Science.gov

Sample records for encoding glycinin gly-1

  1. Differential transcription of multiple copies of a silk worm gene encoding tRNA(Gly1).

    PubMed

    Fournier, A; Taneja, R; Gopalkrishnan, R; Prudhomme, J C; Gopinathan, K P

    1993-12-08

    Ten different tRNA(Gly1) genes from the silk worm, Bombyx mori, have been cloned and characterized. These genes were transcribed in vitro in homologous nuclear extracts from the posterior silk gland (PSG) or nuclear extracts derived from the middle silk gland or ovarian tissues. Although the transcription levels were much higher in the PSG nuclear extracts, the transcriptional efficiency of the individual genes followed a similar pattern in all the extracts. Based on the levels of in vitro transcription, the ten tRNA(Gly1) genes could be divided into three groups, viz., those which were transcribed at very high levels (e.g., clone pR8), high to medium levels (e.g., pBmi1, pBmp1, pBmh1, pBmt1) and low to barely detectable levels (e.g., pBms1, pBmj1 and pBmk1). The coding sequences of all these tRNA genes being identical, the differential transcription suggested that the flanking sequences modulate their transcriptional efficiency. The presence of positive and negative regulatory elements in the 5' flanking regions of these genes was confirmed by transcription competition experiments. A positive element was present in the immediate upstream A+T-rich sequences in all the genes, but no consensus sequences correlating to the transcriptional status could be generated. The presence of negative elements on the other hand was indicated only in some of the genes and therefore may have a role in the differential transcription of these tRNA(Gly1) genes in vivo.

  2. Over-expression of Arabidopsis thaliana SFD1/GLY1, the gene encoding plastid localized glycerol-3-phosphate dehydrogenase, increases plastidic lipid content in transgenic rice plants

    PubMed Central

    Siddiqui, Adnan; Singh, Subaran; Banday, Zeeshan Zahoor; Nandi, Ashis Kumar

    2016-01-01

    Lipids are the major constituents of all membranous structures in plants. Plants possess two pathways for lipid biosynthesis: the prokaryotic pathway (i.e., plastidic pathway) and the eukaryotic pathway (i.e., endoplasmic-reticulum (ER) pathway). Whereas some plants synthesize galactolipids from diacylglycerol assembled in the plastid, others, including rice, derive their galactolipids from diacylglycerols assembled by the eukaryotic pathway. Arabidopsis thaliana glycerol-3-phosphate dehydrogenase (G3pDH), coded by SUPPRESSOR OF FATTY ACID DESATURASE 1 (SFD1; alias GLY1) gene, catalyzes the formation of glycerol 3-phosphate (G3p), the backbone of many membrane lipids. Here SFD1 was introduced to rice as a transgene. Arabidopsis SFD1 localizes in rice plastids and its over-expression increases plastidic membrane lipid content in transgenic rice plants without any major impact on ER lipids. The results suggest that over-expression of plastidic G3pDH enhances biosynthesis of plastid-localized lipids in rice. Lipid composition in the transgenic plants is consistent with increased phosphatidylglycerol synthesis in the plastid and increased galactolipid synthesis from diacylglycerol produced via the ER pathway. The transgenic plants show a higher photosynthetic assimilation rate, suggesting a possible application of this finding in crop improvement. PMID:26747130

  3. Over-expression of Arabidopsis thaliana SFD1/GLY1, the gene encoding plastid localized glycerol-3-phosphate dehydrogenase, increases plastidic lipid content in transgenic rice plants.

    PubMed

    Singh, Vijayata; Singh, Praveen Kumar; Siddiqui, Adnan; Singh, Subaran; Banday, Zeeshan Zahoor; Nandi, Ashis Kumar

    2016-03-01

    Lipids are the major constituents of all membranous structures in plants. Plants possess two pathways for lipid biosynthesis: the prokaryotic pathway (i.e., plastidic pathway) and the eukaryotic pathway (i.e., endoplasmic-reticulum (ER) pathway). Whereas some plants synthesize galactolipids from diacylglycerol assembled in the plastid, others, including rice, derive their galactolipids from diacylglycerols assembled by the eukaryotic pathway. Arabidopsis thaliana glycerol-3-phosphate dehydrogenase (G3pDH), coded by SUPPRESSOR OF FATTY ACID DESATURASE 1 (SFD1; alias GLY1) gene, catalyzes the formation of glycerol 3-phosphate (G3p), the backbone of many membrane lipids. Here SFD1 was introduced to rice as a transgene. Arabidopsis SFD1 localizes in rice plastids and its over-expression increases plastidic membrane lipid content in transgenic rice plants without any major impact on ER lipids. The results suggest that over-expression of plastidic G3pDH enhances biosynthesis of plastid-localized lipids in rice. Lipid composition in the transgenic plants is consistent with increased phosphatidylglycerol synthesis in the plastid and increased galactolipid synthesis from diacylglycerol produced via the ER pathway. The transgenic plants show a higher photosynthetic assimilation rate, suggesting a possible application of this finding in crop improvement.

  4. Identification of novel non-coding RNA-based negative feedback regulating the expression of the oncogenic transcription factor GLI1.

    PubMed

    Villegas, Victoria E; Rahman, Mohammed Ferdous-Ur; Fernandez-Barrena, Maite G; Diao, Yumei; Liapi, Eleni; Sonkoly, Enikö; Ståhle, Mona; Pivarcsi, Andor; Annaratone, Laura; Sapino, Anna; Ramírez Clavijo, Sandra; Bürglin, Thomas R; Shimokawa, Takashi; Ramachandran, Saraswathi; Kapranov, Philipp; Fernandez-Zapico, Martin E; Zaphiropoulos, Peter G

    2014-07-01

    Non-coding RNAs are a complex class of nucleic acids, with growing evidence supporting regulatory roles in gene expression. Here we identify a non-coding RNA located head-to-head with the gene encoding the Glioma-associated oncogene 1 (GLI1), a transcriptional effector of multiple cancer-associated signaling pathways. The expression of this three-exon GLI1 antisense (GLI1AS) RNA in cancer cells was concordant with GLI1 levels. siRNAs knockdown of GLI1AS up-regulated GLI1 and increased cellular proliferation and tumor growth in a xenograft model system. Conversely, GLI1AS overexpression decreased the levels of GLI1, its target genes PTCH1 and PTCH2, and cellular proliferation. Additionally, we demonstrate that GLI1 knockdown reduced GLI1AS, while GLI1 overexpression increased GLI1AS, supporting the role of GLI1AS as a target gene of the GLI1 transcription factor. Activation of TGFβ and Hedgehog signaling, two known regulators of GLI1 expression, conferred a concordant up-regulation of GLI1 and GLI1AS in cancer cells. Finally, analysis of the mechanism underlying the interplay between GLI1 and GLI1AS indicates that the non-coding RNA elicits a local alteration of chromatin structure by increasing the silencing mark H3K27me3 and decreasing the recruitment of RNA polymerase II to this locus. Taken together, the data demonstrate the existence of a novel non-coding RNA-based negative feedback loop controlling GLI1 levels, thus expanding the repertoire of mechanisms regulating the expression of this oncogenic transcription factor.

  5. Fem1b promotes ubiquitylation and suppresses transcriptional activity of Gli1.

    PubMed

    Gilder, Andrew S; Chen, Yong-Bin; Jackson, Ramon J; Jiang, Jin; Maher, Joseph F

    2013-10-25

    The mammalian Fem1b gene encodes a homolog of FEM-1, a protein in the sex-determination pathway of the nematode Caenorhabditis elegans. Fem1b and FEM-1 proteins each contain a VHL-box motif that mediates their interaction with certain E3 ubiquitin ligase complexes. In C. elegans, FEM-1 negatively regulates the transcription factor TRA-1, and functions as an E3 ubiquitin ligase substrate recognition subunit to target TRA-1 for ubiquitylation. TRA-1 is homologous to the mammalian Gli1 protein, a transcription factor that mediates Hedgehog signaling as well as having Hedgehog-independent functions. Whether the interaction between nematode FEM-1 and TRA-1 proteins is conserved, between corresponding mammalian homologs, has not been reported. Herein, we show that Fem1b interacts with Gli1 within cells, and directly binds Gli1. Fem1b also promotes ubiquitylation of Gli1, suppresses transcriptional activation by Gli1, and attenuates an oncogenic Gli1 autoregulatory loop in cancer cells, all dependent on the VHL-box of Fem1b. These findings have implications for understanding the cellular functions of Fem1b, and the regulation of Gli1 oncoprotein activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  6. Epitopes from two soybean glycinin subunits antigenic in pigs

    USDA-ARS?s Scientific Manuscript database

    Background: Glycinin is a seed storage protein in soybean (Glycine max) that is allergenic in pigs. Glycinin is a hexamer composed of subunits consisting of a basic and acidic portion joined by disulfide bridges. There are 5 glycinin subunits designated Gy1-Gy5. Results: Twenty seven out of 30 pi...

  7. Glycinin-gum arabic complex formation: Turbidity measurement and charge neutralization analysis.

    PubMed

    Dong, Die; Hua, Yufei

    2016-11-01

    The interaction between glycinin and anionic polysaccharides has gained considerable attention recently because of its scientific impact on the stability of acid soymilk systems. In this study, the formation of glycinin/gum arabic complexes driven by electrostatic interactions was investigated. Turbidity titrations at different glycinin/gum arabic ratios were conducted and critical pH values (pHφ1) where insoluble complexes began forming were determined firstly. The corresponding pHφ1 values at glycinin/gum arabic ratios of 1:4, 1:2, 1:1, 2:1, 4:1 and 8:1 were 2.85, 3.25, 3.70, 4.40, 4.85 and 5.35, respectively. Afterwards, electromobilities for glycinin and gum arabic at the pH values between 4.1 and 2.6 were measured, and charge densities (ZN) for glycinin and gum arabic were calculated based on the soft particle analysis theory. Further analysis indicated that the product of glycinin/gum arabic ratio (ρ) and ZN ratio of glycinin/gum arabic was approximate 1 at any pHφ1 values. It was revealed that charge neutralization was achieved when glycinin/gum arabic insoluble complexes began forming. NaCl displayed multiple effects on glycinin/gum arabic complex formation according to turbidity and compositional analysis. The present study could provide basic guidance in acid soymilk designing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Mice have a transcribed L-threonine aldolase/GLY1 gene, but the human GLY1 gene is a non-processed pseudogene

    PubMed Central

    Edgar, Alasdair J

    2005-01-01

    Background There are three pathways of L-threonine catabolism. The enzyme L-threonine aldolase (TA) has been shown to catalyse the conversion of L-threonine to yield glycine and acetaldehyde in bacteria, fungi and plants. Low levels of TA enzymatic activity have been found in vertebrates. It has been suggested that any detectable activity is due to serine hydroxymethyltransferase and that mammals lack a genuine threonine aldolase. Results The 7-exon murine L-threonine aldolase gene (GLY1) is located on chromosome 11, spanning 5.6 kb. The cDNA encodes a 400-residue protein. The protein has 81% similarity with the bacterium Thermotoga maritima TA. Almost all known functional residues are conserved between the two proteins including Lys242 that forms a Schiff-base with the cofactor, pyridoxal-5'-phosphate. The human TA gene is located at 17q25. It contains two single nucleotide deletions, in exons 4 and 7, which cause frame-shifts and a premature in-frame stop codon towards the carboxy-terminal. Expression of human TA mRNA was undetectable by RT-PCR. In mice, TA mRNA was found at low levels in a range of adult tissues, being highest in prostate, heart and liver. In contrast, serine/threonine dehydratase, another enzyme that catabolises L-threonine, is expressed very highly only in the liver. Serine dehydratase-like 1, also was most abundant in the liver. In whole mouse embryos TA mRNA expression was low prior to E-15 increasing more than four-fold by E-17. Conclusion Mice, the western-clawed frog and the zebrafish have transcribed threonine aldolase/GLY1 genes, but the human homolog is a non-transcribed pseudogene. Serine dehydratase-like 1 is a putative L-threonine catabolising enzyme. PMID:15757516

  9. Association between polymorphism of GLI1 gene SNP rs2228226 and chronic lymphocytic leukemia in Chinese population.

    PubMed

    Li, Yuan-Yuan; Tian, Tian; Zhang, Run; Wang, Li; Xu, Ji; Fan, Lei; Li, Jian-Yong; Xu, Wei

    2014-12-01

    A non-synonymous single-nucleotide polymorphism (SNP) (rs2228226C>G), in exon 12 of glioma-associated oncogene homolog 1 (GLI1) (Q1100E), encodes a change from glutamine to glutamic acid (Q1100E). The variant GLI1 protein exhibited reduced transactivation function in vivo, decreasing the ability of activating hedgehog signal, which has been proposed as an unfavorable prognostic marker in chronic lymphocytic leukemia (CLL). The GLI1 Q1100E (NCBI SNP ID: rs2228226) genotypes in 155 CLL patients were detected by direct sequencing. The difference between frequencies of GLI1 Q1100E genotype among CLL patients and controls was statistically significant (p < 0.001). Logistic regression analysis revealed that in comparison with G/G, GLI1 SNP1100 C/C genotype was associated with a significantly increased risk of CLL (OR 3.787, 95% CI 1.814-7.907, p < 0.001). Compared with the SNP1100 C/G genotype, C/C genotype significantly increased the risk of CLL (OR 3.860, 95% CI 1.827-8.153, p < 0.001). In addition, combining C/G with G/G, C/C genotype also significantly increased the risk of CLL (OR 3.820, 95% CI 1.885-7.742, p < 0.001). The comparison between frequencies of C and G allele of GLI1 was also statistically significant (p = 0.004). In the entire cohort, SNP1100 genotypes were found in association with Binet stage (p = 0.045) and trisomy 12 (p = 0.036). By comparing C/C with G allele (C/G+G/G) genotype, there was a significant correlation with trisomy 12 (p = 0.013). This study demonstrated that GLI1 Q1100E polymorphism was closely associated with CLL. C/C genotype contributes to the risk of developing CLL and correlates with trisomy 12. Patients with trisomy 12 are susceptible group of CLL.

  10. Negative prognostic effect of low nuclear GLI1 expression in glioblastomas.

    PubMed

    Kim, Yuil; Do, In-Gu; Hong, Mineui; Suh, Yeon-Lim

    2017-05-01

    The hedgehog signaling plays supportive roles in various aspects of tumorigenesis. Increased expression of the key component, GLI1, has been shown to correlate with poor prognosis in many types of cancers. We aimed to investigate the effect of GLI1 expression in glioblastoma focusing on the nuclear localization. Immunohistochemistry for GLI1, GLI2, PTCH1, SMO, and SHH were done in 140 glioblastoma tissues, and the staining was graded. For GLI1, nuclear and cytoplasmic expression was separately assessed. No significant correlation was found between clinicopathologic parameters and expression grades of the five proteins. Low nuclear GLI1 expression was associated with a worse progression-free survival while overall survival was not significantly affected. In contrast, cytoplasmic GLI1 expression did not have a prognostic effect. PTCH1 expression correlated with nuclear GLI1 expression without exerting a significant prognostic effect. Analysis of the TCGA-glioblastoma dataset revealed that low GLI1 mRNA level also correlated with a poor prognosis for both overall and progression-free survival. The adverse effect of low nuclear GLI1 expression in glioblastomas is in contrast with the negative prognostic effect of high GLI1 expression reported in non-cranial malignancies. The relative impact of hedgehog signaling among other oncogenic pathways in the brain may be responsible for the difference. The different implication of GLI1 expression in glioblastomas needs to be considered in studies of hedgehog signaling-targeted therapy.

  11. Inhibition of GLI1 Expression by Targeting the CRD-BP-GLI1 mRNA Interaction Using a Specific Oligonucleotide.

    PubMed

    Mehmood, Kashif; Akhtar, Daud; Mackedenski, Sebastian; Wang, Chuyi; Lee, Chow H

    2016-06-01

    The stabilization of glioma-associated oncogene 1 (GLI1) mRNA by coding region determinant binding protein (CRD-BP) through the Wnt/β-catenin signaling pathway is implicated in the proliferation of colorectal cancer and basal cell carcinoma. Here, we set out to characterize the physical interaction between CRD-BP and GLI1 mRNA so as to find inhibitors for such interaction. Studies using CRD-BP variants with a point mutation in the GXXG motif at each KH domain showed that KH1 and KH2 domain are critical for the binding of GLI1 RNA. The smallest region of GLI1 RNA binding to CRD-BP was mapped to nucleotides (nts) 320-380. A 37-nt S1 RNA sense oligonucleotide, containing two distinct stem-loops present in nts 320-380 of GLI1 RNA, was found to be effective in blocking CRD-BP-GLI1 RNA interaction. Studies using various competitor RNAs with modifications to S1 RNA oligonucleotide further displayed that both the sequences and the structure of the two stem-loops are important for CRD-BP-GLI1 RNA binding. The role of the two-stem-loop motif in influencing CRD-BP-RNA interaction was further investigated in cells. The 2'-O-methyl derivative of the S1 RNA oligonucleotide significantly decreased GLI1, c-myc, and CD44 mRNA levels, in a panel of colon and breast cancer cells. The results from this study demonstrate the potential importance of the two-stem-loop motif as a target region for the inhibition of the CRD-BP-GLI1 RNA interaction and Hedgehog signaling pathway. Such results pave the way for the development of novel inhibitors that act by destabilizing the CRD-BP-GLI1 mRNA interaction.

  12. Wwox suppresses breast cancer cell growth through modulation of the hedgehog–GLI1 signaling pathway

    SciTech Connect

    Xiong, Anwen; Wei, Li; Ying, Mingzhen; Wu, Hongmei; Hua, Jin; Wang, Yajie

    2014-01-24

    Highlights: • We investigated Gli1 as a novel partner of Wwox. • We observed a physical association between Wwox and the Gli1. • Wwox–Gli1 interaction affects Gli1 intracellular localization. • Gli1 Blocks Wwox-induced growth inhibition and apoptosis in T47D cells. - Abstract: Wwox is a tumor suppressor that is frequently deleted or altered in several cancer types, including breast cancer. Previous studies have shown that ectopic expression of Wwox inhibits proliferation of breast cancer cells. However, the underlying mechanism remains unclear. To better understand the molecular mechanisms of Wwox function, we investigated novel partners of this protein. Utilizing the coimmunoprecipitation assay, we observed a physical association between Wwox and the Gli1 zinc-finger transcription factor involved in the hedgehog pathway. Our results further demonstrated that Wwox expression triggered redistribution of nuclear Gli1 to the cytoplasm. Additionally, ectopic expression of Wwox reduced Gli1 expression in vitro. Furthermore, Gli1 Blocks Wwox-induced breast cancer cell growth inhibition. These findings suggest a functional crosstalk between Wwox and hedgehog–GLI1 signaling pathway in tumorigenesis.

  13. Role of GLI1 and NDRG1 in Increased Resistance to Apoptosis Induction.

    PubMed

    Wu, Feng; Rom, William N; Koshiji, Minori; Mo, Yiqun; Hosomi, Yukio; Tchou-Wong, Kam-Meng

    2015-01-01

    We examined the effects of GLI1 expression in PW mouse embryo fibroblasts and H441 lung carcinoma cells. Ectopic expression of GLI1 in PW cells induced anchorage-independent growth and increased resistance to staurosporine-induced apoptosis, and overexpression of GLI1 in H441 cells caused resistance to apoptosis induced by staurosporine and etoposide. GLI1 expression in both H441 and PW cells was associated with increased expression of NDRG1, a gene known to be downregulated by the MYC family of proteins, indicating that upregulation of NDRG1 by GLI1 is not cell-type specific. Consistent with suppression of NDRG1 by c-MYC and N-MYC, increased NDRG1 expression correlated with decreased expression of c-MYC and N-MYC in GLI1-expressing H441 and GLI1-expressing PW cells, respectively. Downregulation of GLI1 expression in A549 cells by siRNA transfection increased sensitivity to etoposide-induced apoptosis, and downregulation of NDRG1 expression in H441 cells by siRNA transfection increased sensitivity to etoposide-induced apoptosis. Of clinical significance, inhibition of GLI1 and NDRG1 expression may increase sensitivity of cancer cells to chemotherapeutic drugs. Strategies that aim to inhibit GLI1 function and NDRG1 expression may be useful for targeted therapy of cancers induced by the SHH-GLI signaling pathway.

  14. Nanoquinacrine induced apoptosis in cervical cancer stem cells through the inhibition of hedgehog-GLI1 cascade: Role of GLI-1.

    PubMed

    Nayak, Anmada; Satapathy, Shakti Ranjan; Das, Dipon; Siddharth, Sumit; Tripathi, Neha; Bharatam, Prasad V; Kundu, ChanakyaNath

    2016-02-05

    To improve the pharmacokinetics and to study the anti-cervical cancer and anti-stem cells (CSCs) mechanism of Quinacrine (QC), a spherical nano particle of QC (i.e. NQC) was prepared and characterized. QC and NQC showed higher cytotoxicity in multiple cancer cells than the normal epithelial cells. NQC exhibited more toxicity in cervical cancer cells and its CSCs than QC. A dose-dependent decreased expression of Hedgehog-GLI (HH-GLI) components were noted in NQC treated HeLa cells and its CSCs. NQC increased the expressions of negatively regulated HH-GLI components (GSK3β, PTEN) and caused apoptosis in CSCs. Reduction of GLI1 at mRNA and promoter level were noted after NQC exposure. The expressions of HH-GLI components, GLI1 promoter activity and apoptosis were unaltered in NQC treated GLI1-knockdown cells. In silico, cell based and in vitro reconstitution assay revealed that NQC inhibit HH-GLI cascade by binding to the consensus sequence (5'GACCACCCA3') of GLI1 in GLI-DNA complex through destabilizing DNA-GLI1 complex. NQC reduced the tumors size and proliferation marker Ki-67 in an in vivo xenograft mice model. Thus, NQC induced apoptosis in cancers through inhibition of HH-GLI cascade by GLI1. Detail interaction of QC-DNA-GLI complex can pave path for anticancer drug design.

  15. Nanoquinacrine induced apoptosis in cervical cancer stem cells through the inhibition of hedgehog-GLI1 cascade: Role of GLI-1

    PubMed Central

    Nayak, Anmada; Satapathy, Shakti Ranjan; Das, Dipon; Siddharth, Sumit; Tripathi, Neha; Bharatam, Prasad V.; Kundu, ChanakyaNath

    2016-01-01

    To improve the pharmacokinetics and to study the anti-cervical cancer and anti-stem cells (CSCs) mechanism of Quinacrine (QC), a spherical nano particle of QC (i.e. NQC) was prepared and characterized. QC and NQC showed higher cytotoxicity in multiple cancer cells than the normal epithelial cells. NQC exhibited more toxicity in cervical cancer cells and its CSCs than QC. A dose-dependent decreased expression of Hedgehog-GLI (HH-GLI) components were noted in NQC treated HeLa cells and its CSCs. NQC increased the expressions of negatively regulated HH-GLI components (GSK3β, PTEN) and caused apoptosis in CSCs. Reduction of GLI1 at mRNA and promoter level were noted after NQC exposure. The expressions of HH-GLI components, GLI1 promoter activity and apoptosis were unaltered in NQC treated GLI1-knockdown cells. In silico, cell based and in vitro reconstitution assay revealed that NQC inhibit HH-GLI cascade by binding to the consensus sequence (5′GACCACCCA3′) of GLI1 in GLI-DNA complex through destabilizing DNA-GLI1 complex. NQC reduced the tumors size and proliferation marker Ki-67 in an in vivo xenograft mice model. Thus, NQC induced apoptosis in cancers through inhibition of HH-GLI cascade by GLI1. Detail interaction of QC-DNA-GLI complex can pave path for anticancer drug design. PMID:26846872

  16. Glioma-Associated Oncogene Homolog1 (Gli1)-Aquaporin1 pathway promotes glioma cell metastasis

    PubMed Central

    Liao, Zheng-qiang; Ye, Ming; Yu, Pei-gen; Xiao, Chun; Lin, Feng-yun

    2016-01-01

    Glioma-Associated Oncogene Homolog1 (Gli1) is known to be activated in malignant glioma; however, its downstream pathway has not been fully explained. The aim of this study was to explore the role of Gli1-Aquaporin1 (AQP1) signal pathway in glioma cell survival. Our data suggests that both Gli1 and AQP1 are upregulated in glioma tissues, as in comparison to in normal tissues. These up-regulation phenomena were also observed in glioma U251 and U87 cells. It was demonstrated that Gli1 positively regulated the AQP1 expression. By luciferase reporter gene and ChIP assay, we observed that this modulation process was realized by combination of Gli1 with AQP1 promotor. In addition, knock down of Gli1 by siRNA interference reduced the viability of glioma cells as well as suppressed cell metastasis. Also, the inhibitory effects of cell survival by silenced Gli1 were abrogated by AQP1 overexpression. In summary, glioma cell survival is a regulatory process and can be mediated by Gli1-AQP1 pathway. [BMB Reports 2016; 49(7): 394-399] PMID:27157540

  17. Wwox suppresses breast cancer cell growth through modulation of the hedgehog-GLI1 signaling pathway.

    PubMed

    Xiong, Anwen; Wei, Li; Ying, Mingzhen; Wu, Hongmei; Hua, Jin; Wang, Yajie

    2014-01-24

    Wwox is a tumor suppressor that is frequently deleted or altered in several cancer types, including breast cancer. Previous studies have shown that ectopic expression of Wwox inhibits proliferation of breast cancer cells. However, the underlying mechanism remains unclear. To better understand the molecular mechanisms of Wwox function, we investigated novel partners of this protein. Utilizing the coimmunoprecipitation assay, we observed a physical association between Wwox and the Gli1 zinc-finger transcription factor involved in the hedgehog pathway. Our results further demonstrated that Wwox expression triggered redistribution of nuclear Gli1 to the cytoplasm. Additionally, ectopic expression of Wwox reduced Gli1 expression in vitro. Furthermore, Gli1 Blocks Wwox-induced breast cancer cell growth inhibition. These findings suggest a functional crosstalk between Wwox and hedgehog-GLI1 signaling pathway in tumorigenesis.

  18. Back to the drawing board: Re-thinking the role of GLI1 in pancreatic carcinogenesis

    PubMed Central

    Hogenson, Tara L.; Lauth, Matthias; Pasca diMagliano, Marina; Fernandez-Zapico, Martin E.

    2016-01-01

    Aberrant activation of the transcription factor GLI1, a central effector of the Hedgehog (HH) pathway, is associated with several malignancies, including pancreatic ductal adenocarcinoma (PDAC), one of most deadly human cancers. GLI1 has been described as an oncogene in PDAC, making it a promising target for drug therapy. Surprisingly, clinical trials targeting HH/GLI1 axis in advanced PDAC were unsuccessful, leaving investigators questioning the mechanism behind these failures. Recent evidence suggests the loss of GLI1 in the later stages of PDAC may actually accelerate disease. This indicates GLI1 may play a dual role in PDAC, acting as an oncogene in the early stages of disease and a tumor-suppressor in the late stages. PMID:25352983

  19. Gli1/DNA interaction is a druggable target for Hedgehog-dependent tumors

    PubMed Central

    Infante, Paola; Mori, Mattia; Alfonsi, Romina; Ghirga, Francesca; Aiello, Federica; Toscano, Sara; Ingallina, Cinzia; Siler, Mariangela; Cucchi, Danilo; Po, Agnese; Miele, Evelina; D'Amico, Davide; Canettieri, Gianluca; De Smaele, Enrico; Ferretti, Elisabetta; Screpanti, Isabella; Uccello Barretta, Gloria; Botta, Maurizio; Botta, Bruno; Gulino, Alberto; Di Marcotullio, Lucia

    2015-01-01

    Hedgehog signaling is essential for tissue development and stemness, and its deregulation has been observed in many tumors. Aberrant activation of Hedgehog signaling is the result of genetic mutations of pathway components or other Smo-dependent or independent mechanisms, all triggering the downstream effector Gli1. For this reason, understanding the poorly elucidated mechanism of Gli1-mediated transcription allows to identify novel molecules blocking the pathway at a downstream level, representing a critical goal in tumor biology. Here, we clarify the structural requirements of the pathway effector Gli1 for binding to DNA and identify Glabrescione B as the first small molecule binding to Gli1 zinc finger and impairing Gli1 activity by interfering with its interaction with DNA. Remarkably, as a consequence of its robust inhibitory effect on Gli1 activity, Glabrescione B inhibited the growth of Hedgehog-dependent tumor cells in vitro and in vivo as well as the self-renewal ability and clonogenicity of tumor-derived stem cells. The identification of the structural requirements of Gli1/DNA interaction highlights their relevance for pharmacologic interference of Gli signaling. PMID:25476449

  20. HAN11 binds mDia1 and controls GLI1 transcriptional activity.

    PubMed

    Morita, Kazumasa; Lo Celso, Cristina; Spencer-Dene, Bradley; Zouboulis, Christos C; Watt, Fiona M

    2006-10-01

    The Hedgehog pathway is important in normal and diseased skin. One of the key transcription factors in the pathway is GLI1. GLI1-dependent transcription is positively regulated by DYRK1A, which is reported to bind HAN11. HAN11 is the human homologue of AN11, which controls flavonoid synthesis in plants. We wanted to identify other binding partners of HAN11 and investigate whether HAN11 regulates GLI1-dependent transcription. We used TAP-tag purification and GST pull down to identify protein-protein interactions and performed luciferase assays of transcriptional activity. We used immunofluorescence microscopy to examine the subcellular distribution of HAN11, mDia1 and GLI1. We performed in situ hybridisation to compare expression of HAN11 with GLI1 and patched in mouse embryos. We identified the cytoskeletal regulator mDia1 as a binding partner of HAN11. We showed that HAN11 binds the FH2 actin binding domain of mDia1 and confirmed that HAN11 also interacts with DYRK1A. Overexpression of mDia1 or active RhoA caused translocation of HAN11 from nucleus to cytoplasm. HAN11 and mDia1 repressed DYRK1A-dependent GLI1 transcriptional activity. HAN11 overexpression decreased SZ95 sebocyte proliferation and increased cytoplasmic GLI1. AN11 was highly expressed in E10.5 mouse embryo limb buds, in an overlapping pattern with Ptc and GLI1. These results suggest that AN11 may be a physiological regulator of GLI1 transcriptional activity.

  1. Combinatorial Chemoprevention Reveals a Novel Smoothened Independent Role of GLI1 in Esophageal Carcinogenesis

    PubMed Central

    Rizvi, Sumera; DeMars, Cathrine J.; Comba, Andrea; Gainullin, Vladimir; Rizvi, Zaheer; Almada, Luciana L.; Wang, Kenneth; Lomberk, Gwen; Fernández-Zapico, Martin E.; Buttar, Navtej S.

    2010-01-01

    Reflux-induced injury promotes esophageal adenocarcinoma, one of the most rapidly increasing, highly lethal cancers in Western countries. Here we investigate the efficacy of a combinatorial chemoprevention strategy for esophageal adenocarcinoma and characterize the underlying molecular mechanisms. Specifically, our approach involves the use of Ursodeoxycholic acid (Urso) due to its ability to decrease injury-inducing bile salts in combination with Aspirin to mitigate the consequences of injury. We find that Urso-Aspirin combination reduces the risk of adenocarcinoma in-vivo in animals with reflux, decreases the proliferation of esophageal adenocarcinoma cells and down-regulates a key cell cycle regulator, CDK2. Mechanistically, using cell growth, luciferase-reporter, expression and ChIP assays, we identify GLI1, a Hedgehog-regulated transcription factor, as a novel target of Urso-Aspirin combination. We demonstrate that GLI1 is upregulated during esophageal carcinogenesis and GLI1 can bind to the CDK2 promoter and activate its expression. While the Urso-Aspirin combination downregulates GLI1, the GLI1 overexpression not only abrogates the effect of this combination on proliferation but it also restores CDK-2 expression. These findings support that the chemopreventive effect of the Urso-Aspirin combination occurs, at least in part, via a novel GLI1-CDK2-dependent mechanism. To further understand the regulation of CDK2 by GLI1, both pharmacologic and RNAi-mediated approaches demonstrate that GLI1 is a transcriptional activator of CDK2 and this regulation occurs independent of Smoothened, the central transducer of the Hedgehog canonical pathway. Collectively, these results identify a novel GLI1-to-CDK2 pathway in esophageal carcinogenesis, which is a bona fide target for effective combinatorial chemoprevention with Urso and Aspirin. PMID:20647328

  2. Impeding Bacillus spore germination in vitro and in milk by soy glycinin during long cold storage.

    PubMed

    Mahgoub, Samir A; Osman, Ali O; Sitohy, Mahmoud Z

    2016-01-01

    This paper presents a study of the magnitude and mechanism of impeding the emergent spore germination of Bacillus subtilis (non-hemolytic strain) and Bacillus licheniformis (hemolytic strain) under the action of soybean glycinin and its basic subunit (BS). Incubating B. licheniformis spores with 100 μg/ml of glycinin or BS at 35°C for 24 h totally prevented the hemolytic activity associated with the emergent vegetative cells on blood agar during 3-5 days of incubation at 35°C in contrast to the control. Glycinin and BS (100 μg/ml) also resulted in the leakage of 70 and 73% of the initially germinating spore contents of A260 absorbing materials of the two bacterial species after 2 h of incubation at 35°C, respectively. Increasing the concentration of glycinin and BS up to 400 μg/ml increased the germinating spore leakage to 83 and 88%, respectively. Spore germination in Muller Hinton Broth containing glycinin and BS (100 μg/ml) was practically nil after 4 days of incubation at 35°C. Supplementing milk preheated at 80°C/5 min with both glycinin and BS kept the final vegetative cell counts down to about 30 and 20% of the corresponding control, respectively, after 50 days of storage at 4°C. Both light, and transmission electron, microscopy images revealed significant morphological and structural distorting changes in BS-treated spores of B. licheniformis.

  3. Antibacterial Actions of Glycinin Basic Peptide against Escherichia coli.

    PubMed

    Zhao, Guo-Ping; Li, Ying-Qiu; Sun, Gui-Jin; Mo, Hai-Zhen

    2017-06-28

    Glycinin basic peptide (GBP) is an antibacterial ingredient that occurs naturally in the basic parts of soybean glycinin. The antibacterial actions of GBP against Escherichia coli ATCC 8739 were investigated in this study. The minimum inhibitory concentration of GBP against E. coli was 200 μg/mL. The exposure of E. coli cells to GBP induced significant cell damage and inactivated intracellular esterases (stressed and dead cells, 70.9% ± 0.04 for 200 μg/mL of GBP and 91.9% ± 0.06 for 400 μg/mL of GBP), as determined through dual staining in flow cytometry. GBP resulted in the exposure of phosphatidylserine in E. coli cells. The analyses of flow cytometry-manifested GBP treatment led to the shrinkage of the cell surface and the complication of cell granularity. The observations in transmission electron microscopy demonstrated that 400 μg/mL of GBP severely disrupted the membrane integrity, resulting in ruptures or pores in the membrane, outflows of intracellular contents, or aggregation of the cytoplasm. Release of alkaline phosphatase, lipopolysaccharide, and reducing sugar further verified that the membrane damage was due to GBP. In addition, GBP treatment changed the helicity and base staking of DNA, as determined by circular dichroism spectroscopy. These results showed that GBP had strong antibacterial activity against E. coli via membrane damage and DNA perturbation. Additionally, GBP exhibited no cytotoxicity on the viability of human embryonic kidney cells. Thus, GBP may be a promising candidate as a natural antibacterial agent.

  4. GLI1 Inactivation is associated with Developmental Phenotypes Overlapping with Ellis-Van Creveld Syndrome.

    PubMed

    Palencia-Campos, Adrian; Ullah, Asmat; Nevado, Julian; Yildirim, Ruken; Unal, Edip; Ciorraga, Maria; Barruz, Pilar; Chico, Lucia; Piceci-Sparascio, Francesca; Guida, Valentina; De Luca, Alessandro; Kayserili, Hülya; Ullah, Irfan; Burmeister, Margit; Lapunzina, Pablo; Ahmad, Wasim; Morales, Aixa; Ruiz-Perez, Victor L

    2017-08-26

    GLI1, GLI2 and GLI3 form a family of transcription factors which regulate development by mediating the action of Hedgehog (Hh) morphogens. Accordingly, inactivating variants in GLI2 and GLI3 are found in several developmental disorders. In contrast, loss-of-function mutations in GLI1 have remained elusive, maintaining enigmatic the role of this gene in the human embryo. We describe eight patients from three independent families having biallelic truncating variants in GLI1 and developmental defects overlapping with Ellis-van Creveld syndrome (EvC), a disease caused by diminished Hh signalling. Two families had mutations in the last exon of the gene and a third family was identified with an N-terminal stop gain variant predicted to be degraded by the NMD-pathway. Analysis of fibroblasts from one of the patients with homozygous C-terminal truncation of GLI1 demonstrated that the corresponding mutant GLI1 protein is fabricated by patient cells and becomes upregulated in response to Hh signalling. However, the transcriptional activity of the truncated GLI1 factor was found to be severely impaired by cell culture and in vivo assays, indicating that the balance between GLI repressors and activators is altered in affected subjects. Consistent with this, reduced expression of the GLI target PTCH1 was observed in patient fibroblasts after chemical induction of the Hh pathway. We conclude that GLI1 inactivation is associated with a phenotypic spectrum extending from isolated postaxial polydactyly to an EvC-like condition. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  5. Aberrant GLI1 Activation in DNA Damage Response, Carcinogenesis and Chemoresistance

    PubMed Central

    Palle, Komaraiah; Mani, Chinnadurai; Tripathi, Kaushlendra; Athar, Mohammad

    2015-01-01

    The canonical hedgehog (HH) pathway is a multicomponent signaling cascade (HH, protein patched homolog 1 (PTCH1), smoothened (SMO)) that plays a pivotal role during embryonic development through activation of downstream effector molecules, namely glioma-associated oncogene homolog 1 (GLI1), GLI2 and GLI3. Activation of GLIs must be tightly regulated as they modulate target genes which control tissue patterning, stem cell maintenance, and differentiation during development. However, dysregulation or mutations in HH signaling leads to genomic instability (GI) and various cancers, for example, germline mutation in PTCH1 lead to Gorlin syndrome, a condition where patients develop numerous basal cell carcinomas and rarely rhabdomyosarcoma (RMS). Activating mutations in SMO have also been recognized in sporadic cases of medulloblastoma and SMO is overexpressed in many other cancers. Recently, studies in several human cancers have shown that GLI1 expression is independent from HH ligand and canonical intracellular signaling through PTCH and SMO. In fact, this aberrantly regulated GLI1 has been linked to several non-canonical oncogenic growth signals such as Kirsten rat sarcoma viral oncogene homolog (KRAS), avian myelocytomatosis virus oncogene cellular homolog (C-MYC), transforming growth factor β (TGFβ), wingless-type MMTV integration site family (WNT) and β-catenin. Recent studies from our lab and other independent studies demonstrate that aberrantly expressed GLI1 influences the integrity of several DNA damage response and repair signals, and if altered, these networks can contribute to GI and impact tumor response to chemo- and radiation therapies. Furthermore, the ineffectiveness of SMO inhibitors in clinical studies argues for the development of GLI1-specific inhibitors in order to develop effective therapeutic modalities to treat these tumors. In this review, we focus on summarizing current understanding of the molecular, biochemical and cellular basis for

  6. Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma

    DOE PAGES

    Yang, Yi -Lin; Ni, Jian; Hsu, Ping -Chih; ...

    2015-07-27

    Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressedmore » and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P < 0.05, chi-square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.« less

  7. Cul4A overexpression associated with Gli1 expression in malignant pleural mesothelioma

    SciTech Connect

    Yang, Yi -Lin; Ni, Jian; Hsu, Ping -Chih; Mao, Jian -Hua; Hsieh, David; Xu, Angela; Chan, Geraldine; Au, Alfred; Xu, Zhidong; Jablons, David M.; You, Liang

    2015-07-27

    Malignant pleural mesothelioma (mesothelioma) is a highly aggressive cancer without an effective treatment. Cul4A, a scaffold protein that recruits substrates for degradation, is amplified in several human cancers, including mesothelioma. We have recently shown that Cul4A plays an oncogenic role in vitro and in a mouse model. In this study, we analysed clinical mesothelioma tumours and found moderate to strong expression of Cul4A in 70.9% (51/72) of these tumours, as shown by immunohistochemistry. In 72.2% mesothelioma tumours with increased Cul4A copy number identified by fluorescence in situ hybridization analysis, Cul4A protein expression was moderate to strong. Similarly, Cul4A was overexpressed and Cul4A copy number was increased in human mesothelioma cell lines. Because Gli1 is highly expressed in human mesothelioma cells, we compared Cul4A and Gli1 expression in mesothelioma tumours and found their expression associated (P < 0.05, chi-square). In mesothelioma cell lines, inhibiting Cul4A by siRNA decreased Gli1 expression, suggesting that Gli1 expression is, at least in part, regulated by Cul4A in mesothelioma cells. Our results suggest a linkage between Cul4A and Gli1 expression in human mesothelioma.

  8. Gli1 is not required for Pdgfralpha expression during mouse embryonic development.

    PubMed

    Zhang, Xiao-Qun; Afink, Gijs B; Hu, Xin-Rong; Forsberg-Nilsson, Karin; Nistér, Monica

    2005-03-01

    Pdgfra is expressed in the mesenchyme of multiple organs during embryonic development and Pdgfralpha is involved in cell proliferation, differentiation, migration, and apoptosis in many tissues. A fine-tuned regulation of gene transcription is required to achieve these effects. To investigate if the Shh signaling pathway is involved in the tightly regulated Pdgfra expression during embryogenesis, we systematically compared Gli1 and Pdgfralpha mRNA expression patterns in vivo from mouse embryonic day 9.5 to 14.5. We found that an initial partly overlapping expression of Gli1 and Pdgfralpha in the mesenchyme of foregut and somites was changed to different expression patterns when the mesenchyme differentiated into specialized structures such as intestinal villi and chondrocytes. Gli1 and Pdgfra were also expressed differently in the developing lung, heart, central nervous system, skin, tooth, and eye. Importantly, neither Pdgfralpha mRNA patterns nor levels were altered in Ihh mutant embryos although Gli1 and Ptc mRNA levels were dramatically reduced. Our results demonstrate that Gli1 is not required to induce Pdgfra expression during embryonic bone development, and are consistent with previous findings that Pdgfralpha and Hh pathways serve different functions in, e.g., bone, gut, and lung development. However, we cannot exclude the possibility that Glis can have more complex regulatory effects on Pdgfra gene activity, nor can we exclude such effects in pathological conditions.

  9. Potential role of Shh-Gli1-BMI1 signaling pathway nexus in glioma chemoresistance.

    PubMed

    Shahi, M H; Farheen, S; Mariyath, M P M; Castresana, J S

    2016-11-01

    Chemoresistance is a common hurdle for the proper treatment of gliomas. The role of Shh-Gli1 signaling in glioma progression has been reported. However, its role in glioma chemoresistance has not been well studied yet. In this work, we found that Shh-Gli1 signaling regulates the expression of one stem cell marker, BMI1 (B cell-specific Moloney murine leukemia virus), in glioma. Interestingly, we also demonstrated high expression of MRP1 (multi-drug resistance protein 1) in glioma. MRP1 expression was decreased by BMI1 siRNA and Shh-Gli1 cell signaling specific inhibitor GANT61 in our experiments. GANT61 very efficiently inhibited cell colony growth in glioma cell lines, compared to temozolomide. Moreover, a synergic effect of GANT61 and temozolomide drastically decreased the LD50 of temozolomide in the cell colony experiments. Therefore, our results suggest that there is a potential nexus of Shh-Gli1-BMI1 cell signaling to regulate MRP1 and to promote chemoresistance in glioma. Henceforth, our study opens the possibility of facing new targets, Gli1 and BMI1, for the effective treatment of glioma suppression of chemoresistance with adjuvant therapy of GANT61 and temozolomide.

  10. P53 Modulates The Activity Of The GLI1 Oncogene Through Interactions With The Shared Coactivator TAF9

    PubMed Central

    Yoon, Joon Won; Lamm, Marilyn; Iannaccone, Stephen; Higashiyama, Nicole; Leong, King Fu; Iannaccone, Philip; Walterhouse, David

    2015-01-01

    The GLI1 oncogene and p53 tumor suppressor gene function in an inhibitory loop that controls stem cell and tumor cell numbers. Since GLI1 and p53 both interact with the coactivator TATA Binding Protein Associated Factor 9 (TAF9), we hypothesized that competition between these transcription factors for TAF9 in cancer cells may contribute to the inhibitory loop and directly affect GLI1 function and cellular phenotype. We showed that TAF9 interacts with the oncogenic GLI family members GLI1 and GLI2 but not GLI3 in cell-free pull-down assays and with GLI1 in rhabdomyosarcoma and osteosarcoma cell lines. Removal of the TAF9-binding acidic alpha helical transactivation domain of GLI1 produced a significant reduction in the ability of GLI1 to transform cells. We then introduced a point mutation into GLI1 (L1052I) that eliminates TAF9 binding and a point mutation into GLI3 (I1510L) that establishes binding. Wild-type and mutant GLI proteins that bind TAF9 showed enhanced transactivating and cell transforming activity compared with those that did not. Therefore, GLI-TAF9 binding appears important for oncogenic activity. We then determined whether wild-type p53 down-regulates GLI function by sequestering TAF9. We showed that p53 binds TAF9 with greater affinity than does GLI1 and that co-expression of p53 with GLI1 or GLI2 down-regulated GLI-induced transactivation, which could be abrogated using mutant forms of GLI1 or p53. This suggests that p53 sequesters TAF9 from GLI1, which may contribute to inhibition of GLI1 activity by p53 and potentially impact therapeutic success of agents targeting GLI-TAF9 interactions in cancer. PMID:26282181

  11. The Transcription Factor GLI1 Modulates the Inflammatory Response during Pancreatic Tissue Remodeling*

    PubMed Central

    Mathew, Esha; Collins, Meredith A.; Fernandez-Barrena, Maite G.; Holtz, Alexander M.; Yan, Wei; Hogan, James O.; Tata, Zachary; Allen, Benjamin L.; Fernandez-Zapico, Martin E.; Pasca di Magliano, Marina

    2014-01-01

    Pancreatic cancer, one of the deadliest human malignancies, is almost uniformly associated with a mutant, constitutively active form of the oncogene Kras. Studies in genetically engineered mouse models have defined a requirement for oncogenic KRAS in both the formation of pancreatic intraepithelial neoplasias, the most common precursor lesions to pancreatic cancer, and in the maintenance and progression of these lesions. Previous work using an inducible model allowing tissue-specific and reversible expression of oncogenic Kras in the pancreas indicates that inactivation of this GTPase at the pancreatic intraepithelial neoplasia stage promotes pancreatic tissue repair. Here, we extend these findings to identify GLI1, a transcriptional effector of the Hedgehog pathway, as a central player in pancreatic tissue repair upon Kras inactivation. Deletion of a single allele of Gli1 results in improper stromal remodeling and perdurance of the inflammatory infiltrate characteristic of pancreatic tumorigenesis. Strikingly, this partial loss of Gli1 affects activated fibroblasts in the pancreas and the recruitment of immune cells that are vital for tissue recovery. Analysis of the mechanism using expression and chromatin immunoprecipitation assays identified a subset of cytokines, including IL-6, mIL-8, Mcp-1, and M-csf (Csf1), as direct GLI1 target genes potentially mediating this phenomenon. Finally, we demonstrate that canonical Hedgehog signaling, a known regulator of Gli1 activity, is required for pancreas recovery. Collectively, these data delineate a new pathway controlling tissue repair and highlight the importance of GLI1 in regulation of the pancreatic microenvironment during this cellular process. PMID:25104358

  12. The Timing of Sonic Hedgehog and Gli1 Expression Segregates Midbrain Dopamine Neurons

    PubMed Central

    Hayes, Lindsay; Zhang, Zhiwei; Albert, Paul; Zervas, Mark; Ahn, Sohyun

    2011-01-01

    The ventral midbrain (vMb) is organized into distinct anatomical domains and contains cohorts of functionally distinct subtypes of midbrain dopamine (mDA) neurons. We tested the hypothesis that genetic history and timing of gene expression within mDA neuron progenitors impart spatial diversity. Using Genetic Inducible Fate Mapping to mark the Sonic hedgehog (Shh) and Gli1 lineages at varying embryonic stages, we performed a quantitative and qualitative comparison of the two lineages’ contribution to the mDA neuron domains. Dynamic changes in Shh and Gli1 expression in the vMb primordia delineated their spatial contribution to the E12.5 vMb: Both lineages first contributed to the medial domain, but subsequently the Gli1 lineage exclusively contributed to the lateral vMb while the Shh lineage expanded more broadly across the vMb. The contribution of both lineages to the differentiated mDA neuron domain was initially biased anteriorly and became more uniform across the anterior/posterior vMb throughout development. Our findings demonstrate that the early Shh and Gli1 lineages specify mDA neurons of the substantia nigra pars compacta while the late Shh and Gli1 lineages maintain their progenitor state longer in the posterior vMb to extend the production of mDA neurons in the ventral tegmental area. Together, our study demonstrates that the timing of gene expression along with the genetic lineage (Shh or Gli1) within the neural progenitors segregate mDA neurons into distinct spatial domains. PMID:21713771

  13. GLI1-mediated regulation of side population is responsible for drug resistance in gastric cancer

    PubMed Central

    Yu, Beiqin; Gu, Dongsheng; Zhang, Xiaoli; Li, Jianfang; Liu, Bingya; Xie, Jingwu

    2017-01-01

    Gastric cancer is the third leading cause of cancer-related mortality worldwide. Chemotherapy is frequently used for gastric cancer treatment. Most patients with advanced gastric cancer eventually succumb to the disease despite some patients responded initially to chemotherapy. Thus, identifying molecular mechanisms responsible for cancer relapse following chemotherapy will help design new ways to treat gastric cancer. In this study, we revealed that the residual cancer cells following treatment with chemotherapeutic reagent cisplatin have elevated expression of hedgehog target genes GLI1, GLI2 and PTCH1, suggestive of hedgehog signaling activation. We showed that GLI1 knockdown sensitized gastric cancer cells to CDDP whereas ectopic GLI1 expression decreased the sensitivity. Further analyses indicate elevated GLI1 expression is associated with an increase in tumor sphere formation, side population and cell surface markers for putative cancer stem cells. We have evidence to support that GLI1 is critical for maintenance of putative cancer stem cells through direct regulation of ABCG2. In fact, GLI1 protein was shown to be associated with the promoter fragment of ABCG2 through a Gli-binding consensus site in gastric cancer cells. Disruption of ABCG2 function, through ectopic expression of an ABCG2 dominant negative construct or a specific ABCG2 inhibitor, increased drug sensitivity of cancer cells both in culture and in mice. The relevance of our studies to gastric cancer patient care is reflected by our discovery that high ABCG2 expression was associated with poor survival in the gastric cancer patients who underwent chemotherapy. Taken together, we have identified a molecular mechanism by which gastric cancer cells gain chemotherapy resistance. PMID:28404967

  14. In vitro and in situ antimicrobial action and mechanism of glycinin and its basic subunit.

    PubMed

    Sitohy, Mahmoud Z; Mahgoub, Samir A; Osman, Ali O

    2012-03-01

    Glycinin, basic subunit and β-conglycinin were isolated from soybean protein isolate and tested for their antimicrobial action against pathogenic and spoilage bacteria as compared to penicillin. The three fractions exhibited antibacterial activities equivalent to or higher than penicillin in the next order; basic subunit>glycinin>β-conglycinin with MIC of 50, 100 and 1000 μg/mL, respectively. The IC(50%) values of the basic subunit, glycinin and β-conglycinin against Listeria\\monocytogenes were 15, 16 and 695 μg/mL, against Bacillussubtilis were 17, 20, and 612 μg/mL, and against S. Enteritidis were 18, 21 and 526 μg/mL, respectively. Transmission electron microscopy images of L. monocytogenes and S. Enteritidis exhibited bigger sizes and separation of cell wall from cell membrane when treated with glycinin or basic subunit. Scanning electron microscopy of B. subtilis indicated signs of irregular wrinkled outer surface, fragmentation, adhesion and aggregation of damaged cells or cellular debris when treated with glycinin or the basic subunits but not with penicillin. All tested substances particularly the basic subunit showed increased concentration-dependent cell permeation assessed by crystal violet uptake. The antimicrobial action of glycinin and basic subunit was swifter than that of penicillin. The cell killing efficiency was in the following descending order; basic subunit>glycinin>penicillin>β-conglycinin and the susceptibility of the bacteria to the antimicrobial agents was in the next order: L. monocytogenes>B. Subtilis>S. Enteritidis. Adding glycinin and the basic subunit to pasteurized milk inoculated with the three bacteria; L. monocytogenes, B. Subtilis and S. Enteritidis (ca. 5 log CFU/mL) could inhibit their propagation after 16-20 days storage at 4 °C by 2.42-2.98, 4.25-4.77 and 2.57-3.01 log and by 3.22-3.78, 5.65-6.27 and 3.35-3.72 log CFU/mL, respectively. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. Hh signaling inhibitors from Vitex negundo; naturally occurring inhibitors of the GLI1-DNA complex.

    PubMed

    Arai, Midori A; Fujimatsu, Teruhisa; Uchida, Kyoko; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

    2013-05-01

    The hedgehog (Hh) signaling pathway has crucial roles in embryonic development, cell maintenance and proliferation, and is also known to contribute to cancer cell growth. New naturally occurring Hh inhibitors (1, 7 and 9) were isolated from Vitex negundo using our previously constructed cell-based assay. Bioactivity guided isolation provided 9 natural compounds including a new diterpene, nishindanol (9). Compounds 7 and 9 showed cytotoxicity against cancer cell lines in which Hh signaling was aberrantly activated. Vitetrifolin D (7; GLI1 transcriptional inhibition IC50 = 20.2 μM) showed inhibition of Hh related protein (PTCH and BCL2) production. Interestingly, the constructed electrophoresis mobility shift assay revealed that vitetrifolin D (7) disrupted GLI1 binding on its DNA binding domain. epi-Sclareol (8; inactive), possessing a similar structure to 7, did not show inhibition of GLI1–DNA complex formation. This is the first example of naturally occurring inhibitors of GLI1–DNA complex formation.

  16. Atoh1 inhibits neuronal differentiation and collaborates with Gli1 to generate medulloblastoma-initiating cells

    PubMed Central

    Ayrault, Olivier; Zhao, Haotian; Zindy, Frederique; Qu, Chunxu; Sherr, Charles J.; Roussel, Martine F.

    2010-01-01

    The morphogen and mitogen Sonic Hedgehog activates a Gli1-dependent transcription program that drives proliferation of granule neuron progenitors (GNPs) within the external germinal layer of the postnatally developing cerebellum. Medulloblastomas with mutations activating the Sonic Hedgehog signaling pathway preferentially arise within the external germinal layer, and the tumor cells closely resemble GNPs. Atoh1/Math1, a basic helix-loop-helix transcription factor essential for GNP histogenesis, does not induce medulloblastomas when expressed in primary mouse GNPs that are explanted from the early postnatal cerebellum and transplanted back into the brains of naïve mice. However, enforced expression of Atoh1 in primary GNPs enhances the oncogenicity of cells overexpressing Gli1 by almost three orders of magnitude. Unlike Gli1, Atoh1 cannot support GNP proliferation in the absence of Sonic Hedgehog signaling and does not govern expression of canonical cell cycle genes. Instead, Atoh1 maintains GNPs in a Sonic Hedgehog-responsive state by regulating genes that trigger neuronal differentiation, including many expressed in response to bone morphogenic protein-4. Therefore, by targeting multiple genes regulating the differentiation state of GNPs, Atoh1 collaborats with the pro-proliferative Gli1-dependent transcriptional program to influence medulloblastoma development. PMID:20516124

  17. Comparison of protein chemical and physicochemical properties of rapeseed cruciferin with those of soybean glycinin.

    PubMed

    Mohamed Salleh, Mohamad Ramlan Bin; Maruyama, Nobuyuki; Adachi, Motoyasu; Hontani, Naho; Saka, Shiori; Kato, Noboru; Ohkawa, Yasunobu; Utsumi, Shigeru

    2002-12-04

    Rapeseeds contain cruciferin (11S globulin), napin (2S albumin), and oleosin (oil body protein) as major seed proteins. The effects of oil expression and drying conditions on the extraction of these proteins from rapeseed meal were examined. The conditions strongly affected the extraction of oleosin and only weakly affected the extraction of cruciferin and napin. The protein chemical and physicochemical properties of cruciferin, the major protein present, were compared with those of glycinin (soybean 11S globulin) under various conditions. In general, cruciferin exhibited higher surface hydrophobicity, lower thermal stability, and lower and higher solubility at mu= 0.5 and mu = 0.08, respectively, than did glycinin. At the pHs (6.0, 7.6, and 9.0) and ionic strengths (mu= 0.08 and 0.5) examined, the emulsifying ability of cruciferin was worse than that of glycinin, except at mu= 0.08 and pH 7.6. The emulsifying abilities of cruciferin and glycinin did not correlate with thermal stability and surface hydrophobicity. Higher protein concentration, higher heating temperature, higher pH, and lower ionic strength were observed to produce harder gels from cruciferin. Gel hardness partly correlated with the structural stability of cruciferin.

  18. Gli1 Deletion Prevents Helicobacter-Induced Gastric Metaplasia and Expansion of Myeloid Cell Subsets

    PubMed Central

    El-Zaatari, Mohamad; Kao, John Y.; Tessier, Art; Bai, Longchuan; Hayes, Michael M.; Fontaine, Clinton; Eaton, Kathryn A.; Merchant, Juanita L.

    2013-01-01

    Chronic inflammation in the stomach induces metaplasia, the pre-cancerous lesion that precedes inflammation-driven neoplastic transformation. While Hedgehog signaling contributes to the initiation of some cancers, its role in gastric transformation remains poorly defined. We found that Helicobacter-infected C57BL/6 mice develop extensive mucous cell metaplasia at 6 month but not at 2 months post-infection. Gastric metaplasia coincided with the appearance of CD45+MHCII+CD11b+CD11c+ myeloid cells that were normally not present in the chronic gastritis at 2 months. The myeloid regulatory gene Schlafen-4 was identified in a microarray analysis comparing infected WT versus Gli1 null mice and was expressed in the CD11b+CD11c+ myeloid population. Moreover this same population expressed IL-1β and TNFα pro-inflammatory cytokines. By 6 months, the mucous neck cell metaplasia (SPEM) expressed IL-6, phosphorylated STAT3 and the proliferative marker Ki67. Expression was not observed in Gli1 mutant mice consistent with the requirement of Gli1 to induce this pre-neoplastic phenotype. Ectopic Shh ligand expression alone was not sufficient to induce SPEM, but with Helicobacter infection synergistically increased the histologic severity observed with the inflammation. Therefore Hedgehog signaling is required, but is not sufficient to generate pre-neoplastic changes during chronic gastritis. Gli1-dependent myeloid cell differentiation plays a pivotal role in the appearance of myeloid cell subtypes ostensibly required for SPEM development. Moreover, it suggests that therapies capable of targeting this phenotypic switch might prevent progression to metaplasia, the pre-neoplastic change that develops prior to dysplasia and gastric cancer, which also occurs in other epithelial-derived neoplasias initiated by chronic inflammation. PMID:23520544

  19. Gli1 deletion prevents Helicobacter-induced gastric metaplasia and expansion of myeloid cell subsets.

    PubMed

    El-Zaatari, Mohamad; Kao, John Y; Tessier, Art; Bai, Longchuan; Hayes, Michael M; Fontaine, Clinton; Eaton, Kathryn A; Merchant, Juanita L

    2013-01-01

    Chronic inflammation in the stomach induces metaplasia, the pre-cancerous lesion that precedes inflammation-driven neoplastic transformation. While Hedgehog signaling contributes to the initiation of some cancers, its role in gastric transformation remains poorly defined. We found that Helicobacter-infected C57BL/6 mice develop extensive mucous cell metaplasia at 6 month but not at 2 months post-infection. Gastric metaplasia coincided with the appearance of CD45(+)MHCII(+)CD11b(+)CD11c(+) myeloid cells that were normally not present in the chronic gastritis at 2 months. The myeloid regulatory gene Schlafen-4 was identified in a microarray analysis comparing infected WT versus Gli1 null mice and was expressed in the CD11b(+)CD11c(+) myeloid population. Moreover this same population expressed IL-1β and TNFα pro-inflammatory cytokines. By 6 months, the mucous neck cell metaplasia (SPEM) expressed IL-6, phosphorylated STAT3 and the proliferative marker Ki67. Expression was not observed in Gli1 mutant mice consistent with the requirement of Gli1 to induce this pre-neoplastic phenotype. Ectopic Shh ligand expression alone was not sufficient to induce SPEM, but with Helicobacter infection synergistically increased the histologic severity observed with the inflammation. Therefore Hedgehog signaling is required, but is not sufficient to generate pre-neoplastic changes during chronic gastritis. Gli1-dependent myeloid cell differentiation plays a pivotal role in the appearance of myeloid cell subtypes ostensibly required for SPEM development. Moreover, it suggests that therapies capable of targeting this phenotypic switch might prevent progression to metaplasia, the pre-neoplastic change that develops prior to dysplasia and gastric cancer, which also occurs in other epithelial-derived neoplasias initiated by chronic inflammation.

  20. Isolation of glycinin (11S) from lipid-reduced soybean flour: effect of processing conditions on yields and purity.

    PubMed

    Deng, Kequan; Huang, Youru; Hua, Yufei

    2012-03-09

    Defatted soybean flour was treated with hexane and ethanol to reduce lipid content and heated to inactivate lipoxygenase (LOX, linoleate:oxygen reductase; EC 1.13.11.12) to obtain lipid-reduced soybean flour (LRSF). The effects of processing conditions such as pH, reducing agent and storage time on yields and purity of glycinin (11S) were evaluated in the fractionation of soybean glycinin isolated from LRSF. Adjusting the pH of protein extract from 6.2 to 6.6, the yield of glycinin decreased by 16.71%, while the purity of the protein increased by 4.60%. Sulfhydryl and disulfide content of proteins increased by degrees with increasing pH. Compared with dithiothreitol (DTT) or β-mercaptoethanol (ME) as reducing agent, the yield of glycinin was the highest when sodium bisulfite (SBS) was added to the protein extract at pH 6.4. The effect of DTT on yields of glycinin was the lowest of the three kinds of reducing agent. The purity of glycinin was similar when the three kinds of reducing agent were used. These results showed that SBS was the best choice for the isolation of 11S-rich fraction. Prolonging storage time in the precipitation stage, 10 h was the best for yields and purity of glycinin in the experiment, while there was no significant difference at P ≥ 0.05 for total sulfhydryl and disulfide content. The decreased free sulfhydryl content of glycinin indicated that the oxidation of free sulfhydryls and the formation of disulfide bonds occurred when the extraction time was prolonged.

  1. Tamoxifen Treatment of Breast Cancer Cells: Impact on Hedgehog/GLI1 Signaling.

    PubMed

    Villegas, Victoria E; Rondón-Lagos, Milena; Annaratone, Laura; Castellano, Isabella; Grismaldo, Adriana; Sapino, Anna; Zaphiropoulos, Peter G

    2016-02-27

    The selective estrogen receptor (ER) modulator tamoxifen (TAM) has become the standard therapy for the treatment of ER+ breast cancer patients. Despite the obvious benefits of TAM, a proportion of patients acquire resistance to treatment, and this is a significant clinical problem. Consequently, the identification of possible mechanisms involved in TAM-resistance should help the development of new therapeutic targets. In this study, we present in vitro data using a panel of different breast cancer cell lines and demonstrate the modulatory effect of TAM on cellular proliferation and expression of Hedgehog signaling components, including the terminal effector of the pathway, the transcription factor GLI1. A variable pattern of expression following TAM administration was observed, reflecting the distinctive properties of the ER+ and ER- cell lines analyzed. Remarkably, the TAM-induced increase in the proliferation of the ER+ ZR-75-1 and BT474 cells parallels a sustained upregulation of GLI1 expression and its translocation to the nucleus. These findings, implicating a TAM-GLI1 signaling cross-talk, could ultimately be exploited not only as a means for novel prognostication markers but also in efforts to effectively target breast cancer subtypes.

  2. The centrosomal deubiquitylase USP21 regulates Gli1 transcriptional activity and stability

    PubMed Central

    Heride, Claire; Rigden, Daniel J.; Bertsoulaki, Erithelgi; Cucchi, Danilo; De Smaele, Enrico; Clague, Michael J.; Urbé, Sylvie

    2016-01-01

    ABSTRACT USP21 is a centrosome-associated deubiquitylase (DUB) that has been implicated in the formation of primary cilia – crucial organelles for the regulation of the Hedgehog (Hh) signaling pathway in vertebrates. Here, we identify KCTD6 – a cullin-3 E3-ligase substrate adapter that has been previously linked to Hh signaling – as well as Gli1, the key transcription factor responsible for Hh signal amplification, as new interacting partners of USP21. We identify a cryptic structured protein interaction domain in KCTD6, which is predicted to have a similar fold to Smr domains. Importantly, we show that both depletion and overexpression of catalytically active USP21 suppress Gli1-dependent transcription. Gli proteins are negatively regulated through protein kinase A (PKA)-dependent phosphorylation. We provide evidence that USP21 recruits and stabilises Gli1 at the centrosome where it promotes its phosphorylation by PKA. By revealing an intriguing functional pairing between a spatially restricted deubiquitylase and a kinase, our study highlights the centrosome as an important hub for signal coordination. PMID:27621083

  3. The Transcription Factor GLI1 Mediates TGFβ1 Driven EMT in Hepatocellular Carcinoma via a SNAI1-Dependent Mechanism

    PubMed Central

    Fernandez-Barrena, Maite G.; Moser, Catherine D.; Hu, Chunling; Almada, Luciana L.; McCleary-Wheeler, Angela L.; Elsawa, Sherine F.; Vrabel, Anne M.; Shire, Abdirashid M.; Comba, Andrea; Thorgeirsson, Snorri S.; Kim, Youngsoo; Liu, Qingguang; Fernandez-Zapico, Martin E.; Roberts, Lewis R.

    2012-01-01

    The role of the epithelial-to-mesenchymal transition (EMT) during hepatocellular carcinoma (HCC) progression is well established, however the regulatory mechanisms modulating this phenomenon remain unclear. Here, we demonstrate that transcription factor glioma-associated oncogene 1 (GLI1) modulates EMT through direct up-regulation of SNAI1 and serves as a downstream effector of the transforming growth factor-β1 (TGFβ1) pathway, a well-known regulator of EMT in cancer cells. Overexpression of GLI1 increased proliferation, viability, migration, invasion, and colony formation by HCC cells. Conversely, GLI1 knockdown led to a decrease in all the above-mentioned cancer-associated phenotypes in HCC cells. Further analysis of GLI1 regulated cellular functions showed that this transcription factor is able to induce EMT and identified SNAI1 as a transcriptional target of GLI1 mediating this cellular effect in HCC cells. Moreover, we demonstrated that an intact GLI1-SNAI1 axis is required by TGFβ1 to induce EMT in these cells. Together, these findings define a novel cellular mechanism regulated by GLI1, which controls the growth and EMT phenotype in HCC. PMID:23185371

  4. CD44, Sonic Hedgehog, and Gli1 Expression Are Prognostic Biomarkers in Gastric Cancer Patients after Radical Resection.

    PubMed

    Jian-Hui, Chen; Er-Tao, Zhai; Si-Le, Chen; Hui, Wu; Kai-Ming, Wu; Xin-Hua, Zhang; Chuang-Qi, Chen; Shi-Rong, Cai; Yu-Long, He

    2016-01-01

    Aim. CD44 and Sonic Hedgehog (Shh) signaling are important for gastric cancer (GC). However, the clinical impact, survival, and recurrence outcome of CD44, Shh, and Gli1 expressions in GC patients following radical resection have not been elucidated. Patients and Methods. CD44, Shh, and Gli1 protein levels were quantified by immunohistochemistry (IHC). The association between CD44, Shh, and Gli1 expression and clinicopathological features or prognosis of GC patients was determined. The biomarker risk score was calculated by the IHC staining score of CD44, Shh, and Gli1 protein. Results. The IHC positive staining of CD44, Shh, and Gli1 proteins was correlated with larger tumour size, worse gross type and histological type, and advanced TNM stage, which also predicted shorter overall survival (OS) and disease-free survival (DFS) after radical resection. Multivariate analysis indicated the Gli1 protein and Gli1, CD44 proteins were predictive biomarkers for OS and DFS, respectively. If biomarker risk score was taken into analysis, it was the independent prognostic factor for OS and DFS. Conclusions. CD44 and Shh signaling are important biomarkers for tumour aggressiveness, survival, and recurrence in GC.

  5. Effect of Allelic Variation at the Glu-3/Gli-1 Loci on Breadmaking Quality Parameters in Hexaploid Wheat (Triticum aestivum L.).

    PubMed

    Bonafede, Marcos D; Tranquilli, Gabriela; Pflüger, Laura A; Peña, Roberto J; Dubcovsky, Jorge

    2015-03-01

    Low molecular weight glutenin subunits (LMW-GS) encoded by the Glu-3 loci are known to contribute to wheat breadmaking quality. However, the specific effect of individual Glu-3 alleles is not well understood due to their complex protein banding patterns in SDS-PAGE and tight linkage with gliadins at the Gli-1 locus. Using DNA markers and a backcross program we developed a set of nine near isogenic lines (NILs) including different Glu-A3/GliA-1 or Glu-B3/Gli-B1 alleles in the genetic background of the Argentine variety ProINTA Imperial. The nine NILs and the control were evaluated in three different field trials in Argentina. Significant genotype-by-environment interactions were detected for most quality parameters indicating that the effects of the Glu-3/Gli-1 alleles are modulated by environmental differences. None of the NILs showed differences in total flour protein content, but relative changes in the abundance of particular classes of proteins cannot be ruled out. On average, the Glu-A3f, Glu-B3b, Glu-B3g and Glu-B3iMan alleles were associated with the highest values in gluten strength-related parameters, while Glu-A3e, Glu-B3a and Glu-B3iChu were consistently associated with weak gluten and low quality values. The value of different Glu3/Gli-1 allele combinations to improve breadmaking quality is discussed.

  6. Effect of Allelic Variation at the Glu-3/Gli-1 Loci on Breadmaking Quality Parameters in Hexaploid Wheat (Triticum aestivum L.)

    PubMed Central

    Bonafede, Marcos D.; Tranquilli, Gabriela; Pflüger, Laura A.; Peña, Roberto J.; Dubcovsky, Jorge

    2016-01-01

    Low molecular weight glutenin subunits (LMW-GS) encoded by the Glu-3 loci are known to contribute to wheat breadmaking quality. However, the specific effect of individual Glu-3 alleles is not well understood due to their complex protein banding patterns in SDS-PAGE and tight linkage with gliadins at the Gli-1 locus. Using DNA markers and a backcross program we developed a set of nine near isogenic lines (NILs) including different Glu-A3/GliA-1 or Glu-B3/Gli-B1 alleles in the genetic background of the Argentine variety ProINTA Imperial. The nine NILs and the control were evaluated in three different field trials in Argentina. Significant genotype-by-environment interactions were detected for most quality parameters indicating that the effects of the Glu-3/Gli-1 alleles are modulated by environmental differences. None of the NILs showed differences in total flour protein content, but relative changes in the abundance of particular classes of proteins cannot be ruled out. On average, the Glu-A3f, Glu-B3b, Glu-B3g and Glu-B3iMan alleles were associated with the highest values in gluten strength-related parameters, while Glu-A3e, Glu-B3a and Glu-B3iChu were consistently associated with weak gluten and low quality values. The value of different Glu3/Gli-1 allele combinations to improve breadmaking quality is discussed. PMID:27818572

  7. The energy sensor AMPK regulates Hedgehog signaling in human cells through a unique Gli1 metabolic checkpoint

    PubMed Central

    Di Magno, Laura; Basile, Alessio; Coni, Sonia; Manni, Simona; Sdruscia, Giulia; D'Amico, Davide; Antonucci, Laura; Infante, Paola; De Smaele, Enrico; Cucchi, Danilo; Ferretti, Elisabetta; Di Marcotullio, Lucia; Screpanti, Isabella; Canettieri, Gianluca

    2016-01-01

    Hedgehog signaling controls proliferation of cerebellar granule cell precursors (GCPs) and its aberrant activation is a leading cause of Medulloblastoma, the most frequent pediatric brain tumor. We show here that the energy sensor AMPK inhibits Hh signaling by phosphorylating a single residue of human Gli1 that is not conserved in other species. Studies with selective agonists and genetic deletion have revealed that AMPK activation inhibits canonical Hh signaling in human, but not in mouse cells. Indeed we show that AMPK phosphorylates Gli1 at the unique residue Ser408, which is conserved only in primates but not in other species. Once phosphorylated, Gli1 is targeted for proteasomal degradation. Notably, we show that selective AMPK activation inhibits Gli1-driven proliferation and that this effect is linked to Ser408 phosphorylation, which represents a key metabolic checkpoint for Hh signaling. Collectively, this data unveil a novel mechanism of inhibition of Gli1 function, which is exclusive for human cells and may be exploited for the treatment of Medulloblastoma or other Gli1 driven tumors. PMID:26843621

  8. Effects of Ca2+ and sulfhydryl reductant on the polymerization of soybean glycinin catalyzed by mammalian and microbial transglutaminases.

    PubMed

    Zhang, Guoyan; Matsumura, Yasuki; Matsumoto, Shinya; Hayashi, Yukako; Mori, Tomohiko

    2003-01-01

    Two types of transglutaminases (TGases), Ca(2+)-dependent TGase derived from guinea pig liver (GTGase) and Ca(2+)-independent TGase derived from a variant of Streptoverticillium mobaraense (MTGase), were used to study the cross-linking of soybean 11S globulin (glycinin). The effects of sulfhydryl reductant (dithiothreitol, DTT) and Ca(2+) on the conformation and TGase-catalyzed polymerization of glycinin were investigated. The conformational change of glycinin was probed by spectral methods. The degree of cross-linking and the polymer (aggregate) formation were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and dynamic light scattering, respectively. Addition of DTT stimulated the TGase-catalyzed cross-linking reactions without destroying the secondary and tertiary structure of glycinin but did not influence the polymer or aggregate formation. It was found that Ca(2+) caused the formation of larger size polymers at lower concentrations, while it suppressed the polymerization at higher concentrations. In addition, the cross-linking behaviors of glycinin were shown to be different between MTGase- and GTGase-catalyzed systems.

  9. Identification of glycinin in vivo as a polyamine-conjugated protein via a gamma-glutamyl linkage.

    PubMed Central

    Kang, H; Lee, S G; Cho, Y D

    1998-01-01

    To identify a polyamine-conjugated protein by the action of transglutaminase in the absence of radiolabelled polyamine, extracts prepared from the leaves and developing soybean seeds were investigated for the specific activity of transglutaminase and the content of free polyamines. We identified the major storage protein, glycinin, as a polyamine-conjugated protein. This was established by the following procedures: (1) immunolocalization with antibody against putrescine prepared in rabbit against putrescine-BSA conjugate; (2) immunocross-reactivity on nitrocellulose transblot of the purified glycinin subunits by using antibody against putrescine; (3) identification of polyamines in acid hydrolysates of purified glycinin; (4) release of polyamines in proteolytic digests through the catalytic action of gamma-glutamylamine cyclotransferase, an enzyme specific for the disassembly of gamma-glutamylamines. The activity of gamma-glutamylamine cyclotransferase was also identified in soybean seeds. PMID:9601076

  10. Genetic variations and alternative splicing: the Glioma associated oncogene 1, GLI1.

    PubMed

    Zaphiropoulos, Peter G

    2012-01-01

    Alternative splicing is a post-transcriptional regulatory process that is attaining stronger recognition as a modulator of gene expression. Alternative splicing occurs when the primary RNA transcript is differentially processed into more than one mature RNAs. This is the result of a variable definition/inclusion of the exons, the sequences that are excised from the primary RNA to form the mature RNAs. Consequently, RNA expression can generate a collection of differentially spliced RNAs, which may distinctly influence subsequent biological events, such as protein synthesis or other biomolecular interactions. Still the mechanisms that control exon definition and exon inclusion are not fully clarified. This mini-review highlights advances in this field as well as the impact of single nucleotide polymorphisms in affecting splicing decisions. The Glioma-associated oncogene 1, GLI1, is taken as an example in addressing the role of nucleotide substitutions for splicing regulation.

  11. Genetic variations and alternative splicing: the Glioma associated oncogene 1, GLI1

    PubMed Central

    Zaphiropoulos, Peter G.

    2012-01-01

    Alternative splicing is a post-transcriptional regulatory process that is attaining stronger recognition as a modulator of gene expression. Alternative splicing occurs when the primary RNA transcript is differentially processed into more than one mature RNAs. This is the result of a variable definition/inclusion of the exons, the sequences that are excised from the primary RNA to form the mature RNAs. Consequently, RNA expression can generate a collection of differentially spliced RNAs, which may distinctly influence subsequent biological events, such as protein synthesis or other biomolecular interactions. Still the mechanisms that control exon definition and exon inclusion are not fully clarified. This mini-review highlights advances in this field as well as the impact of single nucleotide polymorphisms in affecting splicing decisions. The Glioma-associated oncogene 1, GLI1, is taken as an example in addressing the role of nucleotide substitutions for splicing regulation. PMID:22833753

  12. Oral allergy syndrome and anaphylactic reactions in BALB/c mice caused by soybean glycinin and beta-conglycinin.

    PubMed

    Liu, X; Feng, J; Xu, Z R; Wang, Y Z; Liu, J X

    2008-02-01

    Soybean protein is used in a number of food products but is also a common cause of food allergy. Soybean glycinin and beta-conglycinin represent up to one-third of protein in the soybean. Many reports have indicated that glycinin and beta-conglycinin have been characterized as major soybean allergens involved in food hypersensitivity. To investigate oral allergy syndrome and anaphylactic reactions in BALB/c mice caused by soybean glycinin and beta-conglycinin with an intragastric feeding protocol without using an adjuvant. BALB/c mice were sensitized by gavages with glycinin and beta-conglycinin, and allergen-specific IgE and IgG1 responses were studied by a passive cutaneous anaphylaxis assay. Serum histamine release and blood pressure were measured according to other methods. Epithelium and mast cell dye used the method of light microscopy. Sensitization with soybean allergens induced high levels of antigen-specific IgE and IgG1 and increased serum histamine in BALB/c mice. Percentiles of intact mast cell of small intestine in mice sensitized with glycinin and beta-conglyinin significantly decreased for 28 days. Degranulation of mast cells and damage of the epithelium in the small intestine of mice sensitized with globulins were observed. The level of blood pressure in sensitized mice reached a minimum at 3 h. Soybean-specific IgE and IgG1 antibodies increased, with high levels of histamine release, severe degranulation of mast cells and damage of the epithelium of small intestine in mice sensitized with glycinin and beta-conglyinin.

  13. Heat-induced gelation of pea legumin: comparison with soybean glycinin.

    PubMed

    O'Kane, Francesca E; Happe, Randolph P; Vereijken, Johan M; Gruppen, Harry; van Boekel, Martinus A J S

    2004-08-11

    Gel network formation of pea legumin (8.4% on a protein basis, pH 7.6) was monitored via dynamic rheological measurements. Gelation was performed in the absence and presence of the thiol-blocking reagent N-ethylmaleimide, at different rates of heating and cooling. Overall, it was shown that pea legumin gel formation was not effected by changes in the heating rate, and the two differently heated samples were unaffected by the addition of 20 mM NEM, which indicated that disulfide bonds were not essential within the network strands of these legumin gels. However, slowly cooling the legumin samples caused disulfide bonds to become involved within the network; this was observed by a large increase in gel strength that was then substantially reduced when repeating the sample in the presence of NEM. These experiments were repeated with soybean glycinin in order to determine whether a common model for gel formation of legumin-like proteins could be built, based upon molecular reasoning. The two proteins were affected in the same way by changes in the conditions used, but when applying a procedure of reheating and recooling the gel networks responded differently. Pea legumin gel networks were susceptible to rearrangements that caused the gels to become stronger after reheating/recooling, yet glycinin gel networks were not. It was concluded that the same physical and chemical forces drove the processes of denaturation, aggregation, and network formation. Each process can therefore be readily targeted for modification based upon molecular reasoning. Pea legumin and soybean glycinin gel networks had structurally different building blocks, however. A model of gelation aimed at texture control therefore requires additional information.

  14. Physalin H from Solanum nigrum as an Hh signaling inhibitor blocks GLI1-DNA-complex formation.

    PubMed

    Arai, Midori A; Uchida, Kyoko; Sadhu, Samir K; Ahmed, Firoj; Ishibashi, Masami

    2014-01-13

    Hedgehog (Hh) signaling plays an important role in embryonic development, cell maintenance and cell proliferation. Moreover, Hh signaling contributes to the growth of cancer cells. Physalins are highly oxidized natural products with a complex structure. Physalins (1-7) were isolated from Solanum nigrum (Solanaceae) collected in Bangladesh by using our cell-based assay. The isolated physalins included the previously reported Hh inhibitors 5 and 6. Compounds 1 and 4 showed strong inhibition of GLI1 transcriptional activity, and exhibited cytotoxicity against cancer cell lines with an aberrant activation of Hh signaling. Compound 1 inhibited the production of the Hh-related proteins patched (PTCH) and BCL2. Analysis of the structures of different physalins showed that the left part of the physalins was important for Hh inhibitory activity. Interestingly, physalin H (1) disrupted GLI1 binding to its DNA binding domain, while the weak inhibitor physalin G (2) did not show inhibition of GLI1-DNA complex formation.

  15. Gli1 promotes colorectal cancer metastasis in a Foxm1-dependent manner by activating EMT and PI3K-AKT signaling

    PubMed Central

    Zhang, Yue; Ji, Bing; Wang, Sen; Sun, Ye; Zhu, Chunyan; Zhang, Dongsheng; Sun, Yueming

    2016-01-01

    Colorectal cancer(CRC) is one of the most commonly diagnosed cancers in human beings and metastasis is the main death reason. Recently, Gli1 has been reported to be a key regulator of various cancer biologies and genes expressions. However, the detailed molecular mechanism of Gli1 in CRC metastasis remains largely unknown. In this study, we aimed to investigate the role of Gli1 in CRC metastasis. We used qRT-PCR, Immunohistochemistry and Western blot to test the expression levels of Gli1, Foxm1 and other target genes in the tissues and cells; Lentivirus stable transfection to change the expression levels of Gli1 and Foxm1; Wound-healing, cell invasion, migration assays and tail vein metastatic assay to test the role of Gli1 in CRC metastasis in vitro and vivo. We demonstrated that Gli1 was significantly overexpressed in colorectal cancer tissues and cells. Foxm1 level had a positive correlation with Gli1. Furthermore, we found that Gli1 promotes colorectal cancer cells metastasis in a Foxm1-dependent manner by activating EMT and PI3K-AKT signaling. Thus, we proved that Gli1 plays important role in CRC metastasis and provided a new visual field on the therapy of CRC metastasis. PMID:27863385

  16. Targeting GLI1 Suppresses Cell Growth and Enhances Chemosensitivity in CD34+ Enriched Acute Myeloid Leukemia Progenitor Cells.

    PubMed

    Long, Bing; Wang, Le-Xun; Zheng, Fei-Meng; Lai, Shu-Ping; Xu, Duo-Rong; Hu, Yuan; Lin, Dong-Jun; Zhang, Xiang-Zhong; Dong, Lin; Long, Zi-Jie; Tong, Xiu-Zhen; Liu, Quentin

    2016-01-01

    Resistance of leukemia stem cells (LSCs) to chemotherapy in patients with acute myeloid leukemia (AML) causes relapse of disease. Hedgehog (Hh) signaling plays a critical role in the maintenance and differentiation of cancer stem cells. Yet its role in AML remains controversial. The purpose of the present study is to investigate the role of GLI1, the transcriptional activator of Hh signaling, in AML progenitor cells and to explore the anti-AML effects of GLI small-molecule inhibitor GANT61. The expression of GLI1 mRNA and protein were examined in AML progenitor cells and normal cells. The proliferation, colony formation, apoptosis and differentiation of AML progenitor cells were also analyzed in the presence of GANT61. Kasumi-1 and KG1a cells, containing more CD34+ cells, expressed higher level of GLI1 compared to U937 and NB4 cells with fewer CD34+ cells. Consistently, a positive correlation between the protein levels of GLI1 and CD34 was validated in the bone marrow mononuclear cells (BMMC) of AML patients tested. GANT61 inhibited the proliferation and colony formation in AML cell lines. Importantly, GANT61 induced apoptosis in CD34+ enriched Kasumi-1 and KG1a cells, whereas it induced differentiation in U937 and NB4 cells. Furthermore, GANT61 enhanced the cytotoxicity of cytarabine (Ara-c) in primary CD34+ AML cells, indicating that inhibition of GLI1 could be a promising strategy to enhance chemosensitivity. The present findings suggested that Hh signaling was activated in AML progenitor cells. GLI1 acted as a potential target for AML therapy. © 2016 S. Karger AG, Basel.

  17. Nuclear expression of Gli-1 is predictive of pathologic complete response to chemoradiation in trimodality treated oesophageal cancer patients.

    PubMed

    Wadhwa, Roopma; Wang, Xuemei; Baladandayuthapani, Veerabhadran; Liu, Bin; Shiozaki, Hironori; Shimodaira, Yusuke; Lin, Quan; Elimova, Elena; Hofstetter, Wayne L; Swisher, Stephen G; Rice, David C; Maru, Dipen M; Kalhor, Neda; Bhutani, Manoop S; Weston, Brian; Lee, Jeffrey H; Skinner, Heath D; Scott, Ailing W; Kaya, Dilsa Mizrak; Harada, Kazuto; Berry, Donald; Song, Shumei; Ajani, Jaffer A

    2017-08-22

    Predictive biomarkers or signature(s) for oesophageal cancer (OC) patients undergoing preoperative therapy could help administration of effective therapy, avoidance of ineffective ones, and establishment new strategies. Since the hedgehog pathway is often upregulated in OC, we examined its transcriptional factor, Gli-1, which confers therapy resistance, we wanted to assess Gli-1 as a predictive biomarker for chemoradiation response and validate it. Untreated OC tissues from patients who underwent chemoradiation and surgery were assessed for nuclear Gli-1 by immunohistochemistry and labelling indices (LIs) were correlated with pathologic complete response (pathCR) or Gli-1 LIs were highly associated with pathCR based on the fitted logistic regression models (P<0.0001) in TDS and TVS. The areas under the curve (AUCs) for receiver-operating characteristics (ROCs) based on a fitted model were 0.813 (fivefold cross validation (0.813) and bootstrap resampling (0.816) for TDS and 0.902 (fivefold cross validation (0.901) and bootstrap resampling (0.902)) for TVS. Our preclinical (including genetic knockdown) studies with FU or radiation resistant cell lines demonstrated that Gli-1 indeed mediates therapy resistance in OC. Our validated data in OC show that nuclear Gli-1 LIs are predictive of pathCR after chemoradiation with desirable sensitivity and specificity.

  18. Crystal structure of soybean 11S globulin: Glycinin A3B4 homohexamer

    PubMed Central

    Adachi, Motoyasu; Kanamori, Jiro; Masuda, Taro; Yagasaki, Kazuhiro; Kitamura, Keisuke; Mikami, Bunzo; Utsumi, Shigeru

    2003-01-01

    Most plant seeds contain 11S globulins as major storage proteins for their nutrition. Soybean glycinin belongs to the 11S globulin family and consists of five kinds of subunits. We determined the crystal structure of a homohexamer of the glycinin A3B4 subunit at 2.1-Å resolution. The crystal structure shows that the hexamer has 32-point group symmetry formed by face-to-face stacking of two trimers. The interface buries the highly conserved interchain disulfide. Based on the structure, we propose that an ingenious face-to-face mechanism controls the hexamer formation of the 11S globulin by movement of a mobile disordered region to the side of the trimer after posttranslational processing. Electrostatic analysis of the faces suggests that the interchain disulfide-containing face has high positive potential at acidic pH, which induces dissociation of the hexamer into trimers that may be susceptible to proteinases after seed imbibition. This dissociation might result in the degradation and mobilization of 11S globulins as storage proteins in embryos during germination and seedling growth. PMID:12771376

  19. Heat-Induced changes occurring in oil/water emulsions stabilized by soy glycinin and β-conglycinin.

    PubMed

    Keerati-u-rai, Maneephan; Corredig, Milena

    2010-08-25

    Glycinin and β-conglycinin are the two major proteins in soy protein isolate, and their emulsifying behavior was the subject of this study. These proteins form a thin layer of 30-40 nm when adsorbed at the interface. Microcalorimetric experiments showed that the thermal transitions of these proteins in the emulsion were very similar to those of the proteins in solution. The results also suggested that molecular rearrangements occurred during adsorption of β-conglycinin, as an endothermic transition peak appeared at high temperature when this protein was present at the interface. In general, β-conglycinin exhibited greater emulsifying activity than glycinin, confirming previous reports. Heating at 95 °C for 15 min caused a decrease in solubility of glycinin, and interactions between the oil droplets, with an increase in the apparent viscosity, shear thinning behavior, and droplet particle size distribution of the emulsions. While, similar behavior was noted in b-conglycinin after heating at both 75 and 95 °C. Furthermore, the order of processing affected the subunits' composition at the interface. Heating the solution before emulsification caused a higher protein load at the interface and with all of the subunits present. On the other hand, when heating was carried out after homogenization, the basic glycinin polypeptide and the β subunit of β-conglycinin were absent from the interface, suggesting that heat-induced complexes between these subunits formed and remained soluble in the unadsorbed phase.

  20. The regulation of Hh/Gli1 signaling cascade involves Gsk3β- mediated mechanism in estrogen-derived endometrial hyperplasia.

    PubMed

    Kaushal, Jyoti Bala; Sankhwar, Pushplata; Kumari, Suparna; Popli, Pooja; Shukla, Vinay; Hussain, Mohd Kamil; Hajela, Kanchan; Dwivedi, Anila

    2017-07-26

    The present study was undertaken to explore the functional involvement of Hh signaling and its regulatory mechanism in endometrial hyperplasia. Differential expression of Hh signaling molecules i.e., Ihh, Shh, Gli1 or Gsk3β was observed in endometrial hyperplasial (EH) cells as compared to normal endometrial cells. Estradiol induced the expression of Hh signaling molecules and attenuated the expression of Gsk3β whereas anti-estrogen (K1) or progestin (MPA) suppressed these effects in EH cells. Cyclopamine treatment or Gli1 siRNA knockdown suppressed the growth of EH cells and reduced the expression of proliferative markers. Estradiol also induced the nuclear translocation of Gli1 which was suppressed by both MPA and K1 in EH cells. While exploring non-canonical mechanism, LY-294002 (Gsk3β activator) caused a decrease in Gli1 expression indicating the involvement of Gsk3β in Gli1 regulation. Further, Gsk3β silencing promoted the expression and nuclear translocation of Gli1 demonstrating that Gsk3β serves as a negative kinase regulator of Gli1 in EH cells. Similar attenuation of Hh signaling molecules was observed in rats with uterine hyperplasia undergoing anti-estrogen treatment. The study suggested that Hh/Gli1 cascade (canonical pathway) as well as Gsk3β-Gli1 crosstalk (non-canonical pathway) play crucial role in estrogen-dependent cell proliferation in endometrial hyperplasia.

  1. Rapid and sensitive detection of the food allergen glycinin in powdered milk using a lateral flow colloidal gold immunoassay strip test.

    PubMed

    Wang, Yao; Deng, Ruiguang; Zhang, Gaiping; Li, Qingmei; Yang, Jifei; Sun, Yaning; Li, Zhixi; Hu, Xiaofei

    2015-03-04

    A rapid immunochromatographic lateral flow test strip in a sandwich format was developed with the colloidal gold-labeled mouse antiglycinin monoclonal antibody (mAb) and rabbit antiglycinin polyclonal antibody (pAb) to specifically identify glycinin, a soybean allergen. The test strip is composed of a sample pad, a conjugate reagent pad, an absorbent pad, and a test membrane containing a control line and a test line. This test strip has high sensitivity, and results can be obtained within 10 min without sophisticated procedures. The limit of detection (LOD) of the test strip was calculated to be 0.69 mg/kg using an optical density scanner that measures relative optical density. The assay showed high specificity for glycinin, with no cross-reactions with other soybean proteins or other food allergens. The recoveries of the lateral flow test strip in detecting glycinin in powdered milk samples ranged between 80.5 and 89.9% with relative standard deviations of less than 5.29% (intra-assay) and 6.72% (interassay). Therefore, the test strip is useful as a quantitative, semiquantitative, or qualitative detection method for glycinin in powdered milk. In addition, the test strip can be used to detect glycinin in other processed foods and may be a valuable tool in identifying effective approaches for reducing the impact of glycinin.

  2. Reciprocal Regulation of Hypoxia-Inducible Factor 2α and GLI1 Expression Associated With the Radioresistance of Renal Cell Carcinoma

    SciTech Connect

    Zhou, Jiancheng; Wu, Kaijie; Gao, Dexuan; Zhu, Guodong; Wu, Dapeng; Wang, Xinyang; Chen, Yule; Du, Yuefeng; Song, Wenbin; Ma, Zhenkun; Authement, Craig; Saha, Debabrata; Hsieh, Jer-Tsong; He, Dalin

    2014-11-15

    Purpose: Renal cell carcinoma (RCC) is often considered a radioresistant tumor, but the molecular mechanism underlying its radioresistance is poorly understood. This study explored the roles of hypoxia-inducible factor 2α (HIF2α) and sonic hedgehog (SHH)-GLI1 signaling in mediating the radioresistance of RCC cells and to unveil the interaction between these 2 signaling pathways. Methods and Materials: The activities of SHH-GLI1 signaling pathway under normoxia and hypoxia in RCC cells were examined by real-time polymerase chain reaction, Western blot, and luciferase reporter assay. The expression of HIF2α and GLI1 in RCC patients was examined by immunohistochemistry, and their correlation was analyzed. Furthermore, RCC cells were treated with HIF2α-specific shRNA (sh-HIF2α), GLI1 inhibitor GANT61, or a combination to determine the effect of ionizing radiation (IR) on RCC cells based on clonogenic assay and double-strand break repair assay. Results: RCC cells exhibited elevated SHH-GLI1 activities under hypoxia, which was mediated by HIF2α. Hypoxia induced GLI1 activation through SMO-independent pathways that could be ablated by PI3K inhibitor or MEK inhibitor. Remarkably, the SHH-GLI1 pathway also upregulated HIF2α expression in normoxia. Apparently, there was a positive correlation between HIF2α and GLI1 expression in RCC patients. The combination of sh-HIF2α and GLI1 inhibitor significantly sensitized RCC cells to IR. Conclusions: Cross-talk between the HIF2α and SHH-GLI1 pathways was demonstrated in RCC. Cotargeting these 2 pathways, significantly sensitizing RCC cells to IR, provides a novel strategy for RCC treatment.

  3. Synergistic inhibition of colon carcinoma cell growth by Hedgehog-Gli1 inhibitor arsenic trioxide and phosphoinositide 3-kinase inhibitor LY294002.

    PubMed

    Cai, Xinyi; Yu, Kun; Zhang, Lijuan; Li, Yunfeng; Li, Qiang; Yang, Zhibin; Shen, Tao; Duan, Lincan; Xiong, Wei; Wang, Weiya

    2015-01-01

    The Hedgehog (Hh) signaling pathway not only plays important roles in embryogenesis and adult tissue homeostasis, but also in tumorigenesis. Aberrant Hh pathway activation has been reported in a variety of malignant tumors including colon carcinoma. Here, we sought to investigate the regulation of the Hh pathway transcription factor Gli1 by arsenic trioxide and phosphoinositide 3-kinase (PI3K) inhibitor LY294002 in colon carcinoma cells. We transfected cells with siGli1 and observed a significant reduction of Gli1 expression in HCT116 and HT29 cells, which was confirmed by quantitative real-time polymerase chain reaction and Western blots. Knocking down endogenous Gli1 reduced colon carcinoma cell viability through inducing cell apoptosis. Similarly, knocking down Gli2 using short interfering RNA impaired colon carcinoma cell growth in vitro. To elucidate the regulation of Gli1 expression, we found that both Gli inhibitor arsenic trioxide and PI3K inhibitor LY294002 significantly reduced Gli1 protein expression and colon carcinoma cell proliferation. Arsenic trioxide treatment also reduced Gli1 downstream target gene expression, such as Bcl2 and CCND1. More importantly, the inhibition of Hedgehog-Gli1 by arsenic trioxide showed synergistic anticancer effect with the PI3K inhibitor LY294002 in colon carcinoma cells. Our findings suggest that the Hh pathway transcription factor Gli1 is involved in the regulation of colon carcinoma cell viability. Inhibition of Hedgehog-Gli1 expression by arsenic trioxide and PI3K inhibitor synergistically reduces colon cancer cell proliferation, indicating that they could be used as an effective anti-colon cancer combination therapy.

  4. Targeting the hedgehog transcription factors GLI1 and GLI2 restores sensitivity to vemurafenib-resistant human melanoma cells.

    PubMed

    Faião-Flores, F; Alves-Fernandes, D K; Pennacchi, P C; Sandri, S; Vicente, A L S A; Scapulatempo-Neto, C; Vazquez, V L; Reis, R M; Chauhan, J; Goding, C R; Smalley, K S; Maria-Engler, S S

    2017-03-30

    BRAF inhibitor (BRAFi) therapy for melanoma patients harboring the V600E mutation is initially highly effective, but almost all patients relapse within a few months. Understanding the molecular mechanisms underpinning BRAFi-based therapy is therefore an important issue. Here we identified a previously unsuspected mechanism of BRAFi resistance driven by elevated Hedgehog (Hh) pathway activation that is observed in a cohort of melanoma patients after vemurafenib treatment. Specifically, we demonstrate that melanoma cell lines, with acquired in vitro-induced vemurafenib resistance, show increased levels of glioma-associated oncogene homolog 1 and 2 (GLI1/GLI2) compared with naïve cells. We also observed these findings in clinical melanoma specimens. Moreover, the increased expression of the transcription factors GLI1/GLI2 was independent of canonical Hh signaling and was instead correlated with the noncanonical Hh pathway, involving TGFβ/SMAD (transforming growth factor-β/Sma- and Mad-related family) signaling. Knockdown of GLI1 and GLI2 restored sensitivity to vemurafenib-resistant cells, an effect associated with both growth arrest and senescence. Treatment of vemurafenib-resistant cells with the GLI1/GLI2 inhibitor Gant61 led to decreased invasion of the melanoma cells in a three-dimensional skin reconstruct model and was associated with a decrease in metalloproteinase (MMP2/MMP9) expression and microphthalmia transcription factor upregulation. Gant61 monotherapy did not alter the drug sensitivity of naïve cells, but could reverse the resistance of melanoma cells chronically treated with vemurafenib. We further noted that alternating dosing schedules of Gant61 and vemurafenib prevented the onset of BRAFi resistance, suggesting that this could be a potential therapeutic strategy for the prevention of therapeutic escape. Our results suggest that targeting the Hh pathway in BRAFi-resistant melanoma may represent a viable therapeutic strategy to restore vemurafenib

  5. GLI1, a crucial mediator of sonic hedgehog signaling in prostate cancer, functions as a negative modulator for androgen receptor

    SciTech Connect

    Chen, Guangchun; Goto, Yutaka; Sakamoto, Ryuichi; Tanaka, Kimitaka; Matsubara, Eri; Nakamura, Masafumi; Zheng, Hong; Lu, Jian; Takayanagi, Ryoichi; Nomura, Masatoshi

    2011-01-21

    Research highlights: {yields} GLI1, which play a central role in sonic hedgehog signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor-mediated transactivation. {yields} GLI1 directly interacts with AR. {yields} SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from an androgen-dependent to an androgen-independent state. -- Abstract: Sonic hedgehog (SHH) signaling, acting in a combinatorial manner with androgen signaling, is essential for prostate patterning and development. Recently, elevated activation of SHH signaling has been shown to play important roles in proliferation, progression and metastasis of prostate cancer. In this report, we demonstrate for the first time, that GLI1, which has been shown to play a central role in SHH signaling in prostate cancer, can act as a co-repressor to substantially block androgen receptor (AR)-mediated transactivation, at least in part, by directly interacting with AR. Our observations suggest that the SHH-GLI pathway might be one of determinants governing the transition of prostate cancer from an androgen-dependent to an androgen-independent state by compensating, or even superseding androgen signaling.

  6. STAR proteins quaking-6 and GLD-1 regulate translation of the homologues GLI1 and tra-1 through a conserved RNA 3'UTR-based mechanism.

    PubMed

    Lakiza, Olga; Frater, Leah; Yoo, Young; Villavicencio, Elisabeth; Walterhouse, David; Goodwin, Elizabeth B; Iannaccone, Philip

    2005-11-01

    The binding of the STAR protein GLD-1 to an element in the tra-2 3' untranslated region (3'UTR), called the TGE (tra GLI element), represses tra-2 translation, allowing for hermaphrodite spermatogenesis in Caenorhabditis elegans. GLD-1 is a member of the STAR family that includes the mammalian quaking (Qk) proteins. Here, we show that the 3'UTR of the nematode homologue of GLI1, called tra-1, also contains a TGE, through which translation is regulated by GLD-1. We find that GLD-1 activity is required for proper TRA-1 protein expression in hermaphrodites. RNA gel shift assays show that GLD-1 binds the predicted sites. Using reporter transgenes, we show that the human GLI1 (hGLI1) 3'UTR controls translation in the mouse embryo. We demonstrate that the addition of the mouse QK isoform-6 (QKI-6) protein to a mammalian cell line that lacks QKI-6 can confer regulation on reporter and GLI1 mRNAs in a TGE-specific manner, and reduction of QKI-6 activity with siRNA disrupts translational control. Further, siRNA knockdown of QKI-6 increases the activity of a reporter transgene that monitors the transcriptional activity of mouse Gli1 (mGli1) and increases mouse Gli1 protein. We show by immunoprecipitation that QKI-6 antibody specifically co-purifies TGE-containing mRNAs in ribonucleoproteins. Thus, we find that the mouse QKI-6 protein acts through the mGli1 and hGLI1 RNAs to repress translation. Our results suggest that STAR family-dependent translational control of GLI mRNAs is ancient, and that it existed before the division of nematodes and mammals.

  7. Nuclear localization of GLI1 and elevated expression of FOXC2 in breast cancer is associated with the basal-like phenotype.

    PubMed

    Li, Y; Yang, W; Yang, Q; Zhou, S

    2012-04-01

    Aberrant sonic hedgehog (SHH)/glioma-associated oncogene (GLI) signaling has been shown in the development of many tumors. The aims of the present study are to determine the expression of two SHH signaling molecules, the glioma-associated oncogene homolog 1 (GLI1) and forkhead box C2 (FOXC2), in invasive breast cancers (IBC), to evaluate their association with clinicopathological parameters, and to determine their prognostic significance in breast cancer patients. Expression of GLI1 and FOXC2 were assessed by immunohistochemical analysis of a tissue microarray containing 262 unselected IBC cases. A statistical analysis was performed to assess the correlation of GLI1 and FOXC2 expression with the patients' clinicopathological parameters, postoperative survival rate, and molecular subtypes. Immunoreactivity of GLI1 and FOXC2 was observed in 84% and 75% of all breast cancer tissues, respectively. There was a significant correlation between nuclear FOXC2 and GLI1 expressions in these breast cancers, which was associated with estrogen receptor (ER) negativity. Furthermore, there was a significant association between nuclear expression of GLI1 and FOXC2 and a basal-like breast cancer phenotype. Patients with nuclear GLI1 or FOXC2-expressing tumors had a significantly shorter survival time than those without nuclear FOXC2 or GLI1 expression. Multivariate analysis showed that nuclear GLI1 or FOXC2 expression was an independent factor for predicting the prognosis of basal-like breast cancer. In conclusion, there was a significant correlation between expression of nuclear GLI1 or FOXC2 and human breast cancer. More specifically, elevated levels of these proteins were associated with the basal-like breast cancer phenotype and with a poor rate of disease-free survival. These data suggest that GLI1 and FOXC2 are involved in tumorigenesis and that they may be useful as diagnostic and therapeutic targets for human basal-like breast cancers. Additional studies are warranted to

  8. Activation of the Transcription Factor GLI1 by WNT Signaling Underlies the Role of SULFATASE 2 as a Regulator of Tissue Regeneration*

    PubMed Central

    Nakamura, Ikuo; Fernandez-Barrena, Maite G.; Ortiz-Ruiz, Maria C.; Almada, Luciana L.; Hu, Chunling; Elsawa, Sherine F.; Mills, Lisa D.; Romecin, Paola A.; Gulaid, Kadra H.; Moser, Catherine D.; Han, Jing-Jing; Vrabel, Anne; Hanse, Eric A.; Akogyeram, Nicholas A.; Albrecht, Jeffrey H.; Monga, Satdarshan P. S.; Sanderson, Schuyler O.; Prieto, Jesus; Roberts, Lewis R.; Fernandez-Zapico, Martin E.

    2013-01-01

    Tissue regeneration requires the activation of a set of specific growth signaling pathways. The identity of these cascades and their biological roles are known; however, the molecular mechanisms regulating the interplay between these pathways remain poorly understood. Here, we define a new role for SULFATASE 2 (SULF2) in regulating tissue regeneration and define the WNT-GLI1 axis as a novel downstream effector for this sulfatase in a liver model of tissue regeneration. SULF2 is a heparan sulfate 6-O-endosulfatase, which releases growth factors from extracellular storage sites turning active multiple signaling pathways. We demonstrate that SULF2-KO mice display delayed regeneration after partial hepatectomy (PH). Mechanistic analysis of the SULF2-KO phenotype showed a decrease in WNT signaling pathway activity in vivo. In isolated hepatocytes, SULF2 deficiency blocked WNT-induced β-CATENIN nuclear translocation, TCF activation, and proliferation. Furthermore, we identified the transcription factor GLI1 as a novel target of the SULF2-WNT cascade. WNT induces GLI1 expression in a SULF2- and β-CATENIN-dependent manner. GLI1-KO mice phenocopied the SULF2-KO, showing delayed regeneration and decreased hepatocyte proliferation. Moreover, we identified CYCLIN D1, a key mediator of cell growth during tissue regeneration, as a GLI1 transcriptional target. GLI1 binds to the cyclin d1 promoter and regulates its activity and expression. Finally, restoring GLI1 expression in the liver of SULF2-KO mice after PH rescues CYCLIN D1 expression and hepatocyte proliferation to wild-type levels. Thus, together these findings define a novel pathway in which SULF2 regulates tissue regeneration in part via the activation of a novel WNT-GLI1-CYCLIN D1 pathway. PMID:23740243

  9. Activation of the transcription factor GLI1 by WNT signaling underlies the role of SULFATASE 2 as a regulator of tissue regeneration.

    PubMed

    Nakamura, Ikuo; Fernandez-Barrena, Maite G; Ortiz-Ruiz, Maria C; Almada, Luciana L; Hu, Chunling; Elsawa, Sherine F; Mills, Lisa D; Romecin, Paola A; Gulaid, Kadra H; Moser, Catherine D; Han, Jing-Jing; Vrabel, Anne; Hanse, Eric A; Akogyeram, Nicholas A; Albrecht, Jeffrey H; Monga, Satdarshan P S; Sanderson, Schuyler O; Prieto, Jesus; Roberts, Lewis R; Fernandez-Zapico, Martin E

    2013-07-19

    Tissue regeneration requires the activation of a set of specific growth signaling pathways. The identity of these cascades and their biological roles are known; however, the molecular mechanisms regulating the interplay between these pathways remain poorly understood. Here, we define a new role for SULFATASE 2 (SULF2) in regulating tissue regeneration and define the WNT-GLI1 axis as a novel downstream effector for this sulfatase in a liver model of tissue regeneration. SULF2 is a heparan sulfate 6-O-endosulfatase, which releases growth factors from extracellular storage sites turning active multiple signaling pathways. We demonstrate that SULF2-KO mice display delayed regeneration after partial hepatectomy (PH). Mechanistic analysis of the SULF2-KO phenotype showed a decrease in WNT signaling pathway activity in vivo. In isolated hepatocytes, SULF2 deficiency blocked WNT-induced β-CATENIN nuclear translocation, TCF activation, and proliferation. Furthermore, we identified the transcription factor GLI1 as a novel target of the SULF2-WNT cascade. WNT induces GLI1 expression in a SULF2- and β-CATENIN-dependent manner. GLI1-KO mice phenocopied the SULF2-KO, showing delayed regeneration and decreased hepatocyte proliferation. Moreover, we identified CYCLIN D1, a key mediator of cell growth during tissue regeneration, as a GLI1 transcriptional target. GLI1 binds to the cyclin d1 promoter and regulates its activity and expression. Finally, restoring GLI1 expression in the liver of SULF2-KO mice after PH rescues CYCLIN D1 expression and hepatocyte proliferation to wild-type levels. Thus, together these findings define a novel pathway in which SULF2 regulates tissue regeneration in part via the activation of a novel WNT-GLI1-CYCLIN D1 pathway.

  10. Coagulation of β-conglycinin, glycinin and isoflavones induced by calcium chloride in soymilk

    NASA Astrophysics Data System (ADS)

    Hsiao, Yu-Hsuan; Yu, Chia-Jung; Li, Wen-Tai; Hsieh, Jung-Feng

    2015-08-01

    The coagulation of β-conglycinin (7S), glycinin (11S) and isoflavones induced by calcium chloride was investigated. Approximately 92.6% of the soymilk proteins were coagulated into the soymilk pellet fraction (SPF) after the addition of 5 mM calcium chloride. SDS-PAGE and two-dimensional electrophoresis analysis indicated that most of the 7S (α’, α and β), 11S acidic (A1a, A1b, A2, A3 and A4) and 11S basic (B1a) proteins in the SSF were coagulated into the SPF after treatment with 5 mM calcium chloride. Isoflavones, including daidzein and genistein, were also coagulated into the SPF after the addition of 5 mM calcium chloride. The amounts of daidzein and genistein in the SSF decreased to 39.4 ± 1.6 and 11.8 ± 7.0%, respectively. HPLC analysis suggested that daidzein and genistein were bound with 7S and 11S proteins and then were coprecipitated into the SPF by 5 mM calcium chloride.

  11. Coagulation of β-conglycinin, glycinin and isoflavones induced by calcium chloride in soymilk.

    PubMed

    Hsiao, Yu-Hsuan; Yu, Chia-Jung; Li, Wen-Tai; Hsieh, Jung-Feng

    2015-08-11

    The coagulation of β-conglycinin (7S), glycinin (11S) and isoflavones induced by calcium chloride was investigated. Approximately 92.6% of the soymilk proteins were coagulated into the soymilk pellet fraction (SPF) after the addition of 5 mM calcium chloride. SDS-PAGE and two-dimensional electrophoresis analysis indicated that most of the 7S (α', α and β), 11S acidic (A1a, A1b, A2, A3 and A4) and 11S basic (B1a) proteins in the SSF were coagulated into the SPF after treatment with 5 mM calcium chloride. Isoflavones, including daidzein and genistein, were also coagulated into the SPF after the addition of 5 mM calcium chloride. The amounts of daidzein and genistein in the SSF decreased to 39.4 ± 1.6 and 11.8 ± 7.0%, respectively. HPLC analysis suggested that daidzein and genistein were bound with 7S and 11S proteins and then were coprecipitated into the SPF by 5 mM calcium chloride.

  12. Coagulation of β-conglycinin, glycinin and isoflavones induced by calcium chloride in soymilk

    PubMed Central

    Hsiao, Yu-Hsuan; Yu, Chia-Jung; Li, Wen-Tai; Hsieh, Jung-Feng

    2015-01-01

    The coagulation of β-conglycinin (7S), glycinin (11S) and isoflavones induced by calcium chloride was investigated. Approximately 92.6% of the soymilk proteins were coagulated into the soymilk pellet fraction (SPF) after the addition of 5 mM calcium chloride. SDS-PAGE and two-dimensional electrophoresis analysis indicated that most of the 7S (α’, α and β), 11S acidic (A1a, A1b, A2, A3 and A4) and 11S basic (B1a) proteins in the SSF were coagulated into the SPF after treatment with 5 mM calcium chloride. Isoflavones, including daidzein and genistein, were also coagulated into the SPF after the addition of 5 mM calcium chloride. The amounts of daidzein and genistein in the SSF decreased to 39.4 ± 1.6 and 11.8 ± 7.0%, respectively. HPLC analysis suggested that daidzein and genistein were bound with 7S and 11S proteins and then were coprecipitated into the SPF by 5 mM calcium chloride. PMID:26260443

  13. Synergistic foaming and surface properties of a weakly interacting mixture of soy glycinin and biosurfactant stevioside.

    PubMed

    Wan, Zhi-Li; Wang, Li-Ying; Wang, Jin-Mei; Yuan, Yang; Yang, Xiao-Quan

    2014-07-16

    The adsorption of the mixtures of soy glycinin (11S) with a biosurfactant stevioside (STE) at the air-water interface was studied to understand its relation with foaming properties. A combination of several techniques such as dynamic surface tension, dilatational rheology, fluorescence spectroscopy, and isothermal titration calorimetry (ITC) was used. In the presence of intermediate STE concentrations (0.25-0.5%), the weak binding of STE with 11S in bulk occurred by hydrophobic interactions, which could induce conformational changes of 11S, as evidenced by fluorescence and ITC. Accordingly, the strong synergy in reducing surface tension and the plateau in surface elasticity for mixed 11S-STE layers formed from the weakly interacting mixtures were clearly observed. This effect could be explained by the complexation with STE, which might facilitate the partial dissociation and further unfolding of 11S upon adsorption, thus enhancing the protein-protein and protein-STE interfacial interactions. These surface properties were positively reflected in foams produced by the weakly interacting system, which exhibited good foaming capacity and considerable stability probably due to better response to external stresses. However, at high STE concentrations (1-2%), as a consequence of the interface dominated by STE due to the preferential adsorption of STE molecules, the surface elasticity of layers dramatically decreased, and the resultant foams became less stable.

  14. Coacervation of β-conglycinin, glycinin and isoflavones induced by propylene glycol alginate in heated soymilk.

    PubMed

    Hsiao, Yu-Hsuan; Lu, Chun-Ping; Kuo, Meng-I; Hsieh, Jung-Feng

    2016-06-01

    This study investigated the propylene glycol alginate (PGA)-induced coacervation of β-conglycinin (7S), glycinin (11S) and isoflavones in heated soymilk. The addition of 0.9% PGA caused 7S, 11S, daidzein and genistein to coacervate following a 1h incubation period. SDS-PAGE showed that the protein bands corresponding to the 7S α', 7S α, 7S β, 11S A3, and 11S acidic subunits and the 11S basic proteins in the soymilk supernatant fraction (SSF) decreased to 37.7 ± 12.7%, 24.7 ± 3.9%, 4.9 ± 1.8%, 8.5 ± 2.7%, 18.1 ± 1.8% and 6.0 ± 1.6%, respectively. In addition, isoflavones including daidzein and genistein were also coacervated from the SSF into the soymilk pellet fraction (SPF) following incubation with 0.9% PGA for 1h. The amounts of daidzein and genistein in the SSF decreased to 8.6 ± 1.6% and 2.0 ± 1.0%, respectively. HPLC analysis suggested that daidzein and genistein were bound to the 7S and 11S proteins. These results suggested that daidzein and genistein were co-precipitated with the 7S and 11S proteins into the SPF by 0.9% PGA. Our results demonstrated that PGA is a potent coagulant for the coacervation of 7S, 11S, daidzein and genistein.

  15. Identification of a novel actin-dependent signal transducing module allows for the targeted degradation of GLI1.

    PubMed

    Schneider, Philipp; Bayo-Fina, Juan Miguel; Singh, Rajeev; Kumar Dhanyamraju, Pavan; Holz, Philipp; Baier, Aninja; Fendrich, Volker; Ramaswamy, Annette; Baumeister, Stefan; Martinez, Elisabeth D; Lauth, Matthias

    2015-08-27

    The Down syndrome-associated DYRK1A kinase has been reported as a stimulator of the developmentally important Hedgehog (Hh) pathway, but cells from Down syndrome patients paradoxically display reduced Hh signalling activity. Here we find that DYRK1A stimulates GLI transcription factor activity through phosphorylation of general nuclear localization clusters. In contrast, in vivo and in vitro experiments reveal that DYRK1A kinase can also function as an inhibitor of endogenous Hh signalling by negatively regulating ABLIM proteins, the actin cytoskeleton and the transcriptional co-activator MKL1 (MAL). As a final effector of the DYRK1A-ABLIM-actin-MKL1 sequence, we identify the MKL1 interactor Jumonji domain demethylase 1A (JMJD1A) as a novel Hh pathway component stabilizing the GLI1 protein in a demethylase-independent manner. Furthermore, a Jumonji-specific small-molecule antagonist represents a novel and powerful inhibitor of Hh signal transduction by inducing GLI1 protein degradation in vitro and in vivo.

  16. A three-part signal governs differential processing of Gli1 and Gli3 proteins by the proteasome.

    PubMed

    Schrader, Erin K; Harstad, Kristine G; Holmgren, Robert A; Matouschek, Andreas

    2011-11-11

    The Gli proteins are the transcriptional effectors of the mammalian Hedgehog signaling pathway. In an unusual mechanism, the proteasome partially degrades or processes Gli3 in the absence of Hedgehog pathway stimulation to create a Gli3 fragment that opposes the activity of the full-length protein. In contrast, Gli1 is not processed but degraded completely, despite considerable homology with Gli3. We found that these differences in processing can be described by defining a processing signal that is composed of three parts: the zinc finger domain, an adjacent linker sequence, and a degron. Gli3 processing is inhibited when any one component of the processing signal is disrupted. We show that the zinc fingers are required for processing only as a folded structure and that the location but not the identity of the processing degron is critical. Within the linker sequence, regions of low sequence complexity play a crucial role, but other sequence features are also important. Gli1 is not processed because two components of the processing signal, the linker sequence and the degron, are ineffective. These findings provide new insights into the molecular elements that regulate Gli protein processing by the proteasome.

  17. Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma

    PubMed Central

    Coni, Sonia; Mancuso, Anna Barbara; Di Magno, Laura; Sdruscia, Giulia; Manni, Simona; Serrao, Silvia Maria; Rotili, Dante; Spiombi, Eleonora; Bufalieri, Francesca; Petroni, Marialaura; Kusio-Kobialka, Monika; De Smaele, Enrico; Ferretti, Elisabetta; Capalbo, Carlo; Mai, Antonello; Niewiadomski, Pawel; Screpanti, Isabella; Di Marcotullio, Lucia; Canettieri, Gianluca

    2017-01-01

    SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach. We show here that selective inhibition of the downstream Hh effectors HDAC1 and HDAC2 robustly counteracts SHH-MB growth in mouse models. These two deacetylases are upregulated in tumor and their knockdown inhibits Hh signaling and decreases tumor growth. We demonstrate that mocetinostat (MGCD0103), a selective HDAC1/HDAC2 inhibitor, is a potent Hh inhibitor and that its effect is linked to Gli1 acetylation at K518. Of note, we demonstrate that administration of mocetinostat to mouse models of SHH-MB drastically reduces tumor growth, by reducing proliferation and increasing apoptosis of tumor cells and prolongs mouse survival rate. Collectively, these data demonstrate the preclinical efficacy of targeting the downstream HDAC1/2-Gli1 acetylation in the treatment of SHH-MB. PMID:28276480

  18. The Notch Target Hes1 Directly Modulates Gli1 Expression and Hedgehog Signaling: A Potential Mechanism of Therapeutic Resistance

    PubMed Central

    Schreck, Karisa C.; Taylor, Pete; Marchionni, Luigi; Gopalakrishnan, Vidya; Bar, Eli E.; Gaiano, Nicholas; Eberhart, Charles G.

    2010-01-01

    Purpose Multiple developmental pathways including Notch, Hedgehog, and Wnt are active in malignant brain tumors such as medulloblastoma and glioblastoma (GBM). This raises the possibility that tumors might compensate for therapy directed against one pathway by upregulating a different one. We investigated whether brain tumors show resistance to therapies against Notch, and whether targeting multiple pathways simultaneously would kill brain tumor cells more effectively than monotherapy. Experimental Design We used GBM neurosphere lines to investigate the effects of a gamma-secretase inhibitor (MRK-003) on tumor growth, and chromatin immunoprecipitation (ChIP) to study the regulation of other genes by Notch targets. We also evaluated the effect of combined therapy with a Hedgehog inhibitor (cyclopamine) in GBM and medulloblastoma lines, and primary human GBM cultures. Results GBM cells are at least partially resistant to long-term MRK-003 treatment, despite ongoing Notch pathway suppression, and show concomitant upregulation of Wnt and Hedgehog activity. The Notch target Hes1, a repressive transcription factor, bound the Gli1 first intron, and may inhibit its expression. Similar results were observed in a melanoma-derived cell line. Targeting Notch and Hedgehog simultaneously induced apoptosis, decreased cell growth, and inhibited colony-forming ability more dramatically than monotherapy. Low-passage neurospheres isolated from freshly resected human GBMs were also highly susceptible to co-inhibition of the two pathways, indicating that targeting multiple developmental pathways can be more effective than monotherapy at eliminating glioblastoma-derived cells. Conclusion Notch may directly suppress Hedgehog via Hes1 mediated inhibition of Gli1 transcription, and targeting both pathways simultaneously may be more effective at eliminating GBMs cells. PMID:21169257

  19. The hedgehog/Gli-1 signaling pathways is involved in the inhibitory effect of resveratrol on human colorectal cancer HCT116 cells

    PubMed Central

    Du, Zhou; Zhou, Feng; Jia, Zengrong; Zheng, Beishi; Han, Shaoliang; Cheng, Jun; Zhu, Guanbao; Huang, Ping

    2016-01-01

    Objective(s): The study aimed to investigate the effects of resveratrol on colorectal cancer HCT116 cells, including cell viability, apoptosis, and migration, and the partial mechanisms focused on hedgehog/gli-1 signaling pathways. Materials and Methods: We chose the appropriate time and concentration of recombinant human Sonic hedgehog (Shh) stimulation by cell viability. The proportion of cell apoptosis was detected by flow cytometry; HCT116 cell migration was measured by scratch test; the expression of Ptch, Smo, and Gli-1 was measured by Western blot analysis. Results: Shh signaling increased HCT116 cell viability and migration, inhibited cell apoptosis, and upregulated the expression of Ptch, Smo, and Gli-1. Resveratrol obviously inhibited HCT116 cell viability and migration, promoted cell apoptosis, and suppressed the protein of Ptch, Smo, and Gli-1. Furthermore, the effects of resveratrol and Shh on human colorectal cancer HCT116 cells were in a dose- and time-dependent manner. Conclusion: The inhibitory effect of resveratrol on HCT116 cells may be mediated by hedgehog/gli-1 signaling pathways. PMID:27917272

  20. Targeting the PI3K/AKT pathway via GLI1 inhibition enhanced the drug sensitivity of acute myeloid leukemia cells

    PubMed Central

    Liang, Hui; Zheng, Qi-Li; Fang, Peng; Zhang, Jian; Zhang, Tuo; Liu, Wei; Guo, Min; Robinson, Christopher L.; Chen, Shui-bing; Chen, Xiao-Ping; Chen, Fang-Ping; Zeng, Hui

    2017-01-01

    Combination targeted therapy is commonly used to treat acute myeloid leukemia (AML) patients, particularly in refractory/relapse (RR) population. However, concerns have been raised regarding the safety and patient tolerance of combination chemotherapy. It is critical to choose the appropriate treatment for precision therapy. We performed genome-wide RNA profiling using RNA-Seq to compare the RR group and the complete remission (CR) group (a total of 42 adult AML patients). The Hedgehog (Hh) and PI3K/AKT pathways were upregulated in the RR population, which was further confirmed by western blot and/or qPCR. Overexpression of GLI1 in AML cells led to increased AKT phosphorylation and decreased drug sensitivity, which was attenuated by GLI1 inhibition. By contrast, neither the expression of GLI1 nor apoptosis in response to Ara-C treatment of AML cells was significantly affected by PI3K inhibition. Furthermore, co-inhibition of GLI1 and PI3K induced apoptosis of hematopoietic stem/progenitor cells (HSPCs), which raised serious concerns about the side effects of this treatment. These results indicated that GLI1 inhibition alone, but not combined inhibition, is sufficient to enhance AML drug sensitivity, which provides a novel therapeutic strategy for AML treatment. PMID:28098170

  1. Angiotensin I-converting enzyme inhibitory peptide derived from glycinin, the 11S globulin of soybean (Glycine max).

    PubMed

    Mallikarjun Gouda, K G; Gowda, Lalitha R; Rao, A G Appu; Prakash, V

    2006-06-28

    Angiotensin I-converting enzyme (ACE), a dipeptidyl carboxypeptidase, catalyzes the conversion of Angiotensin I to the potent vasoconstrictor Angiotensin II and plays an important physiological role in regulating blood pressure. Inhibitors of angiotensin 1-converting enzyme derived from food proteins are utilized for pharmaceuticals and physiologically functional foods. ACE inhibitory properties of different enzymatic hydrolysates of glycinin, the major storage protein of soybean, have been demonstrated. The IC50 value for the different enzyme digests ranges from 4.5 to 35 microg of N2. The Protease P hydrolysate contained the most potent suite of ACE inhibitory peptides. The ACE inhibitory activity of the Protease P hydrolysate after fractionation by RP-HPLC and ion-pair chromatography was ascribed to a single peptide. The peptide was homogeneous as evidenced by MALDI-TOF and identified to be a pentapeptide. The sequence was Val-Leu-Ile-Val-Pro. This peptide was synthesized using solid-phase FMOC chemistry. The IC50 for ACE inhibition was 1.69 +/- 0.17 microM. The synthetic peptide was a potent competitive inhibitor of ACE with a Ki of 4.5 +/- 0.25 x 10(-6) M. This peptide was resistant to digestion by proteases of the gastrointestinal tract. The antihypertensive property of this peptide derived from glycinin might find importance in the development of therapeutic functional foods.

  2. Adsorption of glycinin and β-conglycinin on silica and cellulose: surface interactions as a function of denaturation, pH, and electrolytes.

    PubMed

    Salas, Carlos; Rojas, Orlando J; Lucia, Lucian A; Hubbe, Martin A; Genzer, Jan

    2012-02-13

    Soybean proteins have found uses in different nonfood applications due to their interesting properties. We report on the kinetics and extent of adsorption on silica and cellulose surfaces of glycinin and β-conglycinin, the main proteins present in soy. Quartz crystal microgravimetry (QCM) experiments indicate that soy protein adsorption is strongly affected by changes in the physicochemical environment. The affinity of glycinin and the mass adsorbed on silica and cellulose increases (by ca. 13 and 89%, respectively) with solution ionic strength (as it increases from 0 to 100 mM NaCl) due to screening of electrostatic interactions. In contrast, β-conglycinin adsorbs on the same substrates to a lower extent and the addition of electrolyte reduces adsorption (by 25 and 57%, respectively). The addition of 10 mM 2-mercaptoethanol, a denaturing agent, reduces the adsorption of both proteins with a significant effect for glycinin. This observation is explained by the cleavage of disulfide bonds which allows unfolding of the molecules and promotes dissociation into subunits that favors more compact adsorbed layer structures. In addition, adsorption of glycinin onto cellulose decreases with lowering the pH from neutral to pH 3 due to dissociation of the macromolecules, resulting in flatter adsorbed layers. The respective adsorption isotherms fit a Langmuir model and QCM shifts in energy dissipation and frequency reveal multiple-step kinetic processes indicative of changes in adlayer structure.

  3. Whole-genome resequencing identifies the molecular genetic cause for the absence of a Gy5 glycinin protein in soybean PI 603408

    USDA-ARS?s Scientific Manuscript database

    During ongoing proteomic analysis of the soybean (Glycine max (L.) Merr) germplasm collection, PI 603408 was identified as a landrace whose seeds lack accumulation of one of the major seed storage glycinin protein subunits. Whole genomic resequencing was used to identify a two-base deletion affectin...

  4. Hepatitis B virus X protein stimulates the Hedgehog-Gli activation through protein stabilization and nuclear localization of Gli1 in liver cancer cells.

    PubMed

    Kim, Hye Young; Cho, Hyun Kook; Hong, Sung Pyo; Cheong, Jaehun

    2011-10-28

    Chronic hepatitis B virus (HBV) infection is a major cause of chronic liver diseases, which frequently results in hepatits, cirrhosis, fibrosis, and ultimately hepatocellular carcinoma (HCC). Recent studies have shown the activation of Hedgehog signaling in HCC. Here, we provide evidences that HBV induces Gli-directed gene transactivation. HBx increases the protein stability of Gli proteins, which are key transcription factors of the Hedgehog signaling pathway, and nucleus translocation of Gli1 through direct protein interaction of HBx and Gli1. This functional synergism of Gli1 protein by HBx increases the Hedgehog activation-directed gene expression. Taken together, these results suggest that HBV infection might induce hepatocellular carcinoma by modulating post-translational activation of the hedgehog signaling components. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  5. Down-regulation of the zinc-finger homeobox protein TSHZ2 releases GLI1 from the nuclear repressor complex to restore its transcriptional activity during mammary tumorigenesis

    PubMed Central

    Riku, Miho; Inaguma, Shingo; Ito, Hideaki; Tsunoda, Takumi; Ikeda, Hiroshi; Kasai, Kenji

    2016-01-01

    Although breast cancer is one of the most common malignancies, the molecular mechanisms underlying its development and progression are not fully understood. To identify key molecules involved, we screened publicly available microarray datasets for genes differentially expressed between breast cancers and normal mammary glands. We found that three of the genes predicted in this analysis were differentially expressed among human mammary tissues and cell lines. Of these genes, we focused on the role of the zinc-finger homeobox protein TSHZ2, which is down-regulated in breast cancer cells. We found that TSHZ2 is a nuclear protein harboring a bipartite nuclear localization signal, and we confirmed its function as a C-terminal binding protein (CtBP)-dependent transcriptional repressor. Through comprehensive screening, we identified TSHZ2-suppressing genes such as AEBP1 and CXCR4, which are conversely up-regulated by GLI1, the downstream transcription factor of Hedgehog signaling. We found that GLI1 forms a ternary complex with CtBP2 in the presence of TSHZ2 and that the transcriptional activity of GLI1 is suppressed by TSHZ2 in a CtBP-dependent manner. Indeed, knockdown of TSHZ2 increases the expression of AEBP1 and CXCR4 in TSHZ2-expressing immortalized mammary duct epithelium. Concordantly, immunohistochemical staining of mammary glands revealed that normal duct cells expresses GLI1 in the nucleus along with TSHZ2 and CtBP2, whereas invasive ductal carcinoma cells, which does not express TSHZ2, show the increase in the expression of AEBP1 and CXCR4 and in the cytoplasmic localization of GLI1. Thus, we propose that down-regulation of TSHZ2 is crucial for mammary tumorigenesis via the activation of GLI1. PMID:26744317

  6. Hedgehog Signaling Pathway Is Active in GBM with GLI1 mRNA Expression Showing a Single Continuous Distribution Rather than Discrete High/Low Clusters

    PubMed Central

    Biswas, Nidhan K.; Rote, Sarang; Chatterjee, Uttara; Ghosh, Samarendra N.; Deb, Sumit; Saha, Suniti K.; Chowdhury, Anup K.; Ghosh, Subhashish; Rudin, Charles M.; Mukherjee, Ankur; Basu, Analabha; Dhara, Surajit

    2015-01-01

    Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression—as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution—unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the “high-Hh” cluster of MB but 5.6 fold higher than that of the “low-Hh” cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them. PMID:25775002

  7. Hedgehog signaling pathway is active in GBM with GLI1 mRNA expression showing a single continuous distribution rather than discrete high/low clusters.

    PubMed

    Chandra, Vikas; Das, Tapojyoti; Gulati, Puneet; Biswas, Nidhan K; Rote, Sarang; Chatterjee, Uttara; Ghosh, Samarendra N; Deb, Sumit; Saha, Suniti K; Chowdhury, Anup K; Ghosh, Subhashish; Rudin, Charles M; Mukherjee, Ankur; Basu, Analabha; Dhara, Surajit

    2015-01-01

    Hedgehog (Hh) signaling pathway is a valid therapeutic target in a wide range of malignancies. We focus here on glioblastoma multiforme (GBM), a lethal malignancy of the central nervous system (CNS). By analyzing RNA-sequencing based transcriptomics data on 149 clinical cases of TCGA-GBM database we show here a strong correlation (r = 0.7) between GLI1 and PTCH1 mRNA expression--as a hallmark of the canonical Hh-pathway activity in this malignancy. GLI1 mRNA expression varied in 3 orders of magnitude among the GBM patients of the same cohort showing a single continuous distribution-unlike the discrete high/low-GLI1 mRNA expressing clusters of medulloblastoma (MB). When compared with MB as a reference, the median GLI1 mRNA expression in GBM appeared 14.8 fold lower than that of the "high-Hh" cluster of MB but 5.6 fold higher than that of the "low-Hh" cluster of MB. Next, we demonstrated statistically significant up- and down-regulation of GLI1 mRNA expressions in GBM patient-derived low-passage neurospheres in vitro by sonic hedgehog ligand-enriched conditioned media (shh-CM) and by Hh-inhibitor drug vismodegib respectively. We also showed clinically achievable dose (50 μM) of vismodegib alone to be sufficient to induce apoptosis and cell cycle arrest in these low-passage GBM neurospheres in vitro. Vismodegib showed an effect on the neurospheres, both by down-regulating GLI1 mRNA expression and by inducing apoptosis/cell cycle arrest, irrespective of their relative endogenous levels of GLI1 mRNA expression. We conclude from our study that this single continuous distribution pattern of GLI1 mRNA expression technically puts almost all GBM patients in a single group rather than discrete high- or low-clusters in terms of Hh-pathway activity. That is suggestive of therapies with Hh-pathway inhibitor drugs in this malignancy without a need for further stratification of patients on the basis of relative levels of Hh-pathway activity among them.

  8. The transcription factor GLI1 interacts with SMAD proteins to modulate transforming growth factor β-induced gene expression in a p300/CREB-binding protein-associated factor (PCAF)-dependent manner.

    PubMed

    Nye, Monica D; Almada, Luciana L; Fernandez-Barrena, Maite G; Marks, David L; Elsawa, Sherine F; Vrabel, Anne; Tolosa, Ezequiel J; Ellenrieder, Volker; Fernandez-Zapico, Martin E

    2014-05-30

    The biological role of the transcription factor GLI1 in the regulation of tumor growth is well established; however, the molecular events modulating this phenomenon remain elusive. Here, we demonstrate a novel mechanism underlying the role of GLI1 as an effector of TGFβ signaling in the regulation of gene expression in cancer cells. TGFβ stimulates GLI1 activity in cancer cells and requires its transcriptional activity to induce BCL2 expression. Analysis of the mechanism regulating this interplay identified a new transcriptional complex including GLI1 and the TGFβ-regulated transcription factor, SMAD4. We demonstrate that SMAD4 physically interacts with GLI1 for concerted regulation of gene expression and cellular survival. Activation of the TGFβ pathway induces GLI1-SMAD4 complex binding to the BCL2 promoter whereas disruption of the complex through SMAD4 RNAi depletion impairs GLI1-mediated transcription of BCL2 and cellular survival. Further characterization demonstrated that SMAD2 and the histone acetyltransferase, PCAF, participate in this regulatory mechanism. Both proteins bind to the BCL2 promoter and are required for TGFβ- and GLI1-stimulated gene expression. Moreover, SMAD2/4 RNAi experiments showed that these factors are required for the recruitment of GLI1 to the BCL2 promoter. Finally, we determined whether this novel GLI1 transcriptional pathway could regulate other TGFβ targets. We found that two additional TGFβ-stimulated genes, INTERLEUKIN-7 and CYCLIN D1, are dependent upon the intact GLI1-SMAD-PCAF complex for transcriptional activation. Collectively, these results define a novel epigenetic mechanism that uses the transcription factor GLI1 and its associated complex as a central effector to regulate gene expression in cancer cells.

  9. The Transcription Factor GLI1 Interacts with SMAD Proteins to Modulate Transforming Growth Factor β-Induced Gene Expression in a p300/CREB-binding Protein-associated Factor (PCAF)-dependent Manner*

    PubMed Central

    Nye, Monica D.; Almada, Luciana L.; Fernandez-Barrena, Maite G.; Marks, David L.; Elsawa, Sherine F.; Vrabel, Anne; Tolosa, Ezequiel J.; Ellenrieder, Volker; Fernandez-Zapico, Martin E.

    2014-01-01

    The biological role of the transcription factor GLI1 in the regulation of tumor growth is well established; however, the molecular events modulating this phenomenon remain elusive. Here, we demonstrate a novel mechanism underlying the role of GLI1 as an effector of TGFβ signaling in the regulation of gene expression in cancer cells. TGFβ stimulates GLI1 activity in cancer cells and requires its transcriptional activity to induce BCL2 expression. Analysis of the mechanism regulating this interplay identified a new transcriptional complex including GLI1 and the TGFβ-regulated transcription factor, SMAD4. We demonstrate that SMAD4 physically interacts with GLI1 for concerted regulation of gene expression and cellular survival. Activation of the TGFβ pathway induces GLI1-SMAD4 complex binding to the BCL2 promoter whereas disruption of the complex through SMAD4 RNAi depletion impairs GLI1-mediated transcription of BCL2 and cellular survival. Further characterization demonstrated that SMAD2 and the histone acetyltransferase, PCAF, participate in this regulatory mechanism. Both proteins bind to the BCL2 promoter and are required for TGFβ- and GLI1-stimulated gene expression. Moreover, SMAD2/4 RNAi experiments showed that these factors are required for the recruitment of GLI1 to the BCL2 promoter. Finally, we determined whether this novel GLI1 transcriptional pathway could regulate other TGFβ targets. We found that two additional TGFβ-stimulated genes, INTERLEUKIN-7 and CYCLIN D1, are dependent upon the intact GLI1-SMAD-PCAF complex for transcriptional activation. Collectively, these results define a novel epigenetic mechanism that uses the transcription factor GLI1 and its associated complex as a central effector to regulate gene expression in cancer cells. PMID:24739390

  10. Nanoquinacrine caused apoptosis in oral cancer stem cells by disrupting the interaction between GLI1 and β catenin through activation of GSK3β.

    PubMed

    Nayak, Anmada; Siddharth, Sumit; Das, Sarita; Nayak, Deepika; Sethy, Chinmayee; Kundu, Chanakya Nath

    2017-09-01

    Presences of cancer stem cells (CSCs) in a bulk of cancer cells are responsible for tumor relapse, metastasis and drug resistance in oral cancer. Due to high drug efflux, DNA repair and self-renewable capacity of CSCs, the conventional chemotherapeutic agents are unable to kill the CSCs. CSCs utilizes Hedgehog (HH-GLI), WNT-β catenin signalling for its growth and development. GSK3β negatively regulates both the pathways in CSCs. Here, we have shown that a nano-formulated bioactive small molecule inhibitor Quinacrine (NQC) caused apoptosis in oral cancer stem cells (OCSCs; isolated from different oral cancer cells and oral cancer patient derived primary cells) by down regulating WNT-β catenin and HH-GLI components through activation of GSK3β. NQC activates GSK3β in transcriptional and translational level and reduces β catenin and GLI1 as well as downstream target gene of both the pathways Cyclin D1, C-Myc. The transcription factor activity of both the pathways was also reduced by NQC treatment. GSK3β, β catenin and GLI1 interacts with each other and NQC disrupts the co-localization and interaction between β catenin and GLI1 in OCSCs in a dose dependent manner through activation of GSK3β. Thus, data suggest NQC caused OCSCs death by disrupting the crosstalk between β catenin and GLI1 by activation of GSK3β. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Loss of WNT-TCF addiction and enhancement of HH-GLI1 signalling define the metastatic transition of human colon carcinomas.

    PubMed

    Varnat, Frédéric; Siegl-Cachedenier, Irene; Malerba, Monica; Gervaz, Pascal; Ruiz i Altaba, Ariel

    2010-11-01

    Previous studies demonstrate the initiation of colon cancers through deregulation of WNT-TCF signalling. An accepted but untested extension of this finding is that incurable metastatic colon carcinomas (CCs) universally remain WNT-TCF-dependent, prompting the search for WNT-TCF inhibitors. CCs and their stem cells also require Hedgehog (HH)-GLI1 activity, but how these pathways interact is unclear. Here we define coincident high-to-low WNT-TCF and low-to-high HH-GLI transitions in patient CCs, most strikingly in their CD133(+) stem cells, that mark the development of metastases. We find that enhanced HH-GLI mimics this transition, driving also an embryonic stem (ES)-like stemness signature and that GLI1 can be regulated by multiple CC oncogenes. The data support a model in which the metastatic transition involves the acquisition or enhancement of a more primitive ES-like phenotype, and the downregulation of the early WNT-TCF programme, driven by oncogene-regulated high GLI1 activity. Consistently, TCF blockade does not generally inhibit tumour growth; instead, it, like enhanced HH-GLI, promotes metastatic growth in vivo. Treatments for metastatic disease should therefore block HH-GLI1 but not WNT-TCF activities.

  12. Inhibition of the CyclinD1 promoter in response to sonic hedgehog signaling pathway transduction is mediated by Gli1

    PubMed Central

    Lin, Zhongxiao; Sheng, Hansong; You, Chaoguo; Cai, Ming; Zhang, Yiping; Yu, Li Sheng; Yu, Xiaoming; Lin, Jian; Zhang, Nu

    2017-01-01

    Medulloblastoma (MB) is the most common malignant tumor of the central nervous system in children. Accumulating evidence suggests a major role for the activation of the sonic hedgehog (SHH) signaling pathway in the development of MB cells; however, the mechanisms underlying the effect of this pathway on tumor survival and growth remain poorly understood. The Gli family zinc finger 1 (Gli1) transcription factor is considered as a mediator of the SHH signaling pathway in MB cells. Therefore, the present study investigated whether the SHH signaling pathway promotes the apoptosis of MB cells via downregulation of Gli1. GANT61, a novel Gli1 inhibitor, is known to have an in vitro activity against tumors. In the current study, Daoy cells were treated with different concentrations of GANT61 for 24 h, and the effect on cell proliferation was assayed by cell counting kit-8 assay. In addition, the cell cycle progression and apoptosis were assayed by flow cytometry analysis and hematoxylin-eosin (HE) staining. The effects of GANT61 treatment on SHH signaling pathway at the mRNA level were assayed by polymerase chain reaction (PCR). To further elucidate the inhibitory effects of GANT61 on the expression of Gli1 and CyclinD1, their protein levels were examined by western blot and immunofluorescence. The results indicated that GANT61 significantly inhibited the proliferation of Daoy cells in a dose-dependent manner, compared with the control group (P<0.05). HE staining revealed that cells had increasingly abnormal protuberance with increasing GANT61 concentration. Flow cytometry analysis also demonstrated that GANT61 induced G1/S arrest and apoptosis of Daoy cells in a dose-dependent manner (P<0.05). Gli1 and CyclinD1 mRNA expression levels were downregulated by GANT61 treatment (P<0.05); similarly, their protein levels were downregulated by GANT61 treatment in a dose-dependent manner (P<0.05). In conclusion, Gli1 expression was significantly associated with CyclinD1 expression

  13. Inhibition of the CyclinD1 promoter in response to sonic hedgehog signaling pathway transduction is mediated by Gli1.

    PubMed

    Lin, Zhongxiao; Sheng, Hansong; You, Chaoguo; Cai, Ming; Zhang, Yiping; Yu, Li Sheng; Yu, Xiaoming; Lin, Jian; Zhang, Nu

    2017-01-01

    Medulloblastoma (MB) is the most common malignant tumor of the central nervous system in children. Accumulating evidence suggests a major role for the activation of the sonic hedgehog (SHH) signaling pathway in the development of MB cells; however, the mechanisms underlying the effect of this pathway on tumor survival and growth remain poorly understood. The Gli family zinc finger 1 (Gli1) transcription factor is considered as a mediator of the SHH signaling pathway in MB cells. Therefore, the present study investigated whether the SHH signaling pathway promotes the apoptosis of MB cells via downregulation of Gli1. GANT61, a novel Gli1 inhibitor, is known to have an in vitro activity against tumors. In the current study, Daoy cells were treated with different concentrations of GANT61 for 24 h, and the effect on cell proliferation was assayed by cell counting kit-8 assay. In addition, the cell cycle progression and apoptosis were assayed by flow cytometry analysis and hematoxylin-eosin (HE) staining. The effects of GANT61 treatment on SHH signaling pathway at the mRNA level were assayed by polymerase chain reaction (PCR). To further elucidate the inhibitory effects of GANT61 on the expression of Gli1 and CyclinD1, their protein levels were examined by western blot and immunofluorescence. The results indicated that GANT61 significantly inhibited the proliferation of Daoy cells in a dose-dependent manner, compared with the control group (P<0.05). HE staining revealed that cells had increasingly abnormal protuberance with increasing GANT61 concentration. Flow cytometry analysis also demonstrated that GANT61 induced G1/S arrest and apoptosis of Daoy cells in a dose-dependent manner (P<0.05). Gli1 and CyclinD1 mRNA expression levels were downregulated by GANT61 treatment (P<0.05); similarly, their protein levels were downregulated by GANT61 treatment in a dose-dependent manner (P<0.05). In conclusion, Gli1 expression was significantly associated with CyclinD1 expression

  14. Epigenomic study identifies a novel mesenchyme homeobox2-GLI1 transcription axis involved in cancer drug resistance, overall survival and therapy prognosis in lung cancer patients

    PubMed Central

    Armas-López, Leonel; Piña-Sánchez, Patricia; Arrieta, Oscar; de Alba, Enrique Guzman; Ortiz-Quintero, Blanca; Santillán-Doherty, Patricio; Christiani, David C.; Zúñiga, Joaquín; Ávila-Moreno, Federico

    2017-01-01

    Several homeobox-related gene (HOX) transcription factors such as mesenchyme HOX-2 (MEOX2) have previously been associated with cancer drug resistance, malignant progression and/or clinical prognostic responses in lung cancer patients; however, the mechanisms involved in these responses have yet to be elucidated. Here, an epigenomic strategy was implemented to identify novel MEOX2 gene promoter transcription targets and propose a new molecular mechanism underlying lung cancer drug resistance and poor clinical prognosis. Chromatin immunoprecipitation (ChIP) assays derived from non-small cell lung carcinomas (NSCLC) hybridized on gene promoter tiling arrays and bioinformatics analyses were performed, and quantitative, functional and clinical validation were also carried out. We statistically identified a common profile consisting of 78 gene promoter targets, including Hedgehog-GLI1 gene promoter sequences (FDR≤0.1 and FDR≤0.2). The GLI-1 gene promoter region from −2,192 to −109 was occupied by MEOX2, accompanied by transcriptionally active RNA Pol II and was epigenetically linked to the active histones H3K27Ac and H3K4me3; these associations were quantitatively validated. Moreover, siRNA genetic silencing assays identified a MEOX2-GLI1 axis involved in cellular cytotoxic resistance to cisplatinum in a dose-dependent manner, as well as cellular migration and proliferation. Finally, Kaplan-Maier survival analyses identified significant MEOX2-dependent GLI-1 protein expression associated with clinical progression and poorer overall survival using an independent cohort of NSCLC patients undergoing platinum-based oncological therapy with both epidermal growth factor receptor (EGFR)-non-mutated and EGFR-mutated status. In conclusion, this is the first study to investigate epigenome-wide MEOX2-transcription factor occupation identifying a novel overexpressed MEOX2-GLI1 axis and its clinical association with platinum-based cancer drug resistance and EGFR

  15. Adenovirus vector-mediated Gli1 siRNA induces growth inhibition and apoptosis in human pancreatic cancer with Smo-dependent or Smo-independent Hh pathway activation in vitro and in vivo.

    PubMed

    Guo, Jiefang; Gao, Jun; Li, Zhaoshen; Gong, Yanfang; Man, Xiaohua; Jin, Jing; Wu, Hongyu

    2013-10-10

    Activation of Hedgehog (Hh) signaling pathway is a core molecular mechanism in pancreatic carcinogenesis. However, the inhibition of upstream Hh signals does not inhibit the growth of a subset of pancreatic cancer (PC). This study was to examine the effect of siRNA targeting Gli1, the downstream component of Hh pathway, on PC cells and to provide some insight into the underlying mechanisms. A Gli1siRNA-expressing adenovirus (Ad-U6-Gli1siRNA) was constructed, and its effect on PC cells was investigated in vitro and in vivo. Gli1 was expressed in 83.3% (20/24) PC tissues, whereas no expression was found in normal pancreatic ductal epithelium. Gli1 was expressed in SW1990 and CFPAC cells in which Smo was completely absent, as well as in PaTu8988, Panc-1 and BxPC-3 cells in which Smo was concomitantly present. Ad-U6-Gli1siRNA induced cell growth inhibition, strong G0/G1 cell cycle arrest and apoptosis in all five human PC cell lines. Meanwhile, Ad-U6-Gli1siRNA significantly suppressed the expression of Gli1, Ptch1 and two target genes, Cyclin D2 and Bcl-2, in all five lines. Furthermore, two tumor xenograft nude mice models were established by subcutaneously injecting Smo-positive Panc-1 cells or Smo-negative SW1990 cells. The in vivo experimental results demonstrated that Ad-U6-Gli1siRNA inhibited the growth of both Panc1-derived and SW1990-derived tumors and induced cell apoptosis. Our study indicates that Gli1-targeting siRNA could induce growth inhibition and apoptosis in PC through knockdown of Gli1 and its target genes; and this method may represent a more effective therapeutic strategy for PC with Smo-dependent or Smo-independent Hh pathway activation.

  16. Daidzein suppresses tumor necrosis factor-α induced migration and invasion by inhibiting hedgehog/Gli1 signaling in human breast cancer cells.

    PubMed

    Bao, Cheng; Namgung, Hyeju; Lee, Jaehoo; Park, Hyun-Chang; Ko, Jiwon; Moon, Heejung; Ko, Hyuk Wan; Lee, Hong Jin

    2014-04-30

    In breast cancer, the cytokine tumor necrosis factor-α (TNF-α) induces cell invasion, although the molecular basis of it has not been clearly elucidated. In this study, we investigated the role of daidzein in regulating TNF-α induced cell invasion and the underlying molecular mechanisms. Daidzein inhibited TNF-α induced cellular migration and invasion in estrogen receptor (ER) negative MCF10DCIS.com human breast cancer cells. TNF-α activated Hedgehog (Hh) signaling by enhancing Gli1 nuclear translocation and transcriptional activity, which resulted in increased invasiveness; these effects were blocked by daidzein and the Hh signaling inhibitors, cyclopamine and vismodegib. Moreover, these compounds suppressed TNF-α induced matrix metalloproteinase (MMP)-9 mRNA expression and activity. Taken together, mammary tumor cell invasiveness was stimulated by TNF-α induced activation of Hh signaling; these effects were abrogated by daidzein, which suppressed Gli1 activation, thereby inhibiting migration and invasion.

  17. GLI1 regulates a novel neuropilin-2/α6β1 integrin based autocrine pathway that contributes to breast cancer initiation

    PubMed Central

    Goel, Hira Lal; Pursell, Bryan; Chang, Cheng; Shaw, Leslie M; Mao, Junhao; Simin, Karl; Kumar, Prashant; Vander Kooi, Craig W; Shultz, Leonard D; Greiner, Dale L; Norum, Jens Henrik; Toftgard, Rune; Kuperwasser, Charlotte; Mercurio, Arthur M

    2013-01-01

    The characterization of cells with tumour initiating potential is significant for advancing our understanding of cancer and improving therapy. Aggressive, triple-negative breast cancers (TNBCs) are enriched for tumour-initiating cells (TICs). We investigated that hypothesis that VEGF receptors expressed on TNBC cells mediate autocrine signalling that contributes to tumour initiation. We discovered the VEGF receptor neuropilin-2 (NRP2) is expressed preferentially on TICs, involved in the genesis of TNBCs and necessary for tumour initiation. The mechanism by which NRP2 signalling promotes tumour initiation involves stimulation of the α6β1 integrin, focal adhesion kinase-mediated activation of Ras/MEK signalling and consequent expression of the Hedgehog effector GLI1. GLI1 also induces BMI-1, a key stem cell factor, and it enhances NRP2 expression and the function of α6β1, establishing an autocrine loop. NRP2 can be targeted in vivo to retard tumour initiation. These findings reveal a novel autocrine pathway involving VEGF/NRP2, α6β1 and GLI1 that contributes to the initiation of TNBC. They also support the feasibility of NRP2-based therapy for the treatment of TNBC that targets and impedes the function of TICs. PMID:23436775

  18. GLI1 regulates a novel neuropilin-2/α6β1 integrin based autocrine pathway that contributes to breast cancer initiation.

    PubMed

    Goel, Hira Lal; Pursell, Bryan; Chang, Cheng; Shaw, Leslie M; Mao, Junhao; Simin, Karl; Kumar, Prashant; Vander Kooi, Craig W; Shultz, Leonard D; Greiner, Dale L; Norum, Jens Henrik; Toftgard, Rune; Kuperwasser, Charlotte; Mercurio, Arthur M

    2013-04-01

    The characterization of cells with tumour initiating potential is significant for advancing our understanding of cancer and improving therapy. Aggressive, triple-negative breast cancers (TNBCs) are enriched for tumour-initiating cells (TICs). We investigated that hypothesis that VEGF receptors expressed on TNBC cells mediate autocrine signalling that contributes to tumour initiation. We discovered the VEGF receptor neuropilin-2 (NRP2) is expressed preferentially on TICs, involved in the genesis of TNBCs and necessary for tumour initiation. The mechanism by which NRP2 signalling promotes tumour initiation involves stimulation of the α6β1 integrin, focal adhesion kinase-mediated activation of Ras/MEK signalling and consequent expression of the Hedgehog effector GLI1. GLI1 also induces BMI-1, a key stem cell factor, and it enhances NRP2 expression and the function of α6β1, establishing an autocrine loop. NRP2 can be targeted in vivo to retard tumour initiation. These findings reveal a novel autocrine pathway involving VEGF/NRP2, α6β1 and GLI1 that contributes to the initiation of TNBC. They also support the feasibility of NRP2-based therapy for the treatment of TNBC that targets and impedes the function of TICs.

  19. Induction of Connective Tissue Growth Factor Expression by Hypoxia in Human Lung Fibroblasts via the MEKK1/MEK1/ERK1/GLI-1/GLI-2 and AP-1 Pathways

    PubMed Central

    Cheng, Yi; Lin, Chien-huang; Chen, Jing-Yun; Li, Chien-Hua; Liu, Yu-Tin; Chen, Bing-Chang

    2016-01-01

    Several reports have indicated that hypoxia, GLI, and connective tissue growth factor (CTGF) contribute to pulmonary fibrosis in idiopathic pulmonary fibrosis. We investigated the participation of mitogen-activated protein kinase kinase (MEK) kinase 1 (MEKK1)/MEK1/ERK1/GLI-1/2 and activator protein-1 (AP-1) signaling in hypoxia-induced CTGF expression in human lung fibroblasts. Hypoxia time-dependently increased CTGF expression, which was attenuated by the small interfering RNA (siRNA) of GLI-1 (GLI-1 siRNA) and GLI-2 (GLI-2 siRNA) in both human lung fibroblast cell line (WI-38) and primary human lung fibroblasts (NHLFs). Moreover, GLI-1 siRNA and GLI-2 siRNA attenuated hypoxia-induced CTGF-luciferase activity, and the treatment of cells with hypoxia induced GLI-1 and GLI-2 translocation. Furthermore, hypoxia-induced CTGF expression was reduced by an MEK inhibitor (PD98059), MEK1 siRNA, ERK inhibitor (U0126), ERK1 siRNA, and MEKK1 siRNA. Both PD98059 and U0126 significantly attenuated hypoxia-induced CTGF-luciferase activity. Hypoxia time-dependently increased MEKK1, ERK, and p38 MAPK phosphorylation. Moreover, SB203580 (a p38 MAPK inhibitor) also apparently inhibited hypoxia-induced CTGF expression. The treatment of cells with hypoxia induced ERK, GLI-1, or GLI-2 complex formation. Hypoxia-induced GLI-1 and GLI-2 translocation into the nucleus was significantly attenuated by U0126. In addition, hypoxia-induced ERK Tyr204 phosphorylation was impeded by MEKK1 siRNA. Moreover, hypoxia-induced CTGF-luciferase activity was attenuated by cells transfected with AP-1 site mutation in a CTGF construct. Exposure to hypoxia caused a time-dependent phosphorylation of c-Jun, but not of c-Fos. Chromatin immunoprecipitation (ChIP) revealed that hypoxia induced the recruitment of c-Jun, GLI-1, and GLI-2 to the AP-1 promoter region of CTGF. Hypoxia-treated cells exhibited an increase in α-smooth muscle actin (α-SMA) and collagen production, which was blocked by GLI-1 siRNA and

  20. Inhibition of Gli1 results in altered c-Jun activation, inhibition of cisplatin-induced upregulation of ERCC1, XPD and XRCC1, and inhibition of platinum-DNA adduct repair.

    PubMed

    Kudo, K; Gavin, E; Das, S; Amable, L; Shevde, L A; Reed, E

    2012-11-01

    The transcription of ERCC1 and other nucleotide excision repair (NER) genes is strongly influenced by c-jun. C-jun is transcriptionally regulated by Gli proteins of the Hedgehog pathway. We therefore studied the possible relationships between Gli1, c-jun, and the upregulation of ERCC1, XPD and XRCC1 in cisplatin-resistant human ovarian cancer cells. We studied the paired human ovarian cancer cell lines A2780 and A2780-CP70. We used a shRNA construct that specifically degrades Gli1 message. Genes we assessed for mRNA and/or protein levels included: c-jun, ERCC1, XPD, XRCC1, Gli1, Gli2, SHH, IHH, GAPDH and α-tubulin. Platinum-DNA adduct repair was assessed by atomic absorbance spectrometry with Zeeman background correction. Use of the anti-Gli1 shRNA in cisplatin-resistant cells resulted in a block of the cell's ability to upregulate genes in response to cisplatin treatment, including: c-jun, ERCC1, XPD and XRCC1. This block in upregulation of c-jun was concurrent with a change in the phosphorylation pattern of the c-jun protein, shifting that pattern from a Ser63/73 dominant pattern, to a Thr91/93 dominant pattern. A2780-CP70 cells were treated at their cisplatin IC50, and DNA repair was assessed after pretreatment with anti-Gli1 shRNA or scrambled shRNA control. Control cells repaired 78% of platinum-DNA adducts at 12 h, compared with 33% repair in cells pretreated with anti-Gli1 shRNA resulting in a 2.4-fold difference. Pretreatment of A2780-CP70 cells with anti-Gli1 shRNA resulted in supra-additive cell killing with cisplatin; shifting the cisplatin IC50 (half maximal inhibitory concentration) from 30 μM to 5 μM. Pretreatment of these cells with cyclopamine did not shift the cisplatin IC50. We conclude that the transcriptional protein Gli1 is important in the upregulation of these three DNA repair genes in human ovarian cancer cells, and that Gli1 strongly influences platinum-DNA adduct repair, and cellular sensitivity to cisplatin. This Gli1 role has c

  1. Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid*

    PubMed Central

    Comba, Andrea; Almada, Luciana L.; Tolosa, Ezequiel J.; Iguchi, Eriko; Marks, David L.; Vara Messler, Marianela; Silva, Renata; Fernandez-Barrena, Maite G.; Enriquez-Hesles, Elisa; Vrabel, Anne L.; Botta, Bruno; Di Marcotulio, Lucia; Ellenrieder, Volker; Eynard, Aldo R.; Pasqualini, Maria E.; Fernandez-Zapico, Martin E.

    2016-01-01

    Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells. We demonstrated that down-regulation of the transcription factor glioma-associated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed that AA represses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AA-induced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches. PMID:26601952

  2. Nuclear Factor of Activated T Cells-dependent Down-regulation of the Transcription Factor Glioma-associated Protein 1 (GLI1) Underlies the Growth Inhibitory Properties of Arachidonic Acid.

    PubMed

    Comba, Andrea; Almada, Luciana L; Tolosa, Ezequiel J; Iguchi, Eriko; Marks, David L; Vara Messler, Marianela; Silva, Renata; Fernandez-Barrena, Maite G; Enriquez-Hesles, Elisa; Vrabel, Anne L; Botta, Bruno; Di Marcotulio, Lucia; Ellenrieder, Volker; Eynard, Aldo R; Pasqualini, Maria E; Fernandez-Zapico, Martin E

    2016-01-22

    Numerous reports have demonstrated a tumor inhibitory effect of polyunsaturated fatty acids (PUFAs). However, the molecular mechanisms modulating this phenomenon are in part poorly understood. Here, we provide evidence of a novel antitumoral mechanism of the PUFA arachidonic acid (AA). In vivo and in vitro experiments showed that AA treatment decreased tumor growth and metastasis and increased apoptosis. Molecular analysis of this effect showed significantly reduced expression of a subset of antiapoptotic proteins, including BCL2, BFL1/A1, and 4-1BB, in AA-treated cells. We demonstrated that down-regulation of the transcription factor glioma-associated protein 1 (GLI1) in AA-treated cells is the underlying mechanism controlling BCL2, BFL1/A1, and 4-1BB expression. Using luciferase reporters, chromatin immunoprecipitation, and expression studies, we found that GLI1 binds to the promoter of these antiapoptotic molecules and regulates their expression and promoter activity. We provide evidence that AA-induced apoptosis and down-regulation of antiapoptotic genes can be inhibited by overexpressing GLI1 in AA-sensitive cells. Conversely, inhibition of GLI1 mimics AA treatments, leading to decreased tumor growth, cell viability, and expression of antiapoptotic molecules. Further characterization showed that AA represses GLI1 expression by stimulating nuclear translocation of NFATc1, which then binds the GLI1 promoter and represses its transcription. AA was shown to increase reactive oxygen species. Treatment with antioxidants impaired the AA-induced apoptosis and down-regulation of GLI1 and NFATc1 activation, indicating that NFATc1 activation and GLI1 repression require the generation of reactive oxygen species. Collectively, these results define a novel mechanism underlying AA antitumoral functions that may serve as a foundation for future PUFA-based therapeutic approaches. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. IL-17A exacerbates cisplatin-based resistance of OVCA via upregulating the expression of ABCG2 and MDR1 through Gli1-mediated Hh signaling.

    PubMed

    Niu, Xiulong; Liu, Wenxing; Wang, Yue; Liu, Xiaomei; Zhang, Hongjian; Li, Zhijun; Li, Hongzhao; Iwakura, Yoichiro; Deng, Weimin

    2016-07-18

    The major obstacle of the tumor chemotherapy, including ovarian cancer (OVCA), is drug resistance. However, the relevance of IL-17A with drug-resistance of OVCA has been poorly elaborated. In this study, we used 2 human OVCA cell lines to investigate the effects of IL-17A on cisplatin (CDDP or DDP)-based resistance in OVCA cells and the underlying mechanisms. Meanwhile, IL-17A-deficient mice and ID8 were used to verify the IL-17A's effects on OVCA chemo-resistance in vivo. Moreover, the relationship between IL-17A level and relevant indices were primarily assessed in ovarian specimens from 55 patients with OVCA. We found that rhIL-17A exacerbated DDP-based resistance of OVCA cells via up-regulating the expression of ABCG2 and MDR1 through Gli1-mediated Hh signal pathway. Animal experiment demonstrated that IL-17A significantly recede DDP-based treatment for ID8 tumor. Similar results were observed in preliminary clinical investigation. Our findings suggest that inhibiting IL-17A/IL-17RA-Gli1 signal may improve the resistance of OVCA to DDP.

  4. Protein and mRNA expression of Shh, Smo and Gli1 and inhibition by cyclopamine in hepatocytes of rats with chronic fluorosis.

    PubMed

    Zhao, Lina; Yu, Yanni; Deng, Chaonan

    2014-03-03

    In order to investigate the Sonic hedgehog (Shh) signaling pathway and the effect of cyclopamine in rat hepatocytes with chronic fluorosis, 48 Wistar rats were randomly divided into 4 groups. The control group was provided with tap water in which the fluorine concentration was <1mg/L, while the remaining three groups were provided with water containing sodium fluoride (NaF) at a concentration of 50mg/L. After 6 months, the blocking and blocking control groups were injected intraperitoneally once every 2 days for 6 days with 10mg/kg cyclopamine or dimethyl sulfoxide, respectively. The urinary and skeletal fluoride contents were determined by the ion selective electrode method. Levels of aspartate transaminase (AST), alanine transaminase (ALT), total protein (TP) and albumin (Alb) in the serum were determined by using autobiochemical machine. Histological changes in liver tissue were evaluated with Hematoxylin & Eeosin (H&E) staining using light microscopy. The protein and mRNA expression of Shh, Smo and Gli1 in hepatocytes of experimental animals was determined by immunohistochemistry (IHC), Western blotting (Wb) and Real-time quantitative PCR (RT-qPCR). Fluoride content of the urine and bone was increased in the fluorosis and blocking groups compared to those in the control group (P<0.05), while fluoride content in the blocking group was decreased compared to the fluorosis and blocking control groups (P<0.05). The expression of Shh, Smo and Gli1 at the mRNA and protein levels was significantly increased in hepatocytes from the fluorosis and blocking control groups compared with the control group, and expression in the blocking group was lower than that of the fluorosis and blocking control groups. The difference between any two groups was considered to be statistically significant (P<0.05). Taken together, our study indicates that the expression of Shh, Smo and Gli1 at the protein and mRNA level in hepatocytes of rats with chronic fluorosis can be increased by

  5. Sclareolide enhances gemcitabine‑induced cell death through mediating the NICD and Gli1 pathways in gemcitabine‑resistant human pancreatic cancer.

    PubMed

    Chen, Sheng; Wang, Ye; Zhang, Wen-Long; Dong, Mao-Sheng; Zhang, Jian-Hua

    2017-04-01

    Pancreatic cancer is a type of cancer, which rapidly develops resistance to chemotherapy. Gemcitabine is the treatment used clinically, however, gemcitabine resistance leads to limited efficacy and patient survival rates of only a few months following diagnosis. The aim of the present study was to investigate the mechanisms underlying gemcitabine resistance in pancreatic cancer and to select targeted agents combined with gemcitabine to promote the treatment of pancreatic cancer. Panc‑1 and ASPC‑1 human pancreatic cancer cells (HPCCs) were used to establish the experimental model, and HPCCs were exposed to gemcitabine of serially increased concentrations to generate gemcitabine‑resistant cells (GR‑HPCCs). The anticancer effect of gemcitabine combined with sclareolide was then assessed. Epithelial to mesenchymal transition (EMT), human equilibrative nucleoside transporter 1 (hENT1) and ribonucleoside diphosphate reductase 1 (RRM1) were detected in the HPCCs and GR‑HPCCs, and the mechanisms were investigated. Sclareolide resensitized the GR‑HPCCs to gemcitabine. The expression levels of hENT1 and RRM1 were lower and higher, respectively, in GR‑HPCCs, compared with HPCCs. Sclareolide upregulated hENT1, downregulated RRM1 and inhibited gemcitabine‑induced EMT through the TWIST1/Slug pathway in the GR‑HPCCs. In addition, sclareolide mediated the NOTCH 1 intracellular cytoplasmic domain (NICD)/glioma‑associated oncogene 1 (Gli1) pathway, which triggered TWIST1/Slug‑hENT1/RRM1 signaling and resensitized GR‑HPCCs to gemcitabine. Finally, sclareolide resensitized GR‑HPCCs to gemcitabine through inducing apoptosis; in vivo, the co‑administraion of sclareolide and gemcitabine effectively suppressed tumor growth. Sclareolide may be a novel agent in combination with gemcitabine for the treatment of gemcitabine‑resistant pancreatic cancer, which resensitizes GR‑HPCCs to gemcitabine through mediating NICD and Gli1.

  6. Regulation of sonic hedgehog-GLI1 downstream target genes PTCH1, Cyclin D2, Plakoglobin, PAX6 and NKX2.2 and their epigenetic status in medulloblastoma and astrocytoma

    PubMed Central

    2010-01-01

    Background The Sonic hedgehog (Shh) signaling pathway is critical for cell growth and differentiation. Impairment of this pathway can result in both birth defects and cancer. Despite its importance in cancer development, the Shh pathway has not been thoroughly investigated in tumorigenesis of brain tumors. In this study, we sought to understand the regulatory roles of GLI1, the immediate downstream activator of the Shh signaling pathway on its downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6 in medulloblastoma and astrocytic tumors. Methods We silenced GLI1 expression in medulloblastoma and astrocytic cell lines by transfection of siRNA against GLI1. Subsequently, we performed RT-PCR and quantitative real time RT-PCR (qRT-PCR) to assay the expression of downstream target genes PTCH1, Cyclin D2, Plakoglobin, NKX2.2 and PAX6. We also attempted to correlate the pattern of expression of GLI1 and its regulated genes in 14 cell lines and 41 primary medulloblastoma and astrocytoma tumor samples. We also assessed the methylation status of the Cyclin D2 and PTCH1 promoters in these 14 cell lines and 58 primary tumor samples. Results Silencing expression of GLI1 resulted up-regulation of all target genes in the medulloblastoma cell line, while only PTCH1 was up-regulated in astrocytoma. We also observed methylation of the cyclin D2 promoter in a significant number of astrocytoma cell lines (63%) and primary astrocytoma tumor samples (32%), but not at all in any medulloblastoma samples. PTCH1 promoter methylation was less frequently observed than Cyclin D2 promoter methylation in astrocytomas, and not at all in medulloblastomas. Conclusions Our results demonstrate different regulatory mechanisms of Shh-GLI1 signaling. These differences vary according to the downstream target gene affected, the origin of the tissue, as well as epigenetic regulation of some of these genes. PMID:21059263

  7. Overexpression of mutant Ptch in rhabdomyosarcomas is associated with promoter hypomethylation and increased Gli1 and H3K4me3 occupancy.

    PubMed

    Nitzki, Frauke; Tolosa, Ezequiel J; Cuvelier, Nicole; Frommhold, Anke; Salinas-Riester, Gabriela; Johnsen, Steven A; Fernandez-Zapico, Martin E; Hahn, Heidi

    2015-04-20

    Mice with heterozygous loss of the tumor suppressor Patched1 (Ptch) develop rhabdomyosarcoma (RMS)-like tumors. However, Ptch transcripts are consistently overexpressed in these tumors. We have recently shown that the upregulated transcripts are derived from the mutated Ptch allele thus leading to the hypothesis that the wild-type allele is repressed during RMS development. Here we describe epigenetic changes taking place at the Ptch locus during RMS development. We showed a lower degree of DNA-methylation in methylation-sensitive CpG regions of the Ptch promoter in RMS compared to normal muscle from heterozygous Ptch animals. In agreement with these results, treatment of heterozygous Ptch mice with the DNA demethylating agent 5-aza-2-deoxycytidine (5-aza-dC) between embryonic days E9.5-E11.5 significantly accelerated RMS formation. Since Ptch promoter methylation occurs after/around E13.5, the window for RMS initiation during embryogenesis, these results provide additional evidence that Ptch promoter hypomethylation may contribute to RMS formation. We have also demonstrated increased trimethylation of histone H3 lysine 4 (H3K4me3) and preferential binding of Gli1, a known Ptch activator, to the mutant locus in RMS. Together, these findings support an alternative model for RMS formation in heterozygous Ptch mice including loss of methylation and concomitant occupancy by activating histone marks of mutant Ptch.

  8. Expression Patterns of Gli-1, Pleckstrin Homology-Like Domain, Family A, Member 1, Transforming Growth Factor-β1/β2, and p63 in Sebaceous and Follicular Tumors

    PubMed Central

    Jeon, Su-Young; Kim, Dae-Cheol; Song, Ki-Hoon

    2014-01-01

    Background Certain epidermal appendage tumors, including hyperplasias (hamartomas), adenomas, benign epitheliomas, primordial epitheliomas, and malignant tumors, can exhibit any stage of differentiation. Several molecules associated with tumorigenesis, such as Gli-1, pleckstrin homology-like domain, family A, member 1 (PHLDA-1), transforming growth factor (TGF)-β1, TGF-β2, and p63, are associated with tumor grade and aggressive behavior in follicular and sebaceous tumors in ways that are not well understood. Objective The aim of this study was to elucidate the expression of Gli-1, PHLDA-1, TGF-β1/β2, and p63 in benign and malignant tumors of the hair and sebaceous glands and to determine their importance in the degree of tumor differentiation. Methods Immunohistochemistry was performed in follicular and sebaceous tumors using antibodies against Gli-1 (sebaceous tumor marker), PHLDA-1 (hair follicle outer root sheath [ORS] cell marker), p63, TGF-β1, and TGF-β2. Results Gli-1 was expressed in basaloid cells, sebocytes, and sebaceous carcinoma cells, and expression levels decreased as differentiation progressed. PHLDA-1 was expressed in ORS cells and some follicular tumor cells. Expression of p63 was observed in the nuclei of the outermost basaloid cells (seboblasts), poorly differentiated sebaceous carcinoma cells, and tumor cells toward the direction of the hair. Remarkably, TGF-β1 was expressed exclusively in the nuclei of benign and malignant follicular (hair) tumors, but not in sebaceous tumors, at levels that correlated with the degree of differentiation. Conclusion We propose that p63 and/or TGF-β1 are useful for predicting the degree of differentiation and malignant potential of sebaceous and follicular tumors and for distinguishing trichilemmal carcinoma from sebaceous carcinoma. PMID:25473223

  9. Synergism between Hedgehog-GLI and EGFR signaling in Hedgehog-responsive human medulloblastoma cells induces downregulation of canonical Hedgehog-target genes and stabilized expression of GLI1.

    PubMed

    Götschel, Frank; Berg, Daniela; Gruber, Wolfgang; Bender, Christian; Eberl, Markus; Friedel, Myriam; Sonntag, Johanna; Rüngeler, Elena; Hache, Hendrik; Wierling, Christoph; Nietfeld, Wilfried; Lehrach, Hans; Frischauf, Annemarie; Schwartz-Albiez, Reinhard; Aberger, Fritz; Korf, Ulrike

    2013-01-01

    Aberrant activation of Hedgehog (HH) signaling has been identified as a key etiologic factor in many human malignancies. Signal strength, target gene specificity, and oncogenic activity of HH signaling depend profoundly on interactions with other pathways, such as epidermal growth factor receptor-mediated signaling, which has been shown to cooperate with HH/GLI in basal cell carcinoma and pancreatic cancer. Our experimental data demonstrated that the Daoy human medulloblastoma cell line possesses a fully inducible endogenous HH pathway. Treatment of Daoy cells with Sonic HH or Smoothened agonist induced expression of GLI1 protein and simultaneously prevented the processing of GLI3 to its repressor form. To study interactions between HH- and EGF-induced signaling in greater detail, time-resolved measurements were carried out and analyzed at the transcriptomic and proteomic levels. The Daoy cells responded to the HH/EGF co-treatment by downregulating GLI1, PTCH, and HHIP at the transcript level; this was also observed when Amphiregulin (AREG) was used instead of EGF. We identified a novel crosstalk mechanism whereby EGFR signaling silences proteins acting as negative regulators of HH signaling, as AKT- and ERK-signaling independent process. EGFR/HH signaling maintained high GLI1 protein levels which contrasted the GLI1 downregulation on the transcript level. Conversely, a high-level synergism was also observed, due to a strong and significant upregulation of numerous canonical EGF-targets with putative tumor-promoting properties such as MMP7, VEGFA, and IL-8. In conclusion, synergistic effects between EGFR and HH signaling can selectively induce a switch from a canonical HH/GLI profile to a modulated specific target gene profile. This suggests that there are more wide-spread, yet context-dependent interactions, between HH/GLI and growth factor receptor signaling in human malignancies.

  10. Synergism between Hedgehog-GLI and EGFR Signaling in Hedgehog-Responsive Human Medulloblastoma Cells Induces Downregulation of Canonical Hedgehog-Target Genes and Stabilized Expression of GLI1

    PubMed Central

    Götschel, Frank; Berg, Daniela; Gruber, Wolfgang; Bender, Christian; Eberl, Markus; Friedel, Myriam; Sonntag, Johanna; Rüngeler, Elena; Hache, Hendrik; Wierling, Christoph; Nietfeld, Wilfried; Lehrach, Hans; Frischauf, Annemarie; Schwartz-Albiez, Reinhard; Aberger, Fritz; Korf, Ulrike

    2013-01-01

    Aberrant activation of Hedgehog (HH) signaling has been identified as a key etiologic factor in many human malignancies. Signal strength, target gene specificity, and oncogenic activity of HH signaling depend profoundly on interactions with other pathways, such as epidermal growth factor receptor-mediated signaling, which has been shown to cooperate with HH/GLI in basal cell carcinoma and pancreatic cancer. Our experimental data demonstrated that the Daoy human medulloblastoma cell line possesses a fully inducible endogenous HH pathway. Treatment of Daoy cells with Sonic HH or Smoothened agonist induced expression of GLI1 protein and simultaneously prevented the processing of GLI3 to its repressor form. To study interactions between HH- and EGF-induced signaling in greater detail, time-resolved measurements were carried out and analyzed at the transcriptomic and proteomic levels. The Daoy cells responded to the HH/EGF co-treatment by downregulating GLI1, PTCH, and HHIP at the transcript level; this was also observed when Amphiregulin (AREG) was used instead of EGF. We identified a novel crosstalk mechanism whereby EGFR signaling silences proteins acting as negative regulators of HH signaling, as AKT- and ERK-signaling independent process. EGFR/HH signaling maintained high GLI1 protein levels which contrasted the GLI1 downregulation on the transcript level. Conversely, a high-level synergism was also observed, due to a strong and significant upregulation of numerous canonical EGF-targets with putative tumor-promoting properties such as MMP7, VEGFA, and IL-8. In conclusion, synergistic effects between EGFR and HH signaling can selectively induce a switch from a canonical HH/GLI profile to a modulated specific target gene profile. This suggests that there are more wide-spread, yet context-dependent interactions, between HH/GLI and growth factor receptor signaling in human malignancies. PMID:23762360

  11. The expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats

    SciTech Connect

    Katayama, Seiichi . E-mail: katayama@ankaken.co.jp; Ashizawa, Koji; Gohma, Hiroshi; Fukuhara, Tadahiro; Narumi, Kazunori; Tsuzuki, Yasuhiro; Tatemoto, Hideki; Nakada, Tadashi; Nagai, Kenji

    2006-12-15

    The objective of this study was to investigate the effects of estrogen receptor (ER) agonists and an ER antagonist on the expression of Hedgehog genes (Indian hedgehog: Ihh; Desert hedgehog: Dhh) and Hedgehog target genes (Patched 1: Ptc1; glioma-associated oncogene homolog 1: Gli1; chicken ovalbumin upstream promoter transcription factor II: Coup-TfII) in the rat uterus. Immature female rats were administered once with 17{alpha}-ethynyl estradiol (EE, an ER agonist), propyl pyrazole triole (PPT, an ER{alpha}-selective agonist), diarylpropionitrile (DPN, an ER{beta}-selective agonist), or ICI 182,780 (an ER antagonist). Expression of mRNA for Ihh, Dhh, and Ptc1 was dose-dependently downregulated by EE in the uterus of immature rats, mediated by ER as confirmed by coadministration of ICI 182,780. The mRNA expression levels of Ptc1, Gli1, and Coup-TfII were simultaneously downregulated during the period in which the mRNA expression levels of Ihh and Dhh were downregulated in the uterus after administration of EE. PPT downregulated the transcription of Ihh, Dhh, Ptc1, Gli1, and Coup-TfII, indicating that expression of these genes was regulated by the ER{alpha}-dependent pathway. DPN also downregulated the transcription of Ihh and Dhh, although the effect was weaker than that of PPT, indicating that the regulation of uterine Ihh and Dhh transcription was also affected by the ER{beta}-dependent pathway. These results suggest that the expression of Hedgehog genes (Ihh, Dhh) and Hedgehog target genes (Ptc1, Gli1, Coup-TfII) is affected by estrogenic stimuli in the uterus of immature female rats.

  12. Effects of ultrasound pre-treatment on the structure of β-conglycinin and glycinin and the antioxidant activity of their hydrolysates.

    PubMed

    Wang, Yuting; Wang, Zhongjiang; Handa, Cíntia Ladeira; Xu, Jing

    2017-03-01

    The effect of power, time and temperature of ultrasound on the structure of β-conglycinin (7S) and glycinin (11S), and on the antioxidant activity of their hydrolysates were investigated. All ultrasound treated 7S and 11S fractions showed an increase in the α-helix and β-turn proportions, and a decrease in β-sheet and random coil proportions. The polarity of 7S and 11S microenvironment increased after ultrasound treatment. Ultrasound treatment significantly increased the reduction capacity and iron chelating capacity of 7S and 11S hydrolysates. The degree of hydrolysis and free SH groups of 7S and 11S hydrolysates increased after ultrasound pre-treatment. The relative content of high molecular weight peptides reduced, and the relative content of low molecular weight peptides increased in ultrasound treated 7S and 11S hydrolysates. The ultrasonication exposed certain groups of 7S and 11S fractions, improved contact with enzymes, and increased the content of highly active soybean antioxidant peptides.

  13. Significance of the hedgehog pathway-associated proteins Gli-1 and Gli-2 and the epithelial-mesenchymal transition-associated proteins Twist and E-cadherin in hepatocellular carcinoma

    PubMed Central

    Chun, Hyung Wook; Hong, Ran

    2016-01-01

    It has been found that abnormal activation of the hedgehog (Hh) signaling pathway is involved in the occurrence, invasion and metastasis of malignant tumors. In addition, epithelial-mesenchymal transition (EMT) also performs an important function in the invasion and metastasis of malignant tumors. However, the significance of the Hh signaling pathway and EMT in hepatocellular carcinoma (HCC) remains unknown. In the present study, the expression of Gli family zinc finger 1 (Gli-1) and Gli family zinc finger 2 (Gli-2), which are key transcriptional factors in the Hh signaling pathway, and Twist and E-cadherin, which are two factors involved in EMT, was examined in 42 patients with HCC and 20 cases of non-tumorous liver (NTL) tissue by immunohistochemistry. Clinicopathological information was collected in order to analyze the correlation of the Hh signaling pathway with EMT. The present study aimed to examine the difference in the expression of Gli-1, Gli-2, E-cadherin and Twist in HCC and NTL to assess the diagnostic value of these factors in HCC. Additionally, the present study aimed to elucidate the correlation between those proteins and other clinicopathological parameters. Whether abnormal activation of the Hh signaling pathway is closely associated with EMT was also evaluated. Gli-1 and Twist expression was found to be significantly increased and E-cadherin expression was found to be decreased in HCC in contrast to NTL (Gli-1, P=0.019; Twist, P=0.003; E-cadherin, P<0.001). Increased Twist expression was associated with the tumor size (P=0.043), and loss of or decreased E-cadherin expression was associated with the histological type of HCC (P=0.021). There was an inverse association between the expression of Twist and E-cadherin (P=0.006). These results showed that Twist overexpression by induction of EMT changes is involved in the occurrence and progression of HCC. However, the role of Hh signaling pathway-associated proteins in HCC may require elucidation by

  14. 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

  15. Miniaturised optical encoder

    NASA Astrophysics Data System (ADS)

    Carr, John; Desmulliez, Marc P. Y.; Weston, Nick; McKendrick, David; Cunningham, Graeme; McFarland, Geoff; Meredith, Wyn; McKee, Andrew; Langton, Conrad; Eddie, Iain

    2008-08-01

    Optical encoders are pervasive in many sectors of industry including metrology, motion systems, electronics, medical, scanning/ printing, scientific instruments, space research and specialist machine tools. The precision of automated manufacture and assembly has been revolutionised by the adoption of optical diffractive measurement methods. Today's optical encoders comprise discrete components: light source(s), reference and analyser gratings, and a photodiode array that utilise diffractive optic methods to achieve high resolution. However the critical alignment requirements between the optical gratings and to the photodiode array, the bulky nature of the encoder devices and subsequent packaging mean that optical encoders can be prohibitively expensive for many applications and unsuitable for others. We report here on the design, manufacture and test of a miniaturised optical encoder to be used in precision measurement systems. Microsystems manufacturing techniques facilitate the monolithic integration of the traditional encoder components onto a single compound semiconductor chip, radically reducing the size, cost and set-up time. Fabrication of the gratings at the wafer level, by standard photo-lithography, allows for the simultaneous alignment of many devices in a single process step. This development coupled with a unique photodiode configuration not only provides increased performance but also significantly improves the alignment tolerances in both manufacture and set-up. A National Research and Development Corporation type optical encoder chip has been successfully demonstrated under test conditions on both amplitude and phase scales with pitches of 20 micron, 8 micron and 4 micron, showing significantly relaxed alignment tolerances with signal-to-noise ratios greater than 60:1. Various reference mark schemes have also been investigated. Results are presented here.

  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.

  17. Video time encoding machines.

    PubMed

    Lazar, Aurel A; Pnevmatikakis, Eftychios A

    2011-03-01

    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.

  18. 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.

  19. Genetically-encoded Reporters

    NASA Astrophysics Data System (ADS)

    Isacoff, Ehud

    2002-03-01

    One of the principle goals of neuroscience has been to understand the cellular basis of information processing and the plasticity that underlies learning and memory. Efforts in this area have mainly relied on electrical recording and optical imaging with chemical dyes. Over the last few years we and others have begun to develop genetically-encoded optical reporter "dyes" which should provide several important advantages over the classical methods for monitoring signal transmission in the nervous system. The advantages are that genetically-encoded reporters can be molecularly targeted a) to specific cell types via cell-specific promoters, and b) to specific subcellular compartments by peptides that are recognized by the protein sorting machinery of the cell. This makes it possible, in principle, to exclude signals from non-neuronal cells and to visualize selectively, in a brain region that contains many cell types with numerous kinds of synaptic connections, the activity of specific types of neurons (e.g. GABAergic interneurons) and specific synaptic elements (e.g. nerve terminals or dendrites), something that has hitherto not been possible. An additional advantage is that protein reporters may be rationally and irrationally "tuned" with mutations in functional domains known to control their dynamic range of operation. The general idea behind genetically-encoded reporters of cell signaling is to encode a protein that is either intrinsically fluorescent, or that can be labeled orthogonally with a fluorescent probe, and where the physiological signal changes fluorescence emission. I will describe recent progress employing both kinds of approaches.

  20. 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.

  1. Time-Encoded Imagers

    SciTech Connect

    Marleau, Peter; Brubaker, Erik; Brennan, James S.; Nowack, Aaron

    2014-09-01

    We have developed two neutron detector systems based on time-encoded imaging and demonstrated their applicability toward non-proliferation missions. The 1D-TEI system was designed for and evaluated against the ability to detect Special Nuclear Material (SNM) in very low signal to noise environments; in particular, very large stand-off and/or weak sources that may be shielded. We have demonstrated significant detection (>5 sigma) of a 2.8e5 n/s neutron fission source at 100 meters stand-off in 30 min. If scaled to an IAEA significant quantity of Pu, we estimate that this could be reduced to as few as ~5 minutes. In contrast to simple counting detectors, this was accomplished without the need of previous background measurements. The 2D-TEI system was designed for high resolution spatial mapping of distributions of SNM and proved feasibility of twodimensional fast neutron imaging using the time encoded modulation of rates on a single pixel detector. Because of the simplicity of the TEI design, there is much lower systematic uncertainty in the detector response typical coded apertures. Other imaging methods require either multiple interactions (e.g. neutron scatter camera or Compton imagers), leading to intrinsically low efficiencies, or spatial modulation of the signal (e.g., Neutron Coded Aperture Imager (Hausladen, 2012)), which requires a complicated, high channel count, and expensive position sensitive detector. In contrast, a single detector using a time-modulated collimator can encode directional information in the time distribution of detected events. This is the first investigation of time-encoded imaging for nuclear nonproliferation applications.

  2. Spectrally encoded confocal microscopy

    SciTech Connect

    Tearney, G.J.; Webb, R.H.; Bouma, B.E.

    1998-08-01

    An endoscope-compatible, submicrometer-resolution scanning confocal microscopy imaging system is presented. This approach, spectrally encoded confocal microscopy (SECM), uses a quasi-monochromatic light source and a transmission diffraction grating to detect the reflectivity simultaneously at multiple points along a transverse line within the sample. Since this method does not require fast spatial scanning within the probe, the equipment can be miniaturized and incorporated into a catheter or endoscope. Confocal images of an electron microscope grid were acquired with SECM to demonstrate the feasibility of this technique. {copyright} {ital 1998} {ital Optical Society of America}

  3. Time Encoded Radiation Imaging

    SciTech Connect

    Marleau, Peter; Brubaker, Erik; Gerling, Mark D.; Schuster, Patricia Frances; Steele, John T.

    2011-09-01

    Passive detection of special nuclear material (SNM) at long range or under heavy shielding can only be achieved by observing the penetrating neutral particles that it emits: gamma rays and neutrons in the MeV energy range. The ultimate SNM standoff detector system would have sensitivity to both gamma and neutron radiation, a large area and high efficiency to capture as many signal particles as possible, and good discrimination against background particles via directional and energy information. Designing such a system is a daunting task. Using timemodulated collimators could be a transformative technique leading to practical gamma-neutron imaging detector systems that are highly efficient with the potential to exhibit simultaneously high angular and energy resolution. A new technique using time encoding to make a compact, high efficiency imaging detector was conceived. Design considerations using Monte Carlo modeling and the construction and demonstration of a prototype imager are described.

  4. Time encoded radiation imaging

    SciTech Connect

    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.

  5. 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.

  6. 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.

  7. 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.

  8. 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).

  9. Genetically encoding new bioreactivity.

    PubMed

    Wang, Lei

    2017-09-25

    The genetic code can be expanded to include unnatural amino acids (Uaas) by engineering orthogonal components involved in protein translation. To be compatible with live cells, side chains of Uaas have been limited to either chemically inert or bio-orthogonal (i.e., nonreactive toward biomolecules) functionalities. To introduce bioreactivity into live systems, the genetic code has recently been engineered to encode a new class of Uaas, the bioreactive Uaas. These Uaas, after being incorporated into proteins, specifically react with target natural amino acid residues via proximity-enabled bioreactivity, enabling the selective formation of new covalent linkages within and between proteins both in vitro and in live systems. The new covalent bonding ability has been harnessed within proteins to enhance photostability, increase thermostability, staple proteins recombinantly, and build optical nano-switches, and between proteins to pinpoint ligand-receptor interaction, target native receptors irreversibly, and generate covalent macromolecular inhibitors. These diverse bioreactivities, inaccessible to natural proteins, thus open doors to novel protein engineering and provide new avenues for biological studies, biotherapeutics and synthetic biology. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Overexpression of genes encoding glycolytic enzymes in Corynebacterium glutamicum enhances glucose metabolism and alanine production under oxygen deprivation conditions.

    PubMed

    Yamamoto, Shogo; Gunji, Wataru; Suzuki, Hiroaki; Toda, Hiroshi; Suda, Masako; Jojima, Toru; Inui, Masayuki; Yukawa, Hideaki

    2012-06-01

    We previously reported that Corynebacterium glutamicum strain ΔldhAΔppc+alaD+gapA, overexpressing glyceraldehyde-3-phosphate dehydrogenase-encoding gapA, shows significantly improved glucose consumption and alanine formation under oxygen deprivation conditions (T. Jojima, M. Fujii, E. Mori, M. Inui, and H. Yukawa, Appl. Microbiol. Biotechnol. 87:159-165, 2010). In this study, we employ stepwise overexpression and chromosomal integration of a total of four genes encoding glycolytic enzymes (herein referred to as glycolytic genes) to demonstrate further successive improvements in C. glutamicum glucose metabolism under oxygen deprivation. In addition to gapA, overexpressing pyruvate kinase-encoding pyk and phosphofructokinase-encoding pfk enabled strain GLY2/pCRD500 to realize respective 13% and 20% improved rates of glucose consumption and alanine formation compared to GLY1/pCRD500. Subsequent overexpression of glucose-6-phosphate isomerase-encoding gpi in strain GLY3/pCRD500 further improved its glucose metabolism. Notably, both alanine productivity and yield increased after each overexpression step. After 48 h of incubation, GLY3/pCRD500 produced 2,430 mM alanine at a yield of 91.8%. This was 6.4-fold higher productivity than that of the wild-type strain. Intracellular metabolite analysis showed that gapA overexpression led to a decreased concentration of metabolites upstream of glyceraldehyde-3-phosphate dehydrogenase, suggesting that the overexpression resolved a bottleneck in glycolysis. Changing ratios of the extracellular metabolites by overexpression of glycolytic genes resulted in reduction of the intracellular NADH/NAD(+) ratio, which also plays an important role on the improvement of glucose consumption. Enhanced alanine dehydrogenase activity using a high-copy-number plasmid further accelerated the overall alanine productivity. Increase in glycolytic enzyme activities is a promising approach to make drastic progress in growth-arrested bioprocesses.

  11. 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…

  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. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. 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.

  15. 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.

  16. PNA-encoded chemical libraries.

    PubMed

    Zambaldo, Claudio; Barluenga, Sofia; Winssinger, Nicolas

    2015-06-01

    Peptide nucleic acid (PNA)-encoded chemical libraries along with DNA-encoded libraries have provided a powerful new paradigm for library synthesis and ligand discovery. PNA-encoding stands out for its compatibility with standard solid phase synthesis and the technology has been used to prepare libraries of peptides, heterocycles and glycoconjugates. Different screening formats have now been reported including selection-based and microarray-based methods that have yielded specific ligands against diverse target classes including membrane receptors, lectins and challenging targets such as Hsp70.

  17. DNA sequences encoding osteoinductive products

    SciTech Connect

    Wang, E.A.; Wozney, J.M.; Rosen, V.

    1991-05-07

    This patent describes an isolated DNA sequence encoding an osteoinductive protein the DNA sequence comprising a coding sequence. It comprises: nucleotide No.1 through nucleotide No.387, nucleotide No.356 through nucleotide No.1543, nucleotide $402 through nucleotide No.1626, naturally occurring allelic sequences and equivalent degenerative codon sequences and sequences which hybridize to any of sequences under stringent hybridization conditions; and encode a protein characterized by the ability to induce the formation of bone and/or cartilage.

  18. Multidimensionally encoded magnetic resonance imaging.

    PubMed

    Lin, Fa-Hsuan

    2013-07-01

    Magnetic resonance imaging (MRI) 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 multidimensionally 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 radiofrequency 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. Copyright © 2012 Wiley Periodicals, Inc.

  19. 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

  20. Synaptic encoding of temporal contiguity

    PubMed Central

    Ostojic, Srdjan; Fusi, Stefano

    2013-01-01

    Often we need to perform tasks in an environment that changes stochastically. In these situations it is important to learn the statistics of sequences of events in order to predict the future and the outcome of our actions. The statistical description of many of these sequences can be reduced to the set of probabilities that a particular event follows another event (temporal contiguity). Under these conditions, it is important to encode and store in our memory these transition probabilities. Here we show that for a large class of synaptic plasticity models, the distribution of synaptic strengths encodes transitions probabilities. Specifically, when the synaptic dynamics depend on pairs of contiguous events and the synapses can remember multiple instances of the transitions, then the average synaptic weights are a monotonic function of the transition probabilities. The synaptic weights converge to the distribution encoding the probabilities also when the correlations between consecutive synaptic modifications are considered. We studied how this distribution depends on the number of synaptic states for a specific model of a multi-state synapse with hard bounds. In the case of bistable synapses, the average synaptic weights are a smooth function of the transition probabilities and the accuracy of the encoding depends on the learning rate. As the number of synaptic states increases, the average synaptic weights become a step function of the transition probabilities. We finally show that the information stored in the synaptic weights can be read out by a simple rate-based neural network. Our study shows that synapses encode transition probabilities under general assumptions and this indicates that temporal contiguity is likely to be encoded and harnessed in almost every neural circuit in the brain. PMID:23641210

  1. Holographically Encoded Volume Phase Masks

    DTIC Science & Technology

    2015-07-13

    yÞAg; (6) where à and B̃ are the Fourier transforms of A and B, respec- tively, and fx and fy are the spatial frequencies along the x and y axes...collimated and directed onto a reflecting spatial light modulator (SLM). Applying the SLM encoding technique by Arrizón et al.,42 the incident beam was...converted into the LP11 and LP21 HOMs. These modes were selected because their spatial phase pattern match the HPM with the encoded four-sector binary

  2. 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…

  3. 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…

  4. Encoding Ownership Types in Java

    NASA Astrophysics Data System (ADS)

    Cameron, Nicholas; Noble, James

    Ownership types systems organise the heap into a hierarchy which can be used to support encapsulation properties, effects, and invariants. Ownership types have many applications including parallelisation, concurrency, memory management, and security. In this paper, we show that several flavours and extensions of ownership types can be entirely encoded using the standard Java type system.

  5. Spectrally-encoded color imaging

    PubMed Central

    Kang, DongKyun; Yelin, Dvir; Bouma, Brett E.; Tearney, Guillermo J.

    2010-01-01

    Spectrally-encoded endoscopy (SEE) is a technique for ultraminiature endoscopy that encodes each spatial location on the sample with a different wavelength. One limitation of previous incarnations of SEE is that it inherently creates monochromatic images, since the spectral bandwidth is expended in the spatial encoding process. Here we present a spectrally-encoded imaging system that has color imaging capability. The new imaging system utilizes three distinct red, green, and blue spectral bands that are configured to illuminate the grating at different incident angles. By careful selection of the incident angles, the three spectral bands can be made to overlap on the sample. To demonstrate the method, a bench-top system was built, comprising a 2400-lpmm grating illuminated by three 525-μm-diameter beams with three different spectral bands. Each spectral band had a bandwidth of 75 nm, producing 189 resolvable points. A resolution target, color phantoms, and excised swine small intestine were imaged to validate the system's performance. The color SEE system showed qualitatively and quantitatively similar color imaging performance to that of a conventional digital camera. PMID:19688002

  6. Encoding information into precipitation structures

    NASA Astrophysics Data System (ADS)

    Martens, Kirsten; Bena, Ioana; Droz, Michel; Rácz, Zoltan

    2008-12-01

    Material design at submicron scales would be profoundly affected if the formation of precipitation patterns could be easily controlled. It would allow the direct building of bulk structures, in contrast to traditional techniques which consist of removing material in order to create patterns. Here, we discuss an extension of our recent proposal of using electrical currents to control precipitation bands which emerge in the wake of reaction fronts in A+ + B- → C reaction-diffusion processes. Our main result, based on simulating the reaction-diffusion-precipitation equations, is that the dynamics of the charged agents can be guided by an appropriately designed time-dependent electric current so that, in addition to the control of the band spacing, the width of the precipitation bands can also be tuned. This makes straightforward the encoding of information into precipitation patterns and, as an amusing example, we demonstrate the feasibility by showing how to encode a musical rhythm.

  7. 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.

  8. 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.

  9. NRZ Data Asymmetry Corrector and Convolutional Encoder

    NASA Technical Reports Server (NTRS)

    Pfiffner, H. J.

    1983-01-01

    Circuit compensates for timing, amplitude and symmetry perturbations. Data asymmetry corrector and convolutional encoder regenerate data and clock signals in spite of signal variations such as data or clock asymmetry, phase errors, and amplitude variations, then encode data for transmission.

  10. 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.

  11. Terahertz wavelength encoding compressive imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Qiong; Wang, Xinke; Zhang, Yan

    2016-11-01

    Terahertz (THz) compressive imaging can obtain two dimensional image with a single or linear detector, which can overcome the bottleneck problem of lacking of THz two dimensional detectors. In this presentation, we propose a method to obtain two dimensional images using a linear detector. A plano-convex cylindrical lens is employed to perform Fourier transform and to encode one dimensional information of an object into wavelengths. After recording, both amplitude and phase information for different frequency at each pixel of the line detector are extracted, two dimensional image of the object can be reconstructed. Numerical simulation demonstrates the validity of the proposed method.

  12. 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.

  13. 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…

  14. [Neurons that encode sound direction].

    PubMed

    Peña, J L

    In the auditory system, the inner ear breaks down complex signals into their spectral components, and encodes the amplitude and phase of each. In order to infer sound direction in space, a computation on each frequency component of the sound must be performed. Space specific neurons in the owl s inferior colliculus respond only to sounds coming from a particular direction and represent the results of this computation. The interaural time difference (ITD) and interaural level difference (ILD define the auditory space for the owl and are processed in separate neural pathways. The parallel pathways that process these cues merge in the external nucleus of the inferior colliculus where the space specific neurons are selective to combinations of ITD and ILD. How do inputs from the two sources interact to produce combination selectivity to ITD ILD pairs? A multiplication of postsynaptic potentials tuned to ITD and ILD can account for the subthreshold responses of these neurons to ITD ILD pairs. Examples of multiplication by neurons or neural circuits are scarce, but many computational models assume the existence of this basic operation. The owl s auditory system uses such operation to create a 2 dimensional map of auditory space. The map of space in the owl s auditory system shows important similarities with representations of space in the cerebral cortex and other sensory systems. In encoding space or other stimulus features, individual neurons appear to possess analogous functional properties related to the synthesis of high order receptive fields.

  15. Molecular mechanisms for protein-encoded inheritance.

    PubMed

    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

    2009-09-01

    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.

  16. 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.

  17. Photolithographic Encoding of Metal Complexes.

    PubMed

    Lang, Christiane; Bestgen, Sebastian; Welle, Alexander; Müller, Rouven; Roesky, Peter W; Barner-Kowollik, Christopher

    2015-10-12

    A platform technology for the creation of spatially resolved surfaces encoded with a monolayer consisting of different metal complexes was developed. The concept entails the light-triggered activation of a self- assembled monolayer (SAM) of UV-labile anchors, that is, phenacylsulfides, and the subsequent cycloaddition of selected diene-functionalized metal complexes at defined areas on the surface. The synthesis and characterization of the metal complexes for the UV-light assisted anchoring on the surface and a detailed study of a short-chain oligomer model system in solution confirm the high efficiency of the photoreaction. The hybrid materials obtained by this concept can potentially be utilized for the design of highly valuable catalytic or (opto-)electronic devices. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. 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

  19. Genetically Encoded Sensors for Metabolites

    PubMed Central

    Deuschle, Karen; Fehr, Marcus; Hilpert, Melanie; Lager, Ida; Lalonde, Sylvie; Looger, Loren L.; Okumoto, Sakiko; Persson, Jörgen; Schmidt, Anja; Frommer, Wolf B.

    2009-01-01

    Background Metabolomics, i.e., the multiparallel analysis of metabolite changes occurring in a cell or an organism, has become feasible with the development of highly efficient mass spectroscopic technologies. Functional genomics as a standard tool helped to identify the function of many of the genes that encode important transporters and metabolic enzymes over the past few years. Advanced expression systems and analysis technologies made it possible to study the biochemical properties of the corresponding proteins in great detail. We begin to understand the biological functions of the gene products by systematic analysis of mutants using systematic PTGS/RNAi, knockout and TILLING approaches. However, one crucial set of data especially relevant in the case of multicellular organisms is lacking: the knowledge of the spatial and temporal profiles of metabolite levels at cellular and subcellular levels. Methods We therefore developed genetically encoded nanosensors for several metabolites to provide a basic set of tools for the determination of cytosolic and subcellular metabolite levels in real time by using fluorescence microscopy. Results Prototypes of these sensors were successfully used in vitro and also in vivo, i.e., to measure sugar levels in fungal and animal cells. Conclusions One of the future goals will be to expand the set of sensors to a wider spectrum of substrates by using the natural spectrum of periplasmic binding proteins from bacteria and by computational design of proteins with altered binding pockets in conjunction with mutagenesis. This toolbox can then be applied for four-dimensional imaging of cells and tissues to elucidate the spatial and temporal distribution of metabolites as a discovery tool in functional genomics, as a tool for high-throughput, high-content screening for drugs, to test metabolic models, and to analyze the interplay of cells in a tissue or organ. PMID:15688353

  20. SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata

    PubMed Central

    Podduturi, Nikhil R.; Glick, David I.; Baymuradov, Ulugbek K.; Malladi, Venkat S.; Chan, Esther T.; Davidson, Jean M.; Gabdank, Idan; Narayana, Aditi K.; Onate, Kathrina C.; Hilton, Jason; Ho, Marcus C.; Lee, Brian T.; Miyasato, Stuart R.; Dreszer, Timothy R.; Sloan, Cricket A.; Strattan, J. Seth; Tanaka, Forrest Y.; Hong, Eurie L.; Cherry, J. Michael

    2017-01-01

    The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package. PMID:28403240

  1. SnoVault and encodeD: A novel object-based storage system and applications to ENCODE metadata.

    PubMed

    Hitz, Benjamin C; Rowe, Laurence D; Podduturi, Nikhil R; Glick, David I; Baymuradov, Ulugbek K; Malladi, Venkat S; Chan, Esther T; Davidson, Jean M; Gabdank, Idan; Narayana, Aditi K; Onate, Kathrina C; Hilton, Jason; Ho, Marcus C; Lee, Brian T; Miyasato, Stuart R; Dreszer, Timothy R; Sloan, Cricket A; Strattan, J Seth; Tanaka, Forrest Y; Hong, Eurie L; Cherry, J Michael

    2017-01-01

    The Encyclopedia of DNA elements (ENCODE) project is an ongoing collaborative effort to create a comprehensive catalog of functional elements initiated shortly after the completion of the Human Genome Project. The current database exceeds 6500 experiments across more than 450 cell lines and tissues using a wide array of experimental techniques to study the chromatin structure, regulatory and transcriptional landscape of the H. sapiens and M. musculus genomes. All ENCODE experimental data, metadata, and associated computational analyses are submitted to the ENCODE Data Coordination Center (DCC) for validation, tracking, storage, unified processing, and distribution to community resources and the scientific community. As the volume of data increases, the identification and organization of experimental details becomes increasingly intricate and demands careful curation. The ENCODE DCC has created a general purpose software system, known as SnoVault, that supports metadata and file submission, a database used for metadata storage, web pages for displaying the metadata and a robust API for querying the metadata. The software is fully open-source, code and installation instructions can be found at: http://github.com/ENCODE-DCC/snovault/ (for the generic database) and http://github.com/ENCODE-DCC/encoded/ to store genomic data in the manner of ENCODE. The core database engine, SnoVault (which is completely independent of ENCODE, genomic data, or bioinformatic data) has been released as a separate Python package.

  2. 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.

  3. Multidimensional encoding of brain connectomes.

    PubMed

    Caiafa, Cesar F; Pestilli, Franco

    2017-09-13

    The ability to map brain networks in living individuals is fundamental in efforts to chart the relation between human behavior, health and disease. Advances in network neuroscience may benefit from developing new frameworks for mapping brain connectomes. We present a framework to encode structural brain connectomes and diffusion-weighted magnetic resonance (dMRI) data using multidimensional arrays. The framework integrates the relation between connectome nodes, edges, white matter fascicles and diffusion data. We demonstrate the utility of the framework for in vivo white matter mapping and anatomical computing by evaluating 1,490 connectomes, thirteen tractography methods, and three data sets. The framework dramatically reduces storage requirements for connectome evaluation methods, with up to 40x compression factors. Evaluation of multiple, diverse datasets demonstrates the importance of spatial resolution in dMRI. We measured large increases in connectome resolution as function of data spatial resolution (up to 52%). Moreover, we demonstrate that the framework allows performing anatomical manipulations on white matter tracts for statistical inference and to study the white matter geometrical organization. Finally, we provide open-source software implementing the method and data to reproduce the results.

  4. 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. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Image encoding with triangulation wavelets

    NASA Astrophysics Data System (ADS)

    Hebert, D. J.; Kim, HyungJun

    1995-09-01

    We demonstrate some wavelet-based image processing applications of a class of simplicial grids arising in finite element computations and computer graphics. The cells of a triangular grid form the set of leaves of a binary tree and the nodes of a directed graph consisting of a single cycle. The leaf cycle of a uniform grid forms a pattern for pixel image scanning and for coherent computation of coefficients of splines and wavelets. A simple form of image encoding is accomplished with a 1D quadrature mirror filter whose coefficients represent an expansion of the image in terms of 2D Haar wavelets with triangular support. A combination the leaf cycle and an inherent quadtree structure allow efficient neighbor finding, grid refinement, tree pruning and storage. Pruning of the simplex tree yields a partially compressed image which requires no decoding, but rather may be rendered as a shaded triangulation. This structure and its generalization to n-dimensions form a convenient setting for wavelet analysis and computations based on simplicial grids.

  6. Unconscious relational encoding depends on hippocampus.

    PubMed

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

    2014-12-01

    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. © The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain.

  7. 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

  8. 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.

  9. Vibrational spectroscopic encoding of polystyrene-based resin beads: converting the encoding peaks into barcodes.

    PubMed

    Liu, Lie-Xiong; Huang, Zhen-Li; Zhao, Yuan-Di

    2005-12-01

    A detailed approach is described for the vibrational spectroscopic encoding of polystyrene-based resin beads by converting the infrared absorption peaks suitable for encoding (encoding peaks) into barcodes. Based on combining the FT-IR measurements and the quantum-chemical computations, the vibrational characteristics of p-tert-butylstyrene monomer, polystyrene and poly(p-tert-butylstyrene) resin beads are analyzed, which are helpful for the selection of encoding peaks. The vibrational spectroscopic encoding of polystyrene-based resin beads could be obtained by converting the wavenumber, intensity and full width at half maximum (FWHM) of the encoding peaks into barcodes automatically through a computer program designed in our laboratory.

  10. 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

  11. Optoelectronic Shaft-Angle Encoder Tolerates Misalignments

    NASA Technical Reports Server (NTRS)

    Osborne, Eric P.

    1991-01-01

    Optoelectronic shaft-angle encoder measures angle of rotation of shaft with high precision while minimizing effects of eccentricity and other misalignments. Grooves on disk serve as reference marks to locate reading heads and measure increments of rotation of disk. Shaft-angle encoder, resembling optical compact-disk drive, includes two tracking heads illuminating grooves on disk and measures reflections from them.

  12. 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…

  13. 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.

  14. Precision Digital Position Encoding For Resonant Scanners

    NASA Astrophysics Data System (ADS)

    Reich, Stanley; Tuchman, Israel

    1984-11-01

    Presented is a versatile precision digital encoding technique for mechanical resonant scanners. Described is it's application to electronic correction of the sinusoidal scan pattern traced. To contrast the flexibility of the electronic encoding technique a number of direct correction methods are described.

  15. 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…

  16. 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.

  17. Recent advances on the encoding and selection methods of DNA-encoded chemical library.

    PubMed

    Shi, Bingbing; Zhou, Yu; Huang, Yiran; Zhang, Jianfu; Li, Xiaoyu

    2017-02-01

    DNA-encoded chemical library (DEL) has emerged as a powerful and versatile tool for ligand discovery in chemical biology research and in drug discovery. Encoding and selection methods are two of the most important technological aspects of DEL that can dictate the performance and utilities of DELs. In this digest, we have summarized recent advances on the encoding and selection strategies of DEL and also discussed the latest developments on DNA-encoded dynamic library, a new frontier in DEL research.

  18. Comparison of H.265/HEVC encoders

    NASA Astrophysics Data System (ADS)

    Trochimiuk, Maciej

    2016-09-01

    The H.265/HEVC is the state-of-the-art video compression standard, which allows the bitrate reduction up to 50% compared with its predecessor, H.264/AVC, maintaining equal perceptual video quality. The growth in coding efficiency was achieved by increasing the number of available intra- and inter-frame prediction features and improvements in existing ones, such as entropy encoding and filtering. Nevertheless, to achieve real-time performance of the encoder, simplifications in algorithm are inevitable. Some features and coding modes shall be skipped, to reduce time needed to evaluate modes forwarded to rate-distortion optimisation. Thus, the potential acceleration of the encoding process comes at the expense of coding efficiency. In this paper, a trade-off between video quality and encoding speed of various H.265/HEVC encoders is discussed.

  19. 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

  20. Encoder: A Connectionist Model of How Learning to Visually Encode Fixated Text Images Improves Reading Fluency

    ERIC Educational Resources Information Center

    Martin, Gale L.

    2004-01-01

    This article proposes that visual encoding learning improves reading fluency by widening the span over which letters are recognized from a fixated text image so that fewer fixations are needed to cover a text line. Encoder is a connectionist model that learns to convert images like the fixated text images human readers encode into the…

  1. A model for visual memory encoding.

    PubMed

    Nenert, Rodolphe; Allendorfer, Jane B; Szaflarski, Jerzy P

    2014-01-01

    Memory encoding engages multiple concurrent and sequential processes. While the individual processes involved in successful encoding have been examined in many studies, a sequence of events and the importance of modules associated with memory encoding has not been established. For this reason, we sought to perform a comprehensive examination of the network for memory encoding using data driven methods and to determine the directionality of the information flow in order to build a viable model of visual memory encoding. Forty healthy controls ages 19-59 performed a visual scene encoding task. FMRI data were preprocessed using SPM8 and then processed using independent component analysis (ICA) with the reliability of the identified components confirmed using ICASSO as implemented in GIFT. The directionality of the information flow was examined using Granger causality analyses (GCA). All participants performed the fMRI task well above the chance level (>90% correct on both active and control conditions) and the post-fMRI testing recall revealed correct memory encoding at 86.33 ± 5.83%. ICA identified involvement of components of five different networks in the process of memory encoding, and the GCA allowed for the directionality of the information flow to be assessed, from visual cortex via ventral stream to the attention network and then to the default mode network (DMN). Two additional networks involved in this process were the cerebellar and the auditory-insular network. This study provides evidence that successful visual memory encoding is dependent on multiple modules that are part of other networks that are only indirectly related to the main process. This model may help to identify the node(s) of the network that are affected by a specific disease processes and explain the presence of memory encoding difficulties in patients in whom focal or global network dysfunction exists.

  2. Efficient reverse time migration with amplitude encoding

    NASA Astrophysics Data System (ADS)

    Hu, Jiangtao; Wang, Huazhong; Zhao, Lei; Shao, Yu; Wang, Meixia; Osen, Are

    2015-08-01

    Reverse time migration (RTM) is an accurate seismic imaging method for imaging the complex subsurface structure. Traditional common shot RTM suffers from low efficiency due to the large number of single shot gathers, especially for marine seismic data. Phase encoding is commonly used to reduce the computational cost of RTM. Phase encoding in the frequency domain is usually related to time shift in the time domain. Therefore, phase-encoding-based RTM needs time padding to avoid information loss which degrades the efficiency of the time-domain wavefield extrapolator. In this paper, an efficient time-domain RTM scheme based on the amplitude encoding is proposed. This scheme uses the orthogonal cosine basis as the encoding function, which has similar physical meaning to plane wave encoding (i.e. plane-wave components with different surface shooting angles). The proposed scheme can generate a qualified imaging result as well as common shot RTM but with less computational cost. Since this scheme does not need time padding, it is more efficient than the phase encoding schemes and can be conveniently implemented in the time domain. Numerical examples on the Sigsbee2a synthetic dataset demonstrate the feasibility of the proposed method.

  3. Encoding entanglement-assisted quantum stabilizer codes

    NASA Astrophysics Data System (ADS)

    Wang, Yun-Jiang; Bai, Bao-Ming; Li, Zhuo; Peng, Jin-Ye; Xiao, He-Ling

    2012-02-01

    We address the problem of encoding entanglement-assisted (EA) quantum error-correcting codes (QECCs) and of the corresponding complexity. We present an iterative algorithm from which a quantum circuit composed of CNOT, H, and S gates can be derived directly with complexity O(n2) to encode the qubits being sent. Moreover, we derive the number of each gate consumed in our algorithm according to which we can design EA QECCs with low encoding complexity. Another advantage brought by our algorithm is the easiness and efficiency of programming on classical computers.

  4. 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.

  5. 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.

  6. 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).

  7. 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.

  8. Chemical Space of DNA-Encoded Libraries.

    PubMed

    Franzini, Raphael M; Randolph, Cassie

    2016-07-28

    In recent years, DNA-encoded chemical libraries (DECLs) have attracted considerable attention as a potential discovery tool in drug development. Screening encoded libraries may offer advantages over conventional hit discovery approaches and has the potential to complement such methods in pharmaceutical research. As a result of the increased application of encoded libraries in drug discovery, a growing number of hit compounds are emerging in scientific literature. In this review we evaluate reported encoded library-derived structures and identify general trends of these compounds in relation to library design parameters. We in particular emphasize the combinatorial nature of these libraries. Generally, the reported molecules demonstrate the ability of this technology to afford hits suitable for further lead development, and on the basis of them, we derive guidelines for DECL design.

  9. Optimal stimulus encoders for natural tasks

    PubMed Central

    Geisler, Wilson S.; Najemnik, Jiri; Ing, Almon D.

    2010-01-01

    Determining the features of natural stimuli that are most useful for specific natural tasks is critical for understanding perceptual systems. A new approach is described that involves finding the optimal encoder for the natural task of interest, given a relatively small population of noisy “neurons” between the encoder and decoder. The optimal encoder, which necessarily specifies the most useful features, is found by maximizing accuracy in the natural task, where the decoder is the Bayesian ideal observer operating on the population responses. The approach is illustrated for a patch identification task, where the goal is to identify patches of natural image, and for a foreground identification task, where the goal is to identify which side of a natural surface boundary belongs to the foreground object. The optimal features (receptive fields) are intuitive and perform well in the two tasks. The approach also provides insight into general principles of neural encoding and decoding. PMID:20055550

  10. A multifunctional rotary photoelectric encoder management system

    NASA Astrophysics Data System (ADS)

    Ye, Zunzhong; Ying, Yibin

    2005-11-01

    The rotary photoelectric encoder can be used in many fields, such as robot research, fruit assembly lines, and so on. If there have many photoelectric encoders in one system, it's difficult to manage them and acquire the right pulse number. So it's important to design a multifunctional management system. It includes a powerful microchip with high processing speed, assuring the acquisition precision of rotary pulse. It uses a special method to judge the rotary direction and will be competent for many occasions which rotary direction changes quickly. Considering encoder data transmission, the management system provides a serial port using RS-485 protocol to transmit current pulse data and rotary direction. It allows linking a maximum of 100 management systems using only two communication lines to up-systems and also configing the encoder counting pattern locally (using the keyboard) or remotely (through the computer).

  11. 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.

  12. Cellobiohydrolase variants and polynucleotides encoding same

    DOEpatents

    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. 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.

  14. Clustering of polarization-encoded images.

    PubMed

    Zallat, Jihad; Collet, Christophe; Takakura, Yoshitate

    2004-01-10

    Polarization-encoded imaging consists of the distributed measurements of polarization parameters for each pixel of an image. We address clustering of multidimensional polarization-encoded images. The spatial coherence of polarization information is considered. Two methods of analysis are proposed: polarization contrast enhancement and a more-sophisticated image-processing algorithm based on a Markovian model. The proposed algorithms are applied and validated with two different Mueller images acquired by a fully polarimetric imaging system.

  15. A Manual for Encoding Probability Distributions.

    DTIC Science & Technology

    1978-09-01

    summary of the most significant information contained in the report. If the report contains a significant bibliography or literature survey, mention it...probability distri- bution. Some terms in the literature that are used synonymously to Encoding: Assessment, Assignment (used for single events in this...sessions conducted as parts of practical decision analyses as well as on experimental evidence in the literature . Probability encoding can be applied

  16. 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.

  17. 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.

  18. Using XML to encode TMA DES metadata

    PubMed Central

    Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

    2011-01-01

    Background: The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs. PMID:21969921

  19. Using XML to encode TMA DES metadata.

    PubMed

    Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

    2011-01-01

    The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

  20. 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

  1. 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

  2. Multichannel compressive sensing MRI using noiselet encoding.

    PubMed

    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.

  3. ERP Correlates of Encoding Success and Encoding Selectivity in Attention Switching

    PubMed Central

    Yeung, Nick

    2016-01-01

    Long-term memory encoding depends critically on effective processing of incoming information. The degree to which participants engage in effective encoding can be indexed in electroencephalographic (EEG) data by studying event-related potential (ERP) subsequent memory effects. The current study investigated ERP correlates of memory success operationalised with two different measures—memory selectivity and global memory—to assess whether previously observed ERP subsequent memory effects reflect focused encoding of task-relevant information (memory selectivity), general encoding success (global memory), or both. Building on previous work, the present study combined an attention switching paradigm—in which participants were presented with compound object-word stimuli and switched between attending to the object or the word across trials—with a later recognition memory test for those stimuli, while recording their EEG. Our results provided clear evidence that subsequent memory effects resulted from selective attentional focusing and effective top-down control (memory selectivity) in contrast to more general encoding success effects (global memory). Further analyses addressed the question of whether successful encoding depended on similar control mechanisms to those involved in attention switching. Interestingly, differences in the ERP correlates of attention switching and successful encoding, particularly during the poststimulus period, indicated that variability in encoding success occurred independently of prestimulus demands for top-down cognitive control. These results suggest that while effects of selective attention and selective encoding co-occur behaviourally their ERP correlates are at least partly dissociable. PMID:27907075

  4. ERP Correlates of Encoding Success and Encoding Selectivity in Attention Switching.

    PubMed

    Richter, Franziska R; Yeung, Nick

    2016-01-01

    Long-term memory encoding depends critically on effective processing of incoming information. The degree to which participants engage in effective encoding can be indexed in electroencephalographic (EEG) data by studying event-related potential (ERP) subsequent memory effects. The current study investigated ERP correlates of memory success operationalised with two different measures-memory selectivity and global memory-to assess whether previously observed ERP subsequent memory effects reflect focused encoding of task-relevant information (memory selectivity), general encoding success (global memory), or both. Building on previous work, the present study combined an attention switching paradigm-in which participants were presented with compound object-word stimuli and switched between attending to the object or the word across trials-with a later recognition memory test for those stimuli, while recording their EEG. Our results provided clear evidence that subsequent memory effects resulted from selective attentional focusing and effective top-down control (memory selectivity) in contrast to more general encoding success effects (global memory). Further analyses addressed the question of whether successful encoding depended on similar control mechanisms to those involved in attention switching. Interestingly, differences in the ERP correlates of attention switching and successful encoding, particularly during the poststimulus period, indicated that variability in encoding success occurred independently of prestimulus demands for top-down cognitive control. These results suggest that while effects of selective attention and selective encoding co-occur behaviourally their ERP correlates are at least partly dissociable.

  5. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    PubMed

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  6. The ENCODE Project at UC Santa Cruz.

    PubMed

    Thomas, Daryl J; Rosenbloom, Kate R; Clawson, Hiram; Hinrichs, Angie S; Trumbower, Heather; Raney, Brian J; Karolchik, Donna; Barber, Galt P; Harte, Rachel A; Hillman-Jackson, Jennifer; Kuhn, Robert M; Rhead, Brooke L; Smith, Kayla E; Thakkapallayil, Archana; Zweig, Ann S; Haussler, David; Kent, W James

    2007-01-01

    The goal of the Encyclopedia Of DNA Elements (ENCODE) Project is to identify all functional elements in the human genome. The pilot phase is for comparison of existing methods and for the development of new methods to rigorously analyze a defined 1% of the human genome sequence. Experimental datasets are focused on the origin of replication, DNase I hypersensitivity, chromatin immunoprecipitation, promoter function, gene structure, pseudogenes, non-protein-coding RNAs, transcribed RNAs, multiple sequence alignment and evolutionarily constrained elements. The ENCODE project at UCSC website (http://genome.ucsc.edu/ENCODE) is the primary portal for the sequence-based data produced as part of the ENCODE project. In the pilot phase of the project, over 30 labs provided experimental results for a total of 56 browser tracks supported by 385 database tables. The site provides researchers with a number of tools that allow them to visualize and analyze the data as well as download data for local analyses. This paper describes the portal to the data, highlights the data that has been made available, and presents the tools that have been developed within the ENCODE project. Access to the data and types of interactive analysis that are possible are illustrated through supplemental examples.

  7. 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

  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. 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.

  10. Fatal attraction: cytomegalovirus-encoded chemokine homologs.

    PubMed

    Saederup, N; Mocarski, E S

    2002-01-01

    Members of the cytomegalovirus (CMV) subfamily of betaherpesviruses infecting primates and rodents encode divergent proteins with sequence characteristics and activities of chemokines, a class of small, secreted proteins that control leukocyte migration and trafficking behavior. Human CMV genes UL146 and UL147 encode proteins with sequence characteristics of CXC chemokines, whereas, murine CMV encodes a CC chemokine homolog (MCK-2). Human CMV UL146 encodes a neutrophil-attracting chemokine denoted viral CXC chemokine-1 (vCXCL1) that is as potent as host IL-8 and functions via the CXCR2 receptor, one of two human IL-8 receptors. Murine CMV MCK-2 is composed of a chemokine domain derived from open reading frame (ORF) m131 (and denoted MCK-1) as well as a domain derived from m129 that does not have sequence similarity to any known class of proteins. A synthetic version of murine CMV m131 (MCK-1) protein carries out many of the activities of a positive-acting chemokine, including transient release of intracellular calcium stores and cell adhesion of peritoneal macrophage populations. In the context of the viral genome and infection of the mouse host, the m131-m129 (MCK-2) gene product confers increased inflammation, higher levels of viremia, and higher titers of virus in salivary glands, consistent with a role in promoting dissemination by attracting an important mononuclear leukocyte population. Other characterized primate CMVs, but not other primate betaherpesviruses, encode gene products similar to human UL146 and UL147. Other characterized rodent CMVs encode a gene product similar to the murine CMV chemokine homolog, although not as a spliced gene product. Thus chemokines, like viral proteins that downmodulate MHC class I expression or have sequence homology to host MHC class I proteins, have evolved in primate and rodent CMVs to carry out an analogous set of immunomodulatory functions during infection of the host even though they arise from distinct origins.

  11. 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.

  12. 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.

  13. Matrix Encoding For Correction Of Errors

    NASA Technical Reports Server (NTRS)

    Dotson, Ronald S.

    1991-01-01

    Method of matrix encoding and associated decoding provides for correction of errors in digital data recorded on magnetic tape. Intended specifically for use with commercial control circuit board and associated software making it possible to use video cassette recorder as backup for hard-disk memory of personal computer.

  14. 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…

  15. 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…

  16. 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…

  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. An extraordinary retrotransposon family encoding dual endonucleases

    PubMed Central

    Kojima, Kenji K.; Fujiwara, Haruhiko

    2005-01-01

    Retrotransposons commonly encode a reverse transcriptase (RT), but other functional domains are variable. The acquisition of new domains is the dominant evolutionary force that brings structural variety to retrotransposons. Non-long-terminal-repeat (non-LTR) retrotransposons are classified into two groups by their structure. Early branched non-LTR retrotransposons encode a restriction-like endonuclease (RLE), and recently branched non-LTR retrotransposons encode an apurinic/apyrimidinic endonuclease-like endonuclease (APE). In this study, we report a novel non-LTR retrotransposon family Dualen, identified from the Chlamydomonas reinhardtii genome. Dualen encodes two endonucleases, RLE and APE, with RT, ribonuclease H, and cysteine protease. Phylogenetic analyses of the RT domains revealed that Dualen is positioned at the midpoint between the early-branched and the recently branched groups. In the APE tree, Dualen was branched earlier than the I group and the Jockey group. The ribonuclease H domains among the Dualen family and other non-LTR retrotransposons are monophyletic. Phylogenies of three domains revealed the monophyly of the Dualen family members. The domain structure and the phylogeny of each domain imply that Dualen is a retrotransposon conserving the domain structure just after the acquisition of APE. From these observations, we discuss the evolution of domain structure of non-LTR retrotransposons. PMID:16077010

  19. 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…

  20. 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.

  1. Gene encoding acetyl-coenzyme A carboxylase

    SciTech Connect

    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.

  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. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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…

  9. 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... that complies with the following: (i) Tone Frequencies. The audio tones shall have fundamental...

  10. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 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... that complies with the following: (i) Tone Frequencies. The audio tones shall have fundamental...

  11. 47 CFR 11.32 - EAS Encoder.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 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... that complies with the following: (i) Tone Frequencies. The audio tones shall have fundamental...

  12. Comparative Analysis of Chromosome-Encoded Microcins

    PubMed Central

    Poey, María Eloisa; Azpiroz, María F.; Laviña, Magela

    2006-01-01

    Microcins are ribosomally synthesized peptide antibiotics that are produced by enterobacterial strains. Although the first studies concentrated on plasmid-encoded activities, in the last years three chromosome-encoded microcins have been described: H47, E492, and M. Here, a new microcin, I47, is presented as a fourth member of this group. Common features exhibited by chromosome-encoded microcins were searched for. The comparison of the genetic clusters responsible for microcin production revealed a preserved general scheme. The clusters essentially comprise a pair of activity-immunity genes which determine antibiotic specificity and a set of microcin maturation and secretion genes which are invariably present and whose protein products are highly homologous among the different producing strains. A strict functional relationship between the maturation and secretion pathways of microcins H47, I47, and E492 was demonstrated through genetic analyses, which included heterologous complementation assays. The peptide precursors of these microcins share a maturation process which implies the addition of a catecholate siderophore of the salmochelin type. Microcins thus acquire the ability to enter gram-negative cells through the catechol receptors. In addition, they employ a common mode of secretion to reach the external milieu by means of a type I export apparatus. The results presented herein lead us to propose that chromosome-encoded microcins constitute a defined subgroup of peptide antibiotics which are strictly related by their modes of synthesis, secretion, and uptake. PMID:16569859

  13. How Attention Modulates Encoding of Dynamic Stimuli

    PubMed Central

    Oren, Noga; Shapira-Lichter, Irit; Lerner, Yulia; Tarrasch, Ricardo; Hendler, Talma; Giladi, Nir; Ash, Elissa L.

    2016-01-01

    When encoding a real-life, continuous stimulus, the same neural circuits support processing and integration of prior as well as new incoming information. This ongoing interplay is modulated by attention, and is evident in regions such as the prefrontal cortex section of the task positive network (TPN), and in the posterior cingulate cortex (PCC), a hub of the default mode network (DMN). Yet the exact nature of such modulation is still unclear. To investigate this issue, we utilized an fMRI task that employed movies as the encoded stimuli and manipulated attentional load via an easy or hard secondary task that was performed simultaneously with encoding. Results showed increased intersubject correlation (inter-SC) levels when encoding movies in a condition of high, as compared to low attentional load. This was evident in bilateral ventrolateral and dorsomedial prefrontal cortices and the dorsal PCC (dPCC). These regions became more attuned to the combination of the movie and the secondary task as the attentional demand of the latter increased. Activation analyses revealed that at higher load the prefrontal TPN regions were more activated, whereas the dPCC was more deactivated. Attentional load also influenced connectivity within and between the networks. At high load the dPCC was anti-correlated to the prefrontal regions, which were more functionally coherent amongst themselves. Finally and critically, greater inter-SC in the dPCC at high load during encoding predicted lower memory strength when that information was retrieved. This association between inter-SC levels and memory strength suggest that as attentional demands increased, the dPCC was more attuned to the secondary task at the expense of the encoded stimulus, thus weakening memory for the encoded stimulus. Together, our findings show that attentional load modulated the function of core TPN and DMN regions. Furthermore, the observed relationship between memory strength and the modulation of the dPCC points

  14. 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

  15. Encoding Orientation and the Remembering of Schizophrenic Young Adults

    ERIC Educational Resources Information Center

    Koh, Soon D.; Peterson, Rolf A.

    1978-01-01

    This research examines different types of encoding strategies, in addition to semantic and organizational encodings, and their effects on schizophrenics' remembering. Based on Craik and Lockhart (1972), i.e., memory performance is a function of depth of encoding processing, this analysis compares schizophrenics' encoding processing with that of…

  16. Amygdala neurons differentially encode motivation and reinforcement.

    PubMed

    Tye, Kay M; Janak, Patricia H

    2007-04-11

    Lesion studies demonstrate that the basolateral amygdala complex (BLA) is important for assigning motivational significance to sensory stimuli, but little is known about how this information is encoded. We used in vivo electrophysiology procedures to investigate how the amygdala encodes motivating and reinforcing properties of cues that induce reinstatement of reward-seeking behavior. Two groups of rats were trained to respond to a sucrose reward. The "paired" group was trained with a reward-predictive cue, whereas the "unpaired" group was trained with a randomly presented cue. Both groups underwent identical extinction and reinstatement procedures during which the reward was withheld. The proportion of neurons that were phasically cue responsive during reinstatement was significantly higher in the paired group (46 of 100) than in the unpaired group (8 of 112). Cues that induce reward-seeking behavior can do so by acting as incentives or reinforcers. Distinct populations of neurons responded to the cue in trials in which the cue acted as an incentive, triggering a motivated reward-seeking state, or as a reinforcer, supporting continued instrumental responding. The incentive motivation-encoding population of neurons (34 of 46 cue-responsive neurons; 74%) extinguished in temporal agreement with a decrease in the rate of instrumental responding. The conditioned reinforcement-encoding population of neurons (12 of 46 cue-responsive neurons; 26%) maintained their response for the duration of cue-reinforced instrumental responding. These data demonstrate that separate populations of cue-responsive neurons in the BLA encode the motivating or reinforcing properties of a cue previously associated with a reward.

  17. Effortful Retrieval Reduces Hippocampal Activity and Impairs Incidental Encoding

    PubMed Central

    Reas, Emilie T.; Brewer, James B.

    2014-01-01

    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

  18. Implement of FGS video encoding based on H.264

    NASA Astrophysics Data System (ADS)

    Lin, Qiwei; Feng, Gui

    2007-01-01

    In H.264 video coding standard, the combination encoding frame was adopted. It introduces some new algorithms, and modifies several aspects of the encoding scheme. So the encoding scheme improves the encoding efficiency obviously. But the H.264 standard is not supporting FGS encoding. So a H.264 based self-adaptive FGS (Fine Granular Scalable)(H.264-FGS) encoding scheme is proposed in this paper. In this encoding scheme, the base layer of encoder is keeping H.264 encoder architecture, which consists of the motion estimation, motion compensation, intra predictive, integer transformation, loop filtering, content based arithmetic encoding, and etc. In the base layer generated block we obtain base code flux of FGS. Subtracting the original image from the reconstruction image of the base layer, we get the residual error. Then after the DCT transform and the variable length encoding compresses, we obtain the enhanced code flux of FGS. Compared with the original MPEG-4 FGS encoding scheme, the proposed FGS encoding scheme has the feature of increasing encoding efficiency by 1~3 dB and keep the all properties that MPEG-4 FGS encoding technology provided.

  19. 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

  20. Asymmetric synthesis using chiral-encoded metal

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. Determination of Laser Tracker Angle Encoder Errors

    NASA Astrophysics Data System (ADS)

    Nasr, Karim M.; Hughes, Ben; Forbes, Alistair; Lewis, Andrew

    2014-08-01

    Errors in the angle encoders of a laser tracker may potentially produce large errors in long range coordinate measurements. To determine the azimuth angle encoder errors and verify their values stored in the tracker's internal error map, several methodologies were evaluated, differing in complexity, measurement time and the need for specialised measuring equipment. These methodologies are: an artefact-based technique developed by NIST; a multi-target network technique developed by NPL; and the classical precision angular indexing table technique. It is shown that the three methodologies agree within their respective measurement uncertainties and that the NPL technique has the advantages of a short measurement time and no reliance on specialised measurement equipment or artefacts.

  7. Encoded Dynamical Recoupling with Shaped Pulses

    NASA Astrophysics Data System (ADS)

    Li, Yunfan; Lidar, Daniel A.; Pryadko, Leonid P.

    2008-03-01

    Encoded Dynamical Recoupling is a passive error correction techique which can be used to enhance the performance of a quantum error correction code (QECC) against low-frequency component of the thermal bath. The elements of the stabilizer group are used in the decoupling cycle which makes the encoded logic operations fault-tolerant. We studied the effectiveness of this techique both analytically and numerically for several three- and five-qubit codes, with decoupling sequences utilizing either Gaussian or self-refocusing pulse shapes. When logic pulses are intercalated between the decoupling cycles, the technique may be very effective in cancelling constant perturbation terms, but its performance is much weaker against a time-dependent perturbation simulated as a classical correlated noise. The decoupling accuracy can be substantially improved if logic is applied slowly and concurrently with the decoupling, so that a certain adiabaticity condition is satisfied.

  8. Polarization encoding for optical security systems

    NASA Astrophysics Data System (ADS)

    Javidi, Bahram; Nomura, Takanori

    1999-10-01

    An idea for security verification of identification such as passports, credit cards, and others in terms of difficulty of reproduction is proposed. The polarization information is used for security verification. As the state of the polarization encoded cannot be seen by an ordinary intensity sensitive device such as a CCD camera, it cannot be copied. For optical validation system, a joint transform correlator is used. Computer simulations and optical experimental results are shown to confirm our proposed method.

  9. 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.

  10. Population Encoding With Hodgkin–Huxley Neurons

    PubMed Central

    Lazar, Aurel A.

    2013-01-01

    The recovery of (weak) stimuli encoded with a population of Hodgkin–Huxley neurons is investigated. In the absence of a stimulus, the Hodgkin–Huxley neurons are assumed to be tonically spiking. The methodology employed calls for 1) finding an input–output (I/O) equivalent description of the Hodgkin–Huxley neuron and 2) devising a recovery algorithm for stimuli encoded with the I/O equivalent neuron(s). A Hodgkin–Huxley neuron with multiplicative coupling is I/O equivalent with an Integrate-and-Fire neuron with a variable threshold sequence. For bandlimited stimuli a perfect recovery of the stimulus can be achieved provided that a Nyquist-type rate condition is satisfied. A Hodgkin–Huxley neuron with additive coupling and deterministic conductances is first-order I/O equivalent with a Project-Integrate-and-Fire neuron that integrates a projection of the stimulus on the phase response curve. The stimulus recovery is formulated as a spline interpolation problem in the space of finite length bounded energy signals. A Hodgkin–Huxley neuron with additive coupling and stochastic conductances is shown to be first-order I/O equivalent with a Project-Integrate-and-Fire neuron with random thresholds. For stimuli modeled as elements of Sobolev spaces the reconstruction algorithm minimizes a regularized quadratic optimality criterion. Finally, all previous recovery results of stimuli encoded with Hodgkin–Huxley neurons with multiplicative and additive coupling, and deterministic and stochastic conductances are extended to stimuli encoded with a population of Hodgkin–Huxley neurons. PMID:24194625

  11. Population Encoding With Hodgkin-Huxley Neurons.

    PubMed

    Lazar, Aurel A

    2010-02-01

    The recovery of (weak) stimuli encoded with a population of Hodgkin-Huxley neurons is investigated. In the absence of a stimulus, the Hodgkin-Huxley neurons are assumed to be tonically spiking. The methodology employed calls for 1) finding an input-output (I/O) equivalent description of the Hodgkin-Huxley neuron and 2) devising a recovery algorithm for stimuli encoded with the I/O equivalent neuron(s). A Hodgkin-Huxley neuron with multiplicative coupling is I/O equivalent with an Integrate-and-Fire neuron with a variable threshold sequence. For bandlimited stimuli a perfect recovery of the stimulus can be achieved provided that a Nyquist-type rate condition is satisfied. A Hodgkin-Huxley neuron with additive coupling and deterministic conductances is first-order I/O equivalent with a Project-Integrate-and-Fire neuron that integrates a projection of the stimulus on the phase response curve. The stimulus recovery is formulated as a spline interpolation problem in the space of finite length bounded energy signals. A Hodgkin-Huxley neuron with additive coupling and stochastic conductances is shown to be first-order I/O equivalent with a Project-Integrate-and-Fire neuron with random thresholds. For stimuli modeled as elements of Sobolev spaces the reconstruction algorithm minimizes a regularized quadratic optimality criterion. Finally, all previous recovery results of stimuli encoded with Hodgkin-Huxley neurons with multiplicative and additive coupling, and deterministic and stochastic conductances are extended to stimuli encoded with a population of Hodgkin-Huxley neurons.

  12. 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.

  13. Genetically Encoded Voltage Indicators: Opportunities and Challenges.

    PubMed

    Yang, Helen H; St-Pierre, François

    2016-09-28

    A longstanding goal in neuroscience is to understand how spatiotemporal patterns of neuronal electrical activity underlie brain function, from sensory representations to decision making. An emerging technology for monitoring electrical dynamics, voltage imaging using genetically encoded voltage indicators (GEVIs), couples the power of genetics with the advantages of light. Here, we review the properties that determine indicator performance and applicability, discussing both recent progress and technical limitations. We then consider GEVI applications, highlighting studies that have already deployed GEVIs for biological discovery. We also examine which classes of biological questions GEVIs are primed to address and which ones are beyond their current capabilities. As GEVIs are further developed, we anticipate that they will become more broadly used by the neuroscience community to eavesdrop on brain activity with unprecedented spatiotemporal resolution. Genetically encoded voltage indicators are engineered light-emitting protein sensors that typically report neuronal voltage dynamics as changes in brightness. In this review, we systematically discuss the current state of this emerging method, considering both its advantages and limitations for imaging neural activity. We also present recent applications of this technology and discuss what is feasible now and what we anticipate will become possible with future indicator development. This review will inform neuroscientists of recent progress in the field and help potential users critically evaluate the suitability of genetically encoded voltage indicator imaging to answer their specific biological questions. Copyright © 2016 the authors 0270-6474/16/369977-13$15.00/0.

  14. Task unrelated thought whilst encoding information.

    PubMed

    Smallwood, Jonathan M; Baracaia, Simona F; Lowe, Michelle; Obonsawin, Marc

    2003-09-01

    Task unrelated thought (TUT) refers to thought directed away from the current situation, for example a daydream. Three experiments were conducted on healthy participants, with two broad aims. First, to contrast distributed and encapsulated views of cognition by comparing the encoding of categorical and random lists of words (Experiments One and Two). Second, to examine the consequences of experiencing TUT during study on the subsequent retrieval of information (Experiments One, Two, and Three). Experiments One and Two demonstrated lower levels of TUT and higher levels of word-fragment completion whilst encoding categorical relative to random stimuli, supporting the role of a distributed resource in the maintenance of TUT. In addition the results of all three experiments suggested that experiencing TUT during study had a measurable effect on subsequent retrieval. TUT was associated with increased frequency of false alarms at retrieval (Experiment One). In the subsequent experiments TUT was associated with no advantage to retrieval based on recollection, by manipulating instructions at encoding (Experiment Two), and/or at retrieval (Experiment Three). The implications of the results of all three experiments are discussed in terms of recent accounts of memory retrieval and conscious awareness.

  15. 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.

  16. 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

  17. Plasmid-Encoded Iron Uptake Systems.

    PubMed

    Di Lorenzo, Manuela; Stork, Michiel

    2014-12-01

    Plasmids confer genetic information that benefits the bacterial cells containing them. In pathogenic bacteria, plasmids often harbor virulence determinants that enhance the pathogenicity of the bacterium. The ability to acquire iron in environments where it is limited, for instance the eukaryotic host, is a critical factor for bacterial growth. To acquire iron, bacteria have evolved specific iron uptake mechanisms. These systems are often chromosomally encoded, while those that are plasmid-encoded are rare. Two main plasmid types, ColV and pJM1, have been shown to harbor determinants that increase virulence by providing the cell with essential iron for growth. It is clear that these two plasmid groups evolved independently from each other since they do not share similarities either in the plasmid backbones or in the iron uptake systems they harbor. The siderophores aerobactin and salmochelin that are found on ColV plasmids fall in the hydroxamate and catechol group, respectively, whereas both functional groups are present in the anguibactin siderophore, the only iron uptake system found on pJM1-type plasmids. Besides siderophore-mediated iron uptake, ColV plasmids carry additional genes involved in iron metabolism. These systems include ABC transporters, hemolysins, and a hemoglobin protease. ColV- and pJM1-like plasmids have been shown to confer virulence to their bacterial host, and this trait can be completely ascribed to their encoded iron uptake systems.

  18. Dual-channel spectrally encoded endoscopic probe.

    PubMed

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

    2012-08-01

    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.

  19. Genetically Encoded Voltage Indicators: Opportunities and Challenges

    PubMed Central

    Yang, Helen H.

    2016-01-01

    A longstanding goal in neuroscience is to understand how spatiotemporal patterns of neuronal electrical activity underlie brain function, from sensory representations to decision making. An emerging technology for monitoring electrical dynamics, voltage imaging using genetically encoded voltage indicators (GEVIs), couples the power of genetics with the advantages of light. Here, we review the properties that determine indicator performance and applicability, discussing both recent progress and technical limitations. We then consider GEVI applications, highlighting studies that have already deployed GEVIs for biological discovery. We also examine which classes of biological questions GEVIs are primed to address and which ones are beyond their current capabilities. As GEVIs are further developed, we anticipate that they will become more broadly used by the neuroscience community to eavesdrop on brain activity with unprecedented spatiotemporal resolution. SIGNIFICANCE STATEMENT Genetically encoded voltage indicators are engineered light-emitting protein sensors that typically report neuronal voltage dynamics as changes in brightness. In this review, we systematically discuss the current state of this emerging method, considering both its advantages and limitations for imaging neural activity. We also present recent applications of this technology and discuss what is feasible now and what we anticipate will become possible with future indicator development. This review will inform neuroscientists of recent progress in the field and help potential users critically evaluate the suitability of genetically encoded voltage indicator imaging to answer their specific biological questions. PMID:27683896

  20. 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

  1. Complementary attentional components of successful memory encoding

    PubMed Central

    Turk-Browne, Nicholas B.; Golomb, Julie D.; Chun, Marvin M.

    2012-01-01

    Attention during encoding improves later memory, but how this happens is poorly understood. To investigate the role of attention in memory formation, we combined a variant of a spatial attention cuing task with a subsequent memory fMRI design. Scene stimuli were presented in the periphery to either the left or right of fixation, preceded by a central face cue whose gaze oriented attention to the probable location of the scene. We contrasted activity for scenes appearing in cued versus uncued locations to identify: (1) regions where cuing facilitated processing, and (2) regions involved in reorienting. We then tested how activity in these facilitation and reorienting regions of interest predicted subsequent long-term memory for individual scenes. In facilitation regions such as parahippocampal cortex, greater activity during encoding predicted memory success. In reorienting regions such as right temporoparietal junction, greater activity during encoding predicted memory failure. We interpret these results as evidence that memory formation benefits from attentional facilitation of perceptual processing combined with suppression of the ventral attention network to prevent reorienting to distractors. PMID:23108276

  2. 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

  3. Encoding and decoding messages with chaotic lasers

    SciTech Connect

    Alsing, P.M.; Gavrielides, A.; Kovanis, V.; Roy, R.; Thornburg, K.S. Jr.

    1997-12-01

    We investigate the structure of the strange attractor of a chaotic loss-modulated solid-state laser utilizing return maps based on a combination of intensity maxima and interspike intervals, as opposed to those utilizing Poincar{acute e} sections defined by the intensity maxima of the laser ({dot I}=0,{umlt I}{lt}0) alone. We find both experimentally and numerically that a simple, intrinsic relationship exists between an intensity maximum and the pair of preceding and succeeding interspike intervals. In addition, we numerically investigate encoding messages on the output of a chaotic transmitter laser and its subsequent decoding by a similar receiver laser. By exploiting the relationship between the intensity maxima and the interspike intervals, we demonstrate that the method utilized to encode the message is vital to the system{close_quote}s ability to hide the signal from unwanted deciphering. In this work alternative methods are studied in order to encode messages by modulating the magnitude of pumping of the transmitter laser and also by driving its loss modulation with more than one frequency. {copyright} {ital 1997} {ital The American Physical Society}

  4. Digital raster timing encoder-decoder

    NASA Astrophysics Data System (ADS)

    Gennetten, E. W.; Gomez, D. A.

    1984-06-01

    The invention presents a digital raster timing encoder/decoder system wherein television raster synchronization pulses and other timing pulses and information data are generated. The invention comprises a digital clock source having coding means which combined with the clock source encodes preselected digital signals containing information on raster synchronization control and timing, and also any other information data that is desired. The encoded signal output is transmitted either directly or via some special transmission link, for example by use of a Manchester Decoder clock multiplier system, to a receiving and decoding means. The received signal is decoded to create timing signals for operation control of the video television scanning system, and to read out other desired digital data that has been also transmitted within the signal. The system takes advantage of the fact that control signals of conventional synchronization pulses contain large deadband areas within which additional data information may be placed. Such additional digital information may be used to add other control pulse capability, or to add information transmission capability. A principle feature of the system is that only a single channel is needed to transmit synchronization pulses and any additional timing pulses or information of interest.

  5. Encoded libraries of chemically modified peptides.

    PubMed

    Heinis, Christian; Winter, Greg

    2015-06-01

    The use of powerful technologies for generating and screening DNA-encoded protein libraries has helped drive the development of proteins as pharmaceutical ligands. However the development of peptides as pharmaceutical ligands has been more limited. Although encoded peptide libraries are typically several orders of magnitude larger than classical chemical libraries, can be more readily screened, and can give rise to higher affinity ligands, their use as pharmaceutical ligands is limited by their intrinsic properties. Two of the intrinsic limitations include the rotational flexibility of the peptide backbone and the limited number (20) of natural amino acids. However these limitations can be overcome by use of chemical modification. For example, the libraries can be modified to introduce topological constraints such as cyclization linkers, or to introduce new chemical entities such as small molecule ligands, fluorophores and photo-switchable compounds. This article reviews the chemistry involved, the properties of the peptide ligands, and the new opportunities offered by chemical modification of DNA-encoded peptide libraries.

  6. 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.

  7. 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.

  8. 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

  9. Automatic medical encoding with SNOMED categories.

    PubMed

    Ruch, Patrick; Gobeill, Julien; Lovis, Christian; Geissbühler, Antoine

    2008-10-27

    In this paper, we describe the design and preliminary evaluation of a new type of tools to speed up the encoding of episodes of care using the SNOMED CT terminology. The proposed system can be used either as a search tool to browse the terminology or as a categorization tool to support automatic annotation of textual contents with SNOMED concepts. The general strategy is similar for both tools and is based on the fusion of two complementary retrieval strategies with thesaural resources. The first classification module uses a traditional vector-space retrieval engine which has been fine-tuned for the task, while the second classifier is based on regular variations of the term list. For evaluating the system, we use a sample of MEDLINE. SNOMED CT categories have been restricted to Medical Subject Headings (MeSH) using the SNOMED-MeSH mapping provided by the UMLS (version 2006). Consistent with previous investigations applied on biomedical terminologies, our results show that performances of the hybrid system are significantly improved as compared to each single module. For top returned concepts, a precision at high ranks (P0) of more than 80% is observed. In addition, a manual and qualitative evaluation on a dozen of MEDLINE abstracts suggests that SNOMED CT could represent an improvement compared to existing medical terminologies such as MeSH. Although the precision of the SNOMED categorizer seems sufficient to help professional encoders, it is concluded that clinical benchmarks as well as usability studies are needed to assess the impact of our SNOMED encoding method in real settings. AVAILABILITIES: The system is available for research purposes on: http://eagl.unige.ch/SNOCat.

  10. Plasmid-encoded trimethoprim resistance in staphylococci.

    PubMed Central

    Archer, G L; Coughter, J P; Johnston, J L

    1986-01-01

    High-level (greater than 1,000 micrograms/ml) resistance to the antimicrobial agent trimethoprim was found in 17 of 101 (17%) coagulase-negative staphylococci and 5 of 51 (10%) Staphylococcus aureus from a number of different hospitals in the United States. Resistance was plasmid encoded and could be transferred by conjugation in 4 of the 17 (24%) Tpr coagulase-negative staphylococci and 3 of the 5 (60%) Tpr S. aureus. A 1.2-kilobase segment of plasmid DNA from one of the plasmids (pG01) was cloned on a high-copy-number vector in Escherichia coli and expressed high-level Tpr (MIC, 1,025 micrograms/ml) in the gram-negative host. In situ filter hybridization demonstrated homology between the cloned Tpr gene probe and plasmid DNA from each conjugative Tpr plasmid, a single nonconjugative plasmid from a United States Staphylococcus epidermidis isolate, a nonconjugative plasmid from an Australian methicillin-resistant S. aureus isolate, and chromosomal DNA from three Tpr S. epidermidis isolates that did not contain any plasmid DNA that was homologous with the probe. No homology was seen between the probe and staphylococcal plasmids not mediating Tpr, plasmid DNA from 12 Tpr S. epidermidis isolates not transferring Tpr by conjugation, or plasmid-encoded Tpr genes derived from gram-negative bacteria. Plasmid-encoded Tpr appears to be a relatively new gene in staphylococci and, because it can be transferred by conjugation, could become more prevalent in nonsocomial isolates. Images PMID:3729338

  11. Fast acceleration-encoded magnetic resonance imaging.

    PubMed

    Forster, J; Sieverding, L; Breuer, J; Lutz, O; Schick, F

    2001-01-01

    Direct acceleration imaging with high spatial resolution was implemented and tested. The well-known principle of phase encoding motion components was applied. Suitable gradient switching provides a signal phase shift proportional to the acceleration perpendicular to the slice in the first scan of the sequences. An additional scan serving as a reference was recorded for compensation of phase effects due to magnetic field inhomogeneities. The first scan compensated for phase shifts from undesired first- and second-order motions; the second scan was completely insensitive to velocity and acceleration in all directions. Advantages of the proposed two-step technique compared to former approaches with Fourier acceleration encoding (with several phase encoding steps) are relatively short echo times and short total measuring times. On the other hand, the new approach does not allow us to assess the velocity or acceleration spectrum simultaneously. The capabilities of the sequences were tested on a modern 1.5 T whole body MR unit providing relatively high gradient amplitudes (25 mT/m) and short rise times (600 micros to maximum amplitude). The results from a mechanical acceleration phantom showed a standard deviation of 0.3 m/s2 in sequences with an acceleration range between -12 and 12 m/s2. This range covers the expected maximum acceleration in the human aorta of 10 m/s2. Further tests were performed on a stenosis phantom with a variable volume flow rate to assess the flow characteristics and possible displacement artifacts of the sequences. Preliminary examinations of volunteers demonstrate the potential applicability of the technique in vivo.

  12. 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

  13. Using the ENCODE Resource for Functional Annotation of Genetic Variants.

    PubMed

    Pazin, Michael J

    2015-03-11

    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. Although the focus of this article is the use of ENCODE data, some of the same approaches can be used with data from other projects.

  14. Mouse redox histology using genetically encoded probes.

    PubMed

    Fujikawa, Yuuta; Roma, Leticia P; Sobotta, Mirko C; Rose, Adam J; Diaz, Mauricio Berriel; Locatelli, Giuseppe; Breckwoldt, Michael O; Misgeld, Thomas; Kerschensteiner, Martin; Herzig, Stephan; Müller-Decker, Karin; Dick, Tobias P

    2016-03-15

    Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation.

  15. 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.

  16. Spatially encoded multiple-quantum excitation.

    PubMed

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

    2013-05-28

    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 ẑ-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.

  17. 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.

  18. Subband image encoder using discrete wavelet transform

    NASA Astrophysics Data System (ADS)

    Seong, Hae Kyung; Rhee, Kang Hyeon

    2004-03-01

    Introduction of digital communication network such as Integrated Services Digital Networks (ISDN) and digital storage media have rapidly developed. Due to a large amount of image data, compression is the key techniques in still image and video using digital signal processing for transmitting and storing. Digital image compression provides solutions for various image applications that represent digital image requiring a large amount of data. In this paper, the proposed DWT (Discrete Wavelet Transform) filter bank is consisted of simple architecture, but it is efficiently designed that a user obtains a wanted compression rate as only input parameter. If it is implemented by FPGA chip, the designed encoder operates in 12 MHz.

  19. Digitally encoded all-optical sensor multiplexing

    NASA Astrophysics Data System (ADS)

    Pervez, Anjum

    1992-01-01

    A digital, all-optical temperature sensor design concept based on optical sampling and digital encoding is presented. The proposed sensor generates 2M binary digital codewords of length M bits. The codewords are generated serially and, therefore, only a single output fiber line is required. A multiplexing scheme, which minimizes the power requirement per sensor array and facilitates a cost-effective digit regeneration for remote monitoring over long distance, is presented. The sensor arrays are used as building blocks to configure large scale sensor networks based on LAN topologies.

  20. Flow cytometry using spectrally encoded confocal microscopy.

    PubMed

    Golan, Lior; Yelin, Dvir

    2010-07-01

    Flow cytometry techniques often rely on detecting fluorescence from single cells flowing through the cross section of a laser beam, providing invaluable information on vast numbers of cells. Such techniques, however, are often limited in their ability to resolve clusters of cells or parallel cell flow through large vessels. We present a confocal imaging technique that images unstained cells flowing in parallel through a wide channel, using spectrally encoded reflectance confocal microscopy that does not require mechanical scanning. Images of red blood cells from our system are compared to conventional transmission microscopy, and imaging of flowing red blood cells in vitro is experimentally demonstrated.

  1. 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.

  2. Rapidly-Indexing Incremental-Angle Encoder

    NASA Technical Reports Server (NTRS)

    Christon, Philip R.; Meyer, Wallace W.

    1989-01-01

    Optoelectronic system measures relative angular position of shaft or other device to be turned, also measures absolute angular position after device turned through small angle. Relative angular position measured with fine resolution by optoelectronically counting finely- and uniformly-spaced light and dark areas on encoder disk as disk turns past position-sensing device. Also includes track containing coarsely- and nonuniformly-spaced light and dark areas, angular widths varying in proportion to absolute angular position. This second track provides gating and indexing signal.

  3. Auditory location as an encoding dimension.

    PubMed

    Weeks, R A

    1975-05-01

    In two experiments, subjects were given five successive short-term memory tests. In Experiment 1, recall was not significantly facilitated when memory material in the final test was delivered to the ear opposite to the one that received the memory material in the four preceding tests. In Experiment 2, events were presented from two differentially located speakers rather than through headphones. A shift across speakers on the final test did produce proactive interference release. These findings suggest spatial location as a potential encoding dimension of verbal material.

  4. The ENCODE (ENCyclopedia Of DNA Elements) Project.

    PubMed

    2004-10-22

    The ENCyclopedia Of DNA Elements (ENCODE) Project aims to identify all functional elements in the human genome sequence. The pilot phase of the Project is focused on a specified 30 megabases (approximately 1%) of the human genome sequence and is organized as an international consortium of computational and laboratory-based scientists working to develop and apply high-throughput approaches for detecting all sequence elements that confer biological function. The results of this pilot phase will guide future efforts to analyze the entire human genome.

  5. 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.

  6. Image compression based on GPU encoding

    NASA Astrophysics Data System (ADS)

    Bai, Zhaofeng; Qiu, Yuehong

    2015-07-01

    With the rapid development of digital technology, the data increased greatly in both static image and dynamic video image. It is noticeable how to decrease the redundant data in order to save or transmit information more efficiently. So the research on image compression becomes more and more important. Using GPU to achieve higher compression ratio has superiority in interactive remote visualization. Contrast to CPU, GPU may be a good way to accelerate the image compression. Currently, GPU of NIVIDIA has evolved into the eighth generation, which increasingly dominates the high-powered general purpose computer field. This paper explains the way of GPU encoding image. Some experiment results are also presented.

  7. Gene encoding herbicide safener binding protein

    DOEpatents

    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. 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.

  9. An encyclopedia of mouse DNA elements (Mouse ENCODE)

    PubMed Central

    2012-01-01

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome. PMID:22889292

  10. Socialization Processes in Encoding and Decoding: Learning Effective Nonverbal Behavior.

    ERIC Educational Resources Information Center

    Feldman, Robert S.; Coats, Erik

    This study examined the relationship of nonverbal encoding and decoding skills to the level of exposure to television. Subjects were children in second through sixth grade. Three nonverbal skills (decoding, spontaneous encoding, and posed encoding) were assessed for each of five emotions: anger, disgust, fear or surprise, happiness, and sadness.…

  11. Self-encoding resin beads of combinatorial library screening

    NASA Astrophysics Data System (ADS)

    Lei, Du; Zhao, Yuandi; Cheng, Tongsheng; Zeng, Shaoqun; Luo, Qingming

    2003-07-01

    The latest self-encoding resin bead is a novel technology for solid phase synthesis combinatorial library screening. A new encode-positional deconvolution strategy which was based on that technology been illustrated compared with positional scanning and iterative strategies. The self-encoding resin beads technology provides an efficient method for improving the high-throughput screening of combinatorial library.

  12. Area MT Encodes Three-Dimensional Motion

    PubMed Central

    Huk, Alexander C.; Cormack, Lawrence K.; Kohn, Adam

    2014-01-01

    We use visual information to determine our dynamic relationship with other objects in a three-dimensional (3D) world. Despite decades of work on visual motion processing, it remains unclear how 3D directions—trajectories that include motion toward or away from the observer—are represented and processed in visual cortex. Area MT is heavily implicated in processing visual motion and depth, yet previous work has found little evidence for 3D direction sensitivity per se. Here we use a rich ensemble of binocular motion stimuli to reveal that most neurons in area MT of the anesthetized macaque encode 3D motion information. This tuning for 3D motion arises from multiple mechanisms, including different motion preferences in the two eyes and a nonlinear interaction of these signals when both eyes are stimulated. Using a novel method for functional binocular alignment, we were able to rule out contributions of static disparity tuning to the 3D motion tuning we observed. We propose that a primary function of MT is to encode 3D motion, critical for judging the movement of objects in dynamic real-world environments. PMID:25411482

  13. 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.

  14. 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.

  15. Encoded multisite two-photon microscopy.

    PubMed

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

    2013-08-06

    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.

  16. Genetically Encoded Libraries of Nonstandard Peptides

    PubMed Central

    Kawakami, Takashi; Murakami, Hiroshi

    2012-01-01

    The presence of a nonproteinogenic moiety in a nonstandard peptide often improves the biological properties of the peptide. Non-standard peptide libraries are therefore used to obtain valuable molecules for biological, therapeutic, and diagnostic applications. Highly diverse non-standard peptide libraries can be generated by chemically or enzymatically modifying standard peptide libraries synthesized by the ribosomal machinery, using posttranslational modifications. Alternatively, strategies for encoding non-proteinogenic amino acids into the genetic code have been developed for the direct ribosomal synthesis of non-standard peptide libraries. In the strategies for genetic code expansion, non-proteinogenic amino acids are assigned to the nonsense codons or 4-base codons in order to add these amino acids to the universal genetic code. In contrast, in the strategies for genetic code reprogramming, some proteinogenic amino acids are erased from the genetic code and non-proteinogenic amino acids are reassigned to the blank codons. Here, we discuss the generation of genetically encoded non-standard peptide libraries using these strategies and also review recent applications of these libraries to the selection of functional non-standard peptides. PMID:23097693

  17. 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.

  18. The First Gene-encoded Amphibian Neurotoxin*

    PubMed Central

    You, Dewen; Hong, Jing; Rong, Mingqiang; Yu, Haining; Liang, Songping; Ma, Yufang; Yang, Hailong; Wu, Jing; Lin, Donghai; Lai, Ren

    2009-01-01

    Many gene-encoded neurotoxins with various functions have been discovered in fish, reptiles, and mammals. A novel 60-residue neurotoxin peptide (anntoxin) that inhibited tetrodotoxin-sensitive (TTX-S) voltage-gated sodium channel (VGSC) was purified and characterized from the skin secretions of the tree frog Hyla annectans (Jerdon). This is the first gene-encoded neurotoxin found in amphibians. The IC50 of anntoxin for the TTX-S channel was about 3.4 μm. Anntoxin shares sequence homology with Kunitz-type toxins but contains only two of three highly conserved cysteine bridges, which are typically found in these small, basic neurotoxin modules, i.e. snake dendrotoxins. Anntoxin showed an inhibitory ability against trypsin with an inhibitory constant (Ki) of 0.025 μm. Anntoxin was distributed in skin, brain, stomach, and liver with a concentration of 25, 7, 3, and 2 μg/g wet tissue, respectively. H. annectans lives on trees or other plants for its entire life cycle, and its skin contains the largest amount of anntoxin, which possibly helps defend against various aggressors or predators. A low dose of anntoxin was found to induce lethal toxicity for several potential predators, including the insect, snake, bird, and mouse. The tissue distribution and functional properties of the current toxin may provide insights into the ecological adaptation of tree-living amphibians. PMID:19535333

  19. Directed forgetting benefits motor sequence encoding.

    PubMed

    Tempel, Tobias; Frings, Christian

    2016-04-01

    Two experiments investigated directed forgetting of newly learned motor sequences. Concurrently with the list method of directed forgetting, participants successively learned two lists of motor sequences. Each sequence consisted of four consecutive finger movements. After a short distractor task, a recall test was given. Both experiments compared a forget group that was instructed to forget list-1 items with a remember group not receiving a forget instruction. We found that the instruction to forget list 1 enhanced recall of subsequently learned motor sequences. This benefit of directed forgetting occurred independently of costs for list 1. A mediation analysis showed that the encoding accuracy of list 2 was a mediator of the recall benefit, that is, the more accurate execution of motor sequences of list 2 after receiving a forget instruction for list 1 accounted for better recall of list 2. Thus, the adaptation of the list method to motor action provided more direct evidence on the effect of directed forgetting on subsequent learning. The results corroborate the assumption of a reset of encoding as a consequence of directed forgetting.

  20. 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

  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. 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.

  3. 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.

  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. Improvement of protein secondary structure prediction using binary word encoding.

    PubMed

    Kawabata, T; Doi, J

    1997-01-01

    We propose a binary word encoding to improve the protein secondary structure prediction. A binary word encoding encodes a local amino acid sequence to a binary word, which consists of 0 or 1. We use an encoding function to map an amino acid to 0 or 1. Using the binary word encoding, we can statistically extract the multiresidue information, which depends on more than one residue. We combine the binary word encoding with the GOR method, its modified version, which shows better accuracy, and the neural network method. The binary word encoding improves the accuracy of GOR by 2.8%. We obtain similar improvement when we combine this with the modified GOR method and the neural network method. When we use multiple sequence alignment data, the binary word encoding similarly improves the accuracy. The accuracy of our best combined method is 68.2%. In this paper, we only show improvement of the GOR and neural network method, we cannot say that the encoding improves the other methods. But the improvement by the encoding suggests that the multiresidue interaction affects the formation of secondary structure. In addition, we find that the optimal encoding function obtained by the simulated annealing method relates to nonpolarity. This means that nonpolarity is important to the multiresidue interaction.

  6. 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.

  7. Hierarchical encoding of behavior: translating perception into action.

    PubMed

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

    2006-11-01

    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 themselves. Hierarchical encoding, measured by segmentation patterns, correlated with more accurate and more hierarchically structured performance of the later assembly task. Furthermore, hierarchical encoding increased when participants (a) segmented coarse units first, (b) explicitly looked for hierarchical structure, and (c) described actions while segmenting them. Improving hierarchical encoding always led to improvements in learning, as well as a surprising shift toward encoding and executing actions from the actor's spatial perspective instead of the participants' own. Hierarchical encoding facilitates observational learning by organizing perceived actions into a representation that can serve as an action plan.

  8. 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.

  9. 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

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

    PubMed

    MacConnell, Andrew B; McEnaney, Patrick J; Cavett, Valerie J; Paegel, Brian M

    2015-09-14

    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 × 10(4) 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 PCR

  11. Genetically encoded sensors for calcium and zinc

    NASA Astrophysics Data System (ADS)

    Palmer, Amy E.; Dittmer, Philip; McCombs, Janet E.

    2008-02-01

    Our lab focuses on developing fluorescent biosensors based on fluorescence resonance energy transfer (FRET) so that we can monitor signaling ions in living cells. These sensors are comprised of two fluorescent proteins and a sensing domain that undergoes a conformational change upon binding the target ligand. These sensors can be genetically encoded and hence incorporated into cells by transgenic technologies. Here we discuss the latest developments in our efforts to reengineer calcium sensors as well as develop new sensors for zinc. In these efforts we employ a combination of naturally occurring calcium and zinc binding domains, combined with protein engineering. We are also developing new methodologies to screen and sort sensor libraries using optically-integrated microfluidic devices. Thus far, we have targeted sensors to the ER, mitochondria, Golgi, nucleus, and plasma membrane in order to examine the spatial heterogeneity and localization of signaling processes.

  12. 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. © 2016 The Authors Development, Growth & Differentiation published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Developmental Biologists.

  13. Schistosome satellite DNA encodes active hammerhead ribozymes.

    PubMed

    Ferbeyre, G; Smith, J M; Cedergren, R

    1998-07-01

    Using a computer program designed to search for RNA structural motifs in sequence databases, we have found a hammerhead ribozyme domain encoded in the Smalpha repetitive DNA of Schistosoma mansoni. Transcripts of these repeats are expressed as long multimeric precursor RNAs that cleave in vitro and in vivo into unit-length fragments. This RNA domain is able to engage in both cis and trans cleavage typical of the hammerhead ribozyme. Further computer analysis of S. mansoni DNA identified a potential trans cleavage site in the gene coding for a synaptobrevin-like protein, and RNA transcribed from this gene was efficiently cleaved by the Smalpha ribozyme in vitro. Similar families of repeats containing the hammerhead domain were found in the closely related Schistosoma haematobium and Schistosomatium douthitti species but were not present in Schistosoma japonicum or Heterobilharzia americana, suggesting that the hammerhead domain was not acquired from a common schistosome ancestor.

  14. 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

  15. Ribosomally encoded cyclic peptide toxins from mushrooms.

    PubMed

    Walton, Jonathan D; Luo, Hong; Hallen-Adams, Heather

    2012-01-01

    The cyclic peptide toxins of poisonous Amanita mushrooms are chemically unique among known natural products. Furthermore, they differ from other fungal cyclic peptides in being synthesized on ribosomes instead of by nonribosomal peptide synthetases. Because of their novel structures and biogenic origins, elucidation of the biosynthetic pathway of the Amanita cyclic peptides presents both challenges and opportunities. In particular, a full understanding of the pathway should lead to the ability to direct synthesis of a large number of novel cyclic peptides based on the Amanita toxin scaffold by genetic engineering of the encoding genes. Here, we highlight some of the principal methods for working with the Amanita cyclic peptides and the known steps in their biosynthesis.

  16. Visually lossless encoding for JPEG2000.

    PubMed

    Oh, Han; Bilgin, Ali; Marcellin, Michael W

    2013-01-01

    Due to exponential growth in image sizes, visually lossless coding is increasingly being considered as an alternative to numerically lossless coding, which has limited compression ratios. This paper presents a method of encoding color images in a visually lossless manner using JPEG2000. In order to hide coding artifacts caused by quantization, visibility thresholds (VTs) are measured and used for quantization of subband signals in JPEG2000. The VTs are experimentally determined from statistically modeled quantization distortion, which is based on the distribution of wavelet coefficients and the dead-zone quantizer of JPEG2000. The resulting VTs are adjusted for locally changing backgrounds through a visual masking model, and then used to determine the minimum number of coding passes to be included in the final codestream for visually lossless quality under the desired viewing conditions. Codestreams produced by this scheme are fully JPEG2000 Part-I compliant.

  17. Ultrasonically encoded photoacoustic flowgraphy in biological tissue.

    PubMed

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

    2013-11-15

    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 0.24  mm·s(-1)} was successfully measured. Deep blood flow imaging was experimentally demonstrated under 5-mm-thick chicken breast tissue.

  18. Ultrathin nonlinear metasurface for optical image encoding.

    PubMed

    Walter, Felicitas; Li, Guixin; Meier, Cedrik; Zhang, Shuang; Zentgraf, Thomas

    2017-04-14

    Security of optical information is of great importance in modern society. Many cryptography techniques based on classical and quantum optics have been widely explored in the linear optical regime. Nonlinear optical encryption, in which encoding and decoding involve nonlinear frequency conversions, represents a new strategy for securing optical information. Here, we demonstrate that an ultrathin nonlinear photonic metasurface, consisting of meta-atoms with three-fold rotational symmetry, can be used to hide optical images under illumination with a fundamental wave. However, the hidden image can be read out from second harmonic generation (SHG) waves. This is achieved by controlling the destructive and constructive interferences of SHG waves from two neighboring meta-atoms. In addition, we apply this concept to obtain grey-scale SHG imaging. Nonlinear metasurfaces based on space variant optical interference open new avenues for multi-level image encryption, anti-counterfeiting and background free image reconstruction.

  19. Photoelectrical encoder employing an optical grating

    SciTech Connect

    Kabaya, Y.

    1985-02-12

    A photoelectrical encoder is disclosed wherein a physical quantity is detected from brightness obtained by moving a first and a second scale. Each scale is provided thereon with an optical grating relative to each other. The grating in one of the scales is constructed such that a first signal lead-out material layer made of a light shielding conductive material, a PN semiconductor layer for converting light into electricity, and a second signal lead-out material layer made of a light transmitting conductive material are laminated on a light transmitting base member to form a narrow belt-shaped light receiving portion and a plurality of narrow belt-shaped light receiving portions arranged at regular pitches. Against the light from the light transmitting base member, the light receiving portions function as light shielding slits, and intervals between the light receiving portions are formed into light transmitting slits.

  20. Brain Circuits Encoding Reward from Pain Relief

    PubMed Central

    Navratilova, Edita; Atcherley, Christopher; Porreca, Frank

    2015-01-01

    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, activation of midbrain dopamine neurons and release of dopamine in the nucleus accumbens. Understanding of circuits that govern the reward of pain relief may allow the discovery of more effective and satisfying therapies for patients with acute and chronic pain. PMID:26603560

  1. 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.

  2. Encoding and Decoding Models in Cognitive Electrophysiology.

    PubMed

    Holdgraf, Christopher R; Rieger, Jochem W; Micheli, Cristiano; Martin, Stephanie; Knight, Robert T; Theunissen, Frederic E

    2017-01-01

    Cognitive neuroscience has seen rapid growth in the size and complexity of data recorded from the human brain as well as in the computational tools available to analyze this data. This data explosion has resulted in an increased use of multivariate, model-based methods for asking neuroscience questions, allowing scientists to investigate multiple hypotheses with a single dataset, to use complex, time-varying stimuli, and to study the human brain under more naturalistic conditions. These tools come in the form of "Encoding" models, in which stimulus features are used to model brain activity, and "Decoding" models, in which neural features are used to generated a stimulus output. Here we review the current state of encoding and decoding models in cognitive electrophysiology and provide a practical guide toward conducting experiments and analyses in this emerging field. Our examples focus on using linear models in the study of human language and audition. We show how to calculate auditory receptive fields from natural sounds as well as how to decode neural recordings to predict speech. The paper aims to be a useful tutorial to these approaches, and a practical introduction to using machine learning and applied statistics to build models of neural activity. The data analytic approaches we discuss may also be applied to other sensory modalities, motor systems, and cognitive systems, and we cover some examples in these areas. In addition, a collection of Jupyter notebooks is publicly available as a complement to the material covered in this paper, providing code examples and tutorials for predictive modeling in python. The aim is to provide a practical understanding of predictive modeling of human brain data and to propose best-practices in conducting these analyses.

  3. The gene encoding proopiomelanocortin in the dog.

    PubMed

    Mol, J A; van Mansfeld, A D; Kwant, M M; van Wolferen, M; Rothuizen, J

    1991-01-01

    The regulation of the synthesis of ACTH in the dog is of interest for studies of the physiology of the pituitary-adrenocortical axis as well as for studies of the pathogenesis of pituitary-dependent hyperadrenocorticism. Despite this broad interest the nucleotide sequence encoding ACTH and its precursor proopiomelanocortin (POMC) is not known, nor is it clear whether there are differences in POMC mRNA from the anterior lobe or the intermediate lobe of the normal pituitary or from pituitary tumours causing ACTH excess. Following the preparation of a cDNA library from the canine intermediate lobe of the pituitary gland, the part of the mRNA that is translated into the proopiomelanocortin prohormone was amplified using a polymerase chain reaction. Sequence analysis revealed the highest homology with the porcine mRNA sequence. Translation in a single reading frame revealed highly homologous areas in the amino-terminal, carboxy-terminal, and ACTH part of the prohormone, whereas a high diversity was noticed at the sequence preceding ACTH and the beginning of beta-lipotropin. Northern blot analysis disclosed the presence of a POMC mRNA of approximately 1300 nucleotides. There were no size differences between the anterior lobe, intermediate lobe, and pituitary tumour derived POMC mRNA. The highest expression levels of POMC mRNA as related to the expression of the gene encoding glyceraldehyde-3-phosphate dehydrogenase were found in the intermediate lobe of the canine pituitary gland. It is concluded that excessive production of ACTH by pituitary tumours is not caused by relatively high expression levels or alterations in the size of mRNA.

  4. Miniature Grating for Spectrally-Encoded Endoscopy

    PubMed Central

    Kang, Dongkyun; Martinez, Ramses V.; Whitesides, George M.

    2013-01-01

    Spectrally-encoded endoscopy (SEE) is an ultraminiature endoscopy technology that acquires high-definition images of internal organs through a sub-mm endoscopic probe. In SEE, a grating at the tip of the imaging optics diffracts the broadband light into multiple beams, where each beam with a distinctive wavelength is illuminated on a unique transverse location of the tissue. By encoding one transverse coordinate with the wavelength, SEE can image a line of the tissue at a time without using any beam scanning devices. This feature of the SEE technology allows the SEE probe to be miniaturized to sub-mm dimensions. While previous studies have shown that SEE has the potential to be utilized for various clinical imaging applications, the translation of SEE for medicine has been hampered by challenges in fabricating the miniature grating inherent to SEE probes. This paper describes a new fabrication method for SEE probes. The new method uses a soft lithographic approach to pattern a high-aspect-ratio grating at the tip of the miniature imaging optics. Using this technique, we have constructed a 500-μm-diameter SEE probe. The miniature grating at the tip of the probe had a measured diffraction efficiency of 75%. The new SEE probe was used to image a human finger and formalin fixed mouse embryos, demonstrating the capability of this device to visualize key anatomic features of tissues with high image contrast. In addition to providing high quality imaging SEE optics, the soft lithography method allows cost-effective and reliable fabrication of these miniature endoscopes, which will facilitate the clinical translation of SEE technology. PMID:23503940

  5. 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

  6. Modular verification of chemical reaction network encodings via serializability analysis

    PubMed Central

    Lakin, Matthew R.; Stefanovic, Darko; Phillips, Andrew

    2015-01-01

    Chemical reaction networks are a powerful means of specifying the intended behaviour of synthetic biochemical systems. A high-level formal specification, expressed as a chemical reaction network, may be compiled into a lower-level encoding, which can be directly implemented in wet chemistry and may itself be expressed as a chemical reaction network. Here we present conditions under which a lower-level encoding correctly emulates the sequential dynamics of a high-level chemical reaction network. We require that encodings are transactional, such that their execution is divided by a “commit reaction” that irreversibly separates the reactant-consuming phase of the encoding from the product-generating phase. We also impose restrictions on the sharing of species between reaction encodings, based on a notion of “extra tolerance”, which defines species that may be shared between encodings without enabling unwanted reactions. Our notion of correctness is serializability of interleaved reaction encodings, and if all reaction encodings satisfy our correctness properties then we can infer that the global dynamics of the system are correct. This allows us to infer correctness of any system constructed using verified encodings. As an example, we show how this approach may be used to verify two- and four-domain DNA strand displacement encodings of chemical reaction networks, and we generalize our result to the limit where the populations of helper species are unlimited. PMID:27325906

  7. Modular verification of chemical reaction network encodings via serializability analysis.

    PubMed

    Lakin, Matthew R; Stefanovic, Darko; Phillips, Andrew

    2016-06-13

    Chemical reaction networks are a powerful means of specifying the intended behaviour of synthetic biochemical systems. A high-level formal specification, expressed as a chemical reaction network, may be compiled into a lower-level encoding, which can be directly implemented in wet chemistry and may itself be expressed as a chemical reaction network. Here we present conditions under which a lower-level encoding correctly emulates the sequential dynamics of a high-level chemical reaction network. We require that encodings are transactional, such that their execution is divided by a "commit reaction" that irreversibly separates the reactant-consuming phase of the encoding from the product-generating phase. We also impose restrictions on the sharing of species between reaction encodings, based on a notion of "extra tolerance", which defines species that may be shared between encodings without enabling unwanted reactions. Our notion of correctness is serializability of interleaved reaction encodings, and if all reaction encodings satisfy our correctness properties then we can infer that the global dynamics of the system are correct. This allows us to infer correctness of any system constructed using verified encodings. As an example, we show how this approach may be used to verify two- and four-domain DNA strand displacement encodings of chemical reaction networks, and we generalize our result to the limit where the populations of helper species are unlimited.

  8. New Ultra-High Sensitivity, Absolute, Linear, and Rotary Encoders

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B.

    1998-01-01

    Several new types of absolute optical encoders of both rotary and linear function are discussed. The means for encoding are complete departures from conventional optical encoders and offer advantages of compact form, immunity to damage-induced dropouts of position information, and about an order of magnitude higher sensitivity over what is commercially available. Rotary versions have sensitivity from 0.02 arcseconds down to 0.003 arcsecond while linear models have sensitivity of 10 nm.

  9. Aging affects neural precision of speech encoding

    PubMed Central

    Anderson, Samira; Parbery-Clark, Alexandra; White-Schwoch, Travis; Kraus, Nina

    2012-01-01

    Older adults frequently report they can hear what is said but cannot understand the meaning, especially in noise. This difficulty may arise from the inability to process rapidly changing elements of speech. Aging is accompanied by a general slowing of neural processing and decreased neural inhibition, both of which likely interfere with temporal processing in auditory and other sensory domains. Age-related reductions in inhibitory neurotransmitter levels and delayed neural recovery can contribute to decreases in the auditory system’s temporal precision. Decreased precision may lead to neural timing delays, reductions in neural response magnitude, and a disadvantage in processing the rapid acoustic changes in speech. The auditory brainstem response (ABR), a scalp-recorded electrical potential, is known for its ability to capture precise neural synchrony within subcortical auditory nuclei; therefore, we hypothesized that a loss of temporal precision results in subcortical timing delays and decreases in response consistency and magnitude. To assess this hypothesis, we recorded ABRs to the speech syllable /da/ in normal hearing younger (ages 18 to 30) and older adult humans (60 to 67). Older adults had delayed ABRs, especially in response to the rapidly changing formant transition, and greater response variability. We also found that older adults had decreased phase locking and smaller response magnitudes than younger adults. Taken together, our results support the theory that older adults have a loss of temporal precision in subcortical encoding of sound, which may account, at least in part, for their difficulties with speech perception. PMID:23055485

  10. Encoding pitch contours using current steering.

    PubMed

    Luo, Xin; Landsberger, David M; Padilla, Monica; Srinivasan, Arthi G

    2010-09-01

    This study investigated cochlear implant (CI) users' ability to perceive pitch cues from time-varying virtual channels (VCs) to identify pitch contours. Seven CI users were tested on apical, medial, and basal electrode pairs with stimulus durations from 100 to 1000 ms. In one stimulus set, 9 pitch contours were created by steering current between the component electrodes and the VC halfway between the electrodes. Another stimulus set only contained 3 pitch contours (flat, falling, and rising). VC discrimination was also tested on the same electrodes. The total current level of dual-electrode stimuli was linearly interpolated between those of single-electrode stimuli to minimize loudness changes. The results showed that pitch contour identification (PCI) scores were similar across electrode locations, and significantly improved at longer durations. For durations longer than 300 ms, 2 subjects had nearly perfect 9-contour identification, and 5 subjects perfectly identified the 3 basic contours. Both PCI and VC discrimination varied greatly across subjects. Cumulative d(') values for VC discrimination were significantly correlated with 100-, 200-, and 500-ms PCI scores. These results verify the feasibility of encoding pitch contours using current steering, and suggest that identification of such pitch contours strongly relies on CI users' sensitivity to VCs.

  11. Categorical encoding of color in the brain

    PubMed Central

    Bird, Chris M.; Berens, Samuel C.; Horner, Aidan J.; Franklin, Anna

    2014-01-01

    The areas of the brain that encode color categorically have not yet been reliably identified. Here, we used functional MRI adaptation to identify neuronal populations that represent color categories irrespective of metric differences in color. Two colors were successively presented within a block of trials. The two colors were either from the same or different categories (e.g., “blue 1 and blue 2” or “blue 1 and green 1”), and the size of the hue difference was varied. Participants performed a target detection task unrelated to the difference in color. In the middle frontal gyrus of both hemispheres and to a lesser extent, the cerebellum, blood-oxygen level-dependent response was greater for colors from different categories relative to colors from the same category. Importantly, activation in these regions was not modulated by the size of the hue difference, suggesting that neurons in these regions represent color categorically, regardless of metric color difference. Representational similarity analyses, which investigated the similarity of the pattern of activity across local groups of voxels, identified other regions of the brain (including the visual cortex), which responded to metric but not categorical color differences. Therefore, categorical and metric hue differences appear to be coded in qualitatively different ways and in different brain regions. These findings have implications for the long-standing debate on the origin and nature of color categories, and also further our understanding of how color is processed by the brain. PMID:24591602

  12. 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

  13. Genes Encoding Enzymes Involved in Ethanol Metabolism

    PubMed Central

    Hurley, Thomas D.; Edenberg, Howard J.

    2012-01-01

    The effects of beverage alcohol (ethanol) on the body are determined largely by the rate at which it and its main breakdown product, acetaldehyde, are metabolized after consumption. The main metabolic pathway for ethanol involves the enzymes alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Seven different ADHs and three different ALDHs that metabolize ethanol have been identified. The genes encoding these enzymes exist in different variants (i.e., alleles), many of which differ by a single DNA building block (i.e., single nucleotide polymorphisms [SNPs]). Some of these SNPs result in enzymes with altered kinetic properties. For example, certain ADH1B and ADH1C variants that are commonly found in East Asian populations lead to more rapid ethanol breakdown and acetaldehyde accumulation in the body. Because acetaldehyde has harmful effects on the body, people carrying these alleles are less likely to drink and have a lower risk of alcohol dependence. Likewise, an ALDH2 variant with reduced activity results in acetaldehyde buildup and also has a protective effect against alcoholism. In addition to affecting drinking behaviors and risk for alcoholism, ADH and ALDH alleles impact the risk for esophageal cancer. PMID:23134050

  14. Dynamical encoding of looming, receding, and focussing

    NASA Astrophysics Data System (ADS)

    Longtin, Andre; Clarke, Stephen Elisha; Maler, Leonard; CenterNeural 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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. PMID:27635230

  20. Categorical encoding of color in the brain.

    PubMed

    Bird, Chris M; Berens, Samuel C; Horner, Aidan J; Franklin, Anna

    2014-03-25

    The areas of the brain that encode color categorically have not yet been reliably identified. Here, we used functional MRI adaptation to identify neuronal populations that represent color categories irrespective of metric differences in color. Two colors were successively presented within a block of trials. The two colors were either from the same or different categories (e.g., "blue 1 and blue 2" or "blue 1 and green 1"), and the size of the hue difference was varied. Participants performed a target detection task unrelated to the difference in color. In the middle frontal gyrus of both hemispheres and to a lesser extent, the cerebellum, blood-oxygen level-dependent response was greater for colors from different categories relative to colors from the same category. Importantly, activation in these regions was not modulated by the size of the hue difference, suggesting that neurons in these regions represent color categorically, regardless of metric color difference. Representational similarity analyses, which investigated the similarity of the pattern of activity across local groups of voxels, identified other regions of the brain (including the visual cortex), which responded to metric but not categorical color differences. Therefore, categorical and metric hue differences appear to be coded in qualitatively different ways and in different brain regions. These findings have implications for the long-standing debate on the origin and nature of color categories, and also further our understanding of how color is processed by the brain.

  1. Retinal Encoding of Ultrabrief Shape Recognition Cues

    PubMed Central

    Greene, Ernest

    2007-01-01

    Shape encoding mechanisms can be probed by the sequential brief display of dots that mark the boundary of the shape, and delays of less that a millisecond between successive dots can impair recognition. It is not entirely clear whether this is accomplished by preserving stimulus timing in the signal being sent to the brain, or calls for a retinal binding mechanism. Two experiments manipulated the degree of simultaneity among and within dot pairs, requiring also that the pair members be in the same half of the visual field or on opposite halves, i.e., across the midline from one another. Recognition performance was impaired the same for these two conditions. The results make it likely that simultaneity of cues is being registered within the retina. A potential mechanism is suggested, calling for linkage of stimulated sites through activation of PA1 cells. A third experiment confirmed a prior finding that the overall level of recognition deficit is partly a function of display-set size, and affirmed submillisecond resolution in binding dot pairs into effective shape-recognition cues. PMID:17849001

  2. 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.

  3. Optical position encoder based on four-section diffraction grating

    NASA Astrophysics Data System (ADS)

    Zherdev, A. Y.; Odinokov, S. B.; Lushnikov, D. S.; Markin, V. V.; Gurylev, O. A.; Shishova, M. V.

    2017-05-01

    Optical position encoder consists of movable coding grating and fixed analyzing grating. Light passing and diffracting through these two gratings creates interference signal on optical detector. Decoding of interference signal phase allows to determinate current position. Known optical position encoders use several accurate adjusted optical channels and detectors to gather several signals with different phase for higher encoder accuracy. We propose to use one optical channel with several-section analyzing diffraction grating for this purpose to simplify optical scheme and adjusting requirements. Optical scheme of position encoder based on four-section analyzing diffraction grating is developed and described in this paper.

  4. Encoding complex values using two DLP spatial light modulators

    NASA Astrophysics Data System (ADS)

    Becker, Michael F.; Wu, Sih-Ying; Liang, Jinyang

    2013-03-01

    We present a method to encode complex values into three or four quantized complex values for wavefront modulation using two digital micromirror devices (DMDs). This encoding offers advantages to eliminate the twin image or suppress the zero order diffraction as well to improve hologram fidelity. The optical architecture utilizes a Michelson interferometer with a DMD in Littrow configuration replacing the mirrors to combine the two holograms with the desired phase shift. System performance was examined using numerical simulations and experimental measurements to explore different encoding methods for hologram reconstruction. Both ZOD and conjugate image suppression were demonstrated for different encoding schemes.

  5. 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.

  6. Novel encoding methods for DNA-templated chemical libraries.

    PubMed

    Li, Gang; Zheng, Wenlu; Liu, Ying; Li, Xiaoyu

    2015-06-01

    Among various types of DNA-encoded chemical libraries, DNA-templated library takes advantage of the sequence-specificity of DNA hybridization, enabling not only highly effective DNA-templated chemical reactions, but also high fidelity in library encoding. This brief review summarizes recent advances that have been made on the encoding strategies for DNA-templated libraries, and it also highlights their respective advantages and limitations for the preparation of DNA-encoded libraries. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Two-layer contractive encodings for learning stable nonlinear features.

    PubMed

    Schulz, Hannes; Cho, Kyunghyun; Raiko, Tapani; Behnke, Sven

    2015-04-01

    Unsupervised learning of feature hierarchies is often a good strategy to initialize deep architectures for supervised learning. Most existing deep learning methods build these feature hierarchies layer by layer in a greedy fashion using either auto-encoders or restricted Boltzmann machines. Both yield encoders which compute linear projections of input followed by a smooth thresholding function. In this work, we demonstrate that these encoders fail to find stable features when the required computation is in the exclusive-or class. To overcome this limitation, we propose a two-layer encoder which is less restricted in the type of features it can learn. The proposed encoder is regularized by an extension of previous work on contractive regularization. This proposed two-layer contractive encoder potentially poses a more difficult optimization problem, and we further propose to linearly transform hidden neurons of the encoder to make learning easier. We demonstrate the advantages of the two-layer encoders qualitatively on artificially constructed datasets as well as commonly used benchmark datasets. We also conduct experiments on a semi-supervised learning task and show the benefits of the proposed two-layer encoders trained with the linear transformation of perceptrons.

  8. Double image encryption based on phase-amplitude mixed encoding and multistage phase encoding in gyrator transform domains

    NASA Astrophysics Data System (ADS)

    Wang, Qu; Guo, Qing; Lei, Liang

    2013-06-01

    We present a novel method for double image encryption that is based on amplitude-phase mixed encoding and multistage random phase encoding in gyrator transform (GT) domains. In the amplitude-phase mixed encoding operation, a random binary distribution matrix is defined to mixed encode two primitive images to a single complex-valued image, which is then encrypted into a stationary white noise distribution by the multistage phase encoding with GTs. Compared with the earlier methods that uses fully phase encoding, the proposed method reduces the difference between two primitive images in key space and sensitivity to the GT orders. The primitive images can be recovered exactly by applying correct keys with initial conditions of chaotic system, the GT orders and the pixel scrambling operation. Numerical simulations demonstrate that the proposed scheme has considerably high security level and certain robustness against data loss and noise disturbance.

  9. 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

  10. 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.

  11. Genetically Encoded Protein Sensors of Membrane Potential.

    PubMed

    Storace, Douglas; Rad, Masoud Sepehri; Han, Zhou; Jin, Lei; Cohen, Lawrence B; Hughes, Thom; Baker, Bradley J; Sung, Uhna

    2015-01-01

    Organic voltage-sensitive dyes offer very high spatial and temporal resolution for imaging neuronal function. However these dyes suffer from the drawbacks of non-specificity of cell staining and low accessibility of the dye to some cell types. Further progress in imaging activity is expected from the development of genetically encoded fluorescent sensors of membrane potential. Cell type specificity of expression of these fluorescent protein (FP) voltage sensors can be obtained via several different mechanisms. One is cell type specificity of infection by individual virus subtypes. A second mechanism is specificity of promoter expression in individual cell types. A third, depends on the offspring of transgenic animals with cell type specific expression of cre recombinase mated with an animal that has the DNA for the FP voltage sensor in all of its cells but its expression is dependent on the recombinase activity. Challenges remain. First, the response time constants of many of the new FP voltage sensors are slower (2-10 ms) than those of organic dyes. This results in a relatively small fractional fluorescence change, ΔF/F, for action potentials. Second, the largest signal presently available is only ~40% for a 100 mV depolarization and many of the new probes have signals that are substantially smaller. Large signals are especially important when attempting to detect fast events because the shorter measurement interval results in a relatively small number of detected photons and therefore a relatively large shot noise (see Chap. 1). Another kind of challenge has occurred when attempts were made to transition from one species to another or from one cell type to another or from cell culture to in vivo measurements.Several laboratories have recently described a number of novel FP voltage sensors. Here we attempt to critically review the current status of these developments in terms of signal size, time course, and in vivo function.

  12. Electrocorticogram encoding of upper extremity movement duration.

    PubMed

    Wang, Po T; King, Christine E; McCrimmon, Colin M; Shaw, Susan J; Millett, David E; Liu, Charles Y; Chui, Luis A; Nenadic, Zoran; Do, An H

    2014-01-01

    Electrocorticogram (ECoG) is a promising long-term signal acquisition platform for brain-computer interface (BCI) systems such as upper extremity prostheses. Several studies have demonstrated decoding of arm and finger trajectories from ECoG high-gamma band (80-160 Hz) signals. In this study, we systematically vary the velocity of three elementary movement types (pincer grasp, elbow and shoulder flexion/extension) to test whether the high-gamma band encodes for the entirety of the movements, or merely the movement onset. To this end, linear regression models were created for the durations and amplitudes of high-gamma power bursts and velocity deflections. One subject with 8×8 high-density ECoG grid (4 mm center-to-center electrode spacing) participated in the experiment. The results of the regression models indicated that the power burst durations varied directly with the movement durations (e.g. R(2)=0.71 and slope=1.0 s/s for elbow). The persistence of power bursts for the duration of the movement suggests that the primary motor cortex (M1) is likely active for the entire duration of a movement, instead of providing a marker for the movement onset. On the other hand, the amplitudes were less co-varied. Furthermore, the electrodes of maximum R(2) conformed to somatotopic arrangement of the brain. Also, electrodes responsible for flexion and extension movements could be resolved on the high-density grid. In summary, these findings suggest that M1 may be directly responsible for activating the individual muscle motor units, and future BCI may be able to utilize them for better control of prostheses.

  13. 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.

  14. 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

  15. Encoding of human action in Broca's area.

    PubMed

    Fazio, Patrik; Cantagallo, Anna; Craighero, Laila; D'Ausilio, Alessandro; Roy, Alice C; Pozzo, Thierry; Calzolari, Ferdinando; Granieri, Enrico; Fadiga, Luciano

    2009-07-01

    Broca's area has been considered, for over a century, as the brain centre responsible for speech production. Modern neuroimaging and neuropsychological evidence have suggested a wider functional role is played by this area. In addition to the evidence that it is involved in syntactical analysis, mathematical calculation and music processing, it has recently been shown that Broca's area may play some role in language comprehension and, more generally, in understanding actions of other individuals. As shown by functional magnetic resonance imaging, Broca's area is one of the cortical areas activated by hand/mouth action observation and it has been proposed that it may form a crucial node of a human mirror-neuron system. If, on the one hand, neuroimaging studies use a correlational approach which cannot offer a final proof for such claims, available neuropsychological data fail to offer a conclusive demonstration for two main reasons: (i) they use tasks taxing both language and action systems; and (ii) they rarely consider the possibility that Broca's aphasics may also be affected by some form of apraxia. We administered a novel action comprehension test--with almost no linguistic requirements--on selected frontal aphasic patients lacking apraxic symptoms. Patients, as well as matched controls, were shown short movies of human actions or of physical events. Their task consisted of ordering, in a temporal sequence, four pictures taken from each movie and randomly presented on the computer screen. Patient's performance showed a specific dissociation in their ability to re-order pictures of human actions (impaired) with respect to physical events (spared). Our study provides a demonstration that frontal aphasics, not affected by apraxia, are specifically impaired in their capability to correctly encode observed human actions.

  16. Stress as a mnemonic filter: Interactions between medial temporal lobe encoding processes and post-encoding stress.

    PubMed

    Ritchey, Maureen; McCullough, Andrew M; Ranganath, Charan; Yonelinas, Andrew P

    2017-01-01

    Acute stress has been shown to modulate memory for recently learned information, an effect attributed to the influence of stress hormones on medial temporal lobe (MTL) consolidation processes. However, little is known about which memories will be affected when stress follows encoding. One possibility is that stress interacts with encoding processes to selectively protect memories that had elicited responses in the hippocampus and amygdala, two MTL structures important for memory formation. There is limited evidence for interactions between encoding processes and consolidation effects in humans, but recent studies of consolidation in rodents have emphasized the importance of encoding "tags" for determining the impact of consolidation manipulations on memory. Here, we used functional magnetic resonance imaging in humans to test the hypothesis that the effects of post-encoding stress depend on MTL processes observed during encoding. We found that changes in stress hormone levels were associated with an increase in the contingency of memory outcomes on hippocampal and amygdala encoding responses. That is, for participants showing high cortisol reactivity, memories became more dependent on MTL activity observed during encoding, thereby shifting the distribution of recollected events toward those that had elicited relatively high activation. Surprisingly, this effect was generally larger for neutral, compared to emotionally negative, memories. The results suggest that stress does not uniformly enhance memory, but instead selectively preserves memories tagged during encoding, effectively acting as mnemonic filter. © 2016 Wiley Periodicals, Inc.

  17. Polypeptides having laccase activity and polynucleotides encoding same

    DOEpatents

    Liu, Ye; Tang, Lan; Duan, Junxin; Zhang, Yu

    2017-08-22

    The present invention relates to isolated polypeptides having laccase activity and polynucleotides encoding the polypeptides 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. 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. 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.

  20. 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.…

  1. 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.

  2. 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. ¤

  3. 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…

  4. 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…

  5. Data-driven encoding for quantitative genetic trait prediction.

    PubMed

    He, Dan; Wang, Zhanyong; Parida, Laxmi

    2015-01-01

    Given a set of biallelic molecular markers, such as SNPs, with genotype values on a collection of plant, animal or human samples, the goal of quantitative genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Quantitative genetic trait prediction is usually represented as linear regression models which require quantitative encodings for the genotypes: the three distinct genotype values, corresponding to one heterozygous and two homozygous alleles, are usually coded as integers, and manipulated algebraically in the model. Further, epistasis between multiple markers is modeled as multiplication between the markers: it is unclear that the regression model continues to be effective under this. In this work we investigate the effects of encodings to the quantitative genetic trait prediction problem. We first showed that different encodings lead to different prediction accuracies, in many test cases. We then proposed a data-driven encoding strategy, where we encode the genotypes according to their distribution in the phenotypes and we allow each marker to have different encodings. We show in our experiments that this encoding strategy is able to improve the performance of the genetic trait prediction method and it is more helpful for the oligogenic traits, whose values rely on a relatively small set of markers. To the best of our knowledge, this is the first paper that discusses the effects of encodings to the genetic trait prediction problem.

  6. 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…

  7. Operation-Specific Encoding in Single-Digit Arithmetic

    ERIC Educational Resources Information Center

    Zhou, Xinlin

    2011-01-01

    Solving simple arithmetic problems involves three stages: encoding the problem, retrieving or calculating the answer, and reporting the answer. This study compared the event-related potentials elicited by single-digit addition and multiplication problems to examine the relationship between encoding and retrieval/calculation stages. Results showed…

  8. Discrete Events in Word Encoding: The Locus of Elaboration

    ERIC Educational Resources Information Center

    Walter, Donald A.

    1977-01-01

    A model dealing with the function of elaboration in word encoding was evaluated using a 2-list recognition procedure that varied encoding time within the presentation list. The model predicted that elaboration, reflected in the incidence of false positives to associates of words presented in the recognition list, would increase as presentation…

  9. 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…

  10. Face Encoding and Recognition in the Human Brain

    NASA Astrophysics Data System (ADS)

    Haxby, James V.; Ungerleider, Leslie G.; Horwitz, Barry; Maisog, Jose Ma.; Rapoport, Stanley I.; Grady, Cheryl L.

    1996-01-01

    A dissociation between human neural systems that participate in the encoding and later recognition of new memories for faces was demonstrated by measuring memory task-related changes in regional cerebral blood flow with positron emission tomography. There was almost no overlap between the brain structures associated with these memory functions. A region in the right hippocampus and adjacent cortex was activated during memory encoding but not during recognition. The most striking finding in neocortex was the lateralization of prefrontal participation. Encoding activated left prefrontal cortex, whereas recognition activated right prefrontal cortex. These results indicate that the hippocampus and adjacent cortex participate in memory function primarily at the time of new memory encoding. Moreover, face recognition is not mediated simply by recapitulation of operations performed at the time of encoding but, rather, involves anatomically dissociable operations.

  11. Unequally spaced four levels phase encoding in holographic data storage

    NASA Astrophysics Data System (ADS)

    Xu, Ke; Huang, Yong; Lin, Xiao; Cheng, Yabin; Li, Xiaotong; Tan, Xiaodi

    2016-12-01

    Holographic data storage system is a candidate for the information recording due to its large storage capacity and high transfer rate. We propose an unequally spaced four levels phase encoding in the holographic data storage system here. Compared with two levels or three levels phase encoding, four levels phase encoding effectively improves the code rate. While more phase levels can further improve code rate, it also puts higher demand for the camera to differentiate the resulting smaller grayscale difference. Unequally spaced quaternary level phases eliminates the ambiguity of pixels with same phase difference relative to reference light compared to equally spaced quaternary levels. Corresponding encoding pattern design with phase pairs as the data element and decoding method were developed. Our encoding improves the code rate up to 0.875, which is 1.75 times of the conventional amplitude method with an error rate of 0.13 % according to our simulation results.

  12. The realization of arithmetic processors for delta modulation encoded signals

    NASA Technical Reports Server (NTRS)

    Locicero, J. L.; Garodnick, J.; Schilling, D. L.

    1975-01-01

    The design and realization of digital devices which add or multiply delta modulation (DM) encoded signals are presented. These systems operate directly on the DM bit stream. It is shown that the devices can be constructed using standard digital hardware and that the hardware complexity needed to add or multiply the two DM encoded signals is equivalent to that needed for pulse code modulation (PCM) signals. Experimental results are presented showing the operation of these systems. The results obtained by adding or multiplying DM encoded signals are compared with those obtained using PCM encoded signals on the basis of signal-to-noise ratio (SNR). A spectral-analysis technique applicable to a DM encoded signal is developed to obtain SNR curves.

  13. 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.

  14. Modeling quantization matrices for perceptual image / video encoding

    NASA Astrophysics Data System (ADS)

    Zhang, Huipin; Cote, Guy

    2008-01-01

    Quantization matrix is an important encoding tool for discrete cosine transform (DCT) based perceptual image / video encoding in that DCT coefficients can be quantized according to the sensitivity of the human visual system to the coefficients' corresponding spatial frequencies. A quadratic model is introduced to parameterize the quantization matrices. This model is then used to optimize quantization matrices for a specific bitrate or bitrate range by maximizing the expected encoding quality via a trial based multidimensional numerical search method. The model is simple yet it characterizes the slope and the convexity of the quantization matrices along the horizontal, the vertical and the diagonal directions. The advantage of the model for improving perceptual video encoding quality is demonstrated with simulations using H.264 / AVC video encoding.

  15. 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

  16. 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. © The Author(s) 2016. Published by Oxford University Press.

  17. Can natural selection encode Bayesian priors?

    PubMed

    Ramírez, Juan Camilo; Marshall, James A R

    2017-08-07

    The evolutionary success of many organisms depends on their ability to make decisions based on estimates of the state of their environment (e.g., predation risk) from uncertain information. These decision problems have optimal solutions and individuals in nature are expected to evolve the behavioural mechanisms to make decisions as if using the optimal solutions. Bayesian inference is the optimal method to produce estimates from uncertain data, thus natural selection is expected to favour individuals with the behavioural mechanisms to make decisions as if they were computing Bayesian estimates in typically-experienced environments, although this does not necessarily imply that favoured decision-makers do perform Bayesian computations exactly. Each individual should evolve to behave as if updating a prior estimate of the unknown environment variable to a posterior estimate as it collects evidence. The prior estimate represents the decision-maker's default belief regarding the environment variable, i.e., the individual's default 'worldview' of the environment. This default belief has been hypothesised to be shaped by natural selection and represent the environment experienced by the individual's ancestors. We present an evolutionary model to explore how accurately Bayesian prior estimates can be encoded genetically and shaped by natural selection when decision-makers learn from uncertain information. The model simulates the evolution of a population of individuals that are required to estimate the probability of an event. Every individual has a prior estimate of this probability and collects noisy cues from the environment in order to update its prior belief to a Bayesian posterior estimate with the evidence gained. The prior is inherited and passed on to offspring. Fitness increases with the accuracy of the posterior estimates produced. Simulations show that prior estimates become accurate over evolutionary time. In addition to these 'Bayesian' individuals, we also

  18. Characteristic and intermingled neocortical circuits encode different visual object discriminations.

    PubMed

    Zhang, Guo-Rong; Zhao, Hua; Cook, Nathan; Svestka, Michael; Choi, Eui M; Jan, Mary; Cook, Robert G; Geller, Alfred I

    2017-07-28

    Synaptic plasticity and neural network theories hypothesize that the essential information for advanced cognitive tasks is encoded in specific circuits and neurons within distributed neocortical networks. However, these circuits are incompletely characterized, and we do not know if a specific discrimination is encoded in characteristic circuits among multiple animals. Here, we determined the spatial distribution of active neurons for a circuit that encodes some of the essential information for a cognitive task. We genetically activated protein kinase C pathways in several hundred spatially-grouped glutamatergic and GABAergic neurons in rat postrhinal cortex, a multimodal associative area that is part of a distributed circuit that encodes visual object discriminations. We previously established that this intervention enhances accuracy for specific discriminations. Moreover, the genetically-modified, local circuit in POR cortex encodes some of the essential information, and this local circuit is preferentially activated during performance, as shown by activity-dependent gene imaging. Here, we mapped the positions of the active neurons, which revealed that two image sets are encoded in characteristic and different circuits. While characteristic circuits are known to process sensory information, in sensory areas, this is the first demonstration that characteristic circuits encode specific discriminations, in a multimodal associative area. Further, the circuits encoding the two image sets are intermingled, and likely overlapping, enabling efficient encoding. Consistent with reconsolidation theories, intermingled and overlapping encoding could facilitate formation of associations between related discriminations, including visually similar discriminations or discriminations learned at the same time or place. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. High-resolution MRI encoding using radiofrequency phase gradients.

    PubMed

    Sharp, Jonathan C; King, Scott B; Deng, Qunli; Volotovskyy, Vyacheslav; Tomanek, Boguslaw

    2013-11-01

    Although MRI offers highly diagnostic medical imagery, patient access to this modality worldwide is very limited when compared with X-ray or ultrasound. One reason for this is the expense and complexity of the equipment used to generate the switched magnetic fields necessary for MRI encoding. These field gradients are also responsible for intense acoustic noise and have the potential to induce nerve stimulation. We present results with a new MRI encoding principle which operates entirely without the use of conventional B0 field gradients. This new approach--'Transmit Array Spatial Encoding' (TRASE)--uses only the resonant radiofrequency (RF) field to produce Fourier spatial encoding equivalent to conventional MRI. k-space traversal (image encoding) is achieved by spin refocusing with phase gradient transmit fields in spin echo trains. A transmit coil array, driven by just a single transmitter channel, was constructed to produce four phase gradient fields, which allows the encoding of two orthogonal spatial axes. High-resolution two-dimensional-encoded in vivo MR images of hand and wrist were obtained at 0.2 T. TRASE exploits RF field phase gradients, and offers the possibility of very low-cost diagnostics and novel experiments exploiting unique capabilities, such as imaging without disturbance of the main B0 magnetic field. Lower field imaging (<1 T) and micro-imaging are favorable application domains as, in both cases, it is technically easier to achieve the short RF pulses desirable for long echo trains, and also to limit RF power deposition. As TRASE is simply an alternative mechanism (and technology) of moving through k space, there are many close analogies between it and conventional B0 -encoded techniques. TRASE is compatible with both B0 gradient encoding and parallel imaging, and so hybrid sequences containing all three spatial encoding approaches are possible.

  20. Characterization of the gene encoding mouse serum amyloid P component. Comparison with genes encoding other pentraxins.

    PubMed Central

    Whitehead, A S; Rits, M

    1989-01-01

    A CBA/J-strain mouse serum amyloid P component (SAP) genomic clone was isolated and analysed. The clone contains the entire SAP gene and specifies a primary transcript of 1065 nucleotide residues. This comprises a first exon of 206 nucleotide residues containing the mRNA 5'-untranslated region and sequence encoding the pre-SAP leader peptide and the first two amino acid residues of mature SAP separated by a single 110-base intron from a 749-nucleotide-residue second exon containing sequence encoding the bulk of the mature SAP and specifying the mRNA 3'-untranslated region. The overall organization is similar to that of the human SAP gene, and the coding region and intron sequences are highly conserved. The SAP RNA cap site was defined by primer extension analysis of polyadenylated acute-phase liver RNA. The 5'-region of the mouse SAP gene contains modified CAAT and TATA promoter elements preceded by a putative hepatocyte-nuclear-factor-1-recognition site; these structures are in a region that is highly homologous to the corresponding region of the human SAP gene. Comparisons of the mouse SAP gene structure and derived amino acid sequence with those of other mammalian pentraxins were made. Images Fig. 3. PMID:2481440

  1. 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…

  2. Datacube Interoperability, Encoding Independence, and Analytics

    NASA Astrophysics Data System (ADS)

    Baumann, Peter; Hirschorn, Eric; Maso, Joan

    2017-04-01

    representations. Further, CIS 1.1 offers a unified model for any kind of regular and irregular grids, also allowing sensor models as per SensorML. Encodings include ASCII formats like GML, JSON, RDF as well as binary formats like GeoTIFF, NetCDF, JPEG2000, and GRIB2; further, a container concept allows mixed representations within one coverage file utilizing zip or other convenient package formats. Through the tight integration with the Sensor Web Enablement (SWE), a lossless "transport" from sensor into coverage world is ensured. The corresponding service model of WCS supports datacube operations ranging from simple data extraction to complex ad-hoc analytics with WPCS. Notably, W3C is working has set out on a coverage model as well; it has been designed relatively independently from the abovementioned standards, but there is informal agreement to link it into the CIS universe (which allows for different, yet interchangeable representations). Particularly interesting in the W3C proposal is the detailed semantic modeling of metadata; as CIS 1.1 supports RDF, a tight coupling seems feasible.

  3. Mollusk genes encoding lysine tRNA (UUU) contain introns.

    PubMed

    Matsuo, M; Abe, Y; Saruta, Y; Okada, N

    1995-11-20

    New intron-containing genes encoding tRNAs were discovered when genomic DNA isolated from various animal species was amplified by the polymerase chain reaction (PCR) with primers based on sequences of rabbit tRNA(Lys). From sequencing analysis of the products of PCR, we found that introns are present in several genes encoding tRNA(Lys) in mollusks, such as Loligo bleekeri (squid) and Octopus vulgaris (octopus). These introns were specific to genes encoding tRNA(Lys)(CUU) and were not present in genes encoding tRNA(Lys)(CUU). In addition, the sequences of the introns were different from one another. To confirm the results of our initial experiments, we isolated and sequenced genes encoding tRNA(Lys)(CUU) and tRNA(Lys)(UUU). The gene for tRNA(Lys)(UUU) from squid contained an intron, whose sequence was the same as that identified by PCR, and the gene formed a cluster with a corresponding pseudogene. Several DNA regions of 2.1 kb containing this cluster appeared to be tandemly arrayed in the squid genome. By contrast, the gene encoding tRNA(Lys)(CUU) did not contain an intron, as shown also by PCR. The tRNA(Lys)(UUU) that corresponded to the analyzed gene was isolated and characterized. The present study provides the first example of an intron-containing gene encoding a tRNA in mollusks and suggests the universality of introns in such genes in higher eukaryotes.

  4. Abstract encoding of auditory objects in cortical activity patterns.

    PubMed

    Giordano, Bruno L; McAdams, Stephen; Zatorre, Robert J; Kriegeskorte, Nikolaus; Belin, Pascal

    2013-09-01

    The human brain is thought to process auditory objects along a hierarchical temporal "what" stream that progressively abstracts object information from the low-level structure (e.g., loudness) as processing proceeds along the middle-to-anterior direction. Empirical demonstrations of abstract object encoding, independent of low-level structure, have relied on speech stimuli, and non-speech studies of object-category encoding (e.g., human vocalizations) often lack a systematic assessment of low-level information (e.g., vocalizations are highly harmonic). It is currently unknown whether abstract encoding constitutes a general functional principle that operates for auditory objects other than speech. We combined multivariate analyses of functional imaging data with an accurate analysis of the low-level acoustical information to examine the abstract encoding of non-speech categories. We observed abstract encoding of the living and human-action sound categories in the fine-grained spatial distribution of activity in the middle-to-posterior temporal cortex (e.g., planum temporale). Abstract encoding of auditory objects appears to extend to non-speech biological sounds and to operate in regions other than the anterior temporal lobe. Neural processes for the abstract encoding of auditory objects might have facilitated the emergence of speech categories in our ancestors.

  5. 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.

  6. Small-molecule discovery from DNA-encoded chemical libraries.

    PubMed

    Kleiner, Ralph E; Dumelin, Christoph E; Liu, David R

    2011-12-01

    Researchers seeking to improve the efficiency and cost effectiveness of the bioactive small-molecule discovery process have recently embraced selection-based approaches, which in principle offer much higher throughput and simpler infrastructure requirements compared with traditional small-molecule screening methods. Since selection methods benefit greatly from an information-encoding molecule that can be readily amplified and decoded, several academic and industrial groups have turned to DNA as the basis for library encoding and, in some cases, library synthesis. The resulting DNA-encoded synthetic small-molecule libraries, integrated with the high sensitivity of PCR and the recent development of ultra high-throughput DNA sequencing technology, can be evaluated very rapidly for binding or bond formation with a target of interest while consuming minimal quantities of material and requiring only modest investments of time and equipment. In this tutorial review we describe the development of two classes of approaches for encoding chemical structures and reactivity with DNA: DNA-recorded library synthesis, in which encoding and library synthesis take place separately, and DNA-directed library synthesis, in which DNA both encodes and templates library synthesis. We also describe in vitro selection methods used to evaluate DNA-encoded libraries and summarize successful applications of these approaches to the discovery of bioactive small molecules and novel chemical reactivity.

  7. Small-Molecule Discovery from DNA-Encoded Chemical Libraries†

    PubMed Central

    Kleiner, Ralph E.; Dumelin, Christoph E.; Liu, David R.

    2015-01-01

    Researchers seeking to improve the efficiency and cost effectiveness of the bioactive small-molecule discovery process have recently embraced selection-based approaches, which in principle offer much higher throughput and simpler infrastructure requirements compared with traditional small-molecule screening methods. Since selection methods benefit greatly from an information-encoding molecule that can be readily amplified and decoded, several academic and industrial groups have turned to DNA as the basis for library encoding and, in some cases, library synthesis. The resulting DNA-encoded synthetic small-molecule libraries, integrated with the high sensitivity of PCR and the recent development of ultra high-throughput DNA sequencing technology, can be evaluated very rapidly for binding or bond formation with a target of interest while consuming minimal quantities of material and requiring only modest investments of time and equipment. In this review we describe the development of two classes of approaches for encoding chemical structures and reactivity with DNA: DNA-recorded library synthesis, in which encoding and library synthesis take place separately, and DNA-directed library synthesis, in which DNA both encodes and templates library synthesis. We also describe in vitro selection methods used to evaluate DNA-encoded libraries and summarize successful applications of these approaches to the discovery of bioactive small molecules and novel chemical reactivity. PMID:21674077

  8. 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.

  9. 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

  10. pENCODE: a plant encyclopedia of DNA elements.

    PubMed

    Lane, Amanda K; Niederhuth, Chad E; Ji, Lexiang; Schmitz, Robert J

    2014-01-01

    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.

  11. Compact optical encoder approach utilizing novel diffractive optics design

    NASA Astrophysics Data System (ADS)

    DeVoe, Catherine E.; Horwitz, Bruce A.; Johnson, Eric G.; Fedor, Adam S.

    1998-04-01

    Diffractive optical encoders have quickly established themselves in the marketplace because of their small seize, high accuracy and relaxed alignment tolerances, but current products are still composed of carefully packages, discrete optical and electro-optical components. MicroE and Digital Optics Corporation have been working together on the next generation of these encoders, which replaces all discrete and refractive elements with DOE's and more completely integrates the requisite optical and electro-optical components. In this paper we describe a monolithic source/optics/detector encoder module we have designed and prototyped for a satellite application under a NASA Phase I SBIR contract.

  12. 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.

  13. 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.

  14. 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.

  15. Multifunctional encoded particles for high-throughput biomolecule analysis.

    PubMed

    Pregibon, Daniel C; Toner, Mehmet; Doyle, Patrick S

    2007-03-09

    High-throughput screening for genetic analysis, combinatorial chemistry, and clinical diagnostics benefits from multiplexing, which allows for the simultaneous assay of several analytes but necessitates an encoding scheme for molecular identification. Current approaches for multiplexed analysis involve complicated or expensive processes for encoding, functionalizing, or decoding active substrates (particles or surfaces) and often yield a very limited number of analyte-specific codes. We present a method based on continuous-flow lithography that combines particle synthesis and encoding and probe incorporation into a single process to generate multifunctional particles bearing over a million unique codes. By using such particles, we demonstrate a multiplexed, single-fluorescence detection of DNA oligomers with encoded particle libraries that can be scanned rapidly in a flow-through microfluidic channel. Furthermore, we demonstrate with high specificity the same multiplexed detection using individual multiprobe particles.

  16. 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.

  17. 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.

  18. Differential encoding for multiple amplitude and phase shift keying systems

    NASA Technical Reports Server (NTRS)

    Weber, W. J., III

    1978-01-01

    Because of the symmetry in most two-dimensional signal constellations, ambiguities exist at the receiver as to the exact phase orientation of the received signal set. In PSK systems, this ambiguity is resolved by the use of differential encoding. This paper presents differential encoding techniques which can be used with a variety of symmetric signal sets to remove their phase ambiguity. While not proven to be optimum, the techniques do have low performance penalties relative to the uncoded performance. The key to reducing the performance penalty is to use the minimum amount of differential encoding necessary to resolve the ambiguity. Examples of encoding techniques for several common signal constellations are given, including their performance penalties.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. Polypeptides having catalase activity and polynucleotides encoding same

    DOEpatents

    Liu, Ye; Duan, Junxin; Zhang, Yu; Tang, Lan

    2017-05-02

    Provided are isolated polypeptides having catalase activity and 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.

  4. 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.

  5. Microfabrication of encoded microparticle array for multiplexed DNA hybridization detection.

    PubMed

    Zhi, Zheng-Liang; Morita, Yasutaka; Yamamura, Shouhei; Tamiya, Eiichi

    2005-05-21

    A strategy for the high-sensitivity, high-selectivity, and multiplexed detection of oligonucleotide hybridizations has been developed with an encoded Ni microparticle random array that was manufactured by a "top-down" approach using micromachining and microfabrication techniques.

  6. Hybrid polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    SciTech Connect

    Liu, Ye; Shaghasi, Tarana

    2016-11-01

    The present invention provides hybrid polypeptides having cellobiohydrolase activity. The present invention also provides polynucleotides encoding the hybrid polypeptides; nucleic acid constructs, vectors and host cells comprising the polynucleotides; and processes of using the hybrid polypeptides.

  7. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    SciTech Connect

    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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Universal Quantum Computing with Arbitrary Continuous-Variable Encoding

    NASA Astrophysics Data System (ADS)

    Lau, Hoi-Kwan; Plenio, Martin B.

    2016-09-01

    Implementing a qubit quantum computer in continuous-variable systems conventionally requires the engineering of specific interactions according to the encoding basis states. In this work, we present a unified formalism to conduct universal quantum computation with a fixed set of operations but arbitrary encoding. By storing a qubit in the parity of two or four qumodes, all computing processes can be implemented by basis state preparations, continuous-variable exponential-swap operations, and swap tests. Our formalism inherits the advantages that the quantum information is decoupled from collective noise, and logical qubits with different encodings can be brought to interact without decoding. We also propose a possible implementation of the required operations by using interactions that are available in a variety of continuous-variable systems. Our work separates the "hardware" problem of engineering quantum-computing-universal interactions, from the "software" problem of designing encodings for specific purposes. The development of quantum computer architecture could hence be simplified.

  14. Rearrangement and Grouping of Data Bits for Efficient Lossless Encoding

    NASA Astrophysics Data System (ADS)

    B, Ajitha Shenoy K.; Ajith, Meghana; Mantoor, Vinayak M.

    2017-01-01

    This paper describes the efficacy of rearranging and grouping of data bits. Lossless encoding techniques like Huffman Coding, Arithmetic Coding etc., works well on data which contains redundant information. The idea behind these techniques is to encode more frequently occurring symbols with less number of bits and more seldom occurring symbols with more number of bits. Most of the methods fail if there is a non-redundant data. We propose a method to re arrange and group data bits there by making the data redundant and then different lossless encoding techniques can be applied. In this paper we propose three different methods to rearrange the data bits, and efficient way of grouping them. This is first such attempt. We also justify the need of rearranging and grouping data bits for efficient lossless encoding.

  15. 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

  16. Enzymatic characterization of a lysin encoded by bacteriophage EL.

    PubMed

    Tafoya, Diana A; Hildenbrand, Zacariah L; Herrera, Nadia; Molugu, Sudheer K; Mesyanzhinov, Vadim V; Miroshnikov, Konstantin A; Bernal, Ricardo A

    2013-04-01

    The bacteriophage EL is a virus that specifically attacks the human pathogen Pseudomonas aeruginosa. This phage carries a large genome that encodes for its own chaperonin which presumably facilitates the proper folding of phage proteins independently of the host chaperonin system. EL also encodes a lysin enzyme, a critical component of the lytic cycle that is responsible for digesting the peptidoglycan layer of the host cell wall. Previously, this lysin was believed to be a substrate of the chaperonin encoded by phage EL. In order to characterize the activity of the EL lysin, and to determine whether lysin activity is contingent on chaperonin-mediated folding, a series of peptidoglycan hydrolysis activity assays were performed. Results indicate that the EL-encoded lysin has similar enzymatic activity to that of the Gallus gallus lysozyme and that the EL lysin folds into a functional enzyme in the absence of phage chaperonin and should not be considered a substrate.

  17. Universal Quantum Computing with Arbitrary Continuous-Variable Encoding.

    PubMed

    Lau, Hoi-Kwan; Plenio, Martin B

    2016-09-02

    Implementing a qubit quantum computer in continuous-variable systems conventionally requires the engineering of specific interactions according to the encoding basis states. In this work, we present a unified formalism to conduct universal quantum computation with a fixed set of operations but arbitrary encoding. By storing a qubit in the parity of two or four qumodes, all computing processes can be implemented by basis state preparations, continuous-variable exponential-swap operations, and swap tests. Our formalism inherits the advantages that the quantum information is decoupled from collective noise, and logical qubits with different encodings can be brought to interact without decoding. We also propose a possible implementation of the required operations by using interactions that are available in a variety of continuous-variable systems. Our work separates the "hardware" problem of engineering quantum-computing-universal interactions, from the "software" problem of designing encodings for specific purposes. The development of quantum computer architecture could hence be simplified.

  18. 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.

  19. Imagining another context during encoding offsets context-dependent forgetting.

    PubMed

    Masicampo, E J; Sahakyan, Lili

    2014-11-01

    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 effect (e.g., Smith & Vela, 2001). Importantly, some participants imagined another mental context during encoding. Some of these participants imagined Context B during encoding, and when they were later tested in Context B or even in a completely new Context C, they did not show forgetting, confirming our predictions. Other participants imagined a new context during encoding simply by transforming the current context (i.e., by imagining that it was snowing in the room), and this likewise counteracted context-dependent forgetting. These data suggest a moderator of context-dependent forgetting. When the context surrounding a memory is largely mentally generated, context-dependent forgetting is eliminated.

  20. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    DOEpatents

    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.

  1. 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.

  2. Quantum dot optical encoded polystyrene beads for DNA detection.

    PubMed

    Cao, Yuan-Cheng; Liu, Tian-Cai; Hua, Xiao-Feng; Zhu, Xiao-Xia; Wang, Hai-Qiao; Huang, Zhen-Li; Zhao, Yuan-Di; Liu, Man-Xi; Luo, Qing-Ming

    2006-01-01

    A novel multiplex analysis technology based on quantum dot (QD) optical encoded beads was studied. Carboxyl functionalized polystyrene beads, about 100 microm in size, were precisely encoded by the various ratios of two types of QDs whose emission wavelengths are 576 and 628 nm, respectively. Then the different encoded beads were covalently immobilized with different probes in the existing of sulfo-NHS and 1-[3-(Dimethylamino) propyl]-3-ethylcarbodiimide methiodide, and the probe density could reach to 3.1 mmol/g. These probe-linked encoded beads were used to detect the target DNA sequences in complex DNA solution by hybridization. Hybridization was visualized using fluorescein isothiocynate-labeled DNA sequences. The results show that the QDs and target signals can be obviously identified from a single-bead-level spectrum. This technology can detect DNA targets effectively with a detection limit of 0.2 microg/mL in complex solution.

  3. Polypeptides having endoglucanase activity and polynucleotides encoding same

    DOEpatents

    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.

  4. 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.

  5. 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.

  6. 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.

  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

    2014-06-24

    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.

  9. 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.

  10. Error correction of photoelectric rotary and angle encoder

    NASA Astrophysics Data System (ADS)

    Zhou, Liang; She, Wen-ji; Huang, Jing

    2014-02-01

    The photoelectric rotary and angle encoder is a digital angle measuring device, which is integrated with optics, mechanics and electrics. Because of its simple structure, high resolution, and high accuracy, it has been widely used in precision measurement of angle, digital control and digital display system. With the needs of fast tracking and accurate orientation on the horizon and air targets, putting forward higher requirements on accuracy of angle measurement and resolution of photoelectric rotary and angle encoder. Influences of manufacturing, electronics segmentation, optical and mechanical structure and eccentric shaft to photoelectric encoder precision and reducing methods are introduced. Focusing on the eccentricity error, building up an error correction model to improve the resolution of angle encoder and the model was verified by test.

  11. 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.

  12. Polypeptides having cellulolytic enhancing activity and polynucleotides encoding same

    SciTech Connect

    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.

  13. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    SciTech Connect

    Spodsberg, Nikolaj

    2016-12-13

    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. Encoding Speed and Memory Span in Dyslexic Children

    ERIC Educational Resources Information Center

    Spring, Carl

    1976-01-01

    Evaluated with 14 dyslexic and 14 normal boys (all 6-12 years old) was the relationship between slow speech-motor encoding to the transfer of information from short-term to long-term memory. (Author/DB)

  15. 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

  16. 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.

  17. Variability and coding efficiency of noisy neural spike encoders.

    PubMed

    Steinmetz, P N; Manwani, A; Koch, C

    2001-01-01

    Encoding synaptic inputs as a train of action potentials is a fundamental function of nerve cells. Although spike trains recorded in vivo have been shown to be highly variable, it is unclear whether variability in spike timing represents faithful encoding of temporally varying synaptic inputs or noise inherent in the spike encoding mechanism. It has been reported that spike timing variability is more pronounced for constant, unvarying inputs than for inputs with rich temporal structure. This could have significant implications for the nature of neural coding, particularly if precise timing of spikes and temporal synchrony between neurons is used to represent information in the nervous system. To study the potential functional role of spike timing variability, we estimate the fraction of spike timing variability which conveys information about the input for two types of noisy spike encoders--an integrate and fire model with randomly chosen thresholds and a model of a patch of neuronal membrane containing stochastic Na(+) and K(+) channels obeying Hodgkin-Huxley kinetics. The quality of signal encoding is assessed by reconstructing the input stimuli from the output spike trains using optimal linear mean square estimation. A comparison of the estimation performance of noisy neuronal models of spike generation enables us to assess the impact of neuronal noise on the efficacy of neural coding. The results for both models suggest that spike timing variability reduces the ability of spike trains to encode rapid time-varying stimuli. Moreover, contrary to expectations based on earlier studies, we find that the noisy spike encoding models encode slowly varying stimuli more effectively than rapidly varying ones.

  18. High-Resolution Optoelectronic Shaft-Angle Encoder

    NASA Technical Reports Server (NTRS)

    Leviton, Douglas B.

    1994-01-01

    Improved optoelectronic encoder measures absolute angle to which shaft has been rotated. Costs little more than older, less capable encoders do, yet measures absolute angles at high resolution and does not lose absolute-angle data because generates those data anew with each reading at up to 1,000 times per second. It accumulates increments to measure total angular interval through which shaft has been turned (including unlimited number of complete turns), as long as power remains on.

  19. Associative encoding of pictures activates the medial temporal lobes.

    PubMed

    Montaldi, D; Mayes, A R; Barnes, A; Pirie, H; Hadley, D M; Patterson, J; Wyper, D J

    1998-01-01

    It remains unresolved whether the medial temporal lobe activations found in recent neuroimaging studies are mediated by novelty detection alone, by specific kinds of encoding or consolidation operations, or both. This study attempted to see whether associative encoding or consolidation is sufficient to cause such activation by matching for novelty across conditions. Using single-photon emission computer tomography (SPECT) (with TC99mHMPAO), we compared the activation patterns produced by the associative encoding and the perceptual matching of novel complex scenes in 10 normal subjects using both statistical parametric mapping (SPM) and a regions-of-interest (ROI) approach. During the encoding condition, significant activations were detected in the left hippocampal/parahippocampal region, the left cingulate cortex, and the right prefrontal cortex, using both statistical techniques. Additionally, activation was found in the right cingulate cortex, and a trend towards activation was found in the right hippocampal/parahippocampal region using the ROI approach. In contrast, no medial temporal activations were found during the matching condition, which produced bilateral occipito-parietal and right posterior inferior parietal (supramarginal gyrus) activations. These results no only confirm that the associative encoding and/or consolidation of complex scenes is partially mediated by medial temporal lobe structures, but also demonstrate, for the first time, that associative encoding/consolidation is sufficient to produce such an activation. The implications of the high degree of consistency revealed by the results of the SPM and ROI comparison are discussed.

  20. Low Complexity HEVC Encoder for Visual Sensor Networks.

    PubMed

    Pan, Zhaoqing; Chen, Liming; Sun, Xingming

    2015-12-02

    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.

  1. Imaging systems based on the encoding of optical coherence functions.

    PubMed

    James, J Christopher; Bennett, Gisele Welch; Rhodes, William T

    2005-09-01

    An imaging scheme is described that is based on the transmission of image-forming information encoded within optical coherence functions. The scheme makes use of dynamic random-valued encoding-decoding masks placed in the input-output planes of any linear optical system. The mask transmittance functions are complex conjugates of each other, as opposed to a similar coherence encoding scheme proposed earlier by two of this paper's authors that used identical masks. [Rhodes and Welch, in Euro-American Workshop on Optoelectronic Information Processing, SPIE Critical Review Series (SPIE, 1999), Vol. CR74, p. 1]. General analyses of the two coherence encoding schemes are performed by using the more general mutual coherence function as opposed to the mutual intensity function used in the earlier scheme. The capabilities and limitations of both encoding schemes are discussed by using simple examples that combine the encoding-decoding masks with free-space propagation, passage through a four-f system, and a single-lens imaging system.

  2. Multicore-based 3D-DWT video encoder

    NASA Astrophysics Data System (ADS)

    Galiano, Vicente; López-Granado, Otoniel; Malumbres, Manuel P.; Migallón, Hector

    2013-12-01

    Three-dimensional wavelet transform (3D-DWT) encoders are good candidates for applications like professional video editing, video surveillance, multi-spectral satellite imaging, etc. where a frame must be reconstructed as quickly as possible. In this paper, we present a new 3D-DWT video encoder based on a fast run-length coding engine. Furthermore, we present several multicore optimizations to speed-up the 3D-DWT computation. An exhaustive evaluation of the proposed encoder (3D-GOP-RL) has been performed, and we have compared the evaluation results with other video encoders in terms of rate/distortion (R/D), coding/decoding delay, and memory consumption. Results show that the proposed encoder obtains good R/D results for high-resolution video sequences with nearly in-place computation using only the memory needed to store a group of pictures. After applying the multicore optimization strategies over the 3D DWT, the proposed encoder is able to compress a full high-definition video sequence in real-time.

  3. Secret key rates for an encoded quantum repeater

    NASA Astrophysics Data System (ADS)

    Bratzik, Sylvia; Kampermann, Hermann; Bruß, Dagmar

    2014-03-01

    We investigate secret key rates for the quantum repeater using encoding [L. Jiang et al., Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325] and compare them to the standard repeater scheme by Briegel, Dür, Cirac, and Zoller. The former scheme has the advantage of a minimal consumption of classical communication. We analyze the trade-off in the secret key rate between the communication time and the required resources. For this purpose we introduce an error model for the repeater using encoding which allows for input Bell states with a fidelity smaller than one, in contrast to the model given by L. Jiang et al. [Phys. Rev. A 79, 032325 (2009), 10.1103/PhysRevA.79.032325]. We show that one can correct additional errors in the encoded connection procedure of this repeater and develop a suitable decoding algorithm. Furthermore, we derive the rate of producing entangled pairs for the quantum repeater using encoding and give the minimal parameter values (gate quality and initial fidelity) for establishing a nonzero secret key. We find that the generic quantum repeater is optimal regarding the secret key rate per memory per second and show that the encoded quantum repeater using the simple three-qubit repetition code can even have an advantage with respect to the resources compared to other recent quantum repeater schemes with encoding.

  4. Aerobic Exercise During Encoding Impairs Hippocampus-Dependent Memory.

    PubMed

    Soga, Keishi; Kamijo, Keita; Masaki, Hiroaki

    2017-10-06

    We investigated how aerobic exercise during encoding affects hippocampus-dependent memory through a source memory task that assessed hippocampus-independent familiarity and hippocampus-dependent recollection processes. Using a within-participants design, young adult participants performed a memory-encoding task while performing a cycling exercise or being seated. The subsequent retrieval phase was conducted while sitting on a chair. We assessed behavioral and event-related brain potential measures of familiarity and recollection processes during the retrieval phase. Results indicated that source accuracy was lower for encoding with exercise than for encoding in the resting condition. Event-related brain potential measures indicated that the parietal old/new effect, which has been linked to recollection processing, was observed in the exercise condition, whereas it was absent in the rest condition, which is indicative of exercise-induced hippocampal activation. These findings suggest that aerobic exercise during encoding impairs hippocampus-dependent memory, which may be attributed to inefficient source encoding during aerobic exercise.

  5. 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

  6. 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

  7. 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.

  8. The new INRIM rotating encoder angle comparator (REAC)

    NASA Astrophysics Data System (ADS)

    Pisani, Marco; Astrua, Milena

    2017-04-01

    A novel angle comparator has been built and tested at INRIM. The device is based on a double air bearing structure embedding a continuously rotating encoder, which is read by two heads: one fixed to the base of the comparator and a second fixed to the upper moving part of the comparator. The phase measurement between the two heads’ signals is proportional to the relative angle suspended between them (and, therefore, the angle between the base and the upper, movable part of the comparator). The advantage of this solution is to reduce the encoder graduation errors and to cancel the cyclic errors due to the interpolation of the encoder lines. By using only two pairs of reading heads, we have achieved an intrinsic accuracy of  ±0.04″ (rectangular distribution) that can be reduced through self-calibration. The residual cyclic errors have shown to be less than 0.01″ peak-to-peak. The random fluctuations are less than 0.01″ rms on a 100 s time interval. A further advantage of the rotating encoder is the intrinsic knowledge of the absolute position without the need of a zeroing procedure. Construction details of the rotating encoder angle comparator (REAC), characterization tests, and examples of practical use are given.

  9. Early remodeling of the neocortex upon episodic memory encoding.

    PubMed

    Bero, Adam W; Meng, Jia; Cho, Sukhee; Shen, Abra H; Canter, Rebecca G; Ericsson, Maria; Tsai, Li-Huei

    2014-08-12

    Understanding the mechanisms by which long-term memories are formed and stored in the brain represents a central aim of neuroscience. Prevailing theory suggests that long-term memory encoding involves early plasticity within hippocampal circuits, whereas reorganization of the neocortex is thought to occur weeks to months later to subserve remote memory storage. Here we report that long-term memory encoding can elicit early transcriptional, structural, and functional remodeling of the neocortex. Parallel studies using genome-wide RNA sequencing, ultrastructural imaging, and whole-cell recording in wild-type mice suggest that contextual fear conditioning initiates a transcriptional program in the medial prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic active zone and postsynaptic density, enhanced dendritic spine plasticity, and increased synaptic efficacy. To address the real-time contribution of the mPFC to long-term memory encoding, we performed temporally precise optogenetic inhibition of excitatory mPFC neurons during contextual fear conditioning. Using this approach, we found that real-time inhibition of the mPFC inhibited activation of the entorhinal-hippocampal circuit and impaired the formation of long-term associative memory. These findings suggest that encoding of long-term episodic memory is associated with early remodeling of neocortical circuits, identify the prefrontal cortex as a critical regulator of encoding-induced hippocampal activation and long-term memory formation, and have important implications for understanding memory processing in healthy and diseased brain states.

  10. Encoding of Coordinated Grasp Trajectories in Primary Motor Cortex

    PubMed Central

    Takahashi, Kazutaka; Amit, Yali; Hatsopoulos, Nicholas G.

    2011-01-01

    Few studies have investigated how the cortex encodes the pre-shaping of the hand as an object is grasped, an ethological movement referred to as prehension. We developed an encoding model of hand kinematics to test whether single motor cortical (MI) neurons encode temporally extensive combinations of joint motions that characterize a prehensile movement. Two female rhesus macaque monkeys were trained to grasp 4 different objects presented by a robot while their arm was held in place by a thermoplastic brace. We used multi-electrode arrays to record MI neurons and an infrared camera motion tracking system to record the 3D positions of 14 markers placed on the monkeys’ wrist and digits. A generalized linear model framework was used to predict the firing rate of each neuron in a 4ms time interval, based on its own spiking history and the spatiotemporal kinematics of the joint angles of the hand. Our results show that the variability of the firing rate of MI neurons is better described by temporally extensive combinations of finger and wrist joint angle kinematics rather than any individual joint motion or any combination of static kinematic parameters at their optimal lag. Moreover, a higher percentage of neurons encoded joint angular velocities than joint angular positions. These results suggest that neurons encode the co-varying trajectories of the hand’s joints during a prehensile movement. PMID:21159978

  11. Human Genomic Signatures of Brain Oscillations During Memory Encoding.

    PubMed

    Berto, Stefano; Wang, Guang-Zhong; Germi, James; Lega, Bradley C; Konopka, Genevieve

    2017-04-05

    Memory encoding is an essential step for all learning. However, the genetic and molecular mechanisms underlying human memory encoding remain poorly understood, and how this molecular framework permits the emergence of specific patterns of brain oscillations observed during mnemonic processing is unknown. Here, we directly compare intracranial electroencephalography recordings from the neocortex in individuals performing an episodic memory task with human gene expression from the same areas. We identify genes correlated with oscillatory memory effects across 6 frequency bands. These genes are enriched for autism-related genes and have preferential expression in neurons, in particular genes encoding synaptic proteins and ion channels, supporting the idea that the genes regulating voltage gradients are involved in the modulation of oscillatory patterns during successful memory encoding across brain areas. Memory-related genes are distinct from those correlated with other forms of cognitive processing and resting state fMRI. These data are the first to identify correlations between gene expression and active human brain states as well as provide a molecular window into memory encoding oscillations in the human brain.

  12. Early remodeling of the neocortex upon episodic memory encoding

    PubMed Central

    Bero, Adam W.; Meng, Jia; Cho, Sukhee; Shen, Abra H.; Canter, Rebecca G.; Ericsson, Maria; Tsai, Li-Huei

    2014-01-01

    Understanding the mechanisms by which long-term memories are formed and stored in the brain represents a central aim of neuroscience. Prevailing theory suggests that long-term memory encoding involves early plasticity within hippocampal circuits, whereas reorganization of the neocortex is thought to occur weeks to months later to subserve remote memory storage. Here we report that long-term memory encoding can elicit early transcriptional, structural, and functional remodeling of the neocortex. Parallel studies using genome-wide RNA sequencing, ultrastructural imaging, and whole-cell recording in wild-type mice suggest that contextual fear conditioning initiates a transcriptional program in the medial prefrontal cortex (mPFC) that is accompanied by rapid expansion of the synaptic active zone and postsynaptic density, enhanced dendritic spine plasticity, and increased synaptic efficacy. To address the real-time contribution of the mPFC to long-term memory encoding, we performed temporally precise optogenetic inhibition of excitatory mPFC neurons during contextual fear conditioning. Using this approach, we found that real-time inhibition of the mPFC inhibited activation of the entorhinal–hippocampal circuit and impaired the formation of long-term associative memory. These findings suggest that encoding of long-term episodic memory is associated with early remodeling of neocortical circuits, identify the prefrontal cortex as a critical regulator of encoding-induced hippocampal activation and long-term memory formation, and have important implications for understanding memory processing in healthy and diseased brain states. PMID:25071187

  13. Functional Neuroimaging of Self-Referential Encoding with Age

    PubMed Central

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

    2009-01-01

    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. Although previous studies identified an intact self-reference effect with age, subserved by robust engagement of medial prefrontal cortex (mPFC) by both young and older adults, we identified a number of age differences. In regions including superior mPFC, inferior prefrontal cortex, and anterior and posterior cingulate cortex, young and older adults exhibited reversals in the pattern of activity for self and other conditions. Whereas young primarily evidenced subsequent forgetting effects in the self-reference condition, older adults demonstrated subsequent memory effects in the other-reference condition. These results indicate fundamental differences across the age groups in the engagement of elaborative encoding processes. We suggest that older adults may encode information about the self in a more normative manner, whereas young adults focus on encoding the unique aspects of the self and distinguishing the self from others. PMID:19765600

  14. Encoding of configural regularity in the human visual system.

    PubMed

    Kubilius, Jonas; Wagemans, Johan; Op de Beeck, Hans P

    2014-08-13

    The visual system is very efficient in encoding stimulus properties by utilizing available regularities in the inputs. To explore the underlying encoding strategies during visual information processing, we presented participants with two-line configurations that varied in the amount of configural regularity (or degrees of freedom in the relative positioning of the two lines) in a fMRI experiment. Configural regularity ranged from a generic configuration to stimuli resembling an "L" (i.e., a right-angle L-junction), a "T" (i.e., a right-angle midpoint T-junction), or a "+",-the latter being the most regular stimulus. We found that the response strength in the shape-selective lateral occipital area was consistently lower for a higher degree of regularity in the stimuli. In the second experiment, using multivoxel pattern analysis, we further show that regularity is encoded in terms of the fMRI signal strength but not in the distributed pattern of responses. Finally, we found that the results of these experiments could not be accounted for by low-level stimulus properties and are distinct from norm-based encoding. Our results suggest that regularity plays an important role in stimulus encoding in the ventral visual processing stream.

  15. The Effects of Temporal Lobe Epilepsy on Scene-Encoding

    PubMed Central

    Bigras, Cristina; Shear, Paula K.; Vannest, Jennifer; Allendorfer, Jane B.; Szaflarski, Jerzy P.

    2012-01-01

    Forty-four TLE patients (25 left) and 40 healthy control participants performed a complex visual scene-encoding fMRI task in a 4T Varian scanner. Healthy controls and left temporal lobe epilepsy (LTLE) patients demonstrated symmetric activation during scene encoding. In contrast, RTLE (RTLE) patients demonstrated left lateralization of scene encoding which differed significantly from healthy controls and LTLE patients (all p ≤ .05). Lateralization of scene encoding to the right hemisphere among LTLE patients was associated with inferior verbal memory performance as measured by neuropsychological testing (WMS-III Logical Memory Immediate, p=0.049; WMS-III Paired Associates Immediate, p=0.036; WMS-III Paired Associates Delayed, p=0.047). In RTLE patients, left lateralization of scene encoding was associated with lower visuospatial memory performance (BVRT, p=0.043) but improved verbal memory performance (WMS-III Word List, p=0.049). These findings indicate that, despite the negative effects of epilepsy, memory functioning is better supported by the affected hemisphere than the hemisphere contralateral to seizure focus. PMID:23207513

  16. Two Pathways to Stimulus Encoding in Category Learning?

    PubMed Central

    Davis, Tyler; Love, Bradley C.; Maddox, W. Todd

    2008-01-01

    Category learning theorists tacitly assume that stimuli are encoded by a single pathway. Motivated by theories of object recognition, we evaluate a dual-pathway account of stimulus encoding. The part-based pathway establishes mappings between sensory input and symbols that encode discrete stimulus features, whereas the image-based pathway applies holistic templates to sensory input. Our experiments use rule-plus-exception structures in which one exception item in each category violates a salient regularity and must be distinguished from other items. In Experiment 1, we find that discrete representations are crucial for recognition of exceptions following brief training. Experiments 2 and 3 involve multi-session training regimens designed to encourage either part or image-based encoding. We find that both pathways are able to support exception encoding, but have unique characteristics. We speculate that one advantage of the part-based pathway is the ability to generalize across domains, whereas the image-based pathway provides faster and more effortless recognition. PMID:19460948

  17. Biomolecular screening with encoded porous-silicon photonic crystals

    NASA Astrophysics Data System (ADS)

    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.

  18. 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.

  19. Structural and Functional Diversity of Nairovirus-Encoded Nucleoproteins

    PubMed Central

    Wang, Wenming; Liu, Xiang; Wang, Xu; Dong, Hui; Ma, Chao; Wang, Jingmin; Liu, Baocheng; Mao, Yonghong; Wang, Ying; Li, Ting

    2015-01-01

    ABSTRACT The nairoviruses include assorted tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals. As negative-sense single-stranded RNA (−ssRNA) viruses, nairoviruses encode nucleoprotein (NP) that encapsidates the genomic RNA and further forms ribonucleoprotein (RNP) complex with viral RNA-dependent RNA polymerase (RdRp). We previously revealed that the monomeric NP encoded by Crimean-Congo hemorrhagic fever virus (CCHFV) presents a racket-shaped structure and shows unusual DNA-specific endonuclease activity. To examine the structural and biological variation of nairovirus-encoded NPs, here, we systematically solved the crystal structures of NPs encoded by various nairoviruses, including Hazara virus (HAZV), Kupe virus (KUPV), and Erve virus (ERVEV). Combined with biochemical analysis, our results generate a clearer picture to aid in the understanding of the functional diversity of nairovirus-encoded NPs and the formation of nairovirus RNPs. IMPORTANCE Nairoviruses comprise several tick-borne bunyaviruses that are emerging as causative agents of infectious diseases among humans and animals; however, little is known of the nairovirus genome assembly and transcription mechanisms. Based on the previous study of CCHFV NP reported by different research groups, we systematically investigate here the structural and functional diversity among three different nairoviruses. This work provides important information on nairovirus nucleoprotein function and the formation of RNPs. PMID:26246561

  20. Color encoding for gamut extension and bit-depth extension

    NASA Astrophysics Data System (ADS)

    Zeng, Huanzhao

    2005-02-01

    Monitor oriented RGB color spaces (e.g. sRGB) are widely applied for digital image representation for the simplicity in displaying images on monitor displays. However, the physical gamut limits its ability to encode colors accurately for color images that are not limited to the display RGB gamut. To extend the encoding gamut, non-physical RGB primaries may be used to define the color space, or the RGB tone ranges may be extended beyond the physical range. An out-of-gamut color has at least one of the R, G, and B channels that are smaller than 0 or higher than 100%. Instead of using wide-gamut RGB primaries for gamut expansion, we may extend the tone ranges to expand the encoding gamut. Negative tone values and tone values over 100% are allowed. Methods to efficiently and accurately encode out-of-gamut colors are discussed in this paper. Interpretation bits are added to interpret the range of color values or to encode color values with a higher bit-depth. The interpretation bits of R, G, and B primaries can be packed and stored in an alpha channel in some image formats (e.g. TIFF) or stored in a data tag (e.g. in JEPG format). If a color image does not have colors that are out of a regular RGB gamut, a regular program (e.g. Photoshop) is able to manipulate the data correctly.

  1. Graph Regularized Auto-Encoders for Image Representation.

    PubMed

    Yiyi Liao; Yue Wang; Yong Liu

    2017-06-01

    Image representation has been intensively explored in the domain of computer vision for its significant influence on the relative tasks such as image clustering and classification. It is valuable to learn a low-dimensional representation of an image which preserves its inherent information from the original image space. At the perspective of manifold learning, this is implemented with the local invariant idea to capture the intrinsic low-dimensional manifold embedded in the high-dimensional input space. Inspired by the recent successes of deep architectures, we propose a local invariant deep nonlinear mapping algorithm, called graph regularized auto-encoder (GAE). With the graph regularization, the proposed method preserves the local connectivity from the original image space to the representation space, while the stacked auto-encoders provide explicit encoding model for fast inference and powerful expressive capacity for complex modeling. Theoretical analysis shows that the graph regularizer penalizes the weighted Frobenius norm of the Jacobian matrix of the encoder mapping, where the weight matrix captures the local property in the input space. Furthermore, the underlying effects on the hidden representation space are revealed, providing insightful explanation to the advantage of the proposed method. Finally, the experimental results on both clustering and classification tasks demonstrate the effectiveness of our GAE as well as the correctness of the proposed theoretical analysis, and it also suggests that GAE is a superior solution to the current deep representation learning techniques comparing with variant auto-encoders and existing local invariant methods.

  2. Robust encoding of scene anticipation during human spatial navigation

    PubMed Central

    Shikauchi, Yumi; Ishii, Shin

    2016-01-01

    In a familiar city, people can recall scene views (e.g., a particular street corner scene) they could encounter again in the future. Complex objects with multiple features are represented by multiple neural units (channels) in the brain, but when anticipating a scene view, the kind of feature that is assigned to a specific channel is unknown. Here, we studied neural encoding of scene view anticipation during spatial navigation, using a novel data-driven analysis to evaluate encoding channels. Our encoding models, based on functional magnetic resonance imaging (fMRI) activity, provided channel error correction via redundant channel assignments that reflected the navigation environment. We also found that our encoding models strongly reflected brain activity in the inferior parietal gyrus and precuneus, and that details of future scenes were locally represented in the superior prefrontal gyrus and temporal pole. Furthermore, a decoder associated with the encoding models accurately predicted future scene views in both passive and active navigation. These results suggest that the human brain uses scene anticipation, mediated especially by parietal and medial prefrontal cortical areas, as a robust and effective navigation processing. PMID:27874089

  3. Brainstem encoding of voiced consonant--vowel stop syllables.

    PubMed

    Johnson, Krista L; Nicol, Trent; Zecker, Steven G; Bradlow, Ann R; Skoe, Erika; Kraus, Nina

    2008-11-01

    The purpose of this study is to expand our understanding of how the human auditory brainstem encodes temporal and spectral acoustic cues in voiced stop consonant-vowel syllables. Auditory evoked potentials measuring activity from the brainstem of 22 normal learning children were recorded to the voiced stop consonant syllables [ga], [da], and [ba]. Spectrotemporal information distinguishing these voiced consonant-vowel syllables is contained within the first few milliseconds of the burst and the formant transition to the vowel. Responses were compared across stimuli with respect to their temporal and spectral content. Brainstem response latencies change in a predictable manner in response to systematic alterations in a speech syllable indicating that the distinguishing acoustic cues are represented by neural response timing (synchrony). Spectral analyses of the responses show frequency distribution differences across stimuli (some of which appear to represent acoustic characteristics created by difference tones of the stimulus formants) indicating that neural phase-locking is also important for encoding these acoustic elements. Considered within the context of existing knowledge of brainstem encoding of speech-sound structure, these data are the beginning of a comprehensive delineation of how the human auditory brainstem encodes perceptually critical features of speech. The results of this study could be used to determine how neural encoding is disrupted in the clinical populations for whom stop consonants pose particular perceptual challenges (e.g., hearing impaired individuals and poor readers).

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Multiple velocity encoding in the phase of an MRI signal

    NASA Astrophysics Data System (ADS)

    Benitez-Read, E. E.

    2017-01-01

    The measurement of fluid velocity by encoding it in the phase of a magnetic resonance imaging (MRI) signal could allow the discrimination of the stationary spins signals from those of moving spins. This results in a wide variety of applications i.e. in medicine, in order to obtain more than angiograms, blood velocity images of veins, arteries and other vessels without having static tissue perturbing the signal of fluid in motion. The work presented in this paper is a theoretical analysis of some novel methods for multiple fluid velocity encoding in the phase of an MRI signal. These methods are based on a tripolar gradient (TPG) and can be an alternative to the conventional methods based on a bipolar gradient (BPG) and could be more suitable for multiple velocity encoding in the phase of an MRI signal.

  9. 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.

  10. Enzymes and Enzyme Activity Encoded by Nonenveloped Viruses.

    PubMed

    Azad, Kimi; Banerjee, Manidipa; Johnson, John E

    2017-06-21

    Viruses are obligate intracellular parasites that rely on host cell machineries for their replication and survival. Although viruses tend to make optimal use of the host cell protein repertoire, they need to encode essential enzymatic or effector functions that may not be available or accessible in the host cellular milieu. The enzymes encoded by nonenveloped viruses-a group of viruses that lack any lipid coating or envelope-play vital roles in all the stages of the viral life cycle. This review summarizes the structural, biochemical, and mechanistic information available for several classes of enzymes and autocatalytic activity encoded by nonenveloped viruses. Advances in research and development of antiviral inhibitors targeting specific viral enzymes are also highlighted. Expected final online publication date for the Annual Review of Virology Volume 4 is September 29, 2017. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.

  11. Multiresolutional encoding and decoding in embedded image and video coders

    NASA Astrophysics Data System (ADS)

    Xiong, Zixiang; Kim, Beong-Jo; Pearlman, William A.

    1998-07-01

    We address multiresolutional encoding and decoding within the embedded zerotree wavelet (EZW) framework for both images and video. By varying a resolution parameter, one can obtain decoded images at different resolutions from one single encoded bitstream, which is already rate scalable for EZW coders. Similarly one can decode video sequences at different rates and different spatial and temporal resolutions from one bitstream. Furthermore, a layered bitstream can be generated with multiresolutional encoding, from which the higher resolution layers can be used to increase the spatial/temporal resolution of the images/video obtained from the low resolution layer. In other words, we have achieved full scalability in rate and partial scalability in space and time. This added spatial/temporal scalability is significant for emerging multimedia applications such as fast decoding, image/video database browsing, telemedicine, multipoint video conferencing, and distance learning.

  12. 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.

  13. Fast Coding Unit Encoding Mechanism for Low Complexity Video Coding.

    PubMed

    Gao, Yuan; Liu, Pengyu; 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.

  14. Degradation of Cortical Representations during Encoding following Sleep Deprivation.

    PubMed

    Poh, Jia-Hou; Chee, Michael W L

    2017-02-01

    A night of total sleep deprivation (TSD) reduces task-related activation of fronto-parietal and higher visual cortical areas. As this reduction in activation corresponds to impaired attention and perceptual processing, it might also be associated with poorer memory encoding. Related animal work has established that cortical columns stochastically enter an 'off' state in sleep deprivation, leading to predictions that neural representations are less stable and distinctive following TSD. To test these predictions participants incidentally encoded scene images while undergoing fMRI, either during rested wakefulness (RW) or after TSD. In scene-selective PPA, TSD reduced stability of neural representations across repetition. This was accompanied by poorer subsequent memory. Greater representational stability benefitted subsequent memory in RW but not TSD. Even for items subsequently recognized, representational distinctiveness was lower in TSD, suggesting that quality of encoding is degraded. Reduced representational stability and distinctiveness are two novel mechanisms by which TSD can contribute to poorer memory formation.

  15. 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.

  16. 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

  17. 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

  18. Experimental design for functional MRI of scene memory encoding.

    PubMed

    Narayan, Veena M; Kimberg, Daniel Y; Tang, Kathy Z; Detre, John A

    2005-03-01

    The use of functional imaging to identify encoding-related areas in the medial temporal lobe has previously been explored for presurgical evaluation in patients with temporal lobe epilepsy. Optimizing sensitivity in such paradigms is critical for the reliable detection of regions most closely engaged in memory encoding. A variety of experimental designs have been used to detect encoding-related activity, including blocked, sparse event-related, and rapid event-related designs. Although blocked designs are generally more sensitive than event-related designs, design and analysis advantages could potentially overcome this difference. In the present study, we directly contrast different experimental designs in terms of the intensity, extent, and lateralization of activation detected in healthy subjects. Our results suggest that although improved design augments the sensitivity of event-related designs, these benefits are not sufficient to overcome the sensitivity advantages of traditional blocked designs.

  19. Genetically-encoded biosensors for monitoring cellular stress in bioprocessing.

    PubMed

    Polizzi, Karen M; Kontoravdi, Cleo

    2015-02-01

    With the current wealth of transcriptomic data, it is possible to design genetically-encoded biosensors for the detection of stress responses and apply these to high-throughput bioprocess development and monitoring of cellular health. Such biosensors can sense extrinsic factors such as nutrient or oxygen deprivation and shear stress, as well as intrinsic stress factors like oxidative damage and unfolded protein accumulation. Alongside, there have been developments in biosensing hardware and software applicable to the field of genetically-encoded biosensors in the near future. This review discusses the current state-of-the-art in biosensors for monitoring cultures during biological manufacturing and the future challenges for the field. Connecting the individual achievements into a coherent whole will enable the application of genetically-encoded biosensors in industry. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Hippocampal-prefrontal input supports spatial encoding in working memory.

    PubMed

    Spellman, Timothy; Rigotti, Mattia; Ahmari, Susanne E; Fusi, Stefano; Gogos, Joseph A; Gordon, Joshua A

    2015-06-18

    Spatial working memory, the caching of behaviourally relevant spatial cues on a timescale of seconds, is a fundamental constituent of cognition. Although the prefrontal cortex and hippocampus are known to contribute jointly to successful spatial working memory, the anatomical pathway and temporal window for the 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 in mice. 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.

  1. Probabilistic Computation in Human Perception under Variability in Encoding Precision

    PubMed Central

    Keshvari, Shaiyan; van den Berg, Ronald; Ma, Wei Ji

    2012-01-01

    A key function of the brain is to interpret noisy sensory information. To do so optimally, observers must, in many tasks, take into account knowledge of the precision with which stimuli are encoded. In an orientation change detection task, we find that encoding precision does not only depend on an experimentally controlled reliability parameter (shape), but also exhibits additional variability. In spite of variability in precision, human subjects seem to take into account precision near-optimally on a trial-to-trial and item-to-item basis. Our results offer a new conceptualization of the encoding of sensory information and highlight the brain’s remarkable ability to incorporate knowledge of uncertainty during complex perceptual decision-making. PMID:22768258

  2. Inline SAW RFID tag using time position and phase encoding.

    PubMed

    Härmä, Sanna; Arthur, Wesley G; Hartmann, Clinton S; Maev, Roman G; Plessky, Victor P

    2008-08-01

    Surface acoustic wave (SAW) radio-frequency identification (RFID) tags are encoded according to partial reflections of an interrogation signal by short metal reflectors. The standard encryption method involves time position encoding that uses time delays of response signals. However, the data capacity of a SAW RFID tag can be significantly enhanced by extracting additional phase information from the tag responses. In this work, we have designed, using FEM-BEM simulations, and fabricated, on 128 degrees -LiNbO3, inline 2.44-GHz SAW RFID tag samples that combine time position and phase encoding. Each reflective echo has 4 possible time positions and a phase of 0 degrees , -90 degrees , -180 degrees , or -270 degrees. This corresponds to 16 different states, i.e., 4 bits of data, per code reflector. In addition to the enhanced data capacity, our samples also exhibit a low loss level of -38 dB for code reflections.

  3. Verb inflections in agrammatic aphasia: Encoding of tense features ⋆

    PubMed Central

    Faroqi-Shah, Yasmeen; Thompson, Cynthia K.

    2008-01-01

    Across most languages, verbs produced by agrammatic aphasic individuals are frequently marked by syntactically and semantically inappropriate inflectional affixes, such as Last night, I walking home. As per language production models, verb inflection errors in English agrammatism could arise from three potential sources: encoding the verbs’ morphology based on temporal information at the conceptual level, accessing syntactic well-formedness constraints of verbal morphology, and encoding morphophonological form. We investigate these aspects of encoding verb inflections in agrammatic aphasia. Using three sentence completion experiments, it was demonstrated that production of verb inflections was impaired whenever temporal reference was involved; while morphological complexity and syntactic constraints were less likely to be the source of verb inflection errors in agrammatism. These findings are discussed in relation to current language production models. PMID:18392120

  4. Prefrontal activity and impaired memory encoding strategies in schizophrenia.

    PubMed

    Guimond, Synthia; Hawco, Colin; Lepage, Martin

    2017-03-08

    Schizophrenia patients have significant memory difficulties that have far-reaching implications in their daily life. These impairments are partly attributed to an inability to self-initiate effective memory encoding strategies, but its core neurobiological correlates remain unknown. The current study addresses this critical gap in our knowledge of episodic memory impairments in schizophrenia. Schizophrenia patients (n = 35) and healthy controls (n = 23) underwent a Semantic Encoding Memory Task (SEMT) during an fMRI scan. Brain activity was examined for conditions where participants were a) prompted to use semantic encoding strategies, or b) not prompted but required to self-initiate such strategies. When prompted to use semantic encoding strategies, schizophrenia patients exhibited similar recognition performance and brain activity as healthy controls. However, when required to self-initiate these strategies, patients had significant reduced recognition performance and brain activity in the left dorsolateral prefrontal cortex, as well as in the left temporal gyrus, left superior parietal lobule, and cerebellum. When patients were divided based on performance on the SEMT, the subgroup with more severe deficits in self-initiation also showed greater reduction in left dorsolateral prefrontal activity. These results suggest that impaired self-initiation of elaborative encoding strategies is a driving feature of memory deficits in schizophrenia. We also identified the neural correlates of impaired self-initiation of semantic encoding strategies, in which a failure to activate the left dorsolateral prefrontal cortex plays a key role. These findings provide important new targets in the development of novel treatments aiming to improve memory and ultimately patients' outcome.

  5. Negative affect promotes encoding of and memory for details at the expense of the gist: affect, encoding, and false memories.

    PubMed

    Storbeck, Justin

    2013-01-01

    I investigated whether negative affective states enhance encoding of and memory for item-specific information reducing false memories. Positive, negative, and neutral moods were induced, and participants then completed a Deese-Roediger-McDermott (DRM) false-memory task. List items were presented in unique spatial locations or unique fonts to serve as measures for item-specific encoding. The negative mood conditions had more accurate memories for item-specific information, and they also had fewer false memories. The final experiment used a manipulation that drew attention to distinctive information, which aided learning for DRM words, but also promoted item-specific encoding. For the condition that promoted item-specific encoding, false memories were reduced for positive and neutral mood conditions to a rate similar to that of the negative mood condition. These experiments demonstrated that negative affective cues promote item-specific processing reducing false memories. People in positive and negative moods encode events differently creating different memories for the same event.

  6. Role of voluntary drive in encoding an elementary motor memory.

    PubMed

    Kaelin-Lang, Alain; Sawaki, Lumy; Cohen, Leonardo G

    2005-02-01

    Motor training consisting of repetitive thumb movements results in encoding of motor memories in the primary motor cortex. It is not known if proprioceptive input originating in the training movements is sufficient to produce this effect. In this study, we compared the ability of training consisting of voluntary (active) and passively-elicited (passive) movements to induce this form of plasticity. Active training led to successful encoding accompanied by characteristic changes in corticomotor excitability, while passive training did not. These results support a pivotal role for voluntary motor drive in coding motor memories in the primary motor cortex.

  7. Hybrid architecture for encoded measurement-based quantum computation

    PubMed Central

    Zwerger, M.; Briegel, H. J.; Dür, W.

    2014-01-01

    We present a hybrid scheme for quantum computation that combines the modular structure of elementary building blocks used in the circuit model with the advantages of a measurement-based approach to quantum computation. We show how to construct optimal resource states of minimal size to implement elementary building blocks for encoded quantum computation in a measurement-based way, including states for error correction and encoded gates. The performance of the scheme is determined by the quality of the resource states, where within the considered error model a threshold of the order of 10% local noise per particle for fault-tolerant quantum computation and quantum communication. PMID:24946906

  8. 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

  9. An ORF from Bacillus licheniformis encodes a putative DNA repressor.

    PubMed

    Naval, J; Aguilar, D; Serra, X; Pérez-Pons, J A; Piñol, J; Lloberas, J; Querol, E

    2000-01-01

    The complete sequence of a reading frame adjacent to the endo-beta-1,3-1,4-D-glucanase gene from Bacillus licheniformis is reported. It encodes a putative 171 amino acid residues protein with either, low significant sequence similarity in data banks or the corresponding orthologue in the recently sequenced Bacillus subtilis genome. Computer analyses predict a canonical Helix-Turn-Helix motif characteristic of bacterial repressors/DNA binding proteins. A maxicells assay shows that the encoded polypeptide is expressed. A DNA-protein binding, assay performed by gel electrophoresis shows that the expressed protein specifically binds to Bacillus licheniformis DNA.

  10. 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.

  11. Mosaic tetracycline resistance genes encoding ribosomal protection proteins

    PubMed Central

    Warburton, Philip J.; Amodeo, Nina; Roberts, Adam P.

    2016-01-01

    First reported in 2003, mosaic tetracycline resistance genes are a subgroup of the genes encoding ribosomal protection proteins (RPPs). They are formed when two or more RPP-encoding genes recombine resulting in a functional chimera. To date, the majority of mosaic genes are derived from sections of three RPP genes, tet(O), tet(W) and tet(32), with others comprising tet(M) and tet(S). In this first review of mosaic genes, we report on their structure, diversity and prevalence, and suggest that these genes may be responsible for an under-reported contribution to tetracycline resistance in bacteria. PMID:27494928

  12. Frequency- and Phase Encoded SSVEP Using Spatiotemporal Beamforming.

    PubMed

    Wittevrongel, Benjamin; 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.

  13. Mosaic tetracycline resistance genes encoding ribosomal protection proteins.

    PubMed

    Warburton, Philip J; Amodeo, Nina; Roberts, Adam P

    2016-12-01

    First reported in 2003, mosaic tetracycline resistance genes are a subgroup of the genes encoding ribosomal protection proteins (RPPs). They are formed when two or more RPP-encoding genes recombine resulting in a functional chimera. To date, the majority of mosaic genes are derived from sections of three RPP genes, tet(O), tet(W) and tet(32), with others comprising tet(M) and tet(S). In this first review of mosaic genes, we report on their structure, diversity and prevalence, and suggest that these genes may be responsible for an under-reported contribution to tetracycline resistance in bacteria.

  14. Authentication of gold nanoparticle encoded pharmaceutical tablets using polarimetric signatures.

    PubMed

    Carnicer, Artur; Arteaga, Oriol; Suñé-Negre, Josep M; Javidi, Bahram

    2016-10-01

    The counterfeiting of pharmaceutical products represents concerns for both industry and the safety of the general public. Falsification produces losses to companies and poses health risks for patients. In order to detect fake pharmaceutical tablets, we propose producing film-coated tablets with gold nanoparticle encoding. These coated tablets contain unique polarimetric signatures. We present experiments to show that ellipsometric optical techniques, in combination with machine learning algorithms, can be used to distinguish genuine and fake samples. To the best of our knowledge, this is the first report using gold nanoparticles encoded with optical polarimetric classifiers to prevent the counterfeiting of pharmaceutical products.

  15. 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.

  16. Identification and Function of MicroRNAs Encoded by Herpesviruses*

    PubMed Central

    Bai, Zhi-Qiang; Lei, Xiu-Fen; Wang, Lin-Ding; Gao, Shou-Jiang

    2009-01-01

    MicroRNAs (miRNAs) play important roles in eukaryotes, plants and some viruses. It is increasingly clear that miRNAs-encoded by viruses can affect the viral life cycle and host physiology. Viral miRNAs could repress the innate and adaptive host immunity, modulate cellular signaling pathways, and regulate the expression of cellular and viral genes. These functions facilitate viral acute and persistent infections, and have profound effects on the host cell survival and disease progression. Here, we discuss the miRNAs encoded by herpesviruses, and their regulatory roles involved in virus-host interactions. PMID:20084183

  17. Heavy Metal Complexation of Thiol-Containing Peptides from Soy Glycinin Hydrolysates

    PubMed Central

    Ding, Xiuzhen; Hua, Yufei; Chen, Yeming; Zhang, Caimeng; Kong, Xiangzhen

    2015-01-01

    Many thiol-containing molecules show heavy metal complexation ability and are used as antidotes. In this study, the potential function associated with thiol-containing peptides (TCPs) from soy protein hydrolysates as natural detoxicants for heavy metals is reported. TCPs enriched by Thiopropyl-Sepharose 6B covalent chromatography had different molecular weight distributions as well as different numbers of proton dissociable groups, depending on the proteases and degree of hydrolysis. The major contribution of sulfhydryl groups was confirmed by the largest pH decrease between 8.0 and 8.5 of the pH titration curves. The complexation of TCPs with heavy metalswas evaluated by stability constants (βn) of TCP-metal complexes whose stoichiometry was found to be 1:1 (ML) and 1:2 (ML2). TCPs from degree of hydrolysis of 25% hydrolysates gave high affinities towards Hg2+, Cd2+, and Pb2+ (giving similar or even bigger lgβ values than that of glutathione). A significantly positive correlation was found between the logarithm of stability constants for ML2 (lgβ2) and the sulfhydryl group content. Molecular weight distribution of TCPs affected the complexation with Pb2+ notably more than Hg2+ and Cd2+. These results suggest that soy TCPs have the potential to be used in the formulation of functional foods to counteract heavy metal accumulation in humans. PMID:25867477

  18. EGVII endoglucanase and nucleic acids encoding the same

    DOEpatents

    Dunn-Coleman, Nigel [Los Gatos, CA; Goedegebuur, Frits [Vlaardingen, NL; Ward, Michael [San Francisco, CA; Yao, Jian [Sunnyvale, CA

    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.

  19. Polypeptides having cellobiohydrolase activity and polynucleotides encoding same

    DOEpatents

    Liu, Ye; Harris, Paul; Tang, Lan; Wu, Wenping

    2013-11-19

    The present invention relates to isolated polypeptides having cellobiohydrolase 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 nucleic acids encoding same

    DOEpatents

    Brown, Kimberly; Harris, Paul; Zaretsky, Elizabeth; Re, Edward; Vlasenko, Elena; McFarland, Keith; Lopez de Leon, Alfredo

    2010-06-22

    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.