particularly optimized for managing quantitative future and past metric temporal operators, typically found in properties of hard real time systems. The encoding is simple and intuitive in principle, but it is made more complex by the presence, typical of the Bounded Model Checking technique, of backward and forward loops used to represent an ultimately periodic infinite domain by a finite structure. We report and comment on the new encoding technique and on an extensive set of experiments carried out to assess its feasibility and effectiveness.

  11. Noise level and MPEG-2 encoder statistics

    NASA Astrophysics Data System (ADS)

    Lee, Jungwoo

    1997-01-01

    Most software in the movie and broadcasting industries are still in analog film or tape format, which typically contains random noise that originated from film, CCD camera, and tape recording. The performance of the MPEG-2 encoder may be significantly degraded by the noise. It is also affected by the scene type that includes spatial and temporal activity. The statistical property of noise originating from camera and tape player is analyzed and the models for the two types of noise are developed. The relationship between the noise, the scene type, and encoder statistics of a number of MPEG-2 parameters such as motion vector magnitude, prediction error, and quant scale are discussed. This analysis is intended to be a tool for designing robust MPEG encoding algorithms such as preprocessing and rate control.

  12. Prediction in Annotation Based Guideline Encoding

    PubMed Central

    Hagerty, C. Greg; Pickens, David S.; Chang, Jaime; Kulikowski, Casimir A.; Sonnenberg, Frank A.

    2006-01-01

    The encoding of clinical practice guidelines into machine operable representations poses numerous challenges and will require considerable human intervention for the foreseeable future. To assist and potentially speed up this process, we have developed an incremental approach to guideline encoding which begins with the annotation of the original guideline text using markup techniques. A modular and flexible sequence of subtasks results in increasingly inter-operable representations while maintaining the connections to all prior source representations and supporting knowledge. To reduce the encoding bottleneck we also employ a number of machine-assisted learning and prediction techniques within a knowledge-based software environment. Promising results with a straightforward incremental learning algorithm illustrate the feasibility of such an approach. PMID:17238354

  13. Template based low data rate speech encoder

    NASA Astrophysics Data System (ADS)

    Fransen, Lawrence

    1993-09-01

    The 2400-b/s linear predictive coder (LPC) is currently being widely deployed to support tactical voice communication over narrowband channels. However, there is a need for lower-data-rate voice encoders for special applications: improved performance in high bit-error conditions, low-probability-of-intercept (LPI) voice communication, and narrowband integrated voice/data systems. An 800-b/s voice encoding algorithm is presented which is an extension of the 2400-b/s LPC. To construct template tables, speech samples of 420 speakers uttering 8 sentences each were excerpted from the Texas Instrument - Massachusetts Institute of Technology (TIMIT) Acoustic-Phonetic Speech Data Base. Speech intelligibility of the 800-b/s voice encoding algorithm measured by the diagnostic rhyme test (DRT) is 91.5 for three male speakers. This score compares favorably with the 2400-b/s LPC of a few years ago.

  14. An Information Theoretic Characterisation of Auditory Encoding

    PubMed Central

    Overath, Tobias; Cusack, Rhodri; Kumar, Sukhbinder; von Kriegstein, Katharina; Warren, Jason D; Grube, Manon; Carlyon, Robert P; Griffiths, Timothy D

    2007-01-01

    The entropy metric derived from information theory provides a means to quantify the amount of information transmitted in acoustic streams like speech or music. By systematically varying the entropy of pitch sequences, we sought brain areas where neural activity and energetic demands increase as a function of entropy. Such a relationship is predicted to occur in an efficient encoding mechanism that uses less computational resource when less information is present in the signal: we specifically tested the hypothesis that such a relationship is present in the planum temporale (PT). In two convergent functional MRI studies, we demonstrated this relationship in PT for encoding, while furthermore showing that a distributed fronto-parietal network for retrieval of acoustic information is independent of entropy. The results establish PT as an efficient neural engine that demands less computational resource to encode redundant signals than those with high information content. PMID:17958472

  15. Single echo acquisition MRI using RF encoding.

    PubMed

    Wright, Steven M; McDougall, Mary Preston

    2009-11-01

    Encoding of spatial information in magnetic resonance imaging is conventionally accomplished by using magnetic field gradients. During gradient encoding, the position in k-space is determined by a time-integral of the gradient field, resulting in a limitation in imaging speed due to either gradient power or secondary effects such as peripheral nerve stimulation. Partial encoding of spatial information through the sensitivity patterns of an array of coils, known as parallel imaging, is widely used to accelerate the imaging, and is complementary to gradient encoding. This paper describes the one-dimensional limit of parallel imaging in which all spatial localization in one dimension is performed through encoding by the radiofrequency (RF) coil. Using a one-dimensional array of long and narrow parallel elements to localize the image information in one direction, an entire image is obtained from a single line of k-space, avoiding rapid or repeated manipulation of gradients. The technique, called single echo acquisition (SEA) imaging, is described, along with the need for a phase compensation gradient pulse to counteract the phase variation contained in the RF coil pattern which would otherwise cause signal cancellation in each imaging voxel. Image reconstruction and resolution enhancement methods compatible with the speed of the technique are discussed. MR movies at frame rates of 125 frames per second are demonstrated, illustrating the ability to monitor the evolution of transverse magnetization to steady state during an MR experiment as well as demonstrating the ability to image rapid motion. Because this technique, like all RF encoding approaches, relies on the inherent spatially varying pattern of the coil and is not a time-integral, it should enable new applications for MRI that were previously inaccessible due to speed constraints, and should be of interest as an approach to extending the limits of detection in MR imaging. PMID:19441080

  16. Optical encoder based on a nondiffractive beam

    NASA Astrophysics Data System (ADS)

    Lutenberg, A.; Perez Quintián, F.; Rebollo, M. A.

    2007-09-01

    Nowadays most industrial and laboratory motion measuring equipment makes use of optical encoders to measure rotation and linear displacements with sub-micrometrical resolution. In this work we introduce a new design of an optical encoder based on a non diffractive beam, a binary amplitude grating and a monolithic photodetector. Two theoretical models of the system are proposed and implemented to obtain numerical results. The performance of the design is also investigated through experimental measurements. Finally, the experimental results are compared with the models predictions.

  17. Vector Adaptive/Predictive Encoding Of Speech

    NASA Technical Reports Server (NTRS)

    Chen, Juin-Hwey; Gersho, Allen

    1989-01-01

    Vector adaptive/predictive technique for digital encoding of speech signals yields decoded speech of very good quality after transmission at coding rate of 9.6 kb/s and of reasonably good quality at 4.8 kb/s. Requires 3 to 4 million multiplications and additions per second. Combines advantages of adaptive/predictive coding, and code-excited linear prediction, yielding speech of high quality but requires 600 million multiplications and additions per second at encoding rate of 4.8 kb/s. Vector adaptive/predictive coding technique bridges gaps in performance and complexity between adaptive/predictive coding and code-excited linear prediction.

  18. Optical encoder based on a nondiffractive beam

    SciTech Connect

    Lutenberg, Ariel; Perez-Quintian, Fernando; Rebollo, Maria A

    2008-05-01

    Optical encoders are used in industrial and laboratory motion equipment to measure rotations and linear displacements. We introduce a design of an optical encoder based on a nondiffractive beam. We expect that the invariant profile and radial symmetry of the nondiffractive beam provide the design with remarkable tolerance to mechanical perturbations. We experimentally demonstrate that the proposed design generates a suitable output sinusoidal signal with low harmonic distortion. Moreover, we present a numerical model of the system based on the angular spectrum approximation whose predictions are in excellent agreement with the experimental results.

  19. Design and application of genetically encoded biosensors

    PubMed Central

    Palmer, Amy E.; Qin, Yan; Park, Jungwon Genevieve; McCombs, Janet E.

    2012-01-01

    In the past 5–10 years, the power of the green fluorescent protein (GFP) and its numerous derivatives has been harnessed toward the development of genetically encoded fluorescent biosensors. These sensors are incorporated into cells or organisms as plasmid DNA, which leads the transcriptional and translational machinery of the cell to express a functional sensor. To date, over 100 different genetically encoded biosensors have been developed for targets as diverse as ions, molecules and enzymes. Such sensors are instrumental in providing a window into the real-time biochemistry of living cells and whole organisms, and are providing unprecedented insight into the inner workings of a cell. PMID:21251723

  20. Polarization-multiplexed encoding at nanometer scales.

    PubMed

    Macias-Romero, C; Munro, P R T; Török, P

    2014-10-20

    Optical data storage was developed using binary encoding primarily due to signal to noise ratio considerations. We report on a multiplexing method that allows a seven fold storage increase, per storage layer, per side, and propose one that can yield theoretically a 20+ fold increase. Multiplexing is achieved by encoding information in polarization via appropriately oriented nanostructures that emit strongly polarized light when excited by unpolarized light. The storage increase is possible due to the significantly reduced crosstalk that results form using unpolarized light. PMID:25401656

  1. Encoding Specificity for Sentences in Connected Discourse.

    ERIC Educational Resources Information Center

    Christiaansen, Robert E.; Dooling, D. James

    The encoding specificity principle predicts that a change in context between input and test will adversely affect recognition memory. Experiment I tested this with sentences from a prose passage and no context effects were obtained. Experiments II, III, and IV compared context effects for words in random sentences versus connected discourse. In…

  2. Encoding of Others' Beliefs without Overt Instruction

    ERIC Educational Resources Information Center

    Cohen, Adam S.; German, Tamsin C.

    2009-01-01

    Under what conditions do people automatically encode and track the mental states of others? A recent investigation showed that when subjects are instructed to track the location of an object but are not instructed to track a belief about that location in a non-verbal false-belief task, they respond more slowly to questions about an agent's belief,…

  3. Young Children's Automatic Encoding of Social Categories

    ERIC Educational Resources Information Center

    Weisman, Kara; Johnson, Marissa V.; Shutts, Kristin

    2015-01-01

    The present research investigated young children's automatic encoding of two social categories that are highly relevant to adults: gender and race. Three- to 6-year-old participants learned facts about unfamiliar target children who varied in either gender or race and were asked to remember which facts went with which targets. When participants…

  4. Encoders for block-circulant LDPC codes

    NASA Technical Reports Server (NTRS)

    Divsalar, Dariush (Inventor); Abbasfar, Aliazam (Inventor); Jones, Christopher R. (Inventor); Dolinar, Samuel J. (Inventor); Thorpe, Jeremy C. (Inventor); Andrews, Kenneth S. (Inventor); Yao, Kung (Inventor)

    2009-01-01

    Methods and apparatus to encode message input symbols in accordance with an accumulate-repeat-accumulate code with repetition three or four are disclosed. Block circulant matrices are used. A first method and apparatus make use of the block-circulant structure of the parity check matrix. A second method and apparatus use block-circulant generator matrices.

  5. Encode/Decode facility for FORTRAN 4

    NASA Technical Reports Server (NTRS)

    Cohn, C. E.

    1969-01-01

    An ENCODE and DECODE facility, a subroutine added to a FORTRAN 4 library, allows alphanumeric data to be transfered to or from an area in memory rather than to or from external input/output devices. A buffer storage array allows the operations on the data prior to writing.

  6. Retrieval during Learning Facilitates Subsequent Memory Encoding

    ERIC Educational Resources Information Center

    Pastotter, Bernhard; Schicker, Sabine; Niedernhuber, Julia; Bauml, Karl-Heinz T.

    2011-01-01

    In multiple-list learning, retrieval during learning has been suggested to improve recall of the single lists by enhancing list discrimination and, at test, reducing interference. Using electrophysiological, oscillatory measures of brain activity, we examined to what extent retrieval during learning facilitates list encoding. Subjects studied 5…

  7. Encoded Archival Description as a Halfway Technology

    ERIC Educational Resources Information Center

    Dow, Elizabeth H.

    2009-01-01

    In the mid 1990s, Encoded Archival Description (EAD) appeared as a revolutionary technology for publishing archival finding aids on the Web. The author explores whether or not, given the advent of Web 2.0, the archival community should abandon EAD and look for something to replace it. (Contains 18 notes.)

  8. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... used for audio messages and at least one input port used for data messages. (3) Outputs. The encoder shall have at least one audio output port and at least one data output port. (4) Calibration. EAS... sent and deactivated at the End of Message code. (8) Spurious Response. All frequency...

  9. Gene encoding acetyl-coenzyme A carboxylase

    DOEpatents

    Roessler, P.G.; Ohlrogge, J.B.

    1996-09-24

    A DNA encoding an acetyl-coenzyme A carboxylase (ACCase) from a photosynthetic organism and functional derivatives are disclosed which are resistant to inhibition from certain herbicides. This gene can be placed in organisms to increase their fatty acid content or to render them resistant to certain herbicides. 5 figs.

  10. Encoding and Retrieval During Bimanual Rhythmic Coordination

    ERIC Educational Resources Information Center

    Shockley, Kevin; Turvey, Michael T.

    2005-01-01

    In 2 experiments, bimanual 1:1 rhythmic coordination was performed concurrently with encoding or retrieval of word lists. Effects of divided attention (DA) on coordination were indexed by changes in mean relative phase and recurrence measures of shared activity between the 2 limbs. Effects of DA on memory were indexed by deficits in recall…

  11. Encoding attentional states during visuomotor adaptation.

    PubMed

    Im, Hee Yeon; Bédard, Patrick; Song, Joo-Hyun

    2015-01-01

    We recently showed that visuomotor adaptation acquired under attentional distraction is better recalled under a similar level of distraction compared to no distraction. This paradoxical effect suggests that attentional state (e.g., divided or undivided) is encoded as an internal context during visuomotor learning and should be reinstated for successful recall (Song & Bédard, 2015). To investigate if there is a critical temporal window for encoding attentional state in visuomotor memory, we manipulated whether participants performed the secondary attention-demanding task concurrently in the early or late phase of visuomotor learning. Recall performance was enhanced when the attentional states between recall and the early phase of visuomotor learning were consistent. However, it reverted to untrained levels when tested under the attentional state of the late-phase learning. This suggests that attentional state is primarily encoded during the early phase of learning before motor errors decrease and reach an asymptote. Furthermore, we demonstrate that when divided and undivided attentional states were mixed during visuomotor adaptation, only divided attention was encoded as an internal cue for memory retrieval. Therefore, a single attentional state appears to be primarily integrated with visuomotor memory while motor error reduction is in progress during learning. PMID:26114683

  12. Synchronizing Heavily Encoded Data in Bad Weather

    NASA Technical Reports Server (NTRS)

    Swanson, L.

    1985-01-01

    Deep space missions choose a data rate to ensure reliable communication under most conditions. Certain critical data can be more heavily encoded, to be decoded under particularly bad atmospheric conditions. It is shown that, in such a system, finding and synchronizing critical data will not be a problem.

  13. Design Primer for Reed-Solomon Encoders

    NASA Technical Reports Server (NTRS)

    Perlman, M.; Lee, J. J.

    1985-01-01

    Design and operation of Reed-Solomon (RS) encoders discussed in document prepared as instruction manual for computer designers and others in dataprocessing field. Conventional and Berlekamp architectures compared. Engineers who equip computer memory chips with burst-error and dropout detection and correction find report especially useful.

  14. Recombinant DNA encoding a desulfurization biocatalyst

    DOEpatents

    Rambosek, J.; Piddington, C.S.; Kovacevich, B.R.; Young, K.D.; Denome, S.A.

    1994-10-18

    This invention relates to a recombinant DNA molecule containing a gene or genes which encode a biocatalyst capable of desulfurizing a fossil fuel which contains organic sulfur molecules. For example, the present invention encompasses a recombinant DNA molecule containing a gene or genes of a strain of Rhodococcus rhodochrous. 13 figs.

  15. [Development genes encoding transcription factors and dysmorphology].

    PubMed

    Lacombe, Didier

    2009-04-01

    Studies of children with developmental abnormalities of genetic origin are necessary for accurate diagnosis, prognostication, patient management, and genetic counseling. Such studies can also help to identify genes involved in normal and abnormal morphogenesis, which often act as patterning genes and are also potential oncogenes. Many encode transcription factors that regulate other genes during embryonic development. PMID:20120282

  16. Gene encoding acetyl-coenzyme A carboxylase

    DOEpatents

    Roessler, Paul G.; Ohlrogge, John B.

    1996-01-01

    A DNA encoding an acetyl-coenzyme A carboxylase (ACCase) from a photosynthetic organism and functional derivatives thereof which are resistant to inhibition from certain herbicides. This gene can be placed in organisms to increase their fatty acid content or to render them resistant to certain herbicides.

  17. Recombinant DNA encoding a desulfurization biocatalyst

    DOEpatents

    Rambosek, John; Piddington, Chris S.; Kovacevich, Brian R.; Young, Kevin D.; Denome, Sylvia A.

    1994-01-01

    This invention relates to a recombinant DNA molecule containing a gene or genes which encode a biocatalyst capable of desulfurizing a fossil fuel which contains organic sulfur molecules. For example, the present invention encompasses a recombinant DNA molecule containing a gene or genes of a strain of Rhodococcus rhodochrous.

  18. JPEG 2000 Encoding with Perceptual Distortion Control

    NASA Technical Reports Server (NTRS)

    Watson, Andrew B.; Liu, Zhen; Karam, Lina J.

    2008-01-01

    An alternative approach has been devised for encoding image data in compliance with JPEG 2000, the most recent still-image data-compression standard of the Joint Photographic Experts Group. Heretofore, JPEG 2000 encoding has been implemented by several related schemes classified as rate-based distortion-minimization encoding. In each of these schemes, the end user specifies a desired bit rate and the encoding algorithm strives to attain that rate while minimizing a mean squared error (MSE). While rate-based distortion minimization is appropriate for transmitting data over a limited-bandwidth channel, it is not the best approach for applications in which the perceptual quality of reconstructed images is a major consideration. A better approach for such applications is the present alternative one, denoted perceptual distortion control, in which the encoding algorithm strives to compress data to the lowest bit rate that yields at least a specified level of perceptual image quality. Some additional background information on JPEG 2000 is prerequisite to a meaningful summary of JPEG encoding with perceptual distortion control. The JPEG 2000 encoding process includes two subprocesses known as tier-1 and tier-2 coding. In order to minimize the MSE for the desired bit rate, a rate-distortion- optimization subprocess is introduced between the tier-1 and tier-2 subprocesses. In tier-1 coding, each coding block is independently bit-plane coded from the most-significant-bit (MSB) plane to the least-significant-bit (LSB) plane, using three coding passes (except for the MSB plane, which is coded using only one "clean up" coding pass). For M bit planes, this subprocess involves a total number of (3M - 2) coding passes. An embedded bit stream is then generated for each coding block. Information on the reduction in distortion and the increase in the bit rate associated with each coding pass is collected. This information is then used in a rate-control procedure to determine the

  19. Effortful retrieval reduces hippocampal activity and impairs incidental encoding.

    PubMed

    Reas, Emilie T; Brewer, James B

    2013-05-01

    Functional imaging studies frequently report that the hippocampus is engaged by successful episodic memory retrieval. However, considering that concurrent encoding of the background environment occurs during retrieval and influences medial temporal lobe activity, it is plausible that hippocampal encoding functions are reduced with increased attentional engagement during effortful retrieval. Expanding upon evidence that retrieval efforts suppress activity in hippocampal regions implicated in encoding, this study examines the influence of retrieval effort on encoding performance and the interactive effects of encoding and retrieval on hippocampal and neocortical activity. Functional magnetic resonance imaging was conducted while subjects performed a word recognition task with incidental picture encoding. Both lower memory strength and increased search duration were associated with encoding failure and reduced hippocampal and default network activity. Activity in the anterior hippocampus tracked encoding, which was more strongly deactivated when incidental encoding was unsuccessful. These findings highlight potential contributions from background encoding processes to hippocampal activations during neuroimaging studies of episodic memory retrieval. PMID:23378272

  20. High-diffraction-efficiency pseudorandom encoding.

    PubMed

    Yang, Y; Stark, H; Gurkan, D; Lawson, C L; Cohn, R W

    2000-02-01

    Pseudorandom encoding (PRE) is a statistics-based procedure in which a pure-phase spatial light modulator (SLM) can yield, on the average, the prescribed diffraction pattern specified by the user. We seek to combine PRE with the optimization of an aperture-based target function. The target function is a fully complex input transmittance, unrealizable by a phase-only SLM, that generates a prescribed light intensity. The optimization is done to increase the diffraction efficiency of the overall process. We compare three optimization methods-Monte Carlo simulation, a genetic algorithm, and a gradient search-for maximizing the diffraction efficiency of a spot-array generator. Calculated solutions are then encoded by PRE, and the resulting diffraction patterns are computer simulated. Details on the complexity of each procedure are furnished, as well as comparisons on the quality, such as uniformity of the output spot array. PMID:10680630

  1. Temporal information encoding in dynamic memristive devices

    SciTech Connect

    Ma, Wen; Chen, Lin; Du, Chao; Lu, Wei D.

    2015-11-09

    We show temporal and frequency information can be effectively encoded in memristive devices with inherent short-term dynamics. Ag/Ag{sub 2}S/Pd based memristive devices with low programming voltage (∼100 mV) were fabricated and tested. At weak programming conditions, the devices exhibit inherent decay due to spontaneous diffusion of the Ag atoms. When the devices were subjected to pulse train inputs emulating different spiking patterns, the switching probability distribution function diverges from the standard Poisson distribution and evolves according to the input pattern. The experimentally observed switching probability distributions and the associated cumulative probability functions can be well-explained using a model accounting for the short-term decay effects. Such devices offer an intriguing opportunity to directly encode neural signals for neural information storage and analysis.

  2. Asymmetric synthesis using chiral-encoded metal

    PubMed Central

    Yutthalekha, Thittaya; Wattanakit, Chularat; Lapeyre, Veronique; Nokbin, Somkiat; Warakulwit, Chompunuch; Limtrakul, Jumras; Kuhn, Alexander

    2016-01-01

    The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity. PMID:27562028

  3. Genetically encoded fluorescent sensors of membrane potential

    PubMed Central

    Baker, B. J.; Mutoh, H.; Dimitrov, D.; Akemann, W.; Perron, A.; Iwamoto, Y.; Jin, L.; Cohen, L. B.; Isacoff, E. Y.; Pieribone, V. A.; Hughes, T.; Knöpfel, T.

    2009-01-01

    Imaging activity of neurons in intact brain tissue was conceived several decades ago and, after many years of development, voltage-sensitive dyes now offer the highest spatial and temporal resolution for imaging neuronal functions in the living brain. Further progress in this field is expected from the emergent development of genetically encoded fluorescent sensors of membrane potential. These fluorescent protein (FP) voltage sensors overcome the drawbacks of organic voltage sensitive dyes such as non-specificity of cell staining and the low accessibility of the dye to some cell types. In a transgenic animal, a genetically encoded sensor could in principle be expressed specifically in any cell type and would have the advantage of staining only the cell population determined by the specificity of the promoter used to drive expression. Here we critically review the current status of these developments. PMID:18679801

  4. Nucleic acid compositions and the encoding proteins

    DOEpatents

    Preston, III, James F.; Chow, Virginia; Nong, Guang; Rice, John D.; St. John, Franz J.

    2014-09-02

    The subject invention provides at least one nucleic acid sequence encoding an aldouronate-utilization regulon isolated from Paenibacillus sp. strain JDR-2, a bacterium which efficiently utilizes xylan and metabolizes aldouronates (methylglucuronoxylosaccharides). The subject invention also provides a means for providing a coordinately regulated process in which xylan depolymerization and product assimilation are coupled in Paenibacillus sp. strain JDR-2 to provide a favorable system for the conversion of lignocellulosic biomass to biobased products. Additionally, the nucleic acid sequences encoding the aldouronate-utilization regulon can be used to transform other bacteria to form organisms capable of producing a desired product (e.g., ethanol, 1-butanol, acetoin, 2,3-butanediol, 1,3-propanediol, succinate, lactate, acetate, malate or alanine) from lignocellulosic biomass.

  5. Genetically Encoded Voltage Indicators in Circulation Research

    PubMed Central

    Kaestner, Lars; Tian, Qinghai; Kaiser, Elisabeth; Xian, Wenying; Müller, Andreas; Oberhofer, Martin; Ruppenthal, Sandra; Sinnecker, Daniel; Tsutsui, Hidekazu; Miyawaki, Atsushi; Moretti, Alessandra; Lipp, Peter

    2015-01-01

    Membrane potentials display the cellular status of non-excitable cells and mediate communication between excitable cells via action potentials. The use of genetically encoded biosensors employing fluorescent proteins allows a non-invasive biocompatible way to read out the membrane potential in cardiac myocytes and other cells of the circulation system. Although the approaches to design such biosensors date back to the time when the first fluorescent-protein based Förster Resonance Energy Transfer (FRET) sensors were constructed, it took 15 years before reliable sensors became readily available. Here, we review different developments of genetically encoded membrane potential sensors. Furthermore, it is shown how such sensors can be used in pharmacological screening applications as well as in circulation related basic biomedical research. Potentials and limitations will be discussed and perspectives of possible future developments will be provided. PMID:26370981

  6. Asymmetric synthesis using chiral-encoded metal.

    PubMed

    Yutthalekha, Thittaya; Wattanakit, Chularat; Lapeyre, Veronique; Nokbin, Somkiat; Warakulwit, Chompunuch; Limtrakul, Jumras; Kuhn, Alexander

    2016-01-01

    The synthesis of chiral compounds is of crucial importance in many areas of society and science, including medicine, biology, chemistry, biotechnology and agriculture. Thus, there is a fundamental interest in developing new approaches for the selective production of enantiomers. Here we report the use of mesoporous metal structures with encoded geometric chiral information for inducing asymmetry in the electrochemical synthesis of mandelic acid as a model molecule. The chiral-encoded mesoporous metal, obtained by the electrochemical reduction of platinum salts in the presence of a liquid crystal phase and the chiral template molecule, perfectly retains the chiral information after removal of the template. Starting from a prochiral compound we demonstrate enantiomeric excess of the (R)-enantiomer when using (R)-imprinted electrodes and vice versa for the (S)-imprinted ones. Moreover, changing the amount of chiral cavities in the material allows tuning the enantioselectivity. PMID:27562028

  7. DNA-Encoded Dynamic Combinatorial Chemical Libraries.

    PubMed

    Reddavide, Francesco V; Lin, Weilin; Lehnert, Sarah; Zhang, Yixin

    2015-06-26

    Dynamic combinatorial chemistry (DCC) explores the thermodynamic equilibrium of reversible reactions. Its application in the discovery of protein binders is largely limited by difficulties in the analysis of complex reaction mixtures. DNA-encoded chemical library (DECL) technology allows the selection of binders from a mixture of up to billions of different compounds; however, experimental results often show low a signal-to-noise ratio and poor correlation between enrichment factor and binding affinity. Herein we describe the design and application of DNA-encoded dynamic combinatorial chemical libraries (EDCCLs). Our experiments have shown that the EDCCL approach can be used not only to convert monovalent binders into high-affinity bivalent binders, but also to cause remarkably enhanced enrichment of potent bivalent binders by driving their in situ synthesis. We also demonstrate the application of EDCCLs in DNA-templated chemical reactions. PMID:26014116

  8. DNA encoding for an efficient 'Omics processing.

    PubMed

    Murovec, Bostjan; Tiedje, James M; Stres, Blaz

    2010-11-01

    The exponential growth of available DNA sequences and the increased interoperability of biological information is triggering intergovernmental efforts aimed at increasing the access, dissemination, and analysis of sequence data. Achieving the efficient storage and processing of DNA material is an important goal that parallels well with the foreseen coding standardization on the horizon. This paper proposes novel coding approaches, for both the dissemination and processing of sequences, where the speed of the DNA processing is shown to be boosted by exploring more than the normally utilized eight bits for encoding a single nucleotide. Further gains are achieved by encoding the nucleotides together with their trailing alignment information as a single 64-bit data structure. The paper also proposes a slight modification to the established FASTA scheme in order to improve on its representation of alignment information. The significance of the propositions is confirmed by the encouraging results from empirical tests. PMID:20444519

  9. Storing data encoded DNA in living organisms

    DOEpatents

    Wong; Pak C. , Wong; Kwong K. , Foote; Harlan P.

    2006-06-06

    Current technologies allow the generation of artificial DNA molecules and/or the ability to alter the DNA sequences of existing DNA molecules. With a careful coding scheme and arrangement, it is possible to encode important information as an artificial DNA strand and store it in a living host safely and permanently. This inventive technology can be used to identify origins and protect R&D investments. It can also be used in environmental research to track generations of organisms and observe the ecological impact of pollutants. Today, there are microorganisms that can survive under extreme conditions. As well, it is advantageous to consider multicellular organisms as hosts for stored information. These living organisms can provide as memory housing and protection for stored data or information. The present invention provides well for data storage in a living organism wherein at least one DNA sequence is encoded to represent data and incorporated into a living organism.

  10. Gene encoding herbicide safener binding protein

    SciTech Connect

    Walton, J.D.; Scott-Craig, J.S.

    1999-10-26

    The cDNA encoding safener binding protein (SafBP), also referred to as SBP1, is presented. The deduced amino acid sequence is provided. Methods of making and using SBP1 and SafBP to alter a plant's sensitivity to certain herbicides or a plant's responsiveness to certain safeners are also provided, as well as expression vectors, transgenic plants or other organisms transfected with vectors and seeds from the plants.

  11. Virus-encoded microRNAs

    PubMed Central

    Grundhoff, Adam; Sullivan, Christopher S.

    2011-01-01

    microRNAs (miRNAs) are the subject of enormous interest. They are small non-coding RNAs that play a regulatory role in numerous and diverse cellular processes such as immune function, apoptosis and tumorigenesis. Several virus families have been shown to encode miRNAs, and an appreciation for their roles in the viral infectious cycle continues to grow. Despite the identification of numerous (>225) viral miRNAs, an in depth functional understanding of most virus-encoded miRNAs is lacking. Here we focus on a few viral miRNAs with well-defined functions. We use these examples to extrapolate general themes of viral miRNA activities including autoregulation of gene expression, avoidance of host defenses, and a likely important role in maintaining latent and persistent infections. We hypothesize that although the molecular mechanisms and machinery are similar, the majority of viral miRNAs may utilize a target strategy that differs from host miRNAs. That is, many viral miRNAs may have evolved to regulate viral-encoded transcripts or networks of host genes that are unique to viral miRNAs. Included in this latter category are a likely abundant class of viral miRNAs that may regulate only one or a few principal host genes. Key steps forward for the field are discussed, including the need for additional functional studies that utilize surgical viral miRNA mutants combined with relevant models of infection. PMID:21277611

  12. Neural signals encoding shifts in beliefs.

    PubMed

    Schwartenbeck, Philipp; FitzGerald, Thomas H B; Dolan, Ray

    2016-01-15

    Dopamine is implicated in a diverse range of cognitive functions including cognitive flexibility, task switching, signalling novel or unexpected stimuli as well as advance information. There is also longstanding line of thought that links dopamine with belief formation and, crucially, aberrant belief formation in psychosis. Integrating these strands of evidence would suggest that dopamine plays a central role in belief updating and more specifically in encoding of meaningful information content in observations. The precise nature of this relationship has remained unclear. To directly address this question we developed a paradigm that allowed us to decompose two distinct types of information content, information-theoretic surprise that reflects the unexpectedness of an observation, and epistemic value that induces shifts in beliefs or, more formally, Bayesian surprise. Using functional magnetic-resonance imaging in humans we show that dopamine-rich midbrain regions encode shifts in beliefs whereas surprise is encoded in prefrontal regions, including the pre-supplementary motor area and dorsal cingulate cortex. By linking putative dopaminergic activity to belief updating these data provide a link to false belief formation that characterises hyperdopaminergic states associated with idiopathic and drug induced psychosis. PMID:26520774

  13. Absolute Position Encoders With Vertical Image Binning

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B.

    2005-01-01

    Improved optoelectronic patternrecognition encoders that measure rotary and linear 1-dimensional positions at conversion rates (numbers of readings per unit time) exceeding 20 kHz have been invented. Heretofore, optoelectronic pattern-recognition absoluteposition encoders have been limited to conversion rates <15 Hz -- too low for emerging industrial applications in which conversion rates ranging from 1 kHz to as much as 100 kHz are required. The high conversion rates of the improved encoders are made possible, in part, by use of vertically compressible or binnable (as described below) scale patterns in combination with modified readout sequences of the image sensors [charge-coupled devices (CCDs)] used to read the scale patterns. The modified readout sequences and the processing of the images thus read out are amenable to implementation by use of modern, high-speed, ultra-compact microprocessors and digital signal processors or field-programmable gate arrays. This combination of improvements makes it possible to greatly increase conversion rates through substantial reductions in all three components of conversion time: exposure time, image-readout time, and image-processing time.

  14. Nucleic acids encoding human trithorax protein

    DOEpatents

    Evans, Glen A.; Djabali, Malek; Selleri, Licia; Parry, Pauline

    2001-01-01

    In accordance with the present invention, there is provided an isolated peptide having the characteristics of human trithorax protein (as well as DNA encoding same, antisense DNA derived therefrom and antagonists therefor). The invention peptide is characterized by having a DNA binding domain comprising multiple zinc fingers and at least 40% amino acid identity with respect to the DNA binding domain of Drosophila trithorax protein and at least 70% conserved sequence with respect to the DNA binding domain of Drosophila trithorax protein, and wherein said peptide is encoded by a gene located at chromosome 11 of the human genome at q23. Also provided are methods for the treatment of subject(s) suffering from immunodeficiency, developmental abnormality, inherited disease, or cancer by administering to said subject a therapeutically effective amount of one of the above-described agents (i.e., peptide, antagonist therefor, DNA encoding said peptide or antisense DNA derived therefrom). Also provided is a method for the diagnosis, in a subject, of immunodeficiency, developmental abnormality, inherited disease, or cancer associated with disruption of chromosome 11 at q23.

  15. Dual-channel spectrally encoded endoscopic probe

    PubMed Central

    Engel, Guy; Genish, Hadar; Rosenbluh, Michael; Yelin, Dvir

    2012-01-01

    High quality imaging through sub-millimeter endoscopic probes provides clinicians with valuable diagnostics capabilities in hard to reach locations within the body. Spectrally encoded endoscopy (SEE) has been shown promising for such task; however, challenging probe fabrication and high speckle noise had prevented its testing in in vivo studies. Here we demonstrate a novel miniature SEE probe which incorporates some of the recent progress in spectrally encoded technology into a compact and robust endoscopic system. A high-quality miniature diffraction grating was fabricated using automated femtosecond laser cutting from a large bulk grating. Using one spectrally encoded channel for imaging and a separate channel for incoherent illumination, the new system has large depth of field, negligible back reflections and well controlled speckle noise which depends on the core diameter of the illumination fiber. Moreover, by using a larger imaging channel, higher groove density grating, shorter wavelength and broader spectrum, the new endoscopic system now allow significant improvements in almost all imaging parameter compared to previous systems, through an ultra-miniature endoscopic probe. PMID:22876349

  16. Neural signals encoding shifts in beliefs

    PubMed Central

    Schwartenbeck, Philipp; FitzGerald, Thomas H.B.; Dolan, Ray

    2016-01-01

    Dopamine is implicated in a diverse range of cognitive functions including cognitive flexibility, task switching, signalling novel or unexpected stimuli as well as advance information. There is also longstanding line of thought that links dopamine with belief formation and, crucially, aberrant belief formation in psychosis. Integrating these strands of evidence would suggest that dopamine plays a central role in belief updating and more specifically in encoding of meaningful information content in observations. The precise nature of this relationship has remained unclear. To directly address this question we developed a paradigm that allowed us to decompose two distinct types of information content, information-theoretic surprise that reflects the unexpectedness of an observation, and epistemic value that induces shifts in beliefs or, more formally, Bayesian surprise. Using functional magnetic-resonance imaging in humans we show that dopamine-rich midbrain regions encode shifts in beliefs whereas surprise is encoded in prefrontal regions, including the pre-supplementary motor area and dorsal cingulate cortex. By linking putative dopaminergic activity to belief updating these data provide a link to false belief formation that characterises hyperdopaminergic states associated with idiopathic and drug induced psychosis. PMID:26520774

  17. Blind Identification of Convolutional Encoder Parameters

    PubMed Central

    Su, Shaojing; Zhou, Jing; Huang, Zhiping; Liu, Chunwu; Zhang, Yimeng

    2014-01-01

    This paper gives a solution to the blind parameter identification of a convolutional encoder. The problem can be addressed in the context of the noncooperative communications or adaptive coding and modulations (ACM) for cognitive radio networks. We consider an intelligent communication receiver which can blindly recognize the coding parameters of the received data stream. The only knowledge is that the stream is encoded using binary convolutional codes, while the coding parameters are unknown. Some previous literatures have significant contributions for the recognition of convolutional encoder parameters in hard-decision situations. However, soft-decision systems are applied more and more as the improvement of signal processing techniques. In this paper we propose a method to utilize the soft information to improve the recognition performances in soft-decision communication systems. Besides, we propose a new recognition method based on correlation attack to meet low signal-to-noise ratio situations. Finally we give the simulation results to show the efficiency of the proposed methods. PMID:24982997

  18. Architecture for VLSI design of Reed-Solomon encoders

    NASA Technical Reports Server (NTRS)

    Liu, K. Y.

    1981-01-01

    The logic structure of a universal VLSI chip called the symbol-slice Reed-Solomon (RS) encoder chip is discussed. An RS encoder can be constructed by cascading and properly interconnecting a group of such VLSI chips. As a design example, it is shown that a (255,223) RD encoder requiring around 40 discrete CMOS ICs may be replaced by an RS encoder consisting of four identical interconnected VLSI RS encoder chips. Besides the size advantage, the VLSI RS encoder also has the potential advantages of requiring less power and having a higher reliability.

  19. The Large Binocular Telescope azimuth and elevation encoder system

    NASA Astrophysics Data System (ADS)

    Ashby, David S.; Sargent, Tom; Cox, Dan; Rosato, Jerry; Brynnel, Joar G.

    2008-08-01

    A typical high-resolution encoder interpolator relies on careful mechanical alignment of the encoder read-heads and tight electrical tolerances of the signal processing electronics to ensure linearity. As the interpolation factor increases, maintaining these tight mechanical and electrical tolerances becomes impractical. The Large Binocular Telescope (LBT) is designed to utilize strip-type encoders on the main axes. Because of the very large scale of the telescope, the accumulative length of the azimuth and elevation encoder strips exceeds 80 meters, making optical tape prohibitively expensive. Consequently, the designers of the LBT incorporated the far less expensive Farrand Controls Inductosyn® linear strip encoder to encode the positions of the main axes and the instrument rotators. Since the cycle pitch of these encoders is very large compared to that of optical strip encoders, the interpolation factor must also be large in order to achieve the 0.005 arcsecond encoder resolution as specified. The authors present a description of the innovative DSP-based hardware / software solution that adaptively characterizes and removes common systematic cycle-to-cycle encoder interpolation errors. These errors can be caused by mechanical misalignment, encoder manufacturing flaws, variations in electrical gain, signal offset or cross-coupling of the encoder signals. Simulation data are presented to illustrate the performance of the interpolation algorithm, and telemetry data are presented to demonstrate the actual performance of the LBT main-axis encoder system.

  20. The Collaborative Encoding Deficit is Attenuated with Specific Warnings

    PubMed Central

    Barber, Sarah J.; Rajaram, Suparna; Paneerselvam, Bavani

    2012-01-01

    Individuals learning together do so less effectively than individuals learning alone, an effect known as the collaborative encoding deficit (Barber, Rajaram, & Aron, 2010). In the present studies we examined whether providing participants with a warning about the collaborative encoding deficit would increase their encoding task performance, and reduce subsequent memory deficits. Across two experiments, specific warnings were beneficial for memory. Collaborating participants who were told about the collaborative encoding deficit, and who received suggestions for how to complete the encoding task, had superior memory than participants who received no warning. This benefit was not due to qualitative changes in encoding task performance, was unrelated to the type of collaboration utilized, was absent when a more general warning was utilized, and was unrelated to self-reported task motivation. Rather, specific warnings appear to protect against the collaborative encoding deficit by increasing time spent on, and attention directed to, the encoding task. PMID:23296389

  1. ChIP-seq guidelines and practices of the ENCODE and modENCODE consortia

    PubMed Central

    Landt, Stephen G.; Marinov, Georgi K.; Kundaje, Anshul; Kheradpour, Pouya; Pauli, Florencia; Batzoglou, Serafim; Bernstein, Bradley E.; Bickel, Peter; Brown, James B.; Cayting, Philip; Chen, Yiwen; DeSalvo, Gilberto; Epstein, Charles; Fisher-Aylor, Katherine I.; Euskirchen, Ghia; Gerstein, Mark; Gertz, Jason; Hartemink, Alexander J.; Hoffman, Michael M.; Iyer, Vishwanath R.; Jung, Youngsook L.; Karmakar, Subhradip; Kellis, Manolis; Kharchenko, Peter V.; Li, Qunhua; Liu, Tao; Liu, X. Shirley; Ma, Lijia; Milosavljevic, Aleksandar; Myers, Richard M.; Park, Peter J.; Pazin, Michael J.; Perry, Marc D.; Raha, Debasish; Reddy, Timothy E.; Rozowsky, Joel; Shoresh, Noam; Sidow, Arend; Slattery, Matthew; Stamatoyannopoulos, John A.; Tolstorukov, Michael Y.; White, Kevin P.; Xi, Simon; Farnham, Peggy J.; Lieb, Jason D.; Wold, Barbara J.; Snyder, Michael

    2012-01-01

    Chromatin immunoprecipitation (ChIP) followed by high-throughput DNA sequencing (ChIP-seq) has become a valuable and widely used approach for mapping the genomic location of transcription-factor binding and histone modifications in living cells. Despite its widespread use, there are considerable differences in how these experiments are conducted, how the results are scored and evaluated for quality, and how the data and metadata are archived for public use. These practices affect the quality and utility of any global ChIP experiment. Through our experience in performing ChIP-seq experiments, the ENCODE and modENCODE consortia have developed a set of working standards and guidelines for ChIP experiments that are updated routinely. The current guidelines address antibody validation, experimental replication, sequencing depth, data and metadata reporting, and data quality assessment. We discuss how ChIP quality, assessed in these ways, affects different uses of ChIP-seq data. All data sets used in the analysis have been deposited for public viewing and downloading at the ENCODE (http://encodeproject.org/ENCODE/) and modENCODE (http://www.modencode.org/) portals. PMID:22955991

  2. Evaluating standard terminologies for encoding allergy information

    PubMed Central

    Goss, Foster R; Zhou, Li; Plasek, Joseph M; Broverman, Carol; Robinson, George; Middleton, Blackford; Rocha, Roberto A

    2013-01-01

    Objective Allergy documentation and exchange are vital to ensuring patient safety. This study aims to analyze and compare various existing standard terminologies for representing allergy information. Methods Five terminologies were identified, including the Systemized Nomenclature of Medical Clinical Terms (SNOMED CT), National Drug File–Reference Terminology (NDF-RT), Medication Dictionary for Regulatory Activities (MedDRA), Unique Ingredient Identifier (UNII), and RxNorm. A qualitative analysis was conducted to compare desirable characteristics of each terminology, including content coverage, concept orientation, formal definitions, multiple granularities, vocabulary structure, subset capability, and maintainability. A quantitative analysis was also performed to compare the content coverage of each terminology for (1) common food, drug, and environmental allergens and (2) descriptive concepts for common drug allergies, adverse reactions (AR), and no known allergies. Results Our qualitative results show that SNOMED CT fulfilled the greatest number of desirable characteristics, followed by NDF-RT, RxNorm, UNII, and MedDRA. Our quantitative results demonstrate that RxNorm had the highest concept coverage for representing drug allergens, followed by UNII, SNOMED CT, NDF-RT, and MedDRA. For food and environmental allergens, UNII demonstrated the highest concept coverage, followed by SNOMED CT. For representing descriptive allergy concepts and adverse reactions, SNOMED CT and NDF-RT showed the highest coverage. Only SNOMED CT was capable of representing unique concepts for encoding no known allergies. Conclusions The proper terminology for encoding a patient's allergy is complex, as multiple elements need to be captured to form a fully structured clinical finding. Our results suggest that while gaps still exist, a combination of SNOMED CT and RxNorm can satisfy most criteria for encoding common allergies and provide sufficient content coverage. PMID:23396542

  3. Encoding the core electrons with graph concepts.

    PubMed

    Pogliani, Lionello

    2004-01-01

    The core electron problem of atoms in chemical graph studies has always been considered as a minor problem. Usually, chemical graphs had to encode just a small set of second row atoms, i.e., C, N, O, and F, thus, graph and, in some cases, pseudograph concepts were enough to "graph" encode the molecules at hand. Molecular connectivity theory, together with its side-branch the electrotopological state, introduced two "ad hoc" algorithms for the core electrons of higher-row atoms based, mainly, on quantum concepts alike. Recently, complete graphs, and, especially, odd complete graphs have been introduced to encode the core electrons of higher-row atoms. By the aid of these types of graphs a double-valued algorithm has been proposed for the valence delta, deltav, of any type of atoms of the periodic table with a principal quantum number n > or =2. The new algorithm is centered on an invariant suggested by the hand-shaking theorem, and the values it gives rise to parallel in some way the values derived by the aid of the two old "quantum" algorithms. A thorough comparative analysis of the newly proposed algorithms has been undertaken for atoms of the group 1A-7A of the periodic table. This comparative study includes the electronegativity, the size of the atoms, the first ionization energy, and the electron affinity. The given algorithm has also been tested with sequential complete graphs, while the even complete graphs give rise to conceptual difficulties. QSAR/QSPR studies do not show a clear-cut preference for any of the two values the algorithm gives rise to, even if recent results seem to prefer one of the two values. PMID:14741009

  4. Wavelet encoding and variable resolution progressive transmission

    NASA Technical Reports Server (NTRS)

    Blanford, Ronald P.

    1993-01-01

    Progressive transmission is a method of transmitting and displaying imagery in stages of successively improving quality. The subsampled lowpass image representations generated by a wavelet transformation suit this purpose well, but for best results the order of presentation is critical. Candidate data for transmission are best selected using dynamic prioritization criteria generated from image contents and viewer guidance. We show that wavelets are not only suitable but superior when used to encode data for progressive transmission at non-uniform resolutions. This application does not preclude additional compression using quantization of highpass coefficients, which to the contrary results in superior image approximations at low data rates.

  5. Spatially encoded multiple-quantum excitation

    NASA Astrophysics Data System (ADS)

    Ridge, Clark D.; Borvayeh, Leila; Walls, Jamie D.

    2013-05-01

    In this work, we present a simple method to spatially encode the transition frequencies of nuclear spin transitions and to read out these frequencies within a single scan. The experiment works by combining pulsed field gradients with an excitation sequence that selectively excites spin transitions within certain sample regions. After the initial excitation, imaging the resulting widehat{z}-magnetization is used to determine the locations where the excitations occurred, from which the corresponding transition frequencies are determined. Simple experimental demonstrations of this technique on one- and two-spin systems are presented.

  6. A space-compatible angular contact encoder

    NASA Astrophysics Data System (ADS)

    Flew, A. R.

    1985-12-01

    An electromechanical digital position encoder, based on existing commercial technology, for spacecraft applications is described. The device contains electrical wiping contacts, a gear mechanism, and plain and rolling-element bearings all operating without wet lubrication. Designed to function continuously for 10 years, certain contacts will perform in excess of 20 million cycles. To investigate the performance of these contacts, automatic test equipment was designed to monitor the accuracy of 8192 separate output conditions on a regular basis throughout an accelerated-life thermal vacuum test. The equipment also checks for missing bits and edge noise and logs any errors that are found.

  7. Gene encoding herbicide safener binding protein

    SciTech Connect

    Walton, Jonathan D.; Scott-Craig, John S.

    1999-01-01

    The cDNA encoding safener binding protein (SafBP), also referred to as SBP1, is set forth in FIG. 5 and SEQ ID No. 1. The deduced amino acid sequence is provided in FIG. 5 and SEQ ID No. 2. Methods of making and using SBP1 and SafBP to alter a plant's sensitivity to certain herbicides or a plant's responsiveness to certain safeners are also provided, as well as expression vectors, transgenic plants or other organisms transfected with said vectors and seeds from said plants.

  8. Polynucleotides encoding TRF1 binding proteins

    DOEpatents

    Campisi, Judith; Kim, Sahn-Ho

    2002-01-01

    The present invention provides a novel telomere associated protein (Trf1-interacting nuclear protein 2 "Tin2") that hinders the binding of Trf1 to its specific telomere repeat sequence and mediates the formation of a Tin2-Trf1-telomeric DNA complex that limits telomerase access to the telomere. Also included are the corresponding nucleic acids that encode the Tin2 of the present invention, as well as mutants of Tin2. Methods of making, purifying and using Tin2 of the present invention are described. In addition, drug screening assays to identify drugs that mimic and/or complement the effect of Tin2 are presented.

  9. Space Qualified High Speed Reed Solomon Encoder

    NASA Technical Reports Server (NTRS)

    Gambles, Jody W.; Winkert, Tom

    1993-01-01

    This paper reports a Class S CCSDS recommendation Reed Solomon encoder circuit baselined for several NASA programs. The chip is fabricated using United Technologies Microelectronics Center's UTE-R radiation-hardened gate array family, contains 64,000 p-n transistor pairs, and operates at a sustained output data rate of 200 MBits/s. The chip features a pin selectable message interleave depth of from 1 to 8 and supports output block lengths of 33 to 255 bytes. The UTE-R process is reported to produce parts that are radiation hardened to 16 Rads (Si) total dose and 1.0(exp -10) errors/bit-day.

  10. Visual Encoding Mechanisms and Their Relationship to Text Presentation Preference

    ERIC Educational Resources Information Center

    Pammer, Kristen; Lavis, Ruth; Cornelissen, Piers

    2004-01-01

    This study was designed to investigate the importance of spatial encoding in reading, with particular emphasis on visuo-spatial encoding mechanisms. Thirty one school children participated in the first study in which they were measured on their ability to solve a centrally presented spatial encoding task, as well as their sensitivity to the…

  11. Shape-encoded silica microparticles for multiplexed bioassays.

    PubMed

    Kim, Lily Nari; Kim, Mira; Jung, Keumsim; Bae, Hyung Jong; Jang, Jisung; Jung, Yushin; Kim, Jiyun; Kwon, Sunghoon

    2015-08-01

    Shape-encoded silica microparticles for use in multiplexed bioassays were fabricated by using optofluidic maskless lithography (OFML) and tetraethylorthosilicate (TEOS) polymerization. These encoded silica microparticles exhibit excellent bioconjugation properties and negligible non-specific analyte adsorption. Encoded silica microparticles could be useful in a wide variety of applications, including DNA- and protein-based diagnostics. PMID:26125980

  12. Optical Pseudocolor Encoding Of Gray-Scale Image

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin; Liu, Hua-Kuang

    1990-01-01

    Optical encoding much faster than digital electronic encoding. In optical pseudocolor-encoding apparatus brightness modulation in image from television camera transformed into polarization modulation in LCTV, and then into pseudocolor modulation in image on projection screen. Advantageous for such purposes as thermography, inspection of circuit boards, mammography, and mapping.

  13. Multiple-encoding retrieval for optical security

    NASA Astrophysics Data System (ADS)

    Barrera, John Fredy; Henao, Rodrigo; Tebaldi, Myrian; Torroba, Roberto; Bolognini, Néstor

    2007-08-01

    We propose a method for image encryption by multiple-step random phase encoding with an undercover multiplexing operation. The true image is stored in a multiple record we call encodegram; and then we can reconstruct it by the use of the appropriate random phase masks and a retrieval protocol. To increase the security of the true hidden image and confuse unauthorized receivers, we add to the encodegram an encoded fake image with different content. This fake image has only a small effect on the retrieval of the true hidden image, owing to the specific property of this protocol. In the decryption step, we can reveal the true image by applying the inverse protocol to two cyphertexts, one the encodegram containing the true image along with the fake image; and the other helping to get the random phase key to achieve the true image. Computer simulations verify the validity of this method for image encryption. Digital implementation of the method makes it particularly suitable for the remote transmission of information.

  14. Spike encoding of olfactory receptor cells.

    PubMed

    Narusuye, Kenji; Kawai, Fusao; Miyachi, Ei-ichi

    2003-08-01

    Olfaction begins with the transduction of the information carried by odorants into electrical signals in olfactory receptor cells (ORCs). The binding of odor molecules to specific receptor proteins on the ciliary surface of ORCs induces the receptor potentials. This initial excitation causes a slow and graded depolarizing voltage change, which is encoded into a train of action potentials. Action potentials of ORCs are generated by voltage-gated Na+ currents and T-type Ca2+ currents in the somatic membrane. Isolated ORCs, which have lost their cilia during the dissociation procedure, are known to exhibit spike frequency accommodation by injecting the steady current. This raises the possibility that somatic ionic channels in ORCs may serve for odor adaptation at the level of spike encoding, although odor adaptation is mainly accomplished by the ciliary transduction machinery. This review discusses current knowledge concerning the mechanisms of spike generation in ORCs. It also reviews how neurotransmitters and hormones modulate ionic currents and action potentials in ORCs. PMID:12871762

  15. Light manipulation with encoded plasmonic nanostructures

    NASA Astrophysics Data System (ADS)

    Zhao, Chenglong; Zhang, Jiasen; Liu, Yongmin

    2014-12-01

    Plasmonics, which allows for manipulation of light field beyond the fundamental diffraction limit, has recently attracted tremendous research efforts. The propagating surface plasmon polaritons (SPPs) confined on a metal-dielectric interface provide an ideal two-dimensional (2D) platform to develop subwavelength optical circuits for on-chip information processing and communication. The surface plasmon resonance of rationally designed metallic nanostructures, on the other hand, enables pronounced phase and polarization modulation for light beams travelling in three-dimensional (3D) free space. Flexible 2D and free-space propagating light manipulation can be achieved by encoding plasmonic nanostructures on a 2D surface, promising the design, fabrication and integration of the next-generation optical architectures with substantially reduced footprint. It is envisioned that the encoded plasmonic nanostructures can significantly expand available toolboxes for novel light manipulation. In this review, we presents the fundamentals, recent developments and future perspectives in this emerging field, aiming to open up new avenues to developing revolutionary photonic devices.

  16. V123 BEAM SYNCHRONOUS ENCODER MODULE.

    SciTech Connect

    KERNER,T.; CONKLING,C.R.; OERTER,B.

    1999-03-29

    The V123 Synchronous Encoder Module transmits events to distributed trigger modules and embedded decoders around the RHIC rings where they are used to provide beam instrumentation triggers [1,2,3]. The RHIC beam synchronous event link hardware is mainly comprised of three VMEbus board designs, the central input modules (V201), and encoder modules (V123), and the distributed trigger modules (V124). Two beam synchronous links, one for each ring, are distributed via fiber optics and fanned out via twisted wire pair cables. The V123 synchronizes with the RF system clock derived from the beam bucket frequency and a revolution fiducial pulse. The RF system clock is used to create the beam synchronous event link carrier and events are synchronized with the rotation fiducial. A low jitter RF clock is later recovered from this carrier by phase lock loops in the trigger modules. Prioritized hardware and software triggers fill up to 15 beam event code transmission slots per revolution while tracking the ramping RF acceleration frequency and storage frequency. The revolution fiducial event is always the first event transmitted which is used to synchronize the firing of the abort kicker and to locate the first bucket for decoders distributed about the ring.

  17. Encoded multisite two-photon microscopy

    PubMed Central

    Ducros, Mathieu; Houssen, Yannick Goulam; Bradley, Jonathan; de Sars, Vincent; Charpak, Serge

    2013-01-01

    The advent of scanning two-photon microscopy (2PM) has created a fertile new avenue for noninvasive investigation of brain activity in depth. One principal weakness of this method, however, lies with the limit of scanning speed, which makes optical interrogation of action potential-like activity in a neuronal network problematic. Encoded multisite two-photon microscopy (eMS2PM), a scanless method that allows simultaneous imaging of multiple targets in depth with high temporal resolution, addresses this drawback. eMS2PM uses a liquid crystal spatial light modulator to split a high-power femto-laser beam into multiple subbeams. To distinguish them, a digital micromirror device encodes each subbeam with a specific binary amplitude modulation sequence. Fluorescence signals from all independently targeted sites are then collected simultaneously onto a single photodetector and site-specifically decoded. We demonstrate that eMS2PM can be used to image spike-like voltage transients in cultured cells and fluorescence transients (calcium signals in neurons and red blood cells in capillaries from the cortex) in depth in vivo. These results establish eMS2PM as a unique method for simultaneous acquisition of neuronal network activity. PMID:23798397

  18. Spectrally encoded confocal scanning laser ophthalmoscope

    NASA Astrophysics Data System (ADS)

    Tao, Yuankai K.; Izatt, Joseph A.

    2010-02-01

    Fundus imaging has become an essential clinical diagnostic tool in ophthalmology. Current generation scanning laser ophthalmoscopes (SLO) offer advantages over conventional fundus photography and indirect ophthalmoscopy in terms of light efficiency and contrast. As a result of the ability of SLO to provide rapid, continuous imaging of retinal structures and its versatility in accommodating a variety of illumination wavelengths, allowing for imaging of both endogenous and exogenous fluorescent contrast agents, SLO has become a powerful tool for the characterization of retinal pathologies. However, common implementations of SLO, such as the confocal scanning laser ophthalmoscope (CSLO) and line-scanning laser ophthalmoscope (LSLO), require imaging or multidimensional scanning elements which are typically implemented in bulk optics placed close to the subject eye. Here, we apply a spectral encoding technique in one dimension combined with single-axis lateral scanning to create a spectrally encoded confocal scanning laser ophthalmoscope (SECSLO) which is fully confocal. This novel implementation of the SLO allows for high contrast, high resolution in vivo human retinal imaging with image transmission through a single-mode optical fiber. Furthermore, the scanning optics are similar and the detection engine is identical to that of current-generation spectral domain optical coherence tomography (SDOCT) systems, potentially allowing for a simplistic implementation of a joint SECSLO-SDOCT imaging system.

  19. Optical Security System with Fourier Plane encoding

    NASA Astrophysics Data System (ADS)

    Javidi, Bahram; Ahouzi, Esmail

    1998-09-01

    We propose a new technique for security verification of personal documents and other forms of personal identifications such as ID cards, passports, or credit cards. In this technique a primary pattern that might be a phase-encoded image is convolved by a random code. The information is phase encoded on the personal document. Therefore the information cannot be reproduced by an intensity detector such as a CCD camera. An optical processor based on the nonlinear joint transform correlator is used to perform the verification and the validation of documents with this technique. By verification of the biometrics information and the random code simultaneously, the proposed optical system determines whether a card is authentic or is being used by an authorized person. We tested the performance of the optical system for security and validation in the presence of input noise and in the presence of distortion of the information on the card. The performance of the proposed method is evaluated by use of a number of metrics. Statistical analysis of the system is performed to investigate the noise tolerance and the discrimination against false inputs for security verification.

  20. Optical Security System with Fourier Plane encoding.

    PubMed

    Javidi, B; Ahouzi, E

    1998-09-10

    We propose a new technique for security verification of personal documents and other forms of personal identifications such as ID cards, passports, or credit cards. In this technique a primary pattern that might be a phase-encoded image is convolved by a random code. The information is phase encoded on the personal document. Therefore the information cannot be reproduced by an intensity detector such as a CCD camera. An optical processor based on the nonlinear joint transform correlator is used to perform the verification and the validation of documents with this technique. By verification of the biometrics information and the random code simultaneously, the proposed optical system determines whether a card is authentic or is being used by an authorized person. We tested the performance of the optical system for security and validation in the presence of input noise and in the presence of distortion of the information on the card. The performance of the proposed method is evaluated by use of a number of metrics. Statistical analysis of the system is performed to investigate the noise tolerance and the discrimination against false inputs for security verification. PMID:18286124

  1. Fast Huffman encoding algorithms in MPEG-4 advanced audio coding

    NASA Astrophysics Data System (ADS)

    Brzuchalski, Grzegorz

    2014-11-01

    This paper addresses the optimisation problem of Huffman encoding in MPEG-4 Advanced Audio Coding stan- dard. At first, the Huffman encoding problem and the need of encoding two side info parameters scale factor and Huffman codebook are presented. Next, Two Loop Search, Maximum Noise Mask Ratio and Trellis Based algorithms of bit allocation are briefly described. Further, Huffman encoding optimisation are shown. New methods try to check and change scale factor bands as little as possible to estimate bitrate cost or its change. Finally, the complexity of old and new methods is calculated, compared and measured time of encoding is given.

  2. On the detection of differentially encoded polyphase signals.

    NASA Technical Reports Server (NTRS)

    Lindsey, W. C.; Simon, M. K.

    1972-01-01

    Consideration of the transmission and detection of differentially encoded multiple phase-shift-keyed (MPSK) signals, paying particular attention to the ambiguity resolution problem resulting from suppression of the transmitted carrier. A study is made of the coherent detection of differentially encoded MPSK signals, and the performance of a differentially encoded MPSK system is compared with that of a system which transmits absolutely encoded polyphase signals and performs perfect ambiguity resolution. Both the perfect and noisy reference signal cases are treated. Also, the performance of coherent detection of differentially encoded MPSK signals is compared with that of differentially coherent reception of the same signal set.

  3. Architecture for VLSI design of Reed-Solomon encoders

    NASA Technical Reports Server (NTRS)

    Liu, K. Y.

    1982-01-01

    A description is given of the logic structure of the universal VLSI symbol-slice Reed-Solomon (RS) encoder chip, from a group of which an RS encoder may be constructed through cascading and proper interconnection. As a design example, it is shown that an RS encoder presently requiring approximately 40 discrete CMOS ICs may be replaced by an RS encoder consisting of four identical, interconnected VLSI RS encoder chips, offering in addition to greater compactness both a lower power requirement and greater reliability.

  4. Negative base encoding in optical linear algebra processors

    NASA Technical Reports Server (NTRS)

    Perlee, C.; Casasent, D.

    1986-01-01

    In the digital multiplication by analog convolution algorithm, the bits of two encoded numbers are convolved to form the product of the two numbers in mixed binary representation; this output can be easily converted to binary. Attention is presently given to negative base encoding, treating base -2 initially, and then showing that the negative base system can be readily extended to any radix. In general, negative base encoding in optical linear algebra processors represents a more efficient technique than either sign magnitude or 2's complement encoding, when the additions of digitally encoded products are performed in parallel.

  5. A Multi-Encoding Approach for LTL Symbolic Satisfiability Checking

    NASA Technical Reports Server (NTRS)

    Rozier, Kristin Y.; Vardi, Moshe Y.

    2011-01-01

    Formal behavioral specifications written early in the system-design process and communicated across all design phases have been shown to increase the efficiency, consistency, and quality of the system under development. To prevent introducing design or verification errors, it is crucial to test specifications for satisfiability. Our focus here is on specifications expressed in linear temporal logic (LTL). We introduce a novel encoding of symbolic transition-based Buchi automata and a novel, "sloppy," transition encoding, both of which result in improved scalability. We also define novel BDD variable orders based on tree decomposition of formula parse trees. We describe and extensively test a new multi-encoding approach utilizing these novel encoding techniques to create 30 encoding variations. We show that our novel encodings translate to significant, sometimes exponential, improvement over the current standard encoding for symbolic LTL satisfiability checking.

  6. When two is too many: Collaborative encoding impairs memory.

    PubMed

    Barber, Sarah J; Rajaram, Suparna; Aron, Arthur

    2010-04-01

    Humans routinely encode and retrieve experiences in interactive, collaborative contexts. Yet much of what we know about human memory comes from research on individuals working in isolation. Some recent research has examined collaboration during retrieval, but not much is known about how collaboration during encoding affects memory. We examined this issue. Participants created episodes by elaborating on study materials alone or collaboratively, and they later performed a cued-recall task alone, with the study partner, or with a different partner (Experiment 1). Collaborative encoding impaired recall. This counterintuitive outcome was found for both individual and group recall, even when the same partners collaborated across encoding and retrieval. This impairment was significantly reduced, but persisted, when the encoding instructions encouraged free-flowing collaboration (Experiment 2). Thus, the collaborative-encoding deficit is robust in nature and likely occurs because collaborative encoding produces less effective cues for later retrieval. PMID:20234016

  7. High-resolution encoding using redundant edge detection

    NASA Astrophysics Data System (ADS)

    Saddlemyer, Leslie K.; McLean, Gerard F.

    1995-06-01

    Encoding the angular position of large telescopes is typically achieved through the use of friction driven rotary encoders, tape style encoders mounted on the circumference of each telescope axis or co-axially mounted high precision rotary encoders. These forms of encoding have very stringent mounting requirements, are expensive, adversely affected by contaminating particles and often difficult to retrofit to existing telescopes. The advent of long CCDs presents the opportunity to develop accurate position encoding for telescope control using digital image metrology. In this paper we present the design of a high precision non- contact encoding system which uses the detection of multiple redundant visual edge features to develop sub-pixel edge position measurements to a precision of 1/50th pixel. The method is described in detail and is validated with both simulation trials and experimental results from a testbed setup.

  8. Digital information encrypted in an image using binary encoding

    NASA Astrophysics Data System (ADS)

    Lin, Kuang Tsan

    2008-07-01

    This paper proposes a new type of encoding methods to encrypt hidden (covert) information in host images. The encrypted information can be plot, fax, word, or network data, and it must be encoded with binary codes. All the pixels in an encoded (overt) image modulated from a host image are classified into three groups. The first group of pixels is called identification codes, used to judge whether the overt image is encoded by a method proposed in this paper or not. The second group of pixels is called type codes, used to judge the encoding type. The third group of pixels is called information codes, used to decode the encoded information. Applying the proposed encoding methods is quite convenient, and host images are not needed for decoding. Decoding covert information from overt images is rather difficult for un-authorized persons, whereas it is very easy for designers or authorized persons. Therefore, the proposed methods are very useful.

  9. Optically coupled digital altitude encoder for general aviation altimeters

    NASA Technical Reports Server (NTRS)

    Bryant, F. R.

    1975-01-01

    An optically coupled pressure altitude encoder which can be incorporated into commercially available inexpensive general aviation altimeters was successfully developed. The encoding of pressure altitude is accomplished in 100-ft (30.48-m) increments from -1000 to 20,000ft (-304.8 to 6096 m). The prototype encoders were retrofitted into two different internal altimeter configurations. A prototype encoder was checked for accuracy of transition points and environmental effects. Each altimeter configuration, with the encoder incorporated, was laboratory tested for performance and was subsequently flight-tested over the specified altitude range. With few exceptions, the assembled altimeter-encoder met aeronautical standards for altimeters and encoders. Design changes are suggested to improve performance to meet required standards consistently.

  10. Non-Fourier-encoded parallel MRI using multiple receiver coils.

    PubMed

    Mitsouras, Dimitris; Hoge, W Scott; Rybicki, Frank J; Kyriakos, Walid E; Edelman, Alan; Zientara, Gary P

    2004-08-01

    This paper describes a general theoretical framework that combines non-Fourier (NF) spatially-encoded MRI with multichannel acquisition parallel MRI. The two spatial-encoding mechanisms are physically and analytically separable, which allows NF encoding to be expressed as complementary to the inherent encoding imposed by RF receiver coil sensitivities. Consequently, the number of NF spatial-encoding steps necessary to fully encode an FOV is reduced. Furthermore, by casting the FOV reduction of parallel imaging techniques as a dimensionality reduction of the k-space that is NF-encoded, one can obtain a speed-up of each digital NF spatial excitation in addition to accelerated imaging. Images acquired at speed-up factors of 2x to 8x with a four-element RF receiver coil array demonstrate the utility of this framework and the efficiency afforded by it. PMID:15282814

  11. DNA-Encoded Solid-Phase Synthesis: Encoding Language Design and Complex Oligomer Library Synthesis

    PubMed Central

    2015-01-01

    The promise of exploiting combinatorial synthesis for small molecule discovery remains unfulfilled due primarily to the “structure elucidation problem”: the back-end mass spectrometric analysis that significantly restricts one-bead-one-compound (OBOC) library complexity. The very molecular features that confer binding potency and specificity, such as stereochemistry, regiochemistry, and scaffold rigidity, are conspicuously absent from most libraries because isomerism introduces mass redundancy and diverse scaffolds yield uninterpretable MS fragmentation. Here we present DNA-encoded solid-phase synthesis (DESPS), comprising parallel compound synthesis in organic solvent and aqueous enzymatic ligation of unprotected encoding dsDNA oligonucleotides. Computational encoding language design yielded 148 thermodynamically optimized sequences with Hamming string distance ≥ 3 and total read length <100 bases for facile sequencing. Ligation is efficient (70% yield), specific, and directional over 6 encoding positions. A series of isomers served as a testbed for DESPS’s utility in split-and-pool diversification. Single-bead quantitative PCR detected 9 × 104 molecules/bead and sequencing allowed for elucidation of each compound’s synthetic history. We applied DESPS to the combinatorial synthesis of a 75 645-member OBOC library containing scaffold, stereochemical and regiochemical diversity using mixed-scale resin (160-μm quality control beads and 10-μm screening beads). Tandem DNA sequencing/MALDI-TOF MS analysis of 19 quality control beads showed excellent agreement (<1 ppt) between DNA sequence-predicted mass and the observed mass. DESPS synergistically unites the advantages of solid-phase synthesis and DNA encoding, enabling single-bead structural elucidation of complex compounds and synthesis using reactions normally considered incompatible with unprotected DNA. The widespread availability of inexpensive oligonucleotide synthesis, enzymes, DNA sequencing, and

  12. An implementation framework for GEM encoded guidelines.

    PubMed Central

    Gershkovich, P.; Shiffman, R. N.

    2001-01-01

    Access to timely decision support information is critical for delivery of high-quality medical care. Transformation of clinical knowledge that is originally expressed in the form of a guideline to a computable format is one of the main obstacles to the integration of knowledge sharing functionality into computerized clinical systems. The Guideline Element Model (GEM) provides a methodology for such a transformation. Although the model has been used to store heterogeneous guideline knowledge, it is important to demonstrate that GEM markup facilitates guideline implementation. This report demonstrates the feasibility of implementation of GEM-encoded guideline recommendations using Apache Group s Cocoon Web Publishing Framework. We further demonstrate how XML-based programming allows for maintaining the separation of guideline content from processing logic and from presentation format. Finally, we analyze whether the guideline authors original intent has been sufficiently captured and conveyed to the end user. PMID:11825181

  13. Brain Circuits Encoding Reward from Pain Relief.

    PubMed

    Navratilova, Edita; Atcherley, Christopher W; Porreca, Frank

    2015-11-01

    Relief from pain in humans is rewarding and pleasurable. Primary rewards, or reward-predictive cues, are encoded in brain reward/motivational circuits. While considerable advances have been made in our understanding of reward circuits underlying positive reinforcement, less is known about the circuits underlying the hedonic and reinforcing actions of pain relief. We review findings from electrophysiological, neuroimaging, and behavioral studies supporting the concept that the rewarding effect of pain relief requires opioid signaling in the anterior cingulate cortex (ACC), activation of midbrain dopamine neurons, and the release of dopamine in the nucleus accumbens (NAc). Understanding of circuits that govern the reward of pain relief may allow the discovery of more effective and satisfying therapies for patients with acute or chronic pain. PMID:26603560

  14. Measurement strategy for spatially encoded photonic qubits

    SciTech Connect

    Solis-Prosser, M. A.; Neves, L.

    2010-11-15

    We propose a measurement strategy which can, probabilistically, reproduce the statistics of any observable for spatially encoded photonic qubits. It comprises the implementation of a two-outcome positive operator-valued measure followed by a detection in a fixed transverse position, making the displacement of the detection system unnecessary, unlike previous methods. This strategy generalizes a scheme recently demonstrated by one of us and co-workers, restricted to measurement of observables with equatorial eigenvectors only. The method presented here can be implemented with the current technology of programmable multipixel liquid-crystal displays. In addition, it can be straightforwardly extended to high-dimensional qudits and may be a valuable tool in optical implementations of quantum information protocols with spatial qubits and qudits.

  15. Premotor and Motor Cortices Encode Reward

    PubMed Central

    Ramkumar, Pavan; Dekleva, Brian; Cooler, Sam; Miller, Lee; Kording, Konrad

    2016-01-01

    Rewards associated with actions are critical for motivation and learning about the consequences of one’s actions on the world. The motor cortices are involved in planning and executing movements, but it is unclear whether they encode reward over and above limb kinematics and dynamics. Here, we report a categorical reward signal in dorsal premotor (PMd) and primary motor (M1) neurons that corresponds to an increase in firing rates when a trial was not rewarded regardless of whether or not a reward was expected. We show that this signal is unrelated to error magnitude, reward prediction error, or other task confounds such as reward consumption, return reach plan, or kinematic differences across rewarded and unrewarded trials. The availability of reward information in motor cortex is crucial for theories of reward-based learning and motivational influences on actions. PMID:27564707

  16. Premotor and Motor Cortices Encode Reward.

    PubMed

    Ramkumar, Pavan; Dekleva, Brian; Cooler, Sam; Miller, Lee; Kording, Konrad

    2016-01-01

    Rewards associated with actions are critical for motivation and learning about the consequences of one's actions on the world. The motor cortices are involved in planning and executing movements, but it is unclear whether they encode reward over and above limb kinematics and dynamics. Here, we report a categorical reward signal in dorsal premotor (PMd) and primary motor (M1) neurons that corresponds to an increase in firing rates when a trial was not rewarded regardless of whether or not a reward was expected. We show that this signal is unrelated to error magnitude, reward prediction error, or other task confounds such as reward consumption, return reach plan, or kinematic differences across rewarded and unrewarded trials. The availability of reward information in motor cortex is crucial for theories of reward-based learning and motivational influences on actions. PMID:27564707

  17. Encoding and decoding time in neural development.

    PubMed

    Toma, Kenichi; Wang, Tien-Cheng; Hanashima, Carina

    2016-01-01

    The development of a multicellular organism involves time-dependent changes in molecular and cellular states; therefore 'time' is an indispensable mathematical parameter of ontogenesis. Regardless of their inextricable relationship, there is a limited number of events for which the output of developmental phenomena primarily uses temporal cues that are generated through multilevel interactions between molecules, cells, and tissues. In this review, we focus on neural stem cells, which serve as a faithful decoder of temporal cues to transmit biological information and generate specific output in the developing nervous system. We further explore the identity of the temporal information that is encoded in neural development, and how this information is decoded into various cellular fate decisions. PMID:26748623

  18. Ultrasonically Encoded Photoacoustic Flowgraphy in Biological Tissue

    NASA Astrophysics Data System (ADS)

    Wang, Lidai; Xia, Jun; Yao, Junjie; Maslov, Konstantin I.; Wang, Lihong V.

    2013-11-01

    Blood flow speed is an important functional parameter. Doppler ultrasound flowmetry lacks sufficient sensitivity to slow blood flow (several to tens of millimeters per second) in deep tissue. To address this challenge, we developed ultrasonically encoded photoacoustic flowgraphy combining ultrasonic thermal tagging with photoacoustic imaging. Focused ultrasound generates a confined heat source in acoustically absorptive fluid. Thermal waves propagate with the flow and are directly visualized in pseudo color using photoacoustic computed tomography. The Doppler shift is employed to calculate the flow speed. This method requires only acoustic and optical absorption, and thus is applicable to continuous fluid. A blood flow speed as low as 0.24mm·s-1 was successfully measured. Deep blood flow imaging was experimentally demonstrated under 5-mm-thick chicken breast tissue.

  19. Adaptive encoding in the visual pathway.

    PubMed

    Lesica, Nicholas A; Boloori, Alireza S; Stanley, Garrett B

    2003-02-01

    In a natural setting, the mean luminance and contrast of the light within a visual neuron's receptive field are constantly changing as the eyes saccade across complex scenes. Adaptive mechanisms modulate filtering properties of the early visual pathway in response to these variations, allowing the system to maintain differential sensitivity to nonstationary stimuli. An adaptive variant of the reverse correlation technique is used to characterize these changes during single trials. Properties of the adaptive reverse correlation algorithm were investigated via simulation. Analysis of data collected from the mammalian visual system demonstrates the ability to continuously track adaptive changes in the encoding scheme. The adaptive estimation approach provides a framework for characterizing the role of adaptation in natural scene viewing. PMID:12613554

  20. Designing and encoding models for synthetic biology

    PubMed Central

    Endler, Lukas; Rodriguez, Nicolas; Juty, Nick; Chelliah, Vijayalakshmi; Laibe, Camille; Li, Chen; Le Novère, Nicolas

    2009-01-01

    A key component of any synthetic biology effort is the use of quantitative models. These models and their corresponding simulations allow optimization of a system design, as well as guiding their subsequent analysis. Once a domain mostly reserved for experts, dynamical modelling of gene regulatory and reaction networks has been an area of growth over the last decade. There has been a concomitant increase in the number of software tools and standards, thereby facilitating model exchange and reuse. We give here an overview of the model creation and analysis processes as well as some software tools in common use. Using markup language to encode the model and associated annotation, we describe the mining of components, their integration in relational models, formularization and parametrization. Evaluation of simulation results and validation of the model close the systems biology ‘loop’. PMID:19364720

  1. MPEG-1 low-cost encoder solution

    NASA Astrophysics Data System (ADS)

    Grueger, Klaus; Schirrmeister, Frank; Filor, Lutz; von Reventlow, Christian; Schneider, Ulrich; Mueller, Gerriet; Sefzik, Nicolai; Fiedrich, Sven

    1995-02-01

    A solution for real-time compression of digital YCRCB video data to an MPEG-1 video data stream has been developed. As an additional option, motion JPEG and video telephone streams (H.261) can be generated. For MPEG-1, up to two bidirectional predicted images are supported. The required computational power for motion estimation and DCT/IDCT, memory size and memory bandwidth have been the main challenges. The design uses fast-page-mode memory accesses and requires only one single 80 ns EDO-DRAM with 256 X 16 organization for video encoding. This can be achieved only by using adequate access and coding strategies. The architecture consists of an input processing and filter unit, a memory interface, a motion estimation unit, a motion compensation unit, a DCT unit, a quantization control, a VLC unit and a bus interface. For using the available memory bandwidth by the processing tasks, a fixed schedule for memory accesses has been applied, that can be interrupted for asynchronous events. The motion estimation unit implements a highly sophisticated hierarchical search strategy based on block matching. The DCT unit uses a separated fast-DCT flowgraph realized by a switchable hardware unit for both DCT and IDCT operation. By appropriate multiplexing, only one multiplier is required for: DCT, quantization, inverse quantization, and IDCT. The VLC unit generates the video-stream up to the video sequence layer and is directly coupled with an intelligent bus-interface. Thus, the assembly of video, audio and system data can easily be performed by the host computer. Having a relatively low complexity and only small requirements for DRAM circuits, the developed solution can be applied to low-cost encoding products for consumer electronics.

  2. Encoding by synchronization in the primate striatum.

    PubMed

    Adler, Avital; Finkes, Inna; Katabi, Shiran; Prut, Yifat; Bergman, Hagai

    2013-03-13

    Information is encoded in the nervous system through the discharge and synchronization of single neurons. The striatum, the input stage of the basal ganglia, is divided into three territories: the putamen, the caudate, and the ventral striatum, all of which converge onto the same motor pathway. This parallel organization suggests that there are multiple and competing systems in the basal ganglia network controlling behavior. To explore which mechanism(s) enables the different striatal domains to encode behavioral events and to control behavior, we compared the neural activity of phasically active neurons [medium spiny neurons (MSNs), presumed projection neurons] and tonically active neurons (presumed cholinergic interneurons) across striatal territories from monkeys during the performance of a well practiced task. Although neurons in all striatal territories displayed similar spontaneous discharge properties and similar temporal modulations of their discharge rates to the behavioral events, their correlation structure was profoundly different. The distributions of signal and noise correlation of pairs of putamen MSNs were strongly shifted toward positive correlations and these two measures were correlated. In contrast, MSN pairs in the caudate and ventral striatum displayed symmetrical, near-zero signal and noise correlation distributions. Furthermore, only putamen MSN pairs displayed different noise correlation dynamics to rewarding versus neutral/aversive cues. Similarly, the noise correlation between tonically active neuron pairs was stronger in the putamen than in the caudate. We suggest that the level of synchronization of the neuronal activity and its temporal dynamics differentiate the striatal territories and may thus account for the different roles that striatal domains play in behavioral control. PMID:23486956

  3. Encoding continuous spatial phenomena in GML

    NASA Astrophysics Data System (ADS)

    de Vries, M. E.; Ledoux, H.

    2009-04-01

    In the discussion about how to model and encode geographic information two meta-models of space exist: the 'object' view and the 'field' view. This difference in conceptual view is also reflected in different data models and encoding formats. Among GIS practitioners, ‘fields' (or ‘coverages') are being used almost exclusively in 2D, while in the geoscience community 3D and higher-dimensional fields are widely used. (Note that the dimensions in oceanographic/atmospheric coverages are not necessarily spatial dimensions, as any parameters (e.g. temperature of the air, or density of water) can be considered a dimension.) While standardisation work in ISO and OGC has led to agreement on how to best encode discrete spatial objects, for the modelling and encoding of continuous ‘fields' there are still a number of open issues. In the presentation we will shortly discuss the current standards related to fields, and look at their shortcomings and potential. In ISO 19123 for example a distinction is made between discrete and continuous coverages, but the difference is not very clear and hard to capture for implementers. As far as encoding is concerned: GML 3.x (ISO 19136) has a discrete coverage data type, but no continuous coverage type. We will then present an alternative solution to model fields, and show how it can be implemented using some parts of GML, but not the ISO/GML coverage type. This alternative data model for fields permits us to represent fields in 2D and 3D, although conceptually it can be easily extended to higher dimensions. Unlike current standards where there is a distinction between discrete and continuous fields/coverages, we argue that a field should always have one - and only one! - value for a given attribute at every location in the spatial domain (be this domain the surface of the Earth, a 3D volume, or even a 4D spatio-temporal hypercube). The principal idea behind the proposed model is that two things are needed to have a coverage: 1. a set

  4. Using The ENCODE Resource For Functional Annotation Of Genetic Variants

    PubMed Central

    Pazin, Michael J.

    2015-01-01

    Summary This article illustrates the use of the Encyclopedia of DNA Elements (ENCODE) resource to generate or refine hypotheses from genomic data on disease and other phenotypic traits. First, the goals and history of ENCODE and related epigenomics projects are reviewed. Second, the rationale for ENCODE and the major data types used by ENCODE are briefly described, as are some standard heuristics for their interpretation. Third, the use of the ENCODE resource is examined. Standard use cases for ENCODE, accessing the ENCODE resource, and accessing data from related projects are discussed. Finally, access to resources from ENCODE and related epigenomics projects are reviewed. (Although the focus of this article is the use of ENCODE data, some of the same approaches can be used with the data from other projects.) While this article is focused on the case of interpreting genetic variation data, essentially the same approaches can be used with the ENCODE resource, or with data from other projects, to interpret epigenomic and gene regulation data, with appropriate modification (Rakyan et al. 2011; Ng et al. 2012). Such approaches could allow investigators to use genomic methods to study environmental and stochastic processes, in addition to genetic processes. PMID:25762420

  5. Peak velocity determination using fast Fourier velocity encoding with minimal spatial encoding.

    PubMed

    Galea, Daniela; Lauzon, M Louis; Drangova, Maria

    2002-08-01

    For quantitative peak velocity determination, a technique was developed that uses Fourier velocity encoding (FVE) for the fast acquisition of images of velocity with no spatial encoding other than slice selection. The technique produces images of velocity versus temporal frequency. In applications where the quantity of interest is the peak velocity and in-plane spatial localization is not required, high SNR images are produced with reduced sensitivity to errors due to slice thickness and motion. The technique was validated using steady and pulsatile flow in a straight tube, and compared to both phase contrast measurements and numerical models using steady flow in a 50% and a 75% cosinusoidal stenosis phantom. Results show that for slices as large as 2 cm and/or undergoing periodic motion, FVE can accurately measure the peak velocity in cases where a distribution of velocities exist. PMID:12201419

  6. Device and method for encoding data in multiple media

    SciTech Connect

    Battelle Memorial Institute K1-53

    2006-06-06

    A system and related device for converting encoded data from one format into one or more formats, including barcode and radio frequency identification tag formats, the system including a programmer configured to read a barcode and using the barcode data encoded thereon automatically write the data to a radio frequency (RF) tag and to read the contents of a RF tag and automatically generate a barcode with the information contained in the tag or information related thereto, preferably without decoding the encoded data.

  7. Neutron-encoded mass signatures for multiplexed proteome quantification.

    PubMed

    Hebert, Alexander S; Merrill, Anna E; Bailey, Derek J; Still, Amelia J; Westphall, Michael S; Strieter, Eric R; Pagliarini, David J; Coon, Joshua J

    2013-04-01

    We describe a protein quantification method called neutron encoding that exploits the subtle mass differences caused by nuclear binding energy variation in stable isotopes. These mass differences are synthetically encoded into amino acids and incorporated into yeast and mouse proteins via metabolic labeling. Mass spectrometry analysis with high mass resolution (>200,000) reveals the isotopologue-embedded peptide signals, permitting quantification. Neutron encoding will enable highly multiplexed proteome analysis with excellent dynamic range and accuracy. PMID:23435260

  8. Polymorphisms in an obesity-related gene (PCSK1) are associated with fat deposition and production traits in Italian heavy pigs.

    PubMed

    Fontanesi, L; Bertolini, F; Scotti, E; Trevisi, P; Buttazzoni, L; Dall'olio, S; Davoli, R; Bosi, P; Russo, V

    2012-12-01

    The proprotein convertase subtilisin/kexin type 1 (PCSK1) gene encodes the prohormone convertase 1/3 enzyme that processes prohormones into functional hormones that, in turn, regulate central and peripheral energy metabolism. Mutations in the human PCSK1 gene cause severe monogenic obesity or confer risk of obesity. We herein investigated the porcine PCSK1 gene with the aim of identifying polymorphisms associated with fat deposition and production traits in Italian heavy pigs. By re-sequencing about 5.1 kb of this gene in 21 pigs of different breeds, we discovered 14 polymorphisms that were organized in nine haplotypes, clearly distributed in two clades of putative European and Asian origin. Then we re-mapped this gene on porcine chromosome 2 and analysed its expression in several tissues including gastric oxyntic mucosa of weanling pigs in which PCSK1 processes the pre-pro-ghrelin into ghrelin, which in turn is involved in the control of feed intake and energy metabolism. Association analyses between PCSK1 single-nucleotide polymorphisms (SNPs) and production, carcass and several other traits were conducted on five groups of pigs from three different experimental designs, for a total of 1221 animals. Results indicated that the analysed SNPs were associated (P < 0.01 or P < 0.05) with several traits including backfat thickness and visible intermuscular fat in Italian Duroc (ID) and growth performances in Italian Large White (ILW) and in ILW × Italian Landrace pigs. However, the effects estimated in the ILW were opposite to the effects reported in the ID pigs. Suggestive association (P < 0.10) was observed with muscle cathepsin B activity, opening, if confirmed, potential applications to reduce the excessive softness defect of the green hams that is of particular concern for the processing industry. The results obtained supported the need to further investigate the PCSK1 gene to fully exploit the value of its variability and apply this information in pig breeding

  9. Payer Perspectives on PCSK9 Inhibitors: A Conversation with Stephen Gorshow, MD, and James T. Kenney, RPh, MBA.

    PubMed

    Mehr, Stanton R

    2016-02-01

    The new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can have significant budget effects, depending on the breadth of the US Food and Drug Administration (FDA)'s approved labeling. American Health & Drug Benefits asked Stephen Gorshow, MD, Regional Medical Director, UnitedHealthcare, and James T. Kenney, RPh, MBA, Manager, Specialty and Pharmacy Contracts, Harvard Pilgrim Health Care, to participate in a teleconference to better understand how payers are approaching the management of these agents. PMID:27066194

  10. Payer Perspectives on PCSK9 Inhibitors: A Conversation with Stephen Gorshow, MD, and James T. Kenney, RPh, MBA

    PubMed Central

    Mehr, Stanton R.

    2016-01-01

    The new proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors can have significant budget effects, depending on the breadth of the US Food and Drug Administration (FDA)'s approved labeling. American Health & Drug Benefits asked Stephen Gorshow, MD, Regional Medical Director, UnitedHealthcare, and James T. Kenney, RPh, MBA, Manager, Specialty and Pharmacy Contracts, Harvard Pilgrim Health Care, to participate in a teleconference to better understand how payers are approaching the management of these agents. PMID:27066194

  11. Improved reader for magnetically-encoded ID cards

    NASA Technical Reports Server (NTRS)

    Wu, T. T.

    1979-01-01

    Hybrid demodulator in electronic card reader for magnetically encoded identification cards, accommodates variations in insertion speeds, yet is simpler and less expensive than equivalent all-digital circuits.

  12. Terahertz encoding approach for secured chipless radio frequency identification.

    PubMed

    Bernier, Maxime; Garet, Frederic; Perret, Etienne; Duvillaret, Lionel; Tedjini, Smail

    2011-08-10

    In this article, we present a new family of chipless tags, which permit encoding of digital data in the terahertz domain. These devices consist of stacked dielectric media whose thicknesses are of the same order as terahertz wavelengths. Since the information is encoded in the volume of these multilayer terahertz tags, they can easily be associated with classical identification techniques (e.g., barcode, radio frequency identification), where information is encoded at the surface of the tag, to provide higher data security. The principle of this encoding approach is studied and experimentally demonstrated in this paper. A 2 bit tag prototype has been realized and measured for validation purposes. PMID:21833143

  13. Apoferritin-Templated Synthesis of Encoded Metallic Phosphate Nanoparticle Tags

    SciTech Connect

    Liu, Guodong; Wu, Hong; Dohnalkova, Alice; Lin, Yuehe

    2007-07-31

    Encoded metallic-phosphate nanoparticle tags, with distinct encoding patterns, have been prepared using an apoferritin template. A center-cavity structure as well as the disassociation and reconstructive characteristics of apoferritin at different pH environments provide a facile route for preparing such encoded nanoparticle tags. Encapsulation and diffusion approaches have been investigated during the preparation. The encapsulation approach, which is based on the dissociation and reconstruction of apoferritin at different pHs, exhibits an effective route to prepare such encoded metallic-phosphate nanoparticle tags. The compositionally encoded nanoparticle tag leads to a high coding capacity with a large number of distinguishable voltammetric signals, reflecting the predetermined composition of the metal mixture solution (and hence the nanoparticle composition). Releasing the metal components from the nanoparticle tags at pH 4.6 acetate buffer avoids harsh dissolution conditions, such as strong acids. Such a synthesis of encoded nanoparticle tags, including single-component and compositionally encoded nanoparticle tags, is substantially simple, fast, and convenient compared to that of encoded metal nanowires and semiconductor nanoparticle (CdS, PbS, and ZnS) incorporated polystyrene beads. The encoded metallic-phosphate nanoparticle tags thus show great promise for bioanalytical or product-tracking/identification/protection applications.

  14. Encoding voice fundamental frequency into vibrotactile frequency.

    PubMed

    Rothenberg, M; Molitor, R D

    1979-10-01

    Measured in this study was the ability of eight hearing and five deaf subjects to identify the stress pattern in a short sentence from the variation in voice fundamental frequency (F0), when presented aurally (for hearing subjects) and when transformed into vibrotactile pulse frequency. Various transformations from F0 to pulse frequency were tested in an attempt to determine an optimum transformation, the amount of F0 information that could be transmitted, and what the limitations in the tactile channel might be. The results indicated that a one- or two-octave reduction of F0 vibrotactile frequency (transmitting every second or third glottal pulse) might result in a significant ability to discriminate the intonation patterns associated with moderate-to-strong patterns of sentence stress in English. However, accurate reception of the details of the intonation pattern may require a slower than normal pronounciation because of an apparent temporal indeterminacy of about 200 ms in the perception of variations in vibrotactile frequency. A performance deficit noted for the two prelingually, profoundly deaf subjects with marginally discriminable encodings offers some support for our previous hypothesis that there is a natural association between auditory pitch and perceived vibrotactile frequency. PMID:159917

  15. Oligonucleotide and Long Polymeric DNA Encoding

    SciTech Connect

    Miller, E; Mariella Jr., R P; Christian, A T; Gardner, S N; Williams, J M

    2003-11-24

    This report summarizes the work done at Lawrence Livermore National Laboratory for the Oligonucleotide and Long Polymeric DNA Encoding project, part of the Microelectronic Bioprocesses Program at DARPA. The goal of the project was to develop a process by which long (circa 10,000 base-pair) synthetic DNA molecules could be synthesized in a timely and economic manner. During construction of the long molecule, errors in DNA sequence occur during hybridization and/or the subsequent enzymatic process. The work done on this project has resulted in a novel synthesis scheme that we call the parallel pyramid synthesis protocol, the development of a suit of computational tools to minimize and quantify errors in the synthesized DNA sequence, and experimental proof of this technique. The modeling consists of three interrelated modules: the bioinformatics code which determines the specifics of parallel pyramid synthesis for a given chain of long DNA, the thermodynamics code which tracks the products of DNA hybridization and polymerase extension during the later steps in the process, and the kinetics model which examines the temporal and spatial processes during one thermocycle. Most importantly, we conducted the first successful syntheses of a gene using small starting oligomers (tetramers). The synthesized sequence, 813 base pairs long, contained a 725 base pair gene, modified green fluorescent protein (mGFP), which has been shown to be a functional gene by cloning into cells and observing its green fluorescent product.

  16. New insights into cochlear sound encoding

    PubMed Central

    Moser, Tobias; Vogl, Christian

    2016-01-01

    The inner ear uses specialized synapses to indefatigably transmit sound information from hair cells to spiral ganglion neurons at high rates with submillisecond precision. The emerging view is that hair cell synapses achieve their demanding function by employing an unconventional presynaptic molecular composition. Hair cell active zones hold the synaptic ribbon, an electron-dense projection made primarily of RIBEYE, which tethers a halo of synaptic vesicles and is thought to enable a large readily releasable pool of vesicles and to contribute to its rapid replenishment. Another important presynaptic player is otoferlin, coded by a deafness gene, which assumes a multi-faceted role in vesicular exocytosis and, when disrupted, causes auditory synaptopathy. A functional peculiarity of hair cell synapses is the massive heterogeneity in the sizes and shapes of excitatory postsynaptic currents. Currently, there is controversy as to whether this reflects multiquantal release with a variable extent of synchronization or uniquantal release through a dynamic fusion pore. Another important question in the field has been the precise mechanisms of coupling presynaptic Ca 2+ channels and vesicular Ca 2+ sensors. This commentary provides an update on the current understanding of sound encoding in the cochlea with a focus on presynaptic mechanisms.

  17. Encoding network states by striatal cell assemblies.

    PubMed

    Carrillo-Reid, Luis; Tecuapetla, Fatuel; Tapia, Dagoberto; Hernández-Cruz, Arturo; Galarraga, Elvira; Drucker-Colin, René; Bargas, José

    2008-03-01

    Correlated activity in cortico-basal ganglia circuits plays a key role in the encoding of movement, associative learning and procedural memory. How correlated activity is assembled by striatal microcircuits is not understood. Calcium imaging of striatal neuronal populations, with single-cell resolution, reveals sporadic and asynchronous activity under control conditions. However, N-methyl-d-aspartate (NMDA) application induces bistability and correlated activity in striatal neurons. Widespread neurons within the field of observation present burst firing. Sets of neurons exhibit episodes of recurrent and synchronized bursting. Dimensionality reduction of network dynamics reveals functional states defined by cell assemblies that alternate their activity and display spatiotemporal pattern generation. Recurrent synchronous activity travels from one cell assembly to the other often returning to the original assembly; suggesting a robust structure. An initial search into the factors that sustain correlated activity of neuronal assemblies showed a critical dependence on both intrinsic and synaptic mechanisms: blockage of fast glutamatergic transmission annihilates all correlated firing, whereas blockage of GABAergic transmission locked the network into a single dominant state that eliminates assembly diversity. Reduction of L-type Ca(2+)-current restrains synchronization. Each cell assembly comprised different cells, but a small set of neurons was shared by different assemblies. A great proportion of the shared neurons was local interneurons with pacemaking properties. The network dynamics set into action by NMDA in the striatal network may reveal important properties of striatal microcircuits under normal and pathological conditions. PMID:18184883

  18. Holladay halftoning using super resolution encoded templates

    NASA Astrophysics Data System (ADS)

    McElvain, Jon S.; Hains, Charles M.

    2007-01-01

    A new method for halftoning using high resolution pattern templates is described, that expands the low level rendering capabilities for engines that support this feature. This approach, denoted super resolution encoded halftoning (SREH) is an extension of the Holladay concept, and provides a compact way to specify high resolution dot growth patterns using a lower resolution Holladay brick. Fundamentally, this new halftoning method involves using the SRE patterns as building blocks for constructing clustered dot growth assemblies. Like the traditional Holladay dot description, the SRE halftone is characterized by a size, height, and shift, all of which are specified at the lower resolution. Each low resolution pixel position in the SRE halftone brick contains a pair of lists. The first of these is a list of digital thresholds at which a transition in SRE patterns occurs for that pixel position, and the second is the corresponding list of SRE codes. For normal cluster dot growth sequences, this provides a simple and compact mechanism for specifying higher resolution halftones. Techniques for emulating traditional high resolution Holladay dots using SREH are discussed, including mechanisms for choosing substitutions for patterns that do not exist among the available SRE patterns.

  19. Comparative genomics of Shiga toxin encoding bacteriophages

    PubMed Central

    2012-01-01

    Background Stx bacteriophages are responsible for driving the dissemination of Stx toxin genes (stx) across their bacterial host range. Lysogens carrying Stx phages can cause severe, life-threatening disease and Stx toxin is an integral virulence factor. The Stx-bacteriophage vB_EcoP-24B, commonly referred to as Ф24B, is capable of multiply infecting a single bacterial host cell at a high frequency, with secondary infection increasing the rate at which subsequent bacteriophage infections can occur. This is biologically unusual, therefore determining the genomic content and context of Ф24B compared to other lambdoid Stx phages is important to understanding the factors controlling this phenomenon and determining whether they occur in other Stx phages. Results The genome of the Stx2 encoding phage, Ф24B was sequenced and annotated. The genomic organisation and general features are similar to other sequenced Stx bacteriophages induced from Enterohaemorrhagic Escherichia coli (EHEC), however Ф24B possesses significant regions of heterogeneity, with implications for phage biology and behaviour. The Ф24B genome was compared to other sequenced Stx phages and the archetypal lambdoid phage, lambda, using the Circos genome comparison tool and a PCR-based multi-loci comparison system. Conclusions The data support the hypothesis that Stx phages are mosaic, and recombination events between the host, phages and their remnants within the same infected bacterial cell will continue to drive the evolution of Stx phage variants and the subsequent dissemination of shigatoxigenic potential. PMID:22799768

  20. Temporal Encoding in a Nervous System

    PubMed Central

    Aldworth, Zane N.; Dimitrov, Alexander G.; Cummins, Graham I.; Gedeon, Tomáš; Miller, John P.

    2011-01-01

    We examined the extent to which temporal encoding may be implemented by single neurons in the cercal sensory system of the house cricket Acheta domesticus. We found that these neurons exhibit a greater-than-expected coding capacity, due in part to an increased precision in brief patterns of action potentials. We developed linear and non-linear models for decoding the activity of these neurons. We found that the stimuli associated with short-interval patterns of spikes (ISIs of 8 ms or less) could be predicted better by second-order models as compared to linear models. Finally, we characterized the difference between these linear and second-order models in a low-dimensional subspace, and showed that modification of the linear models along only a few dimensions improved their predictive power to parity with the second order models. Together these results show that single neurons are capable of using temporal patterns of spikes as fundamental symbols in their neural code, and that they communicate specific stimulus distributions to subsequent neural structures. PMID:21573206

  1. Dynamical encoding of looming, receding, and focussing

    NASA Astrophysics Data System (ADS)

    Longtin, Andre; Clarke, Stephen Elisha; Maler, Leonard; Center for Neural Dynamics Collaboration

    This talk will discuss a non-conventional neural coding task that may apply more broadly to many senses in higher vertebrates. We ask whether and how a non-visual sensory system can focus on an object. We present recent experimental and modeling work that shows how the early sensory circuitry of electric sense can perform such neuronal focusing that is manifested behaviorally. This sense is the main one used by weakly electric fish to navigate, locate prey and communicate in the murky waters of their natural habitat. We show that there is a distance at which the Fisher information of a neuron's response to a looming and receding object is maximized, and that this distance corresponds to a behaviorally relevant one chosen by these animals. Strikingly, this maximum occurs at a bifurcation between tonic firing and bursting. We further discuss how the invariance of this distance to signal attributes can arise, a process that first involves power-law spike frequency adaptation. The talk will also highlight the importance of expanding the classic dual neural encoding of contrast using ON and OFF cells in the context of looming and receding stimuli. The authors acknowledge support from CIHR and NSERC.

  2. EEG Correlates of Relative Motion Encoding.

    PubMed

    Thunell, Evelina; Plomp, Gijs; Ögmen, Haluk; Herzog, Michael H

    2016-03-01

    A large portion of the visual cortex is organized retinotopically, but perception is usually non-retinotopic. For example, a reflector on the spoke of a bicycle wheel appears to move on a circular or prolate cycloidal orbit as the bicycle moves forward, while in fact it traces out a curtate cycloidal trajectory. The moving bicycle serves as a non-retinotopic reference system to which the motion of the reflector is anchored. To study the neural correlates of non-retinotopic motion processing, we used the Ternus-Pikler display, where retinotopic processing in a stationary reference system is contrasted against non-retinotopic processing in a moving one. Using high-density EEG, we found similar brain responses for both retinotopic and non-retinotopic rotational apparent motion from the earliest evoked peak (around 120 ms) and throughout the rest of the visual processing, but only minor correlates of the motion of the reference system itself (mainly around 100-120 ms). We suggest that the visual system efficiently discounts the motion of the reference system from early on, allowing a largely reference system independent encoding of the motion of object parts. PMID:26515560

  3. Neural encoding and retrieval of sound sequences.

    PubMed

    Rauschecker, Josef P

    2005-12-01

    Although considerable progress has been made recently in our understanding of the coding of complex sounds in the cerebral cortex, the processing and storage of tone sequences is still poorly understood. We have used functional magnetic resonance imaging to identify brain mechanisms involved in the encoding and retrieval of melodies by studying the anticipation of familiar music. The results suggest a specific role for each of the following brain structures: the anterior part of the right superior temporal cortex, the right inferior frontal cortex and anterior insula, the left anterior prefrontal cortex, the lateral cerebellum, and the anterior cingulate. In a separate study, we investigated single-neuron responses in the auditory cortex of awake behaving monkeys to alternating tone sequences that in humans evoke the perception of "streaming." Depending on the frequency separation between the tones, an initial single stream may segregate into two streams after a build-up period of several seconds. The neural responses in the monkeys' primary auditory cortex (A1) mirror the psychophysical time course extremely well, suggesting that habituation within A1 may be one reason for stream segregation. However, the higher auditory and prefrontal areas found to be activated by musical melodies are expected to interact with primary areas in both bottom-up and top-down fashion to bring about the perceptual organization of sound sequences. PMID:16597759

  4. Peafowl antipredator calls encode information about signalers.

    PubMed

    Yorzinski, Jessica L

    2014-02-01

    Animals emit vocalizations that convey information about external events. Many of these vocalizations, including those emitted in response to predators, also encode information about the individual that produced the call. The relationship between acoustic features of antipredator calls and information relating to signalers (including sex, identity, body size, and social rank) were examined in peafowl (Pavo cristatus). The "bu-girk" antipredator calls of male and female peafowl were recorded and 20 acoustic parameters were automatically extracted from each call. Both the bu and girk elements of the antipredator call were individually distinctive and calls were classified to the correct signaler with over 90% and 70% accuracy in females and males, respectively. Females produced calls with a higher fundamental frequency (F0) than males. In both females and males, body size was negatively correlated with F0. In addition, peahen rank was related to the duration, end mean frequency, and start harmonicity of the bu element. Peafowl antipredator calls contain detailed information about the signaler and can potentially be used by receivers to respond to dangerous situations. PMID:25234902

  5. What physics is encoded in Maxwell's equations?

    NASA Astrophysics Data System (ADS)

    Kosyakov, B. P.

    2005-08-01

    We reconstruct Maxwell's equations showing that a major part of the information encoded in them is taken from topological properties of spacetime, and the residual information, divorced from geometry, which represents the physical contents of electrodynamics, %these equations, translates into four assumptions:(i) locality; (ii) linearity; %of the dynamical law; (iii) identity of the charge-source and the charge-coupling; and (iv) lack of magnetic monopoles. However, a closer inspection of symmetries peculiar to electrodynamics shows that these assumptions may have much to do with geometry. Maxwell's equations tell us that we live in a three-dimensional space with trivial (Euclidean) topology; time is a one-dimensional unidirectional and noncompact continuum; and spacetime is endowed with a light cone structure readable in the conformal invariance of electrodynamics. Our geometric feelings relate to the fact that Maxwell's equations are built in our brain, hence our space and time orientation, our visualization and imagination capabilities are ensured by perpetual instinctive processes of solving Maxwell's equations. People are usually agree in their observations of angle relations, for example, a right angle is never confused with an angle slightly different from right. By contrast, we may disagree in metric issues, say, a colour-blind person finds the light wave lengths quite different from those found by a man with normal vision. This lends support to the view that conformal invariance of Maxwell's equations is responsible for producing our notion of space. Assuming that our geometric intuition is guided by our innate realization of electrodynamical laws, some abnormal mental phenomena, such as clairvoyance, may have a rational explanation.

  6. Encoding Cortical Dynamics in Sparse Features

    PubMed Central

    Khan, Sheraz; Lefèvre, Julien; Baillet, Sylvain; Michmizos, Konstantinos P.; Ganesan, Santosh; Kitzbichler, Manfred G.; Zetino, Manuel; Hämäläinen, Matti S.; Papadelis, Christos; Kenet, Tal

    2014-01-01

    Distributed cortical solutions of magnetoencephalography (MEG) and electroencephalography (EEG) exhibit complex spatial and temporal dynamics. The extraction of patterns of interest and dynamic features from these cortical signals has so far relied on the expertise of investigators. There is a definite need in both clinical and neuroscience research for a method that will extract critical features from high-dimensional neuroimaging data in an automatic fashion. We have previously demonstrated the use of optical flow techniques for evaluating the kinematic properties of motion field projected on non-flat manifolds like in a cortical surface. We have further extended this framework to automatically detect features in the optical flow vector field by using the modified and extended 2-Riemannian Helmholtz–Hodge decomposition (HHD). Here, we applied these mathematical models on simulation and MEG data recorded from a healthy individual during a somatosensory experiment and an epilepsy pediatric patient during sleep. We tested whether our technique can automatically extract salient dynamical features of cortical activity. Simulation results indicated that we can precisely reproduce the simulated cortical dynamics with HHD; encode them in sparse features and represent the propagation of brain activity between distinct cortical areas. Using HHD, we decoded the somatosensory N20 component into two HHD features and represented the dynamics of brain activity as a traveling source between two primary somatosensory regions. In the epilepsy patient, we displayed the propagation of the epileptic activity around the margins of a brain lesion. Our findings indicate that HHD measures computed from cortical dynamics can: (i) quantitatively access the cortical dynamics in both healthy and disease brain in terms of sparse features and dynamic brain activity propagation between distinct cortical areas, and (ii) facilitate a reproducible, automated analysis of experimental and clinical

  7. Olfactory bulb encoding during learning under anesthesia

    PubMed Central

    Nicol, Alister U.; Sanchez-Andrade, Gabriela; Collado, Paloma; Segonds-Pichon, Anne; Kendrick, Keith M.

    2014-01-01

    Neural plasticity changes within the olfactory bulb are important for olfactory learning, although how neural encoding changes support new associations with specific odors and whether they can be investigated under anesthesia, remain unclear. Using the social transmission of food preference olfactory learning paradigm in mice in conjunction with in vivo microdialysis sampling we have shown firstly that a learned preference for a scented food odor smelled on the breath of a demonstrator animal occurs under isofluorane anesthesia. Furthermore, subsequent exposure to this cued odor under anesthesia promotes the same pattern of increased release of glutamate and gamma-aminobutyric acid (GABA) in the olfactory bulb as previously found in conscious animals following olfactory learning, and evoked GABA release was positively correlated with the amount of scented food eaten. In a second experiment, multiarray (24 electrodes) electrophysiological recordings were made from olfactory bulb mitral cells under isofluorane anesthesia before, during and after a novel scented food odor was paired with carbon disulfide. Results showed significant increases in overall firing frequency to the cued-odor during and after learning and decreases in response to an uncued odor. Analysis of patterns of changes in individual neurons revealed that a substantial proportion (>50%) of them significantly changed their response profiles during and after learning with most of those previously inhibited becoming excited. A large number of cells exhibiting no response to the odors prior to learning were either excited or inhibited afterwards. With the uncued odor many previously responsive cells became unresponsive or inhibited. Learning associated changes only occurred in the posterior part of the olfactory bulb. Thus olfactory learning under anesthesia promotes extensive, but spatially distinct, changes in mitral cell networks to both cued and uncued odors as well as in evoked glutamate and GABA

  8. Neutron Encoded Labeling for Peptide Identification

    PubMed Central

    Rose, Christopher M.; Merrill, Anna E.; Bailey, Derek J.; Hebert, Alexander S.; Westphall, Michael S.; Coon, Joshua J.

    2013-01-01

    Metabolic labeling of cells using heavy amino acids is most commonly used for relative quantitation; however, partner mass shifts also detail the number of heavy amino acids contained within the precursor species. Here, we use a recently developed metabolic labeling technique, NeuCode (neutron encoding) stable isotope labeling with amino acids in cell culture (SILAC), which produces precursor partners spaced ~40 mDa apart to enable amino acid counting. We implement large scale counting of amino acids through a program, “Amino Acid Counter”, which determines the most likely combination of amino acids within a precursor based on NeuCode SILAC partner spacing and filters candidate peptide sequences during a database search using this information. Counting the number of lysine residues for precursors selected for MS/MS decreases the median number of candidate sequences from 44 to 14 as compared to an accurate mass search alone (20 ppm). Furthermore, the ability to co-isolate and fragment NeuCode SILAC partners enables counting of lysines in product ions, and when the information is used, the median number of candidates is reduced to 7. We then demonstrate counting leucine in addition to lysine results in a 6-fold decrease in search space, 43 to 7, when compared to an accurate mass search. We use this scheme to analyze a nanoLC-MS/MS experiment and demonstrate that accurate mass plus lysine and leucine counting reduces the number of candidate sequences to one for ~20% of all precursors selected, demonstrating an ability to identify precursors without MS/MS analysis. PMID:23638792

  9. Neutron encoded labeling for peptide identification.

    PubMed

    Rose, Christopher M; Merrill, Anna E; Bailey, Derek J; Hebert, Alexander S; Westphall, Michael S; Coon, Joshua J

    2013-05-21

    Metabolic labeling of cells using heavy amino acids is most commonly used for relative quantitation; however, partner mass shifts also detail the number of heavy amino acids contained within the precursor species. Here, we use a recently developed metabolic labeling technique, NeuCode (neutron encoding) stable isotope labeling with amino acids in cell culture (SILAC), which produces precursor partners spaced ~40 mDa apart to enable amino acid counting. We implement large scale counting of amino acids through a program, "Amino Acid Counter", which determines the most likely combination of amino acids within a precursor based on NeuCode SILAC partner spacing and filters candidate peptide sequences during a database search using this information. Counting the number of lysine residues for precursors selected for MS/MS decreases the median number of candidate sequences from 44 to 14 as compared to an accurate mass search alone (20 ppm). Furthermore, the ability to co-isolate and fragment NeuCode SILAC partners enables counting of lysines in product ions, and when the information is used, the median number of candidates is reduced to 7. We then demonstrate counting leucine in addition to lysine results in a 6-fold decrease in search space, 43 to 7, when compared to an accurate mass search. We use this scheme to analyze a nanoLC-MS/MS experiment and demonstrate that accurate mass plus lysine and leucine counting reduces the number of candidate sequences to one for ~20% of all precursors selected, demonstrating an ability to identify precursors without MS/MS analysis. PMID:23638792

  10. Encoding frequency contrast in primate auditory cortex

    PubMed Central

    Scott, Brian H.; Semple, Malcolm N.

    2014-01-01

    Changes in amplitude and frequency jointly determine much of the communicative significance of complex acoustic signals, including human speech. We have previously described responses of neurons in the core auditory cortex of awake rhesus macaques to sinusoidal amplitude modulation (SAM) signals. Here we report a complementary study of sinusoidal frequency modulation (SFM) in the same neurons. Responses to SFM were analogous to SAM responses in that changes in multiple parameters defining SFM stimuli (e.g., modulation frequency, modulation depth, carrier frequency) were robustly encoded in the temporal dynamics of the spike trains. For example, changes in the carrier frequency produced highly reproducible changes in shapes of the modulation period histogram, consistent with the notion that the instantaneous probability of discharge mirrors the moment-by-moment spectrum at low modulation rates. The upper limit for phase locking was similar across SAM and SFM within neurons, suggesting shared biophysical constraints on temporal processing. Using spike train classification methods, we found that neural thresholds for modulation depth discrimination are typically far lower than would be predicted from frequency tuning to static tones. This “dynamic hyperacuity” suggests a substantial central enhancement of the neural representation of frequency changes relative to the auditory periphery. Spike timing information was superior to average rate information when discriminating among SFM signals, and even when discriminating among static tones varying in frequency. This finding held even when differences in total spike count across stimuli were normalized, indicating both the primacy and generality of temporal response dynamics in cortical auditory processing. PMID:24598525

  11. Encoding cortical dynamics in sparse features.

    PubMed

    Khan, Sheraz; Lefèvre, Julien; Baillet, Sylvain; Michmizos, Konstantinos P; Ganesan, Santosh; Kitzbichler, Manfred G; Zetino, Manuel; Hämäläinen, Matti S; Papadelis, Christos; Kenet, Tal

    2014-01-01

    Distributed cortical solutions of magnetoencephalography (MEG) and electroencephalography (EEG) exhibit complex spatial and temporal dynamics. The extraction of patterns of interest and dynamic features from these cortical signals has so far relied on the expertise of investigators. There is a definite need in both clinical and neuroscience research for a method that will extract critical features from high-dimensional neuroimaging data in an automatic fashion. We have previously demonstrated the use of optical flow techniques for evaluating the kinematic properties of motion field projected on non-flat manifolds like in a cortical surface. We have further extended this framework to automatically detect features in the optical flow vector field by using the modified and extended 2-Riemannian Helmholtz-Hodge decomposition (HHD). Here, we applied these mathematical models on simulation and MEG data recorded from a healthy individual during a somatosensory experiment and an epilepsy pediatric patient during sleep. We tested whether our technique can automatically extract salient dynamical features of cortical activity. Simulation results indicated that we can precisely reproduce the simulated cortical dynamics with HHD; encode them in sparse features and represent the propagation of brain activity between distinct cortical areas. Using HHD, we decoded the somatosensory N20 component into two HHD features and represented the dynamics of brain activity as a traveling source between two primary somatosensory regions. In the epilepsy patient, we displayed the propagation of the epileptic activity around the margins of a brain lesion. Our findings indicate that HHD measures computed from cortical dynamics can: (i) quantitatively access the cortical dynamics in both healthy and disease brain in terms of sparse features and dynamic brain activity propagation between distinct cortical areas, and (ii) facilitate a reproducible, automated analysis of experimental and clinical

  12. Strategy Training and Semantic Encoding in Mildly Retarded Children.

    ERIC Educational Resources Information Center

    Engle, Randall W.; Nagle, Richard J.

    1979-01-01

    Mildly retarded children were instructed in encoding strategies or rehearsal strategy. Performance was higher for semantic encoding strategies. Seven months later the semantic condition also showed greater improvement after strategies were prompted. Performance on incidental learning tasks was enhanced for 13- but not 10-year olds. (Author/RD)

  13. Evaluation of color encodings for high dynamic range pixels

    NASA Astrophysics Data System (ADS)

    Boitard, Ronan; Mantiuk, Rafal K.; Pouli, Tania

    2015-03-01

    Traditional Low Dynamic Range (LDR) color spaces encode a small fraction of the visible color gamut, which does not encompass the range of colors produced on upcoming High Dynamic Range (HDR) displays. Future imaging systems will require encoding much wider color gamut and luminance range. Such wide color gamut can be represented using floating point HDR pixel values but those are inefficient to encode. They also lack perceptual uniformity of the luminance and color distribution, which is provided (in approximation) by most LDR color spaces. Therefore, there is a need to devise an efficient, perceptually uniform and integer valued representation for high dynamic range pixel values. In this paper we evaluate several methods for encoding colour HDR pixel values, in particular for use in image and video compression. Unlike other studies we test both luminance and color difference encoding in a rigorous 4AFC threshold experiments to determine the minimum bit-depth required. Results show that the Perceptual Quantizer (PQ) encoding provides the best perceptual uniformity in the considered luminance range, however the gain in bit-depth is rather modest. More significant difference can be observed between color difference encoding schemes, from which YDuDv encoding seems to be the most efficient.

  14. Multiple channel secure communication using chaotic system encoding

    SciTech Connect

    Miller, S.L.

    1996-12-31

    fA new method to encrypt signals using chaotic systems has been developed that offers benefits over conventional chaotic encryption methods. The method simultaneously encodes multiple plaintext streams using a chaotic system; a key is required to extract the plaintext from the chaotic cipertext. A working prototype demonstrates feasibility of the method by simultaneously encoding and decoding multiple audio signals using electrical circuits.

  15. Modeling the Control of Phonological Encoding in Bilingual Speakers

    ERIC Educational Resources Information Center

    Roelofs, Ardi; Verhoef, Kim

    2006-01-01

    Phonological encoding is the process by which speakers retrieve phonemic segments for morphemes from memory and use the segments to assemble phonological representations of words to be spoken. When conversing in one language, bilingual speakers have to resist the temptation of encoding word forms using the phonological rules and representations of…

  16. Functional Neuroimaging of Self-Referential Encoding with Age

    ERIC Educational Resources Information Center

    Gutchess, Angela H.; Kensinger, Elizabeth A.; Schacter, Daniel L.

    2010-01-01

    Aging impacts memory formation and the engagement of frontal and medial temporal regions. However, much of the research to date has focused on the encoding of neutral verbal and visual information. The present fMRI study investigated age differences in a social encoding task while participants made judgments about the self or another person.…

  17. A VLSI architecture for high performance CABAC encoding

    NASA Astrophysics Data System (ADS)

    Shojania, Hassan; Sudharsanan, Subramania

    2005-07-01

    One key technique for improving the coding e+/-ciency of H.264 video standard is the entropy coder, context- adaptive binary arithmetic coder (CABAC). However the complexity of the encoding process of CABAC is signicantly higher than the table driven entropy encoding schemes such as the Hu®man coding. CABAC is also bit serial and its multi-bit parallelization is extremely di+/-cult. For a high denition video encoder, multi-giga hertz RISC processors will be needed to implement the CABAC encoder. In this paper, we provide an e+/-cient, pipelined VLSI architecture for CABAC encoding along with an analysis of critical issues. The solution encodes a binary symbol every cycle. An FPGA implementation of the proposed scheme capable of 104 Mbps encoding rate and test results are presented. An ASIC synthesis and simulation for a 0.18 ¹m process technology indicates that the design is capable of encoding 190 million binary symbols per second using an area of 0.35 mm2. ¤

  18. Hierarchical Encoding of Behavior: Translating Perception into Action

    ERIC Educational Resources Information Center

    Hard, Bridgette Martin; Lozano, Sandra C.; Tversky, Barbara

    2006-01-01

    People encode goal-directed behaviors, such as assembling an object, by segmenting them into discrete actions, organized as goal-subgoal hierarchies. Does hierarchical encoding contribute to observational learning? Participants in 3 experiments segmented an object assembly task into coarse and fine units of action and later performed it…

  19. Levels of Processing, Encoding Strategies, and Memory Development.

    ERIC Educational Resources Information Center

    Owings, Richard A.; Baumeister, Alfred A.

    1979-01-01

    In three experiments, memory for intentionally encoded words was compared with memory for encodings, induced by asking semantic, phonemic, or surface questions. Subjects were second-, fourth-, and sixth-grade students, and junior and senior high school students. (Author/MP)

  20. Optical Position Encoders for High or Low Temperatures

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B.

    2004-01-01

    Optoelectronic pattern-recognition systems (optical encoders) for measuring positions of objects of interest at temperatures well below or well above room temperature are undergoing development. At present, the development effort is concentrated on absolute linear, rotary, and Cartesian encoders and Cartesian autocollimators for scientific instruments that operate in cryostats.

  1. The Contribution of Encoding and Retrieval Processes to Proactive Interference

    ERIC Educational Resources Information Center

    Kliegl, Oliver; Pastötter, Bernhard; Bäuml, Karl-Heinz T.

    2015-01-01

    Proactive interference (PI) refers to the finding that memory for recently studied (target) material can be impaired by the prior study of other (nontarget) material. Previous accounts of PI differed in whether they attributed PI to impaired retrieval or impaired encoding. Here, we suggest an integrated encoding-retrieval account, which assigns a…

  2. Incidental and intentional encoding in young and elderly adults.

    PubMed

    Téllez-Alanís, Bernarda; Cansino, Selene

    2004-08-01

    Event-related potentials (ERPs) were recorded in young and elderly adults during the performance of an incidental encoding task (subjects were unexpectedly given a recognition test) followed by an intentional task (subjects expected the recognition test). Both tasks consisted of an encoding stage in which subjects classified words (natural/artificial) and a recognition stage in which they indicated whether the words were old (presented during the encoding stage) or new. In both groups and tasks, the ERPs, during encoding, differed as a function of subsequent recognition: the old words correctly recognized generated greater amplitude potentials than the incorrect ones. The memory processes expressed by these ERPs are preserved in elderly adults, independently of whether the information is incidentally or intentionally encoded. PMID:15257155

  3. Principles of metadata organization at the ENCODE data coordination center.

    PubMed

    Hong, Eurie L; Sloan, Cricket A; Chan, Esther T; Davidson, Jean M; Malladi, Venkat S; Strattan, J Seth; Hitz, Benjamin C; Gabdank, Idan; Narayanan, Aditi K; Ho, Marcus; Lee, Brian T; Rowe, Laurence D; Dreszer, Timothy R; Roe, Greg R; Podduturi, Nikhil R; Tanaka, Forrest; Hilton, Jason A; Cherry, J Michael

    2016-01-01

    The Encyclopedia of DNA Elements (ENCODE) Data Coordinating Center (DCC) is responsible for organizing, describing and providing access to the diverse data generated by the ENCODE project. The description of these data, known as metadata, includes the biological sample used as input, the protocols and assays performed on these samples, the data files generated from the results and the computational methods used to analyze the data. Here, we outline the principles and philosophy used to define the ENCODE metadata in order to create a metadata standard that can be applied to diverse assays and multiple genomic projects. In addition, we present how the data are validated and used by the ENCODE DCC in creating the ENCODE Portal (https://www.encodeproject.org/). Database URL: www.encodeproject.org. PMID:26980513

  4. Encoding of multi-alphabet sources by binary arithmetic coding

    NASA Astrophysics Data System (ADS)

    Guo, Muling; Oka, Takahumi; Kato, Shigeo; Kajiwara, Hiroshi; Kawamura, Naoto

    1998-12-01

    In case of encoding a multi-alphabet source, the multi- alphabet symbol sequence can be encoded directly by a multi- alphabet arithmetic encoder, or the sequence can be first converted into several binary sequences and then each binary sequence is encoded by binary arithmetic encoder, such as the L-R arithmetic coder. Arithmetic coding, however, requires arithmetic operations for each symbol and is computationally heavy. In this paper, a binary representation method using Huffman tree is introduced to reduce the number of arithmetic operations, and a new probability approximation for L-R arithmetic coding is further proposed to improve the coding efficiency when the probability of LPS (Least Probable Symbol) is near 0.5. Simulation results show that our proposed scheme has high coding efficacy and can reduce the number of coding symbols.

  5. Non-Fourier encoding with multiple spin echoes.

    PubMed

    Panych, L P; Mulkern, R V; Saiviroonporn, P; Zientara, G P; Jolesz, F A

    1997-12-01

    The advantages and limitations of multiple spin-echo sequences for non-Fourier encoding are investigated. Complications caused by improper encoding of alternate magnetization pathways due to imperfect refocusing pulses are analyzed. It is shown that mirror image ghosts result if the encoding RF pulse matrix is real-valued. These ghosts can be avoided as long as the rows of the RF pulse matrix are conjugate symmetric, which implies that spatial profiles are real valued. Non-Fourier encoding using bases derived from wavelet, Hadamard, and other real-valued orthogonal functions does not result in a mirror ghost artifact. A RARE sequence for non-Fourier encoding has been implemented on a clinical imaging system and successfully applied for brain imaging. PMID:9402198

  6. Principles of metadata organization at the ENCODE data coordination center

    PubMed Central

    Hong, Eurie L.; Sloan, Cricket A.; Chan, Esther T.; Davidson, Jean M.; Malladi, Venkat S.; Strattan, J. Seth; Hitz, Benjamin C.; Gabdank, Idan; Narayanan, Aditi K.; Ho, Marcus; Lee, Brian T.; Rowe, Laurence D.; Dreszer, Timothy R.; Roe, Greg R.; Podduturi, Nikhil R.; Tanaka, Forrest; Hilton, Jason A.; Cherry, J. Michael

    2016-01-01

    The Encyclopedia of DNA Elements (ENCODE) Data Coordinating Center (DCC) is responsible for organizing, describing and providing access to the diverse data generated by the ENCODE project. The description of these data, known as metadata, includes the biological sample used as input, the protocols and assays performed on these samples, the data files generated from the results and the computational methods used to analyze the data. Here, we outline the principles and philosophy used to define the ENCODE metadata in order to create a metadata standard that can be applied to diverse assays and multiple genomic projects. In addition, we present how the data are validated and used by the ENCODE DCC in creating the ENCODE Portal (https://www.encodeproject.org/). Database URL: www.encodeproject.org PMID:26980513

  7. Evaluative conditioning depends on higher order encoding processes.

    PubMed

    Fiedler, Klaus; Unkelbach, Christian

    2011-06-01

    Evaluative conditioning (EC) is commonly conceived as stimulus-driven associative learning. Here, we show that internally generated encoding activities mediate EC effects: Neutral conditioned stimuli (CS) faces were paired with positive and negative unconditioned stimuli (US) faces. Depending on the encoding task (Is CS a friend vs. enemy of US?), Experiment 1 yielded either normal EC effects (CS adopting US valence) or a reversal. This pattern was conditional on the degree to which encoding judgements affirmed friend or enemy encoding schemes. Experiments 2a and 2b replicated these findings with more clearly valenced US faces and controlling for demand effects. Experiment 3 demonstrated unconditional encoding effects when participants generated friend or enemy relations between CS and US faces. Explicitly stated friend or enemy relations in Experiment 4 left EC effects unaffected. Together, these findings testify to the importance of higher order cognitive processes in conditioning, much in line with recent evidence on the crucial role of conditioning awareness. PMID:21547766

  8. Causal interpretation rules for encoding and decoding models in neuroimaging.

    PubMed

    Weichwald, Sebastian; Meyer, Timm; Özdenizci, Ozan; Schölkopf, Bernhard; Ball, Tonio; Grosse-Wentrup, Moritz

    2015-04-15

    Causal terminology is often introduced in the interpretation of encoding and decoding models trained on neuroimaging data. In this article, we investigate which causal statements are warranted and which ones are not supported by empirical evidence. We argue that the distinction between encoding and decoding models is not sufficient for this purpose: relevant features in encoding and decoding models carry a different meaning in stimulus- and in response-based experimental paradigms.We show that only encoding models in the stimulus-based setting support unambiguous causal interpretations. By combining encoding and decoding models trained on the same data, however, we obtain insights into causal relations beyond those that are implied by each individual model type. We illustrate the empirical relevance of our theoretical findings on EEG data recorded during a visuo-motor learning task. PMID:25623501

  9. Beyond Initial Encoding: Measures of the Post-Encoding Status of Memory Traces Predict Long-Term Recall during Infancy

    ERIC Educational Resources Information Center

    Pathman, Thanujeni; Bauer, Patricia J.

    2013-01-01

    The first years of life are witness to rapid changes in long-term recall ability. In the current research we contributed to an explanation of the changes by testing the absolute and relative contributions to long-term recall of encoding and post-encoding processes. Using elicited imitation, we sampled the status of 16-, 20-, and 24-month-old…

  10. Encoding Active Device Elements at Nanowire Tips.

    PubMed

    No, You-Shin; Gao, Ruixuan; Mankin, Max N; Day, Robert W; Park, Hong-Gyu; Lieber, Charles M

    2016-07-13

    Semiconductor nanowires and other one-dimensional materials are attractive for highly sensitive and spatially confined electrical and optical signal detection in biological and physical systems, although it has been difficult to localize active electronic or optoelectronic device function at one end of such one-dimensional structures. Here we report a new nanowire structure in which the material and dopant are modulated specifically at only one end of nanowires to encode an active two-terminal device element. We present a general bottom-up synthetic scheme for these tip-modulated nanowires and illustrate this with the synthesis of nanoscale p-n junctions. Electron microscopy imaging verifies the designed p-Si nanowire core with SiO2 insulating inner shell and n-Si outer shell with clean p-Si/n-Si tip junction. Electrical transport measurements with independent contacts to the p-Si core and n-Si shell exhibited a current rectification behavior through the tip and no detectable current through the SiO2 shell. Electrical measurements also exhibited an n-type response in conductance versus water-gate voltage with pulsed gate experiments yielding a temporal resolution of at least 0.1 ms and ∼90% device sensitivity localized to within 0.5 μm from the nanowire p-n tip. In addition, photocurrent experiments showed an open-circuit voltage of 0.75 V at illumination power of ∼28.1 μW, exhibited linear dependence of photocurrent with respect to incident illumination power with an estimated responsivity up to ∼0.22 A/W, and revealed localized photocurrent generation at the nanowire tip. The tip-modulated concept was further extended to a top-down/bottom-up hybrid approach that enabled large-scale production of vertical tip-modulated nanowires with a final synthetic yield of >75% with >4300 nanowires. Vertical tip-modulated nanowires were fabricated into >50 individually addressable nanowire device arrays showing diode-like current-voltage characteristics. These tip

  11. [Introduction of PCSK9 inhibitors : New perspectives in treatment and practical implementation].

    PubMed

    Klose, G

    2016-06-01

    Proprotein convertase subtilisin/kexin type 9 (PCSK9) is of critical importance in the regulation of the low-density lipoprotein (LDL) receptor-mediated metabolism of cholesterol. The discovery of mutations in the gene encoding PCSK9 in families with an autosomal dominant form of familial hypercholesterolemia (FH), which were later shown to be "gain-of-function" mutations, led to the development of antibodies against PCSK9. The efficacy in markedly reducing levels of LDL-cholesterol and preliminary evidence for benefits in the prevention of cardiovascular diseases indicated that special groups of patients can be more effectively treated. This includes forms of hypercholesterolemia refractory to conventional treatment as well as patients with FH and/or statin intolerance. Further information on long-term efficacy, tolerability and cost-effectiveness of PCSK9 inhibition and possibilities of implementation in the healthcare system are awaited from ongoing clinical outcome trials, such as FOURIER, ODYSSEY OUTCOMES, SPIRE 1 and 2 involving more than 70,000 high-risk patients. PMID:27193908

  12. Comparison of synganglion neuropeptides, neuropeptide receptors and neurotransmitter receptors and their gene expression in response to feeding in Ixodes scapularis (Ixodidae) vs. Ornithodoros turicata (Argasidae).

    PubMed

    Egekwu, N; Sonenshine, D E; Garman, H; Barshis, D J; Cox, N; Bissinger, B W; Zhu, J; M Roe, R

    2016-02-01

    Illumina GAII high-throughput sequencing was used to compare expressed genes for female synganglion neuropeptides, neuropeptide receptors and neurotransmitter receptors of the soft tick Ornithodoros turicata with the hard tick Ixodes scapularis. Gene ontology molecular level three mapping revealed no significant differences amongst the same categories represented in O. turicata and I. scapularis. Transcripts predicting 22 neuropeptides or their receptors in the O. turicata synganglion were similar to annotations for 23 neuropeptides or receptors previously identified from I scapularis, with minor exceptions. A transcript predicting ecdysis triggering hormone receptor was identified in O. turicata; transcripts encoding for proprotein convertase and glycoprotein B were identified in both species. Transcripts predicting the same neurotransmitter receptors were found in the synganglion of both species. Gene expression of the transcripts showed numerous differences in response to feeding. Major differences were observed in expression of genes believed important in regulating slow vs. rapid feeding, blood water elimination, cuticle synthesis plasticity and in signalling reproductive activity. Although the glutamate receptor was strongly upregulated in both species, the gamma aminobutyric acid receptor, which inhibits glutamate, was upregulated significantly only in I. scapularis. These differences are consistent with the slow vs. rapid action of the pharyngeal pump in the two species. PMID:26783017

  13. Transcription Factor Hepatocyte Nuclear Factor-1β Regulates Renal Cholesterol Metabolism.

    PubMed

    Aboudehen, Karam; Kim, Min Soo; Mitsche, Matthew; Garland, Kristina; Anderson, Norma; Noureddine, Lama; Pontoglio, Marco; Patel, Vishal; Xie, Yang; DeBose-Boyd, Russell; Igarashi, Peter

    2016-08-01

    HNF-1β is a tissue-specific transcription factor that is expressed in the kidney and other epithelial organs. Humans with mutations in HNF-1β develop kidney cysts, and HNF-1β regulates the transcription of several cystic disease genes. However, the complete spectrum of HNF-1β-regulated genes and pathways is not known. Here, using chromatin immunoprecipitation/next generation sequencing and gene expression profiling, we identified 1545 protein-coding genes that are directly regulated by HNF-1β in murine kidney epithelial cells. Pathway analysis predicted that HNF-1β regulates cholesterol metabolism. Expression of dominant negative mutant HNF-1β or kidney-specific inactivation of HNF-1β decreased the expression of genes that are essential for cholesterol synthesis, including sterol regulatory element binding factor 2 (Srebf2) and 3-hydroxy-3-methylglutaryl-CoA reductase (Hmgcr). HNF-1β mutant cells also expressed lower levels of cholesterol biosynthetic intermediates and had a lower rate of cholesterol synthesis than control cells. Additionally, depletion of cholesterol in the culture medium mitigated the inhibitory effects of mutant HNF-1β on the proteins encoded by Srebf2 and Hmgcr, and HNF-1β directly controlled the renal epithelial expression of proprotein convertase subtilisin-like kexin type 9, a key regulator of cholesterol uptake. These findings reveal a novel role of HNF-1β in a transcriptional network that regulates intrarenal cholesterol metabolism. PMID:26712526

  14. Substrate cleavage profiling suggests a distinct function of Bacteroides fragilis metalloproteinases (fragilysin and metalloproteinase II) at the microbiome-inflammation-cancer interface.

    PubMed

    Shiryaev, Sergey A; Remacle, Albert G; Chernov, Andrei V; Golubkov, Vladislav S; Motamedchaboki, Khatereh; Muranaka, Norihito; Dambacher, Corey M; Capek, Petr; Kukreja, Muskan; Kozlov, Igor A; Perucho, Manuel; Cieplak, Piotr; Strongin, Alex Y

    2013-11-29

    Enterotoxigenic anaerobic Bacteroides fragilis is a significant source of inflammatory diarrheal disease and a risk factor for colorectal cancer. Two distinct metalloproteinase types (the homologous 1, 2, and 3 isoforms of fragilysin (FRA1, FRA2, and FRA3, respectively) and metalloproteinase II (MPII)) are encoded by the B. fragilis pathogenicity island. FRA was demonstrated to be important to pathogenesis, whereas MPII, also a potential virulence protein, remained completely uncharacterized. Here, we, for the first time, extensively characterized MPII in comparison with FRA3, a representative of the FRA isoforms. We employed a series of multiplexed peptide cleavage assays to determine substrate specificity and proteolytic characteristics of MPII and FRA. These results enabled implementation of an efficient assay of MPII activity using a fluorescence-quenched peptide and contributed to structural evidence for the distinct substrate cleavage preferences of MPII and FRA. Our data imply that MPII specificity mimics the dibasic Arg↓Arg cleavage motif of furin-like proprotein convertases, whereas the cleavage motif of FRA (Pro-X-X-Leu-(Arg/Ala/Leu)↓) resembles that of human matrix metalloproteinases. To the best of our knowledge, MPII is the first zinc metalloproteinase with the dibasic cleavage preferences, suggesting a high level of versatility of metalloproteinase proteolysis. Based on these data, we now suggest that the combined (rather than individual) activity of MPII and FRA is required for the overall B. fragilis virulence in vivo. PMID:24145028

  15. Substrate Cleavage Profiling Suggests a Distinct Function of Bacteroides fragilis Metalloproteinases (Fragilysin and Metalloproteinase II) at the Microbiome-Inflammation-Cancer Interface*

    PubMed Central

    Shiryaev, Sergey A.; Remacle, Albert G.; Chernov, Andrei V.; Golubkov, Vladislav S.; Motamedchaboki, Khatereh; Muranaka, Norihito; Dambacher, Corey M.; Capek, Petr; Kukreja, Muskan; Kozlov, Igor A.; Perucho, Manuel; Cieplak, Piotr; Strongin, Alex Y.

    2013-01-01

    Enterotoxigenic anaerobic Bacteroides fragilis is a significant source of inflammatory diarrheal disease and a risk factor for colorectal cancer. Two distinct metalloproteinase types (the homologous 1, 2, and 3 isoforms of fragilysin (FRA1, FRA2, and FRA3, respectively) and metalloproteinase II (MPII)) are encoded by the B. fragilis pathogenicity island. FRA was demonstrated to be important to pathogenesis, whereas MPII, also a potential virulence protein, remained completely uncharacterized. Here, we, for the first time, extensively characterized MPII in comparison with FRA3, a representative of the FRA isoforms. We employed a series of multiplexed peptide cleavage assays to determine substrate specificity and proteolytic characteristics of MPII and FRA. These results enabled implementation of an efficient assay of MPII activity using a fluorescence-quenched peptide and contributed to structural evidence for the distinct substrate cleavage preferences of MPII and FRA. Our data imply that MPII specificity mimics the dibasic Arg↓Arg cleavage motif of furin-like proprotein convertases, whereas the cleavage motif of FRA (Pro-X-X-Leu-(Arg/Ala/Leu)↓) resembles that of human matrix metalloproteinases. To the best of our knowledge, MPII is the first zinc metalloproteinase with the dibasic cleavage preferences, suggesting a high level of versatility of metalloproteinase proteolysis. Based on these data, we now suggest that the combined (rather than individual) activity of MPII and FRA is required for the overall B. fragilis virulence in vivo. PMID:24145028

  16. [PCSK9 Inhibitors - the magic bullet for LDL cholesterol reduction?].

    PubMed

    Richter, Kurt; Barthel, Andreas; Bornstein, Stefan R; El-Armouche, Ali; Wagner, Michael

    2016-06-01

    The proprotein convertase subtilisin / kexin type 9 (PCSK9) plays an important role in LDL cholesterol (LDL-C) metabolism. Subjects harboring loss-of-function mutations in the gene encoding for PCSK9 display markedly reduced LDL-C plasma levels. PCSK9 is secreted by the liver, binds to the LDL receptor and, following endocytosis, induces lysosomal degradation of the receptor together with the bound LDL-C. Current PCSK9 inhibitors are monoclonal antibodies that specifically absorb PCSK9. Subsequently, instead of being degraded the receptor can dissociate from LDL-C and recycle, consecutively resulting in an increased hepatocyte LDL receptor density and higher LDL-C clearance. In clinical trials, the PCSK9 inhibitors alirocumab and evolocumab induced reductions in LDL-C of up to 70 % in statin-treated as well as statin-naïve patients. So far, serious side effects (requiring cessation of drug treatment) occurred only in rare cases. Since this new class of lipid lowering drugs promises a high potential benefit, they have been approved by the EMA even before completion of the studies addressing clinically relevant endpoints like cardiovascular events and mortality. Therefore, the expected publication of these study results in 2017 may allow a better assessment of the efficacy and safety of PCSK9 inhibitors. PMID:27305302

  17. Aberrant Fat Metabolism in Caenorhabditis elegans Mutants with Defects in the Defecation Motor Program

    PubMed Central

    Sheng, Ming; Gaur, Rahul; Selstam, Eva; Tuck, Simon

    2015-01-01

    The molecular mechanisms by which dietary fatty acids are absorbed by the intestine, and the way in which the process is regulated are poorly understood. In a genetic screen for mutations affecting fat accumulation in the intestine of Caenorhabditis elegans, nematode worms, we have isolated mutations in the aex-5 gene, which encodes a Kex2/subtilisin-family, Ca2+-sensitive proprotein convertase known to be required for maturation of certain neuropeptides, and for a discrete step in an ultradian rhythmic phenomenon called the defecation motor program. We demonstrate that aex-5 mutants have markedly lower steady-state levels of fat in the intestine, and that this defect is associated with a significant reduction in the rate at which labeled fatty acid derivatives are taken up from the intestinal lumen. Other mutations affecting the defecation motor program also affect steady-state levels of triglycerides, suggesting that the program is required per se for the proper accumulation of neutral lipids. Our results suggest that an important function of the defecation motor program in C. elegans is to promote the uptake of an important class of dietary nutrients. They also imply that modulation of the program might be one way in which worms adjust nutrient uptake in response to altered metabolic status. PMID:25849533

  18. Effects of noise correlations on information encoding and decoding.

    PubMed

    Averbeck, Bruno B; Lee, Daeyeol

    2006-06-01

    Response variability is often correlated across populations of neurons, and these noise correlations may play a role in information coding. In previous studies, this possibility has been examined from the encoding and decoding perspectives. Here we used d prime and related information measures to examine how studies of noise correlations from these two perspectives are related. We found that for a pair of neurons, the effect of noise correlations on information decoding can be zero when the effect of noise correlations on the information encoded obtains its largest positive or negative values. Furthermore, there can be no effect of noise correlations on the information encoded when it has an effect on information decoding. We also measured the effect of noise correlations on information encoding and decoding in simultaneously recorded neurons in the supplementary motor area to see how well d prime accounted for the information actually present in the neural responses and to see how noise correlations affected encoding and decoding in real data. These analyses showed that d prime provides an accurate measure of information encoding and decoding in our population of neurons. We also found that the effect of noise correlations on information encoding was somewhat larger than the effect of noise correlations on information decoding, but both were relatively small. Finally, as predicted theoretically, the effects of correlations were slightly greater for larger ensembles (3-8 neurons) than for pairs of neurons. PMID:16554512

  19. Study on self-calibration angle encoder using simulation method

    NASA Astrophysics Data System (ADS)

    Wang, Yan; Xue, Zi; Huang, Yao; Wang, Xiaona

    2016-01-01

    The angle measurement technology is very important in precision manufacture, optical industry, aerospace, aviation and navigation, etc. Further, the angle encoder, which uses concept `subdivision of full circle (2π rad=360°)' and transforms the angle into number of electronic pulse, is the most common instrument for angle measurement. To improve the accuracy of the angle encoder, a novel self-calibration method was proposed that enables the angle encoder to calibrate itself without angle reference. An angle deviation curve among 0° to 360° was simulated with equal weights Fourier components for the study of the self-calibration method. In addition, a self-calibration algorithm was used in the process of this deviation curve. The simulation result shows the relationship between the arrangement of multi-reading heads and the Fourier components distribution of angle encoder deviation curve. Besides, an actual self-calibration angle encoder was calibrated by polygon angle standard in national institute of metrology, China. The experiment result indicates the actual self-calibration effect on the Fourier components distribution of angle encoder deviation curve. In the end, the comparison, which is between the simulation self-calibration result and the experiment self-calibration result, reflects good consistency and proves the reliability of the self-calibration angle encoder.

  20. Scanned compound document encoding using multiscale recurrent patterns.

    PubMed

    Francisco, Nelson C; Rodrigues, Nuno M M; da Silva, Eduardo A B; de Carvalho, Murilo Bresciani; de Faria, Sérgio M M; Silva, Vitor M M

    2010-10-01

    In this paper, we propose a new encoder for scanned compound documents, based upon a recently introduced coding paradigm called multidimensional multiscale parser (MMP). MMP uses approximate pattern matching, with adaptive multiscale dictionaries that contain concatenations of scaled versions of previously encoded image blocks. These features give MMP the ability to adjust to the input image's characteristics, resulting in high coding efficiencies for a wide range of image types. This versatility makes MMP a good candidate for compound digital document encoding. The proposed algorithm first classifies the image blocks as smooth (texture) and nonsmooth (text and graphics). Smooth and nonsmooth blocks are then compressed using different MMP-based encoders, adapted for encoding either type of blocks. The adaptive use of these two types of encoders resulted in performance gains over the original MMP algorithm, further increasing the performance advantage over the current state-of-the-art image encoders for scanned compound images, without compromising the performance for other image types. PMID:20423803

  1. Improvement of the signal integrity in diffractive optical encoders

    NASA Astrophysics Data System (ADS)

    Kress, Bernard; Mueller, Ulrich

    2014-09-01

    We are presenting several techniques to improve the quality of the signals in diffractive optics encoders, for either linear and rotational encoders. We have developed previously various hybrid incremental/absolute disk based rotary diffractive encoders architectures. While the binary signals for absolute encoding were usually of sufficiently good quality to retrieve the entire Gray code signal over the desired resolutions (10, 12 or 14 bits), the quality and integrity of the sinusoidal signals for the incremental part of the encoder needed to be improved, since these are the signals allowing the encoder to go to much higher interpolated resolutions (20 bits or over). A good precision over the interpolated signals assumes very accurate sinusoidal profiles form the raw signals. Strong interpolation can only be done on high quality sinusoidal native signals (also referred to as pulses per revolution or PPR). A typical high resolution incremental encoder might provide 12 to 16 native sinusoidal PPRs, but the interpolation over these signals can reach way over 20 bits of resolution if the signals are of good quality.

  2. High resolution planar encoder by retro-reflection

    NASA Astrophysics Data System (ADS)

    Kao, Ching-Fen; Lu, Sheng-Hua; Lu, Mao-Hong

    2005-08-01

    This investigation presents a planar diffractive laser encoder system (PDLENS), which serves as a two-dimensional (2D) position detection apparatus for precision machine applications. Traditional 2D position detection utilizes a pair of linear encoders in crossed construction and so maintaining the perpendicularity between this pair of encoders is difficult. Besides, the rigorous alignment requirements among various components of the encoder system impose a serious user adaptation bottleneck. Of all alignment tolerances, the head-to-scale alignment tolerance is the most important problem for applications. In this work, a 2D grating is employed as the scale and the PDLENS is based on the retro-reflection configuration. Therefore the new encoder can provide good perpendicularity and tolerate larger alignment errors than the conventional encoder does. The grating pitch is 1.6μm and the period of the output signal is 0.4μm due to the double diffraction. Electronic interpolation with a factor of 400 leads to a readout resolution of 1 nm. The new encoder and a capacitive sensor were employed to simultaneously measure a circular motion with a radius of 1μm generated by a piezo stage. Comparing the measured positions, the deviation is less than 30 nm and the repeatability is better than 8 nm.

  3. Analysis of Genetic Toggle Switch Systems Encoded on Plasmids

    NASA Astrophysics Data System (ADS)

    Loinger, Adiel; Biham, Ofer

    2009-08-01

    Genetic switch systems with mutual repression of two transcription factors, encoded on plasmids, are studied using stochastic methods. The plasmid copy number is found to strongly affect the behavior of these systems. More specifically, the average time between spontaneous switching events quickly increases with the number of plasmids. It was shown before that for a single copy encoded on the chromosome, the exclusive switch is more stable than the general switch. Here we show that when the switch is encoded on a sufficiently large number of plasmids, the situation is reversed and the general switch is more stable than the exclusive switch. These predictions can be tested experimentally using methods of synthetic biology.

  4. Wavelength-encoded OCDMA system using opto-VLSI processors

    NASA Astrophysics Data System (ADS)

    Aljada, Muhsen; Alameh, Kamal

    2007-07-01

    We propose and experimentally demonstrate a 2.5 Gbits/sper user wavelength-encoded optical code-division multiple-access encoder-decoder structure based on opto-VLSI processing. Each encoder and decoder is constructed using a single 1D opto-very-large-scale-integrated (VLSI) processor in conjunction with a fiber Bragg grating (FBG) array of different Bragg wavelengths. The FBG array spectrally and temporally slices the broadband input pulse into several components and the opto-VLSI processor generates codewords using digital phase holograms. System performance is measured in terms of the autocorrelation and cross-correlation functions as well as the eye diagram.

  5. Method and apparatus for optical encoding with compressible imaging

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B. (Inventor)

    2006-01-01

    The present invention presents an optical encoder with increased conversion rates. Improvement in the conversion rate is a result of combining changes in the pattern recognition encoder's scale pattern with an image sensor readout technique which takes full advantage of those changes, and lends itself to operation by modern, high-speed, ultra-compact microprocessors and digital signal processors (DSP) or field programmable gate array (FPGA) logic elements which can process encoder scale images at the highest speeds. Through these improvements, all three components of conversion time (reciprocal conversion rate)--namely exposure time, image readout time, and image processing time--are minimized.

  6. Spectral imaging using forward-viewing spectrally encoded endoscopy

    PubMed Central

    Zeidan, Adel; Yelin, Dvir

    2016-01-01

    Spectrally encoded endoscopy (SEE) enables miniature, small-diameter endoscopic probes for minimally invasive imaging; however, using the broadband spectrum to encode space makes color and spectral imaging nontrivial and challenging. By careful registration and analysis of image data acquired by a prototype of a forward-viewing dual channel spectrally encoded rigid probe, we demonstrate spectral and color imaging within a narrow cylindrical lumen. Spectral imaging of calibration cylindrical test targets and an ex-vivo blood vessel demonstrates high-resolution spatial-spectral imaging with short (10 μs/line) exposure times. PMID:26977348

  7. On the detection of differentially encoded polyphase signals.

    NASA Technical Reports Server (NTRS)

    Lindsey, W. C.

    1972-01-01

    Discussion of the transmission and detection of differentially encoded polyphase signals and of the ambiguity resolution problem which results from suppression of the transmitted carrier. In particular, an analysis is made of the performance of differentially encoded coherent multiple phase-shift keyed (MPSK) systems which reconstruct coherent reference signals by means of generalized Costas or nth-power loops. The performance of such systems is then compared with that of ideal reception of MPSK signals and differentially coherent detection of differentially encoded MPSK signals. Emphasis is placed upon the special cases of quadriphase and octaphase signaling.

  8. Wavelength-encoded OCDMA system using opto-VLSI processors.

    PubMed

    Aljada, Muhsen; Alameh, Kamal

    2007-07-01

    We propose and experimentally demonstrate a 2.5 Gbits/sper user wavelength-encoded optical code-division multiple-access encoder-decoder structure based on opto-VLSI processing. Each encoder and decoder is constructed using a single 1D opto-very-large-scale-integrated (VLSI) processor in conjunction with a fiber Bragg grating (FBG) array of different Bragg wavelengths. The FBG array spectrally and temporally slices the broadband input pulse into several components and the opto-VLSI processor generates codewords using digital phase holograms. System performance is measured in terms of the autocorrelation and cross-correlation functions as well as the eye diagram. PMID:17603568

  9. Spectral imaging using forward-viewing spectrally encoded endoscopy.

    PubMed

    Zeidan, Adel; Yelin, Dvir

    2016-02-01

    Spectrally encoded endoscopy (SEE) enables miniature, small-diameter endoscopic probes for minimally invasive imaging; however, using the broadband spectrum to encode space makes color and spectral imaging nontrivial and challenging. By careful registration and analysis of image data acquired by a prototype of a forward-viewing dual channel spectrally encoded rigid probe, we demonstrate spectral and color imaging within a narrow cylindrical lumen. Spectral imaging of calibration cylindrical test targets and an ex-vivo blood vessel demonstrates high-resolution spatial-spectral imaging with short (10 μs/line) exposure times. PMID:26977348

  10. pENCODE: A Plant Encyclopedia of DNA Elements

    PubMed Central

    Lane, Amanda K.; Niederhuth, Chad E.; Ji, Lexiang; Schmitz, Robert J.

    2015-01-01

    ENCODE projects exist for many eukaryotes, including humans, but as of yet no defined project exists for plants. A plant ENCODE would be invaluable to the research community and could be more readily produced than its metazoan equivalents by capitalizing on the preexisting infrastructure provided from similar projects. Collecting and normalizing plant epigenomic data for a range of species will facilitate hypothesis generation, cross-species comparisons, annotation of genomes, and an understanding of epigenomic functions throughout plant evolution. Here, we discuss the need for such a project, outline the challenges it faces, and suggest ways forward to build a plant ENCODE. PMID:25149370

  11. Integrated source and channel encoded digital communications system design study

    NASA Technical Reports Server (NTRS)

    Huth, G. K.

    1974-01-01

    Studies on the digital communication system for the direct communication links from ground to space shuttle and the links involving the Tracking and Data Relay Satellite (TDRS). Three main tasks were performed:(1) Channel encoding/decoding parameter optimization for forward and reverse TDRS links,(2)integration of command encoding/decoding and channel encoding/decoding; and (3) modulation coding interface study. The general communication environment is presented to provide the necessary background for the tasks and to provide an understanding of the implications of the results of the studies.

  12. DMD-based spatially Fourier-encoded photoacoustic microscopy

    NASA Astrophysics Data System (ADS)

    Liang, Jinyang; Gao, Liang; Li, Chiye; Wang, Lihong V.

    2015-03-01

    We present spatially Fourier-encoded photoacoustic microscopy using a digital micromirror device (DMD). The spatial fluence distribution of laser pulses is Fourier-encoded by the DMD, and a series of such encoded photoacoustic (PA) measurements enables decoding of the spatial distribution of optical absorption. By imaging a chromium target, we demonstrated the throughput and Fellgett advantages, which increased the PA signal-to-noise ratio (SNR) compared to raster scanning. The system was used to image two biological targets, a monolayer of red blood cells, and melanoma cells. The enhanced SNR benefited PA images by increasing the image's contrast-to-noise ratio and target identifiability.

  13. Method and system for efficiently searching an encoded vector index

    DOEpatents

    Bui, Thuan Quang; Egan, Randy Lynn; Kathmann, Kevin James

    2001-09-04

    Method and system aspects for efficiently searching an encoded vector index are provided. The aspects include the translation of a search query into a candidate bitmap, and the mapping of data from the candidate bitmap into a search result bitmap according to entry values in the encoded vector index. Further, the translation includes the setting of a bit in the candidate bitmap for each entry in a symbol table that corresponds to candidate of the search query. Also included in the mapping is the identification of a bit value in the candidate bitmap pointed to by an entry in an encoded vector.

  14. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Zhang, Yu; Tang, Lan; Henriksen, Svend Hostgaard Bang

    2016-05-17

    The present invention provides isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also provides nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  15. Isolated menthone reductase and nucleic acid molecules encoding same

    DOEpatents

    Croteau, Rodney B; Davis, Edward M; Ringer, Kerry L

    2013-04-23

    The present invention provides isolated menthone reductase proteins, isolated nucleic acid molecules encoding menthone reductase proteins, methods for expressing and isolating menthone reductase proteins, and transgenic plants expressing elevated levels of menthone reductase protein.

  16. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    SciTech Connect

    Spodsberg, Nikolaj

    2015-07-14

    The present invention relates to isolated polypeptides having cellobiohydrolase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  17. A User's Guide to the Encyclopedia of DNA Elements (ENCODE)

    PubMed Central

    2011-01-01

    The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome. PMID:21526222

  18. T2 distribution mapping profiles with phase-encode MRI

    NASA Astrophysics Data System (ADS)

    Petrov, Oleg V.; Ersland, Geir; Balcom, Bruce J.

    2011-03-01

    Two 1-D phase-encode sequences for T2 mapping, namely CPMG-prepared SPRITE and spin-echo SPI, are presented and compared in terms of image quality, accuracy of T2 measurements and the measurement time. The sequences implement two different approaches to acquiring T2-weighted images: in the CPMG-prepared SPRITE, the T2-weighting of magnetization precedes the spatial encoding, while in the spin-echo SPI, the T2-weighting follows the spatial encoding. The sequences are intended primarily for T2 mapping of fluids in porous solids, where using frequency encode techniques may be problematic either due to local gradient distortions or too short T2. Their possible applications include monitoring fluid-flow processes in rocks, cement paste hydration, curing of rubber, filtering paramagnetic impurities and other processes accomplished by changing site-specific T2.

  19. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    SciTech Connect

    Liu, Ye; Tang, Lan

    2015-07-14

    The present invention provides isolated polypeptides having cellobiohydrolase activity and isolated polynucleotides encoding the polypeptides. The invention also provides nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  20. Noise and neuronal populations conspire to encode simple waveforms reliably

    NASA Technical Reports Server (NTRS)

    Parnas, B. R.

    1996-01-01

    Sensory systems rely on populations of neurons to encode information transduced at the periphery into meaningful patterns of neuronal population activity. This transduction occurs in the presence of intrinsic neuronal noise. This is fortunate. The presence of noise allows more reliable encoding of the temporal structure present in the stimulus than would be possible in a noise-free environment. Simulations with a parallel model of signal processing at the auditory periphery have been used to explore the effects of noise and a neuronal population on the encoding of signal information. The results show that, for a given set of neuronal modeling parameters and stimulus amplitude, there is an optimal amount of noise for stimulus encoding with maximum fidelity.

  1. A user's guide to the encyclopedia of DNA elements (ENCODE).

    PubMed

    2011-04-01

    The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome. PMID:21526222

  2. A New Methodology for Vibration Error Compensation of Optical Encoders

    PubMed Central

    Lopez, Jesus; Artes, Mariano

    2012-01-01

    Optical encoders are sensors based on grating interference patterns. Tolerances inherent to the manufacturing process can induce errors in the position accuracy as the measurement signals stand apart from the ideal conditions. In case the encoder is working under vibrations, the oscillating movement of the scanning head is registered by the encoder system as a displacement, introducing an error into the counter to be added up to graduation, system and installation errors. Behavior improvement can be based on different techniques trying to compensate the error from measurement signals processing. In this work a new “ad hoc” methodology is presented to compensate the error of the encoder when is working under the influence of vibration. The methodology is based on fitting techniques to the Lissajous figure of the deteriorated measurement signals and the use of a look up table, giving as a result a compensation procedure in which a higher accuracy of the sensor is obtained. PMID:22666067

  3. Polypeptides having endoglucanase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2015-11-17

    The present invention relates to isolated polypeptides having endoglucanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  4. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2015-11-17

    The present invention relates to isolated polypeptides having cellobiohydrolase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  5. Polypeptides having xylanase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2015-10-27

    The present invention relates to isolated polypeptides having xylanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  6. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2015-03-10

    The present invention relates to isolated polypeptides having cellobiohydrolase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  7. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2014-07-15

    The present invention relates to isolated polypeptides having cellobiohydrolase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  8. Polypeptides having xylanase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2014-10-14

    The present invention relates to isolated polypeptides having xylanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  9. Polypeptides having endoglucanase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2015-07-14

    The present invention relates to isolated polypeptides having endoglucanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  10. Polypeptides having endoglucanase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2015-02-10

    The present invention relates to isolated polypeptides having endoglucanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  11. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2015-03-31

    The present invention relates to isolated polypeptides having cellobiohydrolase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  12. Polypeptides having xylanase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2015-08-18

    The present invention relates to isolated polypeptides having xylanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  13. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2014-06-24

    The present invention relates to isolated polypeptides having cellobiohydrolase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  14. Polypeptides having endoglucanse activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2014-07-08

    The present invention relates to isolated polypeptides having endoglucanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  15. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2014-07-08

    The present invention relates to isolated polypeptides having cellobiohydrolase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  16. Polypeptides having xylanase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2014-06-24

    The present invention relates to isolated polypeptides having xylanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  17. Polypeptides having endoglucanase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2014-07-15

    The present invention relates to isolated polypeptides having endoglucanase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  18. Motion corrected intracranial MRA using PROPELLER with RF quadratic encoding.

    PubMed

    Zwart, Nicholas R; Pipe, James G

    2009-06-01

    A new motion corrected Time-of-Flight MRA technique named Variable Pitch PROPELLER is presented. This technique employs the PROPELLER acquisition and reconstruction scheme for in-plane bulk motion correction. A non- Fourier through-plane encoding mechanism called quadratic encoding boosts SNR, relative to conventional 2D MRA, in lieu of traditional 3D encoding. Partial Fourier encoding is applied in the slice direction for a further reduction in scan time. This work details the construction and optimization of this technique. VPPROP MRAs are compared with a clinical MOTSA protocol. Initial results show promising robustness to bulk motion effects. The comparisons with MOTSA provide insight as to the additions required to create a comparable scan. PMID:19353668

  19. Research on Optimization of Encoding Algorithm of PDF417 Barcodes

    NASA Astrophysics Data System (ADS)

    Sun, Ming; Fu, Longsheng; Han, Shuqing

    The purpose of this research is to develop software to optimize the data compression of a PDF417 barcode using VC++6.0. According to the different compression mode and the particularities of Chinese, the relevant approaches which optimize the encoding algorithm of data compression such as spillage and the Chinese characters encoding are proposed, a simple approach to compute complex polynomial is introduced. After the whole data compression is finished, the number of the codeword is reduced and then the encoding algorithm is optimized. The developed encoding system of PDF 417 barcodes will be applied in the logistics management of fruits, therefore also will promote the fast development of the two-dimensional bar codes.

  20. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Zhang, Yu; Duan, Junxin; Tang, Lan; Wu, Wenping

    2015-06-09

    Provided are isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. Also provided are nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  1. Polypeptides having endoglucanase activity and polynucleotides encoding same

    SciTech Connect

    Liu, Ye; Duan, Junxin; Tang, Lan

    2015-09-22

    The present invention provides isolated polypeptides having endoglucanase activity and isolated polynucleotides encoding the polypeptides. The invention also provides nucleic acid constructs, vectors, and host cell comprising the polynucleotides as well as methods of producing and using the polypeptides.

  2. Polypeptides having cellobiohydrolase activitiy and polynucleotides encoding same

    SciTech Connect

    Liu, Ye; Tang, Lan; Duan, Junxin

    2015-12-15

    The present invention provides isolated polypeptides having cellobiohydrolase activity and isolated polynucleotides encoding the polypeptides. The invention also provides nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  3. ENCODE Data in the UCSC Genome Browser: year 5 update

    PubMed Central

    Rosenbloom, Kate R.; Sloan, Cricket A.; Malladi, Venkat S.; Dreszer, Timothy R.; Learned, Katrina; Kirkup, Vanessa M.; Wong, Matthew C.; Maddren, Morgan; Fang, Ruihua; Heitner, Steven G.; Lee, Brian T.; Barber, Galt P.; Harte, Rachel A.; Diekhans, Mark; Long, Jeffrey C.; Wilder, Steven P.; Zweig, Ann S.; Karolchik, Donna; Kuhn, Robert M.; Haussler, David; Kent, W. James

    2013-01-01

    The Encyclopedia of DNA Elements (ENCODE), http://encodeproject.org, has completed its fifth year of scientific collaboration to create a comprehensive catalog of functional elements in the human genome, and its third year of investigations in the mouse genome. Since the last report in this journal, the ENCODE human data repertoire has grown by 898 new experiments (totaling 2886), accompanied by a major integrative analysis. In the mouse genome, results from 404 new experiments became available this year, increasing the total to 583, collected during the course of the project. The University of California, Santa Cruz, makes this data available on the public Genome Browser http://genome.ucsc.edu for visual browsing and data mining. Download of raw and processed data files are all supported. The ENCODE portal provides specialized tools and information about the ENCODE data sets. PMID:23193274

  4. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2016-06-28

    The present invention relates to isolated polypeptides having cellobiohydrolase activity and polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  5. Fast full-wave seismic inversion using source encoding.

    SciTech Connect

    Ho Cha, Young; Baumstein, Anatoly; Lee, Sunwoong; Hinkley, David; Anderson, John E.; Neelamani, Ramesh; Krebs, Jerome R.; Lacasse, Martin-Daniel

    2010-05-01

    Full Wavefield Seismic Inversion (FWI) estimates a subsurface elastic model by iteratively minimizing the difference between observed and simulated data. This process is extremely compute intensive, with a cost on the order of at least hundreds of prestack reverse time migrations. For time-domain and Krylov-based frequency-domain FWI, the cost of FWI is proportional to the number of seismic sources inverted. We have found that the cost of FWI can be significantly reduced by applying it to data processed by encoding and summing individual source gathers, and by changing the encoding functions between iterations. The encoding step forms a single gather from many input source gathers. This gather represents data that would have been acquired from a spatially distributed set of sources operating simultaneously with different source signatures. We demonstrate, using synthetic data, significant cost reduction by applying FWI to encoded simultaneous-source data.

  6. Data Encoding using Periodic Nano-Optical Features

    NASA Astrophysics Data System (ADS)

    Vosoogh-Grayli, Siamack

    Successful trials have been made through a designed algorithm to quantize, compress and optically encode unsigned 8 bit integer values in the form of images using Nano optical features. The periodicity of the Nano-scale features (Nano-gratings) have been designed and investigated both theoretically and experimentally to create distinct states of variation (three on states and one off state). The use of easy to manufacture and machine readable encoded data in secured authentication media has been employed previously in bar-codes for bi-state (binary) models and in color barcodes for multiple state models. This work has focused on implementing 4 states of variation for unit information through periodic Nano-optical structures that separate an incident wavelength into distinct colors (variation states) in order to create an encoding system. Compared to barcodes and magnetic stripes in secured finite length storage media the proposed system encodes and stores more data. The benefits of multiple states of variation in an encoding unit are 1) increased numerically representable range 2) increased storage density and 3) decreased number of typical set elements for any ergodic or semi-ergodic source that emits these encoding units. A thorough investigation has targeted the effects of the use of multi-varied state Nano-optical features on data storage density and consequent data transmission rates. The results show that use of Nano-optical features for encoding data yields a data storage density of circa 800 Kbits/in2 via the implementation of commercially available high resolution flatbed scanner systems for readout. Such storage density is far greater than commercial finite length secured storage media such as Barcode family with maximum practical density of 1kbits/in2 and highest density magnetic stripe cards with maximum density circa 3 Kbits/in2. The numerically representable range of the proposed encoding unit for 4 states of variation is [0 255]. The number of

  7. Security enhanced BioEncoding for protecting iris codes

    NASA Astrophysics Data System (ADS)

    Ouda, Osama; Tsumura, Norimichi; Nakaguchi, Toshiya

    2011-06-01

    Improving the security of biometric template protection techniques is a key prerequisite for the widespread deployment of biometric technologies. BioEncoding is a recently proposed template protection scheme, based on the concept of cancelable biometrics, for protecting biometric templates represented as binary strings such as iris codes. The main advantage of BioEncoding over other template protection schemes is that it does not require user-specific keys and/or tokens during verification. Besides, it satisfies all the requirements of the cancelable biometrics construct without deteriorating the matching accuracy. However, although it has been shown that BioEncoding is secure enough against simple brute-force search attacks, the security of BioEncoded templates against more smart attacks, such as record multiplicity attacks, has not been sufficiently investigated. In this paper, a rigorous security analysis of BioEncoding is presented. Firstly, resistance of BioEncoded templates against brute-force attacks is revisited thoroughly. Secondly, we show that although the cancelable transformation employed in BioEncoding might be non-invertible for a single protected template, the original iris code could be inverted by correlating several templates used in different applications but created from the same iris. Accordingly, we propose an important modification to the BioEncoding transformation process in order to hinder attackers from exploiting this type of attacks. The effectiveness of adopting the suggested modification is validated and its impact on the matching accuracy is investigated empirically using CASIA-IrisV3-Interval dataset. Experimental results confirm the efficacy of the proposed approach and show that it preserves the matching accuracy of the unprotected iris recognition system.

  8. A SAT Encoding for Multi-dimensional Packing Problems

    NASA Astrophysics Data System (ADS)

    Grandcolas, Stéphane; Pinto, Cédric

    The Orthogonal Packing Problem (OPP) consists in determining if a set of items can be packed into a given container. This decision problem is NP-complete. Fekete et al. modelled the problem in which the overlaps between the objects in each dimension are represented by interval graphs. In this paper we propose a SAT encoding of Fekete et al. characterization. Some results are presented, and the efficiency of this approach is compared with other SAT encodings.

  9. Biological movement and the encoding of its motion and orientation

    PubMed Central

    Benton, Christopher P.; Thirkettle, Martin; Scott-Samuel, Nicholas E.

    2016-01-01

    Are you walking at me? Biological movement and the encoding of its motion and orientation. A person’s motion conveys a wealth of information that ranges from the complex, such as intention or emotional state, to the simple, such as direction of locomotion. How we recognise and recover people’s motion is addressed by models of biological motion processing. Single channel models propose that this occurs through the operation of form template neurons which respond to viewpoint dependent snapshots of posture. More controversially, a dual channel approach proposes a second stream containing motion template neurons sensitive to view dependent snapshots of biological movement’s characteristic local velocity field. We used behavioural adaptation to look for the co-encoding of viewpoint and walker motion, a hallmark of motion template analysis. We show that opposite viewpoint aftereffects can simultaneously be induced for forwards and reversed walkers. This demonstrates that distinct populations of neurons encode forwards and reversed walking. To account for such aftereffects, these units must either be able to inhibit viewpoint-encoding neurons, or they must encode viewpoint directly. Whereas current single channel models would need extending to incorporate these characteristics, the idea that walker motion is encoded directly, such that viewpoint and motion are intrinsically interlinked, is a fundamental component of the dual channel model. PMID:26925870

  10. The Human Brain Encodes Event Frequencies While Forming Subjective Beliefs

    PubMed Central

    d’Acremont, Mathieu; Schultz, Wolfram; Bossaerts, Peter

    2015-01-01

    To make adaptive choices, humans need to estimate the probability of future events. Based on a Bayesian approach, it is assumed that probabilities are inferred by combining a priori, potentially subjective, knowledge with factual observations, but the precise neurobiological mechanism remains unknown. Here, we study whether neural encoding centers on subjective posterior probabilities, and data merely lead to updates of posteriors, or whether objective data are encoded separately alongside subjective knowledge. During fMRI, young adults acquired prior knowledge regarding uncertain events, repeatedly observed evidence in the form of stimuli, and estimated event probabilities. Participants combined prior knowledge with factual evidence using Bayesian principles. Expected reward inferred from prior knowledge was encoded in striatum. BOLD response in specific nodes of the default mode network (angular gyri, posterior cingulate, and medial prefrontal cortex) encoded the actual frequency of stimuli, unaffected by prior knowledge. In this network, activity increased with frequencies and thus reflected the accumulation of evidence. In contrast, Bayesian posterior probabilities, computed from prior knowledge and stimulus frequencies, were encoded in bilateral inferior frontal gyrus. Here activity increased for improbable events and thus signaled the violation of Bayesian predictions. Thus, subjective beliefs and stimulus frequencies were encoded in separate cortical regions. The advantage of such a separation is that objective evidence can be recombined with newly acquired knowledge when a reinterpretation of the evidence is called for. Overall this study reveals the coexistence in the brain of an experience-based system of inference and a knowledge-based system of inference. PMID:23804108

  11. Evolving scalable and modular adaptive networks with Developmental Symbolic Encoding.

    PubMed

    Suchorzewski, Marcin

    2011-09-01

    Evolutionary neural networks, or neuroevolution, appear to be a promising way to build versatile adaptive systems, combining evolution and learning. One of the most challenging problems of neuroevolution is finding a scalable and robust genetic representation, which would allow to effectively grow increasingly complex networks for increasingly complex tasks. In this paper we propose a novel developmental encoding for networks, featuring scalability, modularity, regularity and hierarchy. The encoding allows to represent structural regularities of networks and build them from encapsulated and possibly reused subnetworks. These capabilities are demonstrated on several test problems. In particular for parity and symmetry problems we evolve solutions, which are fully general with respect to the number of inputs. We also evolve scalable and modular weightless recurrent networks capable of autonomous learning in a simple generic classification task. The encoding is very flexible and we demonstrate this by evolving networks capable of learning via neuromodulation. Finally, we evolve modular solutions to the retina problem, for which another well known neuroevolution method-HyperNEAT-was previously shown to fail. The proposed encoding outperformed HyperNEAT and Cellular Encoding also in another experiment, in which certain connectivity patterns must be discovered between layers. Therefore we conclude the proposed encoding is an interesting and competitive approach to evolve networks. PMID:21957432

  12. Low Complexity HEVC Encoder for Visual Sensor Networks

    PubMed Central

    Pan, Zhaoqing; Chen, Liming; Sun, Xingming

    2015-01-01

    Visual sensor networks (VSNs) can be widely applied in security surveillance, environmental monitoring, smart rooms, etc. However, with the increased number of camera nodes in VSNs, the volume of the visual information data increases significantly, which becomes a challenge for storage, processing and transmitting the visual data. The state-of-the-art video compression standard, high efficiency video coding (HEVC), can effectively compress the raw visual data, while the higher compression rate comes at the cost of heavy computational complexity. Hence, reducing the encoding complexity becomes vital for the HEVC encoder to be used in VSNs. In this paper, we propose a fast coding unit (CU) depth decision method to reduce the encoding complexity of the HEVC encoder for VSNs. Firstly, the content property of the CU is analyzed. Then, an early CU depth decision method and a low complexity distortion calculation method are proposed for the CUs with homogenous content. Experimental results show that the proposed method achieves 71.91% on average encoding time savings for the HEVC encoder for VSNs. PMID:26633415

  13. Ontology application and use at the ENCODE DCC

    PubMed Central

    Malladi, Venkat S.; Erickson, Drew T.; Podduturi, Nikhil R.; Rowe, Laurence D.; Chan, Esther T.; Davidson, Jean M.; Hitz, Benjamin C.; Ho, Marcus; Lee, Brian T.; Miyasato, Stuart; Roe, Gregory R.; Simison, Matt; Sloan, Cricket A.; Strattan, J. Seth; Tanaka, Forrest; Kent, W. James; Cherry, J. Michael; Hong, Eurie L.

    2015-01-01

    The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a catalog of genomic annotations. To date, the project has generated over 4000 experiments across more than 350 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory network and transcriptional landscape of the Homo sapiens and Mus musculus genomes. All ENCODE experimental data, metadata and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage and distribution to community resources and the scientific community. As the volume of data increases, the organization of experimental details becomes increasingly complicated and demands careful curation to identify related experiments. Here, we describe the ENCODE DCC’s use of ontologies to standardize experimental metadata. We discuss how ontologies, when used to annotate metadata, provide improved searching capabilities and facilitate the ability to find connections within a set of experiments. Additionally, we provide examples of how ontologies are used to annotate ENCODE metadata and how the annotations can be identified via ontology-driven searches at the ENCODE portal. As genomic datasets grow larger and more interconnected, standardization of metadata becomes increasingly vital to allow for exploration and comparison of data between different scientific projects. Database URL: https://www.encodeproject.org/ PMID:25776021

  14. The role of depth of encoding in attentional capture.

    PubMed

    Sasin, Edyta; Nieuwenstein, Mark; Johnson, Addie

    2015-10-01

    The aim of the current study was to examine whether depth of encoding influences attentional capture by recently attended objects. In Experiment 1, participants first had to judge whether a word referred to a living or a nonliving thing (deep encoding condition) or whether the word was written in lower- or uppercase (shallow encoding condition), and they then had to identify a digit displayed midway in a rapid serial visual presentation (RSVP) stream of 8 pictures. A picture corresponding to the previously processed word was presented either before or after the target digit. The results showed that this picture captured attention, thus resulting in an attentional blink for identification of a target digit, in the deep encoding condition but not in the shallow encoding condition. In Experiment 2, this capture effect was found to be abolished when an additional working-memory (WM) task was performed directly after the word-judgment task, suggesting that the capture effect stemmed from residual WM activation that could be erased by means of a secondary WM task. Taken together, these results suggest that deep and shallow encoding result in different degrees of WM activation, which in turn influences the likelihood of memory-driven attentional capture. PMID:25690580

  15. Low Complexity HEVC Encoder for Visual Sensor Networks.

    PubMed

    Pan, Zhaoqing; Chen, Liming; Sun, Xingming

    2015-01-01

    Visual sensor networks (VSNs) can be widely applied in security surveillance, environmental monitoring, smart rooms, etc. However, with the increased number of camera nodes in VSNs, the volume of the visual information data increases significantly, which becomes a challenge for storage, processing and transmitting the visual data. The state-of-the-art video compression standard, high efficiency video coding (HEVC), can effectively compress the raw visual data, while the higher compression rate comes at the cost of heavy computational complexity. Hence, reducing the encoding complexity becomes vital for the HEVC encoder to be used in VSNs. In this paper, we propose a fast coding unit (CU) depth decision method to reduce the encoding complexity of the HEVC encoder for VSNs. Firstly, the content property of the CU is analyzed. Then, an early CU depth decision method and a low complexity distortion calculation method are proposed for the CUs with homogenous content. Experimental results show that the proposed method achieves 71.91% on average encoding time savings for the HEVC encoder for VSNs. PMID:26633415

  16. Ontology application and use at the ENCODE DCC.

    PubMed

    Malladi, Venkat S; Erickson, Drew T; Podduturi, Nikhil R; Rowe, Laurence D; Chan, Esther T; Davidson, Jean M; Hitz, Benjamin C; Ho, Marcus; Lee, Brian T; Miyasato, Stuart; Roe, Gregory R; Simison, Matt; Sloan, Cricket A; Strattan, J Seth; Tanaka, Forrest; Kent, W James; Cherry, J Michael; Hong, Eurie L

    2015-01-01

    The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a catalog of genomic annotations. To date, the project has generated over 4000 experiments across more than 350 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory network and transcriptional landscape of the Homo sapiens and Mus musculus genomes. All ENCODE experimental data, metadata and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage and distribution to community resources and the scientific community. As the volume of data increases, the organization of experimental details becomes increasingly complicated and demands careful curation to identify related experiments. Here, we describe the ENCODE DCC's use of ontologies to standardize experimental metadata. We discuss how ontologies, when used to annotate metadata, provide improved searching capabilities and facilitate the ability to find connections within a set of experiments. Additionally, we provide examples of how ontologies are used to annotate ENCODE metadata and how the annotations can be identified via ontology-driven searches at the ENCODE portal. As genomic datasets grow larger and more interconnected, standardization of metadata becomes increasingly vital to allow for exploration and comparison of data between different scientific projects. PMID:25776021

  17. Feedback-tuned, noise resilient gates for encoded spin qubits

    NASA Astrophysics Data System (ADS)

    Bluhm, Hendrik

    Spin 1/2 particles form native two level systems and thus lend themselves as a natural qubit implementation. However, encoding a single qubit in several spins entails benefits, such as reducing the resources necessary for qubit control and protection from certain decoherence channels. While several varieties of such encoded spin qubits have been implemented, accurate control remains challenging, and leakage out of the subspace of valid qubit states is a potential issue. Optimal performance typically requires large pulse amplitudes for fast control, which is prone to systematic errors and prohibits standard control approaches based on Rabi flopping. Furthermore, the exchange interaction typically used to electrically manipulate encoded spin qubits is inherently sensitive to charge noise. I will discuss all-electrical, high-fidelity single qubit operations for a spin qubit encoded in two electrons in a GaAs double quantum dot. Starting from a set of numerically optimized control pulses, we employ an iterative tuning procedure based on measured error syndromes to remove systematic errors.Randomized benchmarking yields an average gate fidelity exceeding 98 % and a leakage rate into invalid states of 0.2 %. These gates exhibit a certain degree of resilience to both slow charge and nuclear spin fluctuations due to dynamical correction analogous to a spin echo. Furthermore, the numerical optimization minimizes the impact of fast charge noise. Both types of noise make relevant contributions to gate errors. The general approach is also adaptable to other qubit encodings and exchange based two-qubit gates.

  18. Efficient Encoding and Rendering of Time-Varying Volume Data

    NASA Technical Reports Server (NTRS)

    Ma, Kwan-Liu; Smith, Diann; Shih, Ming-Yun; Shen, Han-Wei

    1998-01-01

    Visualization of time-varying volumetric data sets, which may be obtained from numerical simulations or sensing instruments, provides scientists insights into the detailed dynamics of the phenomenon under study. This paper describes a coherent solution based on quantization, coupled with octree and difference encoding for visualizing time-varying volumetric data. Quantization is used to attain voxel-level compression and may have a significant influence on the performance of the subsequent encoding and visualization steps. Octree encoding is used for spatial domain compression, and difference encoding for temporal domain compression. In essence, neighboring voxels may be fused into macro voxels if they have similar values, and subtrees at consecutive time steps may be merged if they are identical. The software rendering process is tailored according to the tree structures and the volume visualization process. With the tree representation, selective rendering may be performed very efficiently. Additionally, the I/O costs are reduced. With these combined savings, a higher level of user interactivity is achieved. We have studied a variety of time-varying volume datasets, performed encoding based on data statistics, and optimized the rendering calculations wherever possible. Preliminary tests on workstations have shown in many cases tremendous reduction by as high as 90% in both storage space and inter-frame delay.

  19. When encoding yields remembering: insights from event-related neuroimaging.

    PubMed Central

    Wagner, A D; Koutstaal, W; Schacter, D L

    1999-01-01

    To understand human memory, it is important to determine why some experiences are remembered whereas others are forgotten. Until recently, insights into the neural bases of human memory encoding, the processes by which information is transformed into an enduring memory trace, have primarily been derived from neuropsychological studies of humans with select brain lesions. The advent of functional neuroimaging methods, such as positron emission tomography (PET) and functional magnetic resonance imaging (fMRI), has provided a new opportunity to gain additional understanding of how the brain supports memory formation. Importantly, the recent development of event-related fMRI methods now allows for examination of trial-by-trial differences in neural activity during encoding and of the consequences of these differences for later remembering. In this review, we consider the contributions of PET and fMRI studies to the understanding of memory encoding, placing a particular emphasis on recent event-related fMRI studies of the Dm effect: that is, differences in neural activity during encoding that are related to differences in subsequent memory. We then turn our attention to the rich literature on the Dm effect that has emerged from studies using event-related potentials (ERPs). It is hoped that the integration of findings from ERP studies, which offer higher temporal resolution, with those from event-related fMRI studies, which offer higher spatial resolution, will shed new light on when and why encoding yields subsequent remembering. PMID:10466153

  20. Excitation and geometrically matched local encoding of curved slices.

    PubMed

    Weber, Hans; Gallichan, Daniel; Schultz, Gerrit; Cocosco, Chris A; Littin, Sebastian; Reichardt, Wilfried; Welz, Anna; Witschey, Walter; Hennig, Jürgen; Zaitsev, Maxim

    2013-05-01

    In this work, the concept of excitation and geometrically matched local in-plane encoding of curved slices (ExLoc) is introduced. ExLoc is based on a set of locally near-orthogonal spatial encoding magnetic fields, thus maintaining a local rectangular shape of the individual voxels and avoiding potential problems arising due to highly irregular voxel shapes. Unlike existing methods for exciting curved slices based on multidimensional radiofrequency-pulses, excitation and geometrically matched local encoding of curved slices does not require long duration or computationally expensive radiofrequency-pulses. As each encoding field consists of a superposition of potentially arbitrary (spatially linear or nonlinear) magnetic field components, the resulting field shape can be adapted with high flexibility to the specific region of interest. For extended nonplanar structures, this results in improved relevant volume coverage for fewer excited slices and thus increased efficiency. In addition to the mathematical description for the generation of dedicated encoding fields and data reconstruction, a verification of the ExLoc concept in phantom experiments and examples for in vivo curved single and multislice imaging are presented. PMID:22711656

  1. Toddlers encode similarities among novel words from meaningful sentences

    PubMed Central

    Saffran, Jenny R.

    2015-01-01

    Toddlers can learn about the meanings of individual words from the structure and semantics of the sentences in which they are embedded. However, it remains unknown whether toddlers encode similarities amongst novel words based on their positions within sentences. In three experiments, two-year-olds listened to novel words embedded in familiar sentence frames. Some novel words consistently occurred in the subject position across sentences, and others in the object position across sentences. An auditory semantic task was used to test whether toddlers encoded similarities based on sentential position, for (a) pairs of novel words that occurred within the same sentence, and (b) pairs of novel words that occurred in the same position across sentences. The results suggest that while toddlers readily encoded similarity based on within-sentence occurrences, only toddlers with more advanced grammatical knowledge encoded the positional similarities of novel words across sentences. Moreover, the encoding of these cross-sentential relationships only occurred if the exposure sentences included a familiar verb. These studies suggest that the types of lexical relationships that toddlers learn depend on the child’s current level of language development, as well as the structure and meaning of the sentences surrounding the novel words. PMID:25704579

  2. Dissociating distractor-filtering at encoding and during maintenance.

    PubMed

    McNab, Fiona; Dolan, Raymond J

    2014-06-01

    The effectiveness of distractor-filtering is a potentially important determinant of working memory capacity (WMC). However, a distinction between the contributions of distractor-filtering at WM encoding as opposed to filtering during maintenance has not been made and the assumption is that these rely on the same mechanism. Within 2 experiments, 1 conducted in the laboratory with 21 participants, and the other played as a game on smartphones (n = 3,247) we measure WMC without distractors, and present distractors during encoding or during the delay period of a WM task to determine performance associated with distraction at encoding and during maintenance. Despite differences in experimental setting and paradigm design between the 2 studies, we show a unique contribution to WMC from both encoding and delay distractor performance in both experiments, while controlling for performance in the absence of distraction. Thus, within 2 separate experiments, 1 involving an extremely large cohort of 3,247 participants, we show a dissociation between encoding and delay distractor-filtering, indicating that separate mechanisms may contribute to WMC. PMID:24512609

  3. Forgetting from working memory: does novelty encoding matter?

    PubMed

    Plancher, Gaën; Barrouillet, Pierre

    2013-01-01

    The sources of forgetting in working memory remain the matter of intense debate. According to the SOB model (serial order in a box; Farrell & Lewandowsky, 2002), forgetting in complex span tasks does not result from temporal decay but from interference produced by the encoding of distractors that are superimposed over memory items onto a composite memory. The main tenet of the model is that the encoding strength of a distractor is a function of its novelty, with novel distractors being encoded with a large encoding weight that interferes with other memories, whereas repeated distractors would result in negligible encoding weight and no further forgetting. In the present study, we tested the 2 main predictions issuing from this model. First, recall performance should be better in complex span tasks in which distractors are repeated than in tasks in which every distractor is novel. Second, increasing the number of novel distractors should lead to more interference and poorer recall. In 5 experiments in which we controlled for attentional demand and temporal factors, none of these predictions were verified, whereas a strong effect of the pace at which distracting tasks were performed testified that they involved forgetting. We conclude that, contrary to the SOB model, the novelty of distractors plays no role per se in forgetting. (PsycINFO Database Record (c) 2013 APA, all rights reserved). PMID:22563635

  4. Biomolecular screening with encoded porous-silicon photonic crystals.

    PubMed

    Cunin, Frédérique; Schmedake, Thomas A; Link, Jamie R; Li, Yang Yang; Koh, Jennifer; Bhatia, Sangeeta N; Sailor, Michael J

    2002-09-01

    Strategies to encode or label small particles or beads for use in high-throughput screening and bioassay applications focus on either spatially differentiated, on-chip arrays or random distributions of encoded beads. Attempts to encode large numbers of polymeric, metallic or glass beads in random arrays or in fluid suspension have used a variety of entities to provide coded elements (bits)--fluorescent molecules, molecules with specific vibrational signatures, quantum dots, or discrete metallic layers. Here we report a method for optically encoding micrometre-sized nanostructured particles of porous silicon. We generate multilayered porous films in crystalline silicon using a periodic electrochemical etch. This results in photonic crystals with well-resolved and narrow optical reflectivity features, whose wavelengths are determined by the etching parameters. Millions of possible codes can be prepared this way. Micrometre-sized particles are then produced by ultrasonic fracture, mechanical grinding or by lithographic means. A simple antibody-based bioassay using fluorescently tagged proteins demonstrates the encoding strategy in biologically relevant media. PMID:12618846

  5. Brain activity underlying encoding and retrieval of source memory.

    PubMed

    Cansino, Selene; Maquet, Pierre; Dolan, Raymond J; Rugg, Michael D

    2002-10-01

    Neural activity elicited during the encoding and retrieval of source information was investigated with event-related functional magnetic resonance imaging (efMRI). During encoding, 17 subjects performed a natural/artificial judgement on pictures of common objects which were presented randomly in one of the four quadrants of the display. At retrieval, old pictures were mixed with new ones and subjects judged whether each picture was new or old and, if old, indicated in which quadrant it was presented at encoding. During encoding, study items that were later recognized and assigned a correct source judgement elicited greater activity than recognized items given incorrect judgements in a variety of regions, including right lateral occipital and left prefrontal cortex. At retrieval, regions showing greater activity for recognized items given correct versus incorrect source judgements included the right hippocampal formation and the left prefrontal cortex. These findings indicate a role for these regions in the encoding and retrieval of episodic information beyond that required for simple item recognition. PMID:12217968

  6. Assembly of NADH: ubiquinone reductase (complex I) in Neurospora mitochondria. Independent pathways of nuclear-encoded and mitochondrially encoded subunits.

    PubMed

    Tuschen, G; Sackmann, U; Nehls, U; Haiker, H; Buse, G; Weiss, H

    1990-06-20

    NADH:ubiquinone reductase, the respiratory chain complex I of mitochondria, consists of some 25 nuclear-encoded and seven mitochondrially encoded subunits, and contains as redox groups one FMN, probably one internal ubiquinone and at least four iron-sulphur clusters. We are studying the assembly of the enzyme in Neurospora crassa. The flux of radioactivity in cells that were pulse-labelled with [35S]methionine was followed through immunoprecipitable assembly intermediates into the holoenzyme. Labelled polypeptides were observed to accumulate transiently in a Mr 350,000 intermediate complex. This complex contains all mitochondrially encoded subunits of the enzyme as well as subunits encoded in the nucleus that have no homologous counterparts in a small, merely nuclear-encoded form of the NADH:ubiquinone reductase made by Neurospora crassa cells poisoned with chloramphenicol. With regard to their subunit compositions, the assembly intermediate and small NADH:ubiquinone reductase complement each other almost perfectly to give the subunit composition of the large complex I. These results suggest that two pathways exist in the assembly of complex I that independently lead to the preassembly of two major parts, which subsequently join to form the complex. One preassembled part is related to the small form of NADH:ubiquinone reductase and contributes most of the nuclear-encoded subunits, FMN, three iron-sulphur clusters and the site for the internal ubiquinone. The other part is the assembly intermediate and contributes all mitochondrially encoded subunits, one iron-sulphur cluster and the catalytic site for the substrate ubiquinone. We discuss the results with regard to the evolution of the electron pathway through complex I. PMID:2141652

  7. The Nutrient and Energy Sensor Sirt1 Regulates the Hypothalamic-Pituitary-Adrenal (HPA) Axis by Altering the Production of the Prohormone Convertase 2 (PC2) Essential in the Maturation of Corticotropin-releasing Hormone (CRH) from Its Prohormone in Male Rats.

    PubMed

    Toorie, Anika M; Cyr, Nicole E; Steger, Jennifer S; Beckman, Ross; Farah, George; Nillni, Eduardo A

    2016-03-11

    Understanding the role of hypothalamic neuropeptides and hormones in energy balance is paramount in the search for approaches to mitigate the obese state. Increased hypothalamic-pituitary-adrenal axis activity leads to increased levels of glucocorticoids (GC) that are known to regulate body weight. The axis initiates the production and release of corticotropin-releasing hormone (CRH) from the paraventricular nucleus (PVN) of the hypothalamus. Levels of active CRH peptide are dependent on the processing of its precursor pro-CRH by the action of two members of the family of prohormone convertases 1 and 2 (PC1 and PC2). Here, we propose that the nutrient sensor sirtuin 1 (Sirt1) regulates the production of CRH post-translationally by affecting PC2. Data suggest that Sirt1 may alter the preproPC2 gene directly or via deacetylation of the transcription factor Forkhead box protein O1 (FoxO1). Data also suggest that Sirt1 may alter PC2 via a post-translational mechanism. Our results show that Sirt1 levels in the PVN increase in rats fed a high fat diet for 12 weeks. Furthermore, elevated Sirt1 increased PC2 levels, which in turn increased the production of active CRH and GC. Collectively, this study provides the first evidence supporting the hypothesis that PVN Sirt1 activates the hypothalamic-pituitary-adrenal axis and basal GC levels by enhancing the production of CRH through an increase in the biosynthesis of PC2, which is essential in the maturation of CRH from its prohormone, pro-CRH. PMID:26755731

  8. Encoding degree testing in a 4f architecture

    NASA Astrophysics Data System (ADS)

    Amaya, Dafne; Tebaldi, Myrian; Torroba, Roberto; Bolognini, Néstor

    2011-08-01

    The distribution of the encrypted information at the output of an encoding system is of major concern. When the encrypted information is conveyed to the final user, the finite size of the recording medium affects the quality of the encoded information. In this case, we face possible information degradation when recovering. In the present contribution we focus our attention on the finite size of the recorder medium in an actual experimental situation. In order to improve the quality of the decrypted data, we study the role that both the scattering element size of the masks and the input object size play in the encrypting system. Therefore, we analyze the optimal spatial distribution of the encoded information at the output of a 4f encrypting system. We present examples that support our proposal.

  9. Subversion of cytokine networks by virally encoded decoy receptors

    PubMed Central

    Epperson, Megan L.; Lee, Chung A.; Fremont, Daved H.

    2012-01-01

    Summary During the course of evolution, viruses have captured or created a diverse array of open reading frames that encode for proteins that serve to evade and sabotage the host innate and adaptive immune responses, which would otherwise lead to their elimination. These viral genomes are some of the best textbooks of immunology ever written. The established arsenal of immunomodulatory proteins encoded by viruses is large and growing and includes specificities for virtually all known inflammatory pathways and targets. The focus of this review is on herpes and poxvirus-encoded cytokine and chemokine binding proteins that serve to undermine the coordination of host immune surveillance. Structural and mechanistic studies of these decoy receptors have provided a wealth of information, not only about viral pathogenesis but also about the inner workings of cytokine signaling networks. PMID:23046131

  10. Tree encoding of Gaussian sources. [in data compression

    NASA Technical Reports Server (NTRS)

    Dick, R. J.; Berger, T.; Jelinek, F.

    1974-01-01

    Tree codes are known to be capable of performing arbitrarily close to the rate-distortion function for any memoryless source and single-letter fidelity criterion. Tree coding and tree search strategies are investigated for the discrete-time memoryless Gaussian source encoded for a signal-power-to-mean-squared-error ratio of about 30 dB (about 5 binary digits per source output). Also, a theoretical lower bound on average search effort is derived. Two code search strategies (the Viterbi algorithm and the stack algorithm) were simulated in assembly language on a large digital computer. After suitable modifications, both strategies yielded encoding with a signal-to-distortion ratio about 1 dB below the limit set by the rate-distortion function. Although this performance is better than that of any previously known instrumentable scheme, it unfortunately requires search computation of the order of 100,000 machine cycles per source output encoded.

  11. Selection for genes encoding secreted proteins and receptors.

    PubMed Central

    Klein, R D; Gu, Q; Goddard, A; Rosenthal, A

    1996-01-01

    Extracellular proteins play an essential role in the formation, differentiation, and maintenance of multicellular organisms. Despite that, the systematic identification of genes encoding these proteins has not been possible. We describe here a highly efficient method to isolate genes encoding secreted and membrane-bound proteins by using a single-step selection in yeast. Application of this method, termed signal peptide selection, to various tissues yielded 559 clones that appear to encode known or novel extracellular proteins. These include members of the transforming growth factor and epidermal growth factor protein families, endocrine hormones, tyrosine kinase receptors, serine/threonine kinase receptors, seven transmembrane receptors, cell adhesion molecules, extracellular matrix proteins, plasma proteins, and ion channels. The eventual identification of most, or all, extracellular signaling molecules will advance our understanding of fundamental biological processes and our ability to intervene in disease states. Images Fig. 1 PMID:8692953

  12. Fast Coding Unit Encoding Mechanism for Low Complexity Video Coding

    PubMed Central

    Wu, Yueying; Jia, Kebin; Gao, Guandong

    2016-01-01

    In high efficiency video coding (HEVC), coding tree contributes to excellent compression performance. However, coding tree brings extremely high computational complexity. Innovative works for improving coding tree to further reduce encoding time are stated in this paper. A novel low complexity coding tree mechanism is proposed for HEVC fast coding unit (CU) encoding. Firstly, this paper makes an in-depth study of the relationship among CU distribution, quantization parameter (QP) and content change (CC). Secondly, a CU coding tree probability model is proposed for modeling and predicting CU distribution. Eventually, a CU coding tree probability update is proposed, aiming to address probabilistic model distortion problems caused by CC. Experimental results show that the proposed low complexity CU coding tree mechanism significantly reduces encoding time by 27% for lossy coding and 42% for visually lossless coding and lossless coding. The proposed low complexity CU coding tree mechanism devotes to improving coding performance under various application conditions. PMID:26999741

  13. Encoding, training and retrieval in ferroelectric tunnel junctions.

    PubMed

    Xu, Hanni; Xia, Yidong; Xu, Bo; Yin, Jiang; Yuan, Guoliang; Liu, Zhiguo

    2016-01-01

    Ferroelectric tunnel junctions (FTJs) are quantum nanostructures that have great potential in the hardware basis for future neuromorphic applications. Among recently proposed possibilities, the artificial cognition has high hopes, where encoding, training, memory solidification and retrieval constitute a whole chain that is inseparable. However, it is yet envisioned but experimentally unconfirmed. The poor retention or short-term store of tunneling electroresistance, in particular the intermediate states, is still a key challenge in FTJs. Here we report the encoding, training and retrieval in BaTiO3 FTJs, emulating the key features of information processing in terms of cognitive neuroscience. This is implemented and exemplified through processing characters. Using training inputs that are validated by the evolution of both barrier profile and domain configuration, accurate recalling of encoded characters in the retrieval stage is demonstrated. PMID:27244092

  14. Phonetic Feature Encoding in Human Superior Temporal Gyrus

    PubMed Central

    Mesgarani, Nima; Cheung, Connie; Johnson, Keith; Chang, Edward F.

    2015-01-01

    During speech perception, linguistic elements such as consonants and vowels are extracted from a complex acoustic speech signal. The superior temporal gyrus (STG) participates in high-order auditory processing of speech, but how it encodes phonetic information is poorly understood. We used high-density direct cortical surface recordings in humans while they listened to natural, continuous speech to reveal the STG representation of the entire English phonetic inventory. At single electrodes, we found response selectivity to distinct phonetic features. Encoding of acoustic properties was mediated by a distributed population response. Phonetic features could be directly related to tuning for spectrotemporal acoustic cues, some of which were encoded in a nonlinear fashion or by integration of multiple cues. These findings demonstrate the acoustic-phonetic representation of speech in human STG. PMID:24482117

  15. Encoding, training and retrieval in ferroelectric tunnel junctions

    PubMed Central

    Xu, Hanni; Xia, Yidong; Xu, Bo; Yin, Jiang; Yuan, Guoliang; Liu, Zhiguo

    2016-01-01

    Ferroelectric tunnel junctions (FTJs) are quantum nanostructures that have great potential in the hardware basis for future neuromorphic applications. Among recently proposed possibilities, the artificial cognition has high hopes, where encoding, training, memory solidification and retrieval constitute a whole chain that is inseparable. However, it is yet envisioned but experimentally unconfirmed. The poor retention or short-term store of tunneling electroresistance, in particular the intermediate states, is still a key challenge in FTJs. Here we report the encoding, training and retrieval in BaTiO3 FTJs, emulating the key features of information processing in terms of cognitive neuroscience. This is implemented and exemplified through processing characters. Using training inputs that are validated by the evolution of both barrier profile and domain configuration, accurate recalling of encoded characters in the retrieval stage is demonstrated. PMID:27244092

  16. Subversion of cytokine networks by virally encoded decoy receptors.

    PubMed

    Epperson, Megan L; Lee, Chung A; Fremont, Daved H

    2012-11-01

    During the course of evolution, viruses have captured or created a diverse array of open reading frames, which encode for proteins that serve to evade and sabotage the host innate and adaptive immune responses that would otherwise lead to their elimination. These viral genomes are some of the best textbooks of immunology ever written. The established arsenal of immunomodulatory proteins encoded by viruses is large and growing, and includes specificities for virtually all known inflammatory pathways and targets. The focus of this review is on herpes and poxvirus-encoded cytokine and chemokine-binding proteins that serve to undermine the coordination of host immune surveillance. Structural and mechanistic studies of these decoy receptors have provided a wealth of information, not only about viral pathogenesis but also about the inner workings of cytokine signaling networks. PMID:23046131

  17. Method and apparatus for two-dimensional absolute optical encoding

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B. (Inventor)

    2004-01-01

    This invention presents a two-dimensional absolute optical encoder and a method for determining position of an object in accordance with information from the encoder. The encoder of the present invention comprises a scale having a pattern being predetermined to indicate an absolute location on the scale, means for illuminating the scale, means for forming an image of the pattern; and detector means for outputting signals derived from the portion of the image of the pattern which lies within a field of view of the detector means, the field of view defining an image reference coordinate system, and analyzing means, receiving the signals from the detector means, for determining the absolute location of the object. There are two types of scale patterns presented in this invention: grid type and starfield type.

  18. Color image encoding in DOST domain using DWT and SVD

    NASA Astrophysics Data System (ADS)

    Kumar, Manoj; Agrawal, Smita

    2015-12-01

    In this paper, a new color image encoding and decoding technique based on Discrete Orthonormal Stockwell Transform (DOST) using Discrete Wavelet Transform (DWT) and Singular Value Decomposition (SVD) is proposed. The images are encrypted using bands of DOST and wavelets along with singular values of wavelet subbands. We have used the number of bands of DOST, values and arrangement of some predefined parameters using singular values of all wavelet subbands and arrangement of wavelet subbands as encoding and decoding keys in all three color planes. To ensure the correct decoding of the encoded image, it is necessary to use all the keys in correct order along with their exact values. The comparison of our technique with one of the recently proposed techniques and experimental results is used to analyze the effectiveness of the proposed technique. The proposed technique can be used for transmitting a color image more securely and efficiently through both secured and unsecured communication network.

  19. The Generation Effect: Activating Broad Neural Circuits During Memory Encoding

    PubMed Central

    Rosner, Zachary A.; Elman, Jeremy A.; Shimamura, Arthur P.

    2012-01-01

    The generation effect is a robust memory phenomenon in which actively producing material during encoding acts to improve later memory performance. In an fMRI analysis, we explored the neural basis of this effect. During encoding, participants generated synonyms from word-fragment cues (e.g. GARBAGE-W_ST_) or read other synonym pairs (e.g. GARBAGE-WASTE). Compared to simply reading target words, generating target words significantly improved later recognition memory performance. During encoding, this benefit was associated with a broad neural network that involved both prefrontal (inferior frontal gyrus, middle frontal gyrus) and posterior cortex (inferior temporal gyrus, lateral occipital cortex, parahippocampal gyrus, ventral posterior parietal cortex). These findings define the prefrontal-posterior cortical dynamics associated with the mnemonic benefits underlying the generation effect. PMID:23079490

  20. Long distance quantum communication using continuous variable encoding

    NASA Astrophysics Data System (ADS)

    Li, Linshu; Albert, Victor; Michael, Marios; Muralidharan, Sreraman; Zou, Changling; Jiang, Liang

    Quantum communication enables faithful quantum state transfer between different parties and protocols for cryptographic purposes. However, quantum communication over long distances (>1000km) remains challenging due to optical channel attenuation. This calls for investigation on developing novel encoding schemes that correct photon loss errors efficiently. In this talk, we introduce the generalization of multi-component Schrödinger cat states and propose to encode quantum information in these cat states for ultrafast quantum repeaters. We detail the quantum error correction procedures at each repeater station and characterize the performance of this novel encoding scheme given practical imperfections, such as coupling loss. A comparison with other quantum error correcting codes for bosonic modes will be discussed.

  1. Hippocampal-prefrontal input supports spatial encoding in working memory

    PubMed Central

    Spellman, Timothy; Rigotti, Mattia; Ahmari, Susanne E.; Fusi, Stefano; Gogos, Joseph A.; Gordon, Joshua A.

    2015-01-01

    Summary Spatial working memory, the caching of behaviorally relevant spatial cues on a timescale of seconds, is a fundamental constituent of cognition. While the prefrontal cortex and hippocampus are known to jointly contribute to successful spatial working memory, the anatomical pathway and temporal window for interaction of these structures critical to spatial working memory has not yet been established. Here, we find that direct hippocampal-prefrontal afferents are critical for encoding, but not for maintenance or retrieval, of spatial cues. These cues are represented by the activity of individual prefrontal units in a manner that is dependent on hippocampal input only during the cue-encoding phase of a spatial working memory task. Successful encoding of these cues appears to be mediated by gamma-frequency synchrony between the two structures. These findings indicate a critical role for the direct hippocampal-prefrontal afferent pathway in the continuous updating of task-related spatial information during spatial working memory. PMID:26053122

  2. Nucleic acids encoding antifungal polypeptides and uses thereof

    DOEpatents

    Altier, Daniel J.; Ellanskaya, I. A.; Gilliam, Jacob T.; Hunter-Cevera, Jennie; Presnail, James K; Schepers, Eric; Simmons, Carl R.; Torok, Tamas; Yalpani, Nasser

    2010-11-02

    Compositions and methods for protecting a plant from a pathogen, particularly a fungal pathogen, are provided. Compositions include an amino acid sequence, and variants and fragments thereof, for an antipathogenic polypeptide that was isolated from a fungal fermentation broth. Nucleic acid molecules that encode the antipathogenic polypeptides of the invention, and antipathogenic domains thereof, are also provided. A method for inducing pathogen resistance in a plant using the nucleotide sequences disclosed herein is further provided. The method comprises introducing into a plant an expression cassette comprising a promoter operably linked to a nucleotide sequence that encodes an antipathogenic polypeptide of the invention. Compositions comprising an antipathogenic polypeptide or a transformed microorganism comprising a nucleic acid of the invention in combination with a carrier and methods of using these compositions to protect a plant from a pathogen are further provided. Transformed plants, plant cells, seeds, and microorganisms comprising a nucleotide sequence that encodes an antipathogenic polypeptide of the invention are also disclosed.

  3. Isolated nucleic acids encoding antipathogenic polypeptides and uses thereof

    DOEpatents

    Altier, Daniel J.; Crane, Virginia C.; Ellanskaya, Irina; Ellanskaya, Natalia; Gilliam, Jacob T.; Hunter-Cevera, Jennie; Presnail, James K.; Schepers, Eric J.; Simmons, Carl R.; Torok, Tamas; Yalpani, Nasser

    2010-04-20

    Compositions and methods for protecting a plant from a pathogen, particularly a fungal pathogen, are provided. Compositions include amino acid sequences, and variants and fragments thereof, for antipathogenic polypeptides that were isolated from fungal fermentation broths. Nucleic acids that encode the antipathogenic polypeptides are also provided. A method for inducing pathogen resistance in a plant using the nucleotide sequences disclosed herein is further provided. The method comprises introducing into a plant an expression cassette comprising a promoter operably linked to a nucleotide sequence that encodes an antipathogenic polypeptide of the invention. Compositions comprising an antipathogenic polypeptide or a transformed microorganism comprising a nucleic acid of the invention in combination with a carrier and methods of using these compositions to protect a plant from a pathogen are further provided. Transformed plants, plant cells, seeds, and microorganisms comprising a nucleotide sequence that encodes an antipathogenic polypeptide of the invention are also disclosed.

  4. Learning from number board games: you learn what you encode.

    PubMed

    Laski, Elida V; Siegler, Robert S

    2014-03-01

    We tested the hypothesis that encoding the numerical-spatial relations in a number board game is a key process in promoting learning from playing such games. Experiment 1 used a microgenetic design to examine the effects on learning of the type of counting procedure that children use. As predicted, having kindergartners count-on from their current number on the board while playing a 0-100 number board game facilitated their encoding of the numerical-spatial relations on the game board and improved their number line estimates, numeral identification, and count-on skill. Playing the same game using the standard count-from-1 procedure led to considerably less learning. Experiment 2 demonstrated that comparable improvement in number line estimation does not occur with practice encoding the numerals 1-100 outside of the context of a number board game. The general importance of aligning learning activities and physical materials with desired mental representations is discussed. PMID:24099546

  5. Encoding techniques for complex information structures in connectionist systems

    NASA Technical Reports Server (NTRS)

    Barnden, John; Srinivas, Kankanahalli

    1990-01-01

    Two general information encoding techniques called relative position encoding and pattern similarity association are presented. They are claimed to be a convenient basis for the connectionist implementation of complex, short term information processing of the sort needed in common sense reasoning, semantic/pragmatic interpretation of natural language utterances, and other types of high level cognitive processing. The relationships of the techniques to other connectionist information-structuring methods, and also to methods used in computers, are discussed in detail. The rich inter-relationships of these other connectionist and computer methods are also clarified. The particular, simple forms are discussed that the relative position encoding and pattern similarity association techniques take in the author's own connectionist system, called Conposit, in order to clarify some issues and to provide evidence that the techniques are indeed useful in practice.

  6. Encoding, training and retrieval in ferroelectric tunnel junctions

    NASA Astrophysics Data System (ADS)

    Xu, Hanni; Xia, Yidong; Xu, Bo; Yin, Jiang; Yuan, Guoliang; Liu, Zhiguo

    2016-05-01

    Ferroelectric tunnel junctions (FTJs) are quantum nanostructures that have great potential in the hardware basis for future neuromorphic applications. Among recently proposed possibilities, the artificial cognition has high hopes, where encoding, training, memory solidification and retrieval constitute a whole chain that is inseparable. However, it is yet envisioned but experimentally unconfirmed. The poor retention or short-term store of tunneling electroresistance, in particular the intermediate states, is still a key challenge in FTJs. Here we report the encoding, training and retrieval in BaTiO3 FTJs, emulating the key features of information processing in terms of cognitive neuroscience. This is implemented and exemplified through processing characters. Using training inputs that are validated by the evolution of both barrier profile and domain configuration, accurate recalling of encoded characters in the retrieval stage is demonstrated.

  7. Information quality measurement of medical encoding support based on usability.

    PubMed

    Puentes, John; Montagner, Julien; Lecornu, Laurent; Cauvin, Jean-Michel

    2013-12-01

    Medical encoding support systems for diagnoses and medical procedures are an emerging technology that begins to play a key role in billing, reimbursement, and health policies decisions. A significant problem to exploit these systems is how to measure the appropriateness of any automatically generated list of codes, in terms of fitness for use, i.e. their quality. Until now, only information retrieval performance measurements have been applied to estimate the accuracy of codes lists as quality indicator. Such measurements do not give the value of codes lists for practical medical encoding, and cannot be used to globally compare the quality of multiple codes lists. This paper defines and validates a new encoding information quality measure that addresses the problem of measuring medical codes lists quality. It is based on a usability study of how expert coders and physicians apply computer-assisted medical encoding. The proposed measure, named ADN, evaluates codes Accuracy, Dispersion and Noise, and is adapted to the variable length and content of generated codes lists, coping with limitations of previous measures. According to the ADN measure, the information quality of a codes list is fully represented by a single point, within a suitably constrained feature space. Using one scheme, our approach is reliable to measure and compare the information quality of hundreds of codes lists, showing their practical value for medical encoding. Its pertinence is demonstrated by simulation and application to real data corresponding to 502 inpatient stays in four clinic departments. Results are compared to the consensus of three expert coders who also coded this anonymized database of discharge summaries, and to five information retrieval measures. Information quality assessment applying the ADN measure showed the degree of encoding-support system variability from one clinic department to another, providing a global evaluation of quality measurement trends. PMID:23958646

  8. THE RELATIONSHIP BETWEEN ENCODING ABILITY AND AGGRESSIVE BEHAVIOR.

    PubMed

    Tsamis, Vasiliki J; Rebok, George W; Montague, David R

    2009-03-26

    While past research efforts have reported a relationship between encoding ability and aggressive behavior in children, the relationship between encoding ability and adult aggressiveness has not been examined. Encoding, an element of attention, refers to the ability to recall and reorder information stored in memory. Using selected cognitive tests and a self-report measure of aggressive behavior in a sample of community college students (n=55), this study investigated the relationship between encoding ability and aggressive behavior, (i.e., physical aggression, verbal aggression, anger, hostility, indirect aggression, and total aggression). Aggressive behavior was assessed by the Aggression Questionnaire of the Buss-Durkee Hostility Inventory, a widely-used measure of aggressive behavior. Encoding was measured using the WAIS-III Digit Span and Arithmetic subtests. Initial analyses showed no significant correlations between the cognitive measures and the five scales of aggressive behavior. However, there was a significant age-related association between scores on the cognitive measures and the indices of aggressive behavior. Two groups were created, those who reported attention problems and those who did not report attention problems. When the two groups were compared, participants who had a history of attention problems were verbally more aggressive than participants with a negative history of attention problems, and they were generally more aggressive. A composite score, called an "encoding score," was related to scores on the aggressive behavior scales. Moreover, the age-related relationship between these two variables suggests that the relationship is maturational and may disappear as an individual ages. Concerning the latter, participants in the current study were enrolled in junior college. Therefore, persons who had attention problems and were aggressive may not have pursued higher education. PMID:19953190

  9. Study of an incremental optical encoder using speckle

    NASA Astrophysics Data System (ADS)

    Perez Quintián, Fernando; Lutenberg, Ariel; Rebollo, María Aurora

    2006-09-01

    We present a study of the performance of an incremental optical encoder that works using speckle pattern illumination and a phase grating. The operational principle of the encoder lies in measuring the variations of a speckle pattern passing through the phase grating that can be displaced. This study is described theoretically by a model based on the scalar diffraction theory in the Fresnel zone. The intensity correlation of the modified speckle as a function of the grating displacement is obtained and compared with experimental results. Likewise, the mounting tolerances of the proposed system are analyzed.

  10. Engineering a fully GPU-accelerated H.264 encoder

    NASA Astrophysics Data System (ADS)

    Li, Bowei; Deng, Yangdong S.

    2013-07-01

    H.264/AVC is the most popular video coding standard and playing an essential role in today's Internet based content-delivery businesses. H.264's encoding process is highly computationally expensive due to the integration of complex video coding techniques. As a result, transcoding has become a bottleneck of content-hosting services. Recently, general purpose computing on graphics processing units (GPUs) is rapidly rising as a popular computing model to expedite time-consuming applications. In this paper, we propose a fully GPU-accelerated H.264 encoder. Experimental results show that a 100% speed-up ratio can be achieved.

  11. Modified 8×8 quantization table and Huffman encoding steganography

    NASA Astrophysics Data System (ADS)

    Guo, Yongning; Sun, Shuliang

    2014-10-01

    A new secure steganography, which is based on Huffman encoding and modified quantized discrete cosine transform (DCT) coefficients, is provided in this paper. Firstly, the cover image is segmented into 8×8 blocks and modified DCT transformation is applied on each block. Huffman encoding is applied to code the secret image before embedding. DCT coefficients are quantized by modified quantization table. Inverse DCT(IDCT) is conducted on each block. All the blocks are combined together and the steg image is finally achieved. The experiment shows that the proposed method is better than DCT and Mahender Singh's in PSNR and Capacity.

  12. The design and implementation of TPC encoder and decoder

    NASA Astrophysics Data System (ADS)

    Xiang, L. J.; Wang, Z. B.; Yuan, J. B.; Zheng, L. H.

    2016-02-01

    Based on the analysis and simulation of TPC codec principle and iteration decoding algorithm based on Chase 2, the design and implementation methods of TPC encoder and decoder are presented in this paper. In particular, circuit design and implementation flow of soft-input soft-output modified method in decoder algorithm and iteration decoding are analyzed. Aiming at (64,57,4) TPC, when the iteration times is 3 and the uncertain position number is 3, simulation and implementation results show that at least 6.8dB encoding gain can be obtained under the condition of BER=10-6

  13. Toward Better Genetically Encoded Sensors of Membrane Potential.

    PubMed

    Storace, Douglas; Sepehri Rad, Masoud; Kang, BokEum; Cohen, Lawrence B; Hughes, Thom; Baker, Bradley J

    2016-05-01

    Genetically encoded optical sensors of cell activity are powerful tools that can be targeted to specific cell types. This is especially important in neuroscience because individual brain regions can include a multitude of different cell types. Optical imaging allows for simultaneous recording from numerous neurons or brain regions. Optical signals of membrane potential are useful because membrane potential changes are a direct sign of both synaptic and action potentials. Here we describe recent improvements in the in vitro and in vivo signal size and kinetics of genetically encoded voltage indicators (GEVIs) and discuss their relationship to alternative sensors of neural activity. PMID:27130905

  14. Proteins encoded near the adenovirus late messenger RNA leader segments

    SciTech Connect

    Lewis, J.B.; Anderson, C.W.

    1983-01-01

    Small fragments of adenovirus 2 DNA cloned into the single-strand phage M13 were used to select adenoviral messenger RNAs transcribed from the R-strand between map positions 16 and 30. Cell-free translation of these mRNAs produced proteins of 13.5K, 13.6K, and 11.5K, respectively encoded between the first and second segments of the tripartite major late leader, within the ''i''-leader segment, and immediately preceding the third leader segment. Partial sequence analysis of the 13.6K protein is consistent with the hypothesis that it is encoded within the i-leader segment.

  15. Frequency- and Phase Encoded SSVEP Using Spatiotemporal Beamforming

    PubMed Central

    Van Hulle, Marc M.

    2016-01-01

    In brain-computer interfaces (BCIs) based on steady-state visual evoked potentials (SSVEPs) the number of selectable targets is rather limited when each target has its own stimulation frequency. One way to remedy this is by combining frequency- with phase encoding. We introduce a new multivariate spatiotemporal filter, based on Linearly Constrained Minimum Variance (LCMV) beamforming, for discriminating between frequency-phase encoded targets more accurately, even when using short signal lengths than with (extended) Canonical Correlation Analysis (CCA), which is traditionally posited for this stimulation paradigm. PMID:27486801

  16. The Reed-Solomon encoders: Conventional versus Berlekamp's architecture

    NASA Technical Reports Server (NTRS)

    Perlman, M.; Lee, J. J.

    1982-01-01

    Concatenated coding was adopted for interplanetary space missions. Concatenated coding was employed with a convolutional inner code and a Reed-Solomon (RS) outer code for spacecraft telemetry. Conventional RS encoders are compared with those that incorporate two architectural features which approximately halve the number of multiplications of a set of fixed arguments by any RS codeword symbol. The fixed arguments and the RS symbols are taken from a nonbinary finite field. Each set of multiplications is bit-serially performed and completed during one (bit-serial) symbol shift. All firmware employed by conventional RS encoders is eliminated.

  17. Error analysis for encoding a qubit in an oscillator

    SciTech Connect

    Glancy, S.; Knill, E.

    2006-01-15

    In Phys. Rev. A 64, 012310 (2001), Gottesman, Kitaev, and Preskill described a method to encode a qubit in the continuous Hilbert space of an oscillator's position and momentum variables. This encoding provides a natural error-correction scheme that can correct errors due to small shifts of the position or momentum wave functions (i.e., use of the displacement operator). We present bounds on the size of correctable shift errors when both qubit and ancilla states may contain errors. We then use these bounds to constrain the quality of input qubit and ancilla states.

  18. Effect of PCM encoding on wide band telemetry data

    NASA Astrophysics Data System (ADS)

    Cox, T. F.; Nichols, M. H.

    In order to comply with certain mission requirements, it is necessary to encode telemetry data into pulse code modulation (PCM). For this reason, test data have been obtained in order to determine the effects of quantization errors and bit errors with special reference to wide-band noise-like data signals involving data reduction by spectral analysis. The use of notch noises tests for determining coder/decoder (CODEC) performance has been evaluated. Test procedures and test results are given using CODEC configurations of 4 to 12 bits per word. Parameters for encoding constant bandwidth (CBW) and proportional bandwidth (PBW) subcarrier multiplexes for PCM transmission are included.

  19. Polypeptides having endoglucanase activity and polynucleotides encoding same

    DOEpatents

    Spodsberg, Nikolaj

    2016-02-23

    The present invention relates to isolated polypeptides having endoglucanase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  20. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Zhang, Yu; Duan, Junxin; Tang, Lan; Wu, Wenping

    2016-06-14

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  1. Polypeptides having xylanase activity and polynucleotides encoding same

    DOEpatents

    Lopez de Leon, Alfredo; Rey, Michael

    2016-05-31

    The present invention relates to isolated polypeptides having xylanase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  2. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Schnorr, Kirk; Kramer, Randall

    2016-04-05

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  3. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    DOEpatents

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2016-08-09

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  4. Hearing What the Body Feels: Auditory Encoding of Rhythmic Movement

    ERIC Educational Resources Information Center

    Phillips-Silver, Jessica; Trainor, Laurel J.

    2007-01-01

    Phillips-Silver and Trainor (Phillips-Silver, J., Trainor, L.J., (2005). Feeling the beat: movement influences infants' rhythm perception. "Science", 308, 1430) demonstrated an early cross-modal interaction between body movement and auditory encoding of musical rhythm in infants. Here we show that the way adults move their bodies to music…

  5. Imagining Another Context during Encoding Offsets Context-Dependent Forgetting

    ERIC Educational Resources Information Center

    Masicampo, E. J.; Sahakyan, Lili

    2014-01-01

    We tested whether imagining another context during encoding would offset context-dependent forgetting. All participants studied a list of words in Context A. Participants who remained in Context A during the test recalled more than participants who were tested in another context (Context B), demonstrating the standard context-dependent forgetting…

  6. Prefrontal contributions to relational encoding in amnestic mild cognitive impairment

    PubMed Central

    Foster, Chris M.; Addis, Donna Rose; Ford, Jaclyn H.; Kaufer, Daniel I.; Burke, James R.; Browndyke, Jeffrey N.; Welsh-Bohmer, Kathleen A.; Giovanello, Kelly S.

    2016-01-01

    Relational memory declines are well documented as an early marker for amnestic mild cognitive impairment (aMCI). Episodic memory formation relies on relational processing supported by two mnemonic mechanisms, generation and binding. Neuroimaging studies using functional magnetic resonance imaging (fMRI) have primarily focused on binding deficits which are thought to be mediated by medial temporal lobe dysfunction. In this study, prefrontal contributions to relational encoding were also investigated using fMRI by parametrically manipulating generation demands during the encoding of word triads. Participants diagnosed with aMCI and healthy control subjects encoded word triads consisting of a category word with either, zero, one, or two semantically related exemplars. As the need to generate increased (i.e., two- to one- to zero-link triads), both groups recruited a core set of regions associated with the encoding of word triads including the parahippocampal gyrus, superior temporal gyrus, and superior parietal lobule. Participants diagnosed with aMCI also parametrically recruited several frontal regions including the inferior frontal gyrus and middle frontal gyrus as the need to generate increased, whereas the control participants did not show this modulation. While there is some functional overlap in regions recruited by generation demands between the groups, the recruitment of frontal regions in the aMCI participants coincides with worse memory performance, likely representing a form of neural inefficiency associated with Alzheimer's disease. PMID:26937384

  7. Nucleic acid encoding TGF-. beta. and its uses

    SciTech Connect

    Derynck, R.M.A.; Goeddel, D.V.

    1989-12-12

    This patent describes a method. It comprises: constructing a vector which includes nucleic acid encoding biologically active TGF-{beta}, transforming a host eukaryotic cell with the vector, culturing the transformed cell and recovering mature TGF-{beta} from the culture medium.

  8. Breast ultrasound computed tomography using waveform inversion with source encoding

    NASA Astrophysics Data System (ADS)

    Wang, Kun; Matthews, Thomas; Anis, Fatima; Li, Cuiping; Duric, Neb; Anastasio, Mark A.

    2015-03-01

    Ultrasound computed tomography (USCT) holds great promise for improving the detection and management of breast cancer. Because they are based on the acoustic wave equation, waveform inversion-based reconstruction methods can produce images that possess improved spatial resolution properties over those produced by ray-based methods. However, waveform inversion methods are computationally demanding and have not been applied widely in USCT breast imaging. In this work, source encoding concepts are employed to develop an accelerated USCT reconstruction method that circumvents the large computational burden of conventional waveform inversion methods. This method, referred to as the waveform inversion with source encoding (WISE) method, encodes the measurement data using a random encoding vector and determines an estimate of the speed-of-sound distribution by solving a stochastic optimization problem by use of a stochastic gradient descent algorithm. Computer-simulation studies are conducted to demonstrate the use of the WISE method. Using a single graphics processing unit card, each iteration can be completed within 25 seconds for a 128 × 128 mm2 reconstruction region. The results suggest that the WISE method maintains the high spatial resolution of waveform inversion methods while significantly reducing the computational burden.

  9. It Is All Relative: How Young Children Encode Extent

    ERIC Educational Resources Information Center

    Duffy, Sean; Huttenlocher, Janellen; Levine, Susan

    2005-01-01

    Two experiments tested the ability of 4- and 8-year-old children to encode the extent of a target dowel and later discriminate between the target and a foil having a novel extent. By manipulating the heights of containers in which we presented the stimuli we tested whether children used the relation between the dowels and containers for encoding…

  10. Neural Activity during Encoding Predicts False Memories Created by Misinformation

    ERIC Educational Resources Information Center

    Okado, Yoko; Stark, Craig E. L.

    2005-01-01

    False memories are often demonstrated using the misinformation paradigm, in which a person's recollection of a witnessed event is altered after exposure to misinformation about the event. The neural basis of this phenomenon, however, remains unknown. The authors used fMRI to investigate encoding processes during the viewing of an event and…

  11. Polypeptides having endoglucanase activity and polynucleotides encoding same

    DOEpatents

    Lopez de Leon, Alfredo; Rey, Michael

    2010-06-22

    The present invention relates to isolated polypeptides having endoglucanase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  12. Polypeptides having endoglucanase activity and polynucleotides encoding same

    DOEpatents

    Harris, Paul; Lopez de Leon, Alfredo; Rey, Micheal; Ding, Hanshu; Vlasenko, Elena

    2012-02-21

    The present invention relates to isolated polypeptides having endoglucanase activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  13. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    DOEpatents

    Lopez de Leon, Alfredo; Ding, Hanshu; Brown, Kimberly

    2011-10-25

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods of producing and using the polypeptides.

  14. Robust EPI Nyquist ghost elimination via spatial and temporal encoding.

    PubMed

    Hoge, W Scott; Tan, Huan; Kraft, Robert A

    2010-12-01

    Nyquist ghosts are an inherent artifact in echo planar imaging acquisitions. An approach to robustly eliminate Nyquist ghosts is presented that integrates two previous Nyquist ghost correction techniques: temporal domain encoding (phase labeling for additional coordinate encoding: PLACE and spatial domain encoding (phased array ghost elimination: PAGE). Temporal encoding modulates the echo planar imaging acquisition trajectory from frame to frame, enabling one to interleave data to remove inconsistencies that occur between sampling on positive and negative gradient readouts. With PLACE, one can coherently combine the interleaved data to cancel residual Nyquist ghosts. If the level of ghosting varies significantly from image to image, however, the signal cancellation that occurs with PLACE can adversely affect SNR-sensitive applications such as perfusion imaging with arterial spin labeling. This work proposes integrating PLACE into a PAGE-based reconstruction process to yield significantly better Nyquist ghost correction that is more robust than PLACE or PAGE alone. The robustness of this method is demonstrated in the presence of magnetic field drift with an in-vivo arterial spin labeling perfusion experiment. PMID:20665898

  15. EGVII endoglucanase and nucleic acids encoding the same

    SciTech Connect

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

    2014-02-25

    The present invention provides a novel endoglucanase nucleic acid sequence, designated egl7, and the corresponding EGVII amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVII, recombinant EGVII proteins and methods for producing the same.

  16. EGVII endoglucanase and nucleic acids encoding the same

    SciTech Connect

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

    2015-04-14

    The present invention provides a novel endoglucanase nucleic acid sequence, designated egl7, and the corresponding EGVII amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVII, recombinant EGVII proteins and methods for producing the same.

  17. EGVII endoglucanase and nucleic acids encoding the same

    SciTech Connect

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

    2013-07-16

    The present invention provides a novel endoglucanase nucleic acid sequence, designated egl7, and the corresponding EGVII amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVII, recombinant EGVII proteins and methods for producing the same.

  18. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    SciTech Connect

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2014-09-30

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  19. Polypeptides having cellulolytic enhancing activity and nucleic acids encoding same

    SciTech Connect

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2012-10-16

    The present invention relates to isolated polypeptides having cellulolytic enhancing activity and isolated polynucleotides encoding the polypeptides. The invention also relates to nucleic acid constructs, vectors, and host cells comprising the polynucleotides as well as methods for producing and using the polypeptides.

  20. EGVII endoglucanase and nucleic acids encoding the same

    SciTech Connect

    Dunn-Coleman, Nigel; Goedegebuur, Frits; Ward, Michael; Yao, Jian

    2012-02-14

    The present invention provides a novel endoglucanase nucleic acid sequence, designated egl7, and the corresponding EGVII amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVII, recombinant EGVII proteins and methods for producing the same.