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Sample records for encoding il-5 gata-3

  1. Methylation of Gata3 protein at Arg-261 regulates transactivation of the Il5 gene in T helper 2 cells.

    PubMed

    Hosokawa, Hiroyuki; Kato, Miki; Tohyama, Hiroyuki; Tamaki, Yuuki; Endo, Yusuke; Kimura, Motoko Y; Tumes, Damon John; Motohashi, Shinichiro; Matsumoto, Masaki; Nakayama, Keiichi I; Tanaka, Tomoaki; Nakayama, Toshinori

    2015-05-22

    Gata3 acts as a master regulator for T helper 2 (Th2) cell differentiation by inducing chromatin remodeling of the Th2 cytokine loci, accelerating Th2 cell proliferation, and repressing Th1 cell differentiation. Gata3 also directly transactivates the interleukin-5 (Il5) gene via additional mechanisms that have not been fully elucidated. We herein identified a mechanism whereby the methylation of Gata3 at Arg-261 regulates the transcriptional activation of the Il5 gene in Th2 cells. Although the methylation-mimicking Gata3 mutant retained the ability to induce IL-4 and repress IFNγ production, the IL-5 production was selectively impaired. We also demonstrated that heat shock protein (Hsp) 60 strongly associates with the methylation-mimicking Gata3 mutant and negatively regulates elongation of the Il5 transcript by RNA polymerase II. Thus, arginine methylation appears to play a pivotal role in the organization of Gata3 complexes and the target gene specificity of Gata3.

  2. Eomesodermin controls interleukin-5 production in memory T helper 2 cells through inhibition of activity of the transcription factor GATA3.

    PubMed

    Endo, Yusuke; Iwamura, Chiaki; Kuwahara, Makoto; Suzuki, Akane; Sugaya, Kaoru; Tumes, Damon J; Tokoyoda, Koji; Hosokawa, Hiroyuki; Yamashita, Masakatsu; Nakayama, Toshinori

    2011-11-23

    The regulation of memory CD4(+) helper T (Th) cell function, such as polarized cytokine production, remains unclear. Here we show that memory T helper 2 (Th2) cells are divided into four subpopulations by CD62L and CXCR3 expression. All four subpopulations produced interleukin-4 (IL-4) and IL-13, whereas only the CD62L(lo)CXCR3(lo) population produced IL-5 accompanied by increased H3-K4 methylation at the Il5 gene locus. The transcription factor Eomesodermin (encoded by Eomes) was highly expressed in memory Th2 cells, whereas its expression was selectively downregulated in the IL-5-producing cells. Il5 expression was enhanced in Eomes-deficient cells, and Eomesodermin was shown to interact with the transcription factor GATA3, preventing GATA3 binding to the Il5 promoter. Memory Th2 cell-dependent airway inflammation was attenuated in the absence of the CD62L(lo)CXCR3(lo) population but was enhanced by Eomes-deficient memory Th2 cells. Thus, IL-5 production in memory Th2 cells is regulated by Eomesodermin via the inhibition of GATA3 activity.

  3. GATA-3 function in innate and adaptive immunity.

    PubMed

    Tindemans, Irma; Serafini, Nicolas; Di Santo, James P; Hendriks, Rudi W

    2014-08-21

    The zinc-finger transcription factor GATA-3 has received much attention as a master regulator of T helper 2 (Th2) cell differentiation, during which it controls interleukin-4 (IL-4), IL-5, and IL-13 expression. More recently, GATA-3 was shown to contribute to type 2 immunity through regulation of group 2 innate lymphoid cell (ILC2) development and function. Furthermore, during thymopoiesis, GATA-3 represses B cell potential in early T cell precursors, activates TCR signaling in pre-T cells, and promotes the CD4(+) T cell lineage after positive selection. GATA-3 also functions outside the thymus in hematopoietic stem cells, regulatory T cells, CD8(+) T cells, thymic natural killer cells, and ILC precursors. Here we discuss the varied functions of GATA-3 in innate and adaptive immune cells, with emphasis on its activity in T cells and ILCs, and examine the mechanistic basis for the dose-dependent, developmental-stage- and cell-lineage-specific activity of this transcription factor.

  4. Gata3 drives development of RORγt+ group 3 innate lymphoid cells

    PubMed Central

    Serafini, Nicolas; Klein Wolterink, Roel G.J.; Satoh-Takayama, Naoko; Xu, Wei; Vosshenrich, Christian A.J.; Hendriks, Rudi W.

    2014-01-01

    Group 3 innate lymphoid cells (ILC3) include IL-22–producing NKp46+ cells and IL-17A/IL-22–producing CD4+ lymphoid tissue inducerlike cells that express RORγt and are implicated in protective immunity at mucosal surfaces. Whereas the transcription factor Gata3 is essential for T cell and ILC2 development from hematopoietic stem cells (HSCs) and for IL-5 and IL-13 production by T cells and ILC2, the role for Gata3 in the generation or function of other ILC subsets is not known. We found that abundant GATA-3 protein is expressed in mucosa-associated ILC3 subsets with levels intermediate between mature B cells and ILC2. Chimeric mice generated with Gata3-deficient fetal liver hematopoietic precursors lack all intestinal RORγt+ ILC3 subsets, and these mice show defective production of IL-22 early after infection with the intestinal pathogen Citrobacter rodentium, leading to impaired survival. Further analyses demonstrated that ILC3 development requires cell-intrinsic Gata3 expression in fetal liver hematopoietic precursors. Our results demonstrate that Gata3 plays a generalized role in ILC lineage determination and is critical for the development of gut RORγt+ ILC3 subsets that maintain mucosal barrier homeostasis. These results further extend the paradigm of Gata3-dependent regulation of diversified innate ILC and adaptive T cell subsets. PMID:24419270

  5. GATA3 expression correlates with poor prognosis and tumor-associated macrophage infiltration in peripheral T cell lymphoma

    PubMed Central

    Luo, Yunping; Zhong, Dingrong; Luo, Yufeng; Zhou, Daobin

    2016-01-01

    Peripheral T cell lymphoma (PTCL) is an aggressive form of non-Hodgkin's lymphoma characterized by a poor prognosis. In this study, we examined the prognostic value of two T-cell-specific transcription factors, GATA3 and T-bet, in PTCL, uncovered the pathogenesis of PTCL, and investigated new PTCL therapeutic targets. Samples from 109 PTCL patients were examined for expression of GATA3, T-bet and CD68. High GATA3 expression correlated with poor survival in PTCL patients and with tumor-associated macrophage (TAM) infiltration, as indicated by the presence of CD68-positive cells. Multivariate analysis further confirmed that high GATA3 expression and Eastern Cooperative Oncology Group (ECOG) scores higher than 2 were independent predictors of patient survival. Using lentiviral transfection to induce stable GATA3 knockdown in a PTCL cell line, we observed that GATA-3 knockdown in Hut78 cells decreased levels of IL4, IL5, IL13 and VEGF mRNA and reduced the number of co-cultured U937 cells that differentiated towards the M2 phenotype. These results suggest that high GATA3 expression is a predictor of a poor prognosis in PTCL, and that T lymphoma cells promote M2-type macrophage differentiation through a GATA3-dependent mechanism. PMID:27589565

  6. Hierarchical IL-5 expression defines a subpopulation of highly differentiated human Th2 cells.

    PubMed

    Upadhyaya, Bhaskar; Yin, Yuzhi; Hill, Brenna J; Douek, Daniel C; Prussin, Calman

    2011-09-15

    Each of the three Th2 cytokine genes, IL-4, IL-5, and IL-13, has different functions. We hypothesized that Th2 heterogeneity could yield Th2 subpopulations with different cytokine expression and effector functions. Using multiple approaches, we demonstrate that human Th2 cells are composed of two major subpopulations: a minority IL-5(+) (IL-5(+), IL-4(+), IL-13(+)) and majority IL-5(-) Th2 (IL-5(-), IL-4(+), IL-13(+)) population. IL-5(+) Th2 cells comprised only 20% of all Th2 cells. Serial rounds of in vitro differentiation initially yielded IL-5(-) Th2, but required multiple rounds of differentiation to generate IL-5(+) Th2 cells. IL-5(+) Th2 cells expressed less CD27 and greater programmed cell death-1 than IL-5(-) Th2 cells, consistent with their being more highly differentiated, Ag-exposed memory cells. IL-5(+) Th2 cells expressed greater IL-4, IL-13, and GATA-3 relative to IL-5(-) Th2 cells. GATA-3 and H3K4me(3) binding to the IL5 promoter (IL5p) was greater in IL-5(+) relative to IL-5(-) Th2 cells, whereas there was no difference in their binding to the IL4p and IL13p. Conversely, H3K27me(3) binding to the IL5p was greater in IL-5(-) Th2 cells. These findings demonstrate Th2 lineage heterogeneity, in which the IL5 gene is regulated in a hierarchical manner relative to other Th2 genes. IL-5(+) Th2 cells are phenotypically distinct and have epigenetic changes consistent with greater IL5p accessibility. Recurrent antigenic exposure preferentially drives the differentiation of IL-5(+) Th2 cells. These results demonstrate that IL-5(+) and IL-5(-) Th2 cells, respectively, represent more and less highly differentiated Th2 cell subpopulations. Such Th2 subpopulations may differentially contribute to Th2-driven pathology.

  7. Akt1-mediated Gata3 phosphorylation controls the repression of IFNγ in memory-type Th2 cells

    PubMed Central

    Hosokawa, Hiroyuki; Tanaka, Tomoaki; Endo, Yusuke; Kato, Miki; Shinoda, Kenta; Suzuki, Akane; Motohashi, Shinichiro; Matsumoto, Masaki; Nakayama, Keiichi I.; Nakayama, Toshinori

    2016-01-01

    Th2 cells produce Th2 cytokines such as IL-4, IL-5 and IL-13, but repress Th1 cytokine IFNγ. Recent studies have revealed various distinct memory-type Th2 cell subsets, one of which produces a substantial amount of IFNγ in addition to Th2 cytokines, however it remains unclear precisely how these Th2 cells produce IFNγ. We herein show that phosphorylation of Gata3 at Ser308, Thr315 and Ser316 induces dissociation of a histone deacetylase Hdac2 from the Gata3/Chd4 repressive complex in Th2 cells. We also identify Akt1 as a Gata3-phosphorylating kinase, and the activation of Akt1 induces derepression of Tbx21 and Ifng expression in Th2 cells. Moreover, T-bet-dependent IFNγ expression in IFNγ-producing memory Th2 cells appears to be controlled by the phosphorylation status of Gata3 in human and murine systems. Thus, this study highlights the molecular basis for posttranslational modifications of Gata3 that control the regulation of IFNγ expression in memory Th2 cells. PMID:27053161

  8. Differential expression of GATA-3 in urothelial carcinoma variants.

    PubMed

    Liang, Yu; Heitzman, Joseph; Kamat, Ashish M; Dinney, Colin P; Czerniak, Bogdan; Guo, Charles C

    2014-07-01

    GATA binding protein 3 (GATA-3) is a novel immunohistochemical marker for urothelial carcinoma (UC); however, few studies have investigated GATA-3's role as a marker for UC variants. We used immunohistochemistry to assess GATA-3 expression in different UC variants, including micropapillary (n = 46), sarcomatoid (n = 43), small cell carcinoma (n = 22), and plasmacytoid (n = 16) variants, and we also compared GATA-3 expression in conventional bladder UC (n = 103) to that in squamous cell carcinoma (n = 14). GATA-3 expression was present in 70% (72/103) of conventional bladder UCs and highly concordant between matched primary and metastatic UCs. The GATA-3 expression levels of the micropapillary variants (57%; 26/46) and plasmacytoid variants (44%; 7/16) were not significantly different from that of conventional UC. However, the GATA-3 expression levels of the sarcomatoid variants (16%; 7/43) and small cell carcinoma variants (5%; 1/22), which only weakly expressed the protein, were significantly lower than that of conventional UC (P < .001). Only 7% of squamous cell carcinomas (1/14) expressed GATA-3, and it was also significantly lower than that of conventional UC (P < .001). GATA-3 expression was not significantly associated with tumor stage or patients' clinical outcomes. In conclusion, GATA-3 expression differed among UC variants. GATA-3 is a useful marker for confirming the urothelial origin of micropapillary and plasmacytoid UC variants but not that of sarcomatoid or small cell carcinoma variants. GATA-3 can also be used in differentiating UC from squamous cell carcinoma.

  9. Rectal Delivery of a DNAzyme That Specifically Blocks the Transcription Factor GATA3 and Reduces Colitis in Mice.

    PubMed

    Popp, Vanessa; Gerlach, Katharina; Mott, Stefanie; Turowska, Agnieszka; Garn, Holger; Atreya, Raja; Lehr, Hans-Anton; Ho, I-Cheng; Renz, Harald; Weigmann, Benno; Neurath, Markus F

    2017-01-01

    GATA3 is a transcription factor that regulates T-cell production of cytokines. We investigated the role of GATA3 in development of colitis in mice. We performed quantitative polymerase chain reaction and immunofluorescence analyses of colon tissues from patients with Crohn's disease (n = 61) or ulcerative colitis (UC, n = 74) or from patients without inflammatory bowel diseases (n = 22), to measure levels of GATA3. Colitis was induced by administration of oxazolone or 2,4,6-trinitrobenzenesulfonic acid to control mice, mice with T-cell-specific deletion of GATA3, and mice with deletion of tumor necrosis factor receptor (TNFR) 1 and TNFR2 (TNFR double knockouts); some mice were given a GATA3-specific DNAzyme (hgd40) or a control DNAzyme via intrarectal administration, or systemic injections of an antibody to TNF before or during sensitization and challenge phase of colitis induction. Colon tissues were collected and immunofluorescence and histochemical analyses were performed. Lamina propria mononuclear cells and T cells were isolated and analyzed by flow cytometry or cytokine assays. Colonic distribution of labeled DNAzyme and inflammation were monitored by in vivo imaging (endoscopy) of mice. Levels of GATA3 messenger RNA were higher in colon tissues from patients with UC, but not ileal Crohn's disease, than control tissues; levels of GATA3 correlated with levels of inflammatory cytokines (interleukin [IL] 9, IL17A, IL6, IL5, IL4, IL13, and TNF). We observed increased expression of GATA3 by lamina propria T cells from mice with colitis compared with controls. Mice with T-cell-specific deletion of GATA3 did not develop colitis and their colonic tissues did not produce inflammatory cytokines (IL6, IL9, or IL13). The DNAzyme hgd40 inhibited expression of GATA3 messenger RNA by unstimulated and stimulated T cells, and distributed throughout the inflamed colons of mice with colitis. Colon tissues from mice given hgd40 had reduced expression of GATA3 messenger RNA

  10. T-bet and GATA3 orchestrate Th1 and Th2 differentiation through lineage-specific targeting of distal regulatory elements

    PubMed Central

    Kanhere, Aditi; Hertweck, Arnulf; Bhatia, Urvashi; Gökmen, M. Refik; Perucha, Esperanza; Jackson, Ian; Lord, Graham M.; Jenner, Richard G.

    2012-01-01

    T-bet and GATA3 regulate the CD4+ T cell Th1/Th2 cell fate decision but little is known about the interplay between these factors outside of the murine Ifng and Il4/Il5/Il13 loci. Here we show that T-bet and GATA3 bind to multiple distal sites at immune regulatory genes in human effector T cells. These sites display markers of functional elements, act as enhancers in reporter assays and are associated with a requirement for T-bet and GATA3. Furthermore, we demonstrate that both factors bind distal sites at Tbx21 and that T-bet directly activates its own expression. We also show that in Th1 cells, GATA3 is distributed away from Th2 genes, instead occupying T-bet binding sites at Th1 genes, and that T-bet is sufficient to induce GATA3 binding at these sites. We propose these aspects of T-bet and GATA3 function are important for Th1/Th2 differentiation and for understanding transcription factor interactions in other T cell lineage decisions. PMID:23232398

  11. GATA3 immunohistochemical expression in salivary gland neoplasms.

    PubMed

    Schwartz, Lauren E; Begum, Shahnaz; Westra, William H; Bishop, Justin A

    2013-12-01

    GATA3 is a zinc finger transcription factor that regulates the normal development of many tissues and cell types. Recent studies have shown that immunohistochemical nuclear staining for GATA3 among tumors is highly restricted to carcinomas of breast and urothelial origin; however salivary gland tumors have not been tested. Given that breast and salivary gland tissues are very similar with respect to embryologic development and structure, we performed GATA3 staining on a spectrum of salivary gland neoplasms. GATA3 immunohistochemistry was performed on a diverse collection of 180 benign and malignant salivary gland neoplasms including 10 acinic cell carcinomas, 2 adenocarcinomas not otherwise specified, 41 adenoid cystic carcinomas, 2 epithelial-myoepithelial carcinomas, 1 low grade cribriform cystadenocarcinoma, 15 mammary analogue secretory carcinomas, 7 metastatic squamous cell carcinomas, 27 mucoepidermoid carcinomas, 2 oncocytic carcinomas, 5 oncocytomas, 34 pleomorphic adenomas, 4 polymorphous low grade adenocarcinomas, 25 salivary duct carcinomas, and 5 Warthin tumors. Staining for GATA3 was observed in 92/180 (51 %) of salivary gland tumors. GATA3 staining was observed in most of the tumor types, but diffuse immunolabeling was consistently seen in salivary duct carcinoma (25 of 25) and mammary analogue secretory carcinoma (15 of 15)-the two tumor types that most closely resemble breast neoplasia. Background benign salivary gland tissue was also usually weakly positive in both acini and ducts. GATA3 immunostaining is not restricted to tumors of breast and urothelial origin. Rather, it is expressed across many different types of salivary gland neoplasms. As a result, salivary gland origin should be considered in the differential diagnosis of a GATA3-positive carcinoma, particularly in the head and neck. Although GATA3 immunohistochemistry is not helpful in resolving the differential diagnosis between a primary salivary gland neoplasm and metastatic breast

  12. Expression of GATA-3 During Lymphocyte Differentiation and Mouse Embryogenesis

    PubMed Central

    Oosterwegel, Mariëtte; Timmerman, Janneke; Leiden, Jeffrey

    1992-01-01

    The GATA family of C4 zinc-finger transcription factors has been implicated in tissuespecific gene regulation in birds and mammals. One of the members of this family, GATA-3, is reportedly expressed specifically in the T-cell lineage, where it interacts with GATA motifs in the TCR-αα, TCR-β/, and TCR-δ enhancers, thereby controlling the T-cell phenotype. To evaluate the differentiation control properties of GATA-3, we have now documented its expression pattern during lymphoid differentiation and murine embryogenesis. The onset of GATA-3 expression in the lymphoid lineage was studied in a panel of lymphoid (precursor) cell lines by Northern blot analysis. GATA-3 was uniquely expressed in T-lineage lymphocytes expressing TCR and CD3 genes; it was absent from TCR/CD3 mRNA-negative prothymocytes and from all B-lineage cells. In order to obtain information on the expression of GATA-3 outside the immune system, in situ hybridization was performed on mouse embryos on day 11.5-14.5 of gestation. GATA-3 mRNA was detected in fetal thymus and in erythroid cells. Outside the haemopoietic system, we detected GATA-3 mRNA throughout the central nervous system, in kidney, in the epidermis, lens fibers, the inner ear, whisker follicles, and in the primary palate. These data provide new clues about the potential role of GATA-3 during mouse development, and will aid the interpretation of currently ongoing gene knockout experiments. PMID:1343100

  13. GATA3 Expression Is a Poor Prognostic Factor in Soft Tissue Sarcomas

    PubMed Central

    Haraguchi, Toshiaki; Miyoshi, Hiroaki; Hiraoka, Koji; Yokoyama, Shintaro; Ishibashi, Yukinao; Hashiguchi, Toshihiro; Matsuda, Koutaro; Hamada, Tetsuya; Okawa, Takahiro; Shiba, Naoto; Ohshima, Koichi

    2016-01-01

    Objective Recent studies have investigated the significance of GATA3 expression in patients with various malignant tumors. However, no previous studies have evaluated the clinicopathological importance of GATA3 expression in soft tissue sarcomas (STS) patients. Methods We evaluated GATA3 expression in 76 STS cases using immunohistochemical analysis, and statistically compared clinicopathological characteristics between GATA3-positive and GATA3-negative cases. Result GATA3-positive expression was significantly associated with a higher mitotic count (P < 0.0001). Disease-free survival (DFS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0104). Overall survival (OS) of GATA3-positive cases was significantly shorter than that of cases without GATA3 expression (P = 0.0006). GATA3-positive expression was significantly associated with shorter DFS in both univariate analysis (hazard ratio [HR], 2.719; P = 0.012) and multivariate analysis (HR, 2.711; P = 0.014). GATA3-positive expression was also significantly associated with worse OS in both univariate analysis (HR, 5.730; P = 0.0007) and multivariate analysis (HR, 5.789; P = 0.0008). Conclusion These results indicate that GATA3 is an independent prognostic factor and suggest that evaluation of GATA3 expression might enable more effective clinical follow-up using prognostic stratification of STS patients. PMID:27249072

  14. Gata3 is a critical regulator of cochlear wiring

    PubMed Central

    Appler, Jessica M.; Lu, Cindy C.; Druckenbrod, Noah R.; Yu, Wei-Ming; Koundakjian, Edmund J.; Goodrich, Lisa V.

    2013-01-01

    Spiral ganglion neurons (SGNs) play a key role in hearing by rapidly and faithfully transmitting signals from the cochlea to the brain. Identification of the transcriptional networks that ensure the proper specification and wiring of SGNs during development will lay the foundation for efforts to rewire a damaged cochlea. Here, we show that the transcription factor Gata3, which is expressed in SGNs throughout their development, is essential for formation of the intricately patterned connections in the cochlea. We generated conditional knock-out mice in which Gata3 is deleted after SGNs are specified. Cochlear wiring is severely disrupted in these animals, with premature extension of neurites that follow highly abnormal trajectories towards their targets, as shown using in vitro neurite outgrowth assays together with time-lapse imaging of whole embryonic cochleae. Expression profiling of mutant neurons revealed a broad shift in gene expression towards a more differentiated state, concomitant with minor changes in SGN identity. Thus, Gata3 appears to serve as an “intermediate regulator” that guides SGNs through differentiation and preserves the auditory fate. As the first auditory-specific regulator of SGN development, Gata3 provides a useful molecular entry point for efforts to engineer SGNs for the restoration of hearing. PMID:23426694

  15. Compound A, a Dissociated Glucocorticoid Receptor Modulator, Inhibits T-bet (Th1) and Induces GATA-3 (Th2) Activity in Immune Cells

    PubMed Central

    Ferraz-de-Paula, Viviane; Palermo-Neto, Joao; Castro, Carla N.; Druker, Jimena; Holsboer, Florian; Perone, Marcelo J.; Gerlo, Sarah; De Bosscher, Karolien; Haegeman, Guy; Arzt, Eduardo

    2012-01-01

    Background Compound A (CpdA) is a dissociating non-steroidal glucocorticoid receptor (GR) ligand which has anti-inflammatory properties exerted by down-modulating proinflammatory gene expression. By favouring GR monomer formation, CpdA does not enhance glucocorticoid (GC) response element-driven gene expression, resulting in a reduced side effect profile as compared to GCs. Considering the importance of Th1/Th2 balance in the final outcome of immune and inflammatory responses, we analyzed how selective GR modulation differentially regulates the activity of T-bet and GATA-3, master drivers of Th1 and Th2 differentiation, respectively. Results Using Western analysis and reporter gene assays, we show in murine T cells that, similar to GCs, CpdA inhibits T-bet activity via a transrepressive mechanism. Different from GCs, CpdA induces GATA-3 activity by p38 MAPK-induction of GATA-3 phosphorylation and nuclear translocation. CpdA effects are reversed by the GR antagonist RU38486, proving the involvement of GR in these actions. ELISA assays demonstrate that modulation of T-bet and GATA-3 impacts on cytokine production shown by a decrease in IFN-γ and an increase in IL-5 production, respectively. Conclusions Taken together, through their effect favoring Th2 over Th1 responses, particular dissociated GR ligands, for which CpdA represents a paradigm, hold potential for the application in Th1-mediated immune disorders. PMID:22496903

  16. GATA-3 expression in male and female breast cancers: comparison of clinicopathologic parameters and prognostic relevance.

    PubMed

    Gonzalez, Raul S; Wang, Jason; Kraus, Teresa; Sullivan, Harold; Adams, Amy L; Cohen, Cynthia

    2013-06-01

    Expression of GATA-3 in female breast cancers has been linked to estrogen receptor (ER) expression and, in turn, to improved outcomes. However, GATA-3 has not been studied in male breast cancers. Nineteen male breast carcinomas (average age: 63 years) and 164 female breast carcinomas (average age: 57 years) were immunostained for GATA-3. Results were compared to age, tumor size, tumor grade, lymph node status, distant metastases, survival, and positivity for ER, progesterone receptor (PR), and HER2/neu. Six of 19 (31.6%) male and 135 of 164 (82.3%) female breast carcinomas were GATA-3 positive (P < .001). In women, 82.1% of GATA-3-positive cancers were grade 1 or 2, whereas 75.9% of GATA-3-negative cancers were grade 3 (P < .001); no such significant correlation was seen in men. Unlike female cancers, male cancers showed no correlation between GATA-3 positivity and ER positivity, PR positivity, or distant metastases. Nodal metastasis and HER2 status were not linked to GATA-3 in either sex. Seventeen (89.5%) men were alive at follow-up (average: 61 months); only 1 died of disease. Most women (159/164, 97.0%) were also alive at follow-up (average: 41 months), with a higher proportion of GATA-3-negative women dead than GATA-3-positive women (3/29 [10.3%] vs. 2/135 [1.5%], P = .039). GATA-3 is expressed less often in male than female breast cancers. Male cancers show no correlation between GATA-3 positivity and ER/PR positivity or distant metastases, unlike female cancers. There appears to be no link between GATA-3 positivity and survival in men, whereas in women, GATA-3-positive tumors are typically lower grade with a better prognosis.

  17. Higher Levels of GATA3 Predict Better Survival in Women with Breast Cancer

    PubMed Central

    Yoon, Nam K.; Maresh, Erin L.; Shen, Dejun; Elshimali, Yahya; Apple, Sophia; Horvath, Steve; Mah, Vei; Bose, Shikha; Chia, David; Chang, Helena R.; Goodglick, Lee

    2010-01-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. GATA3 in particular is necessary for mammary gland maturation, and its loss has been implicated in breast cancer development. Our goal was to validate the ability of GATA3 expression to predict survival in breast cancer patients. Protein expression of GATA3 was analyzed on a high density tissue microarray consisting of 242 cases of breast cancer. We associated GATA3 expression with patient outcomes and clinicopathological variables. Expression of GATA3 was significantly increased in breast cancer, in situ lesions, and hyperplastic tissue compared to normal breast tissue. GATA3 expression decreased with increasing tumor grade. Low GATA3 expression was a significant predictor of disease-related death in all patients, as well as in subgroups of estrogen receptor positive or low grade patients. Additionally, low GATA3 expression correlated with increased tumor size and estrogen and progesterone receptor negativity. GATA3 is an important predictor of disease outcome in breast cancer patients. This finding has been validated in a diverse set of populations. Thus, GATA3 expression has utility as a prognostic indicator in breast cancer. PMID:21078439

  18. Cloning, expression and biological activity of equine interleukin (IL)-5.

    PubMed

    Cunningham, F M; Vandergrifft, E; Bailey, S R; Sepulveda, M F; Goode, N T; Horohov, D W

    2003-09-15

    The cytokine, interleukin (IL)-5 stimulates eosinophil differentiation, activation and survival and can prime these cells, increasing the response to other mediators. In view of its many effects on eosinophils, IL-5 has been implicated in the pathogenesis of allergic disease in man. Here we report the cloning of equine IL-5 and expression of the recombinant protein by transfection of Chinese hamster ovary (CHO) cells. The cloned cDNA sequence consisted of 405 nucleotides and encoded a protein of 135 amino acids. There is >85% identity with feline, bovine, ovine, canine, and human IL-5 sequences at the nucleotide and protein level. Supernatants containing equine IL-5 were also examined for biological activity. CHO supernatant containing equine recombinant (eqr) IL-5, like the human ortholog (hrIL-5), induced concentration dependent equine eosinophil adherence to autologous serum-coated plastic (9.7+/-1.5% with a 1:100 dilution of eqrIL-5 and 9.1+/-1.6% adherence with 1 nM hrIL-5; n = 4). The eqr protein also caused concentration dependent superoxide production (11.9+/-2.4 nmol (reduced cytochrome (cyt) C)/10(6) cells at a 1:50 dilution, n = 4). In contrast, hrIL-5 only caused significant superoxide production when diluted in conditioned CHO medium, an effect that was inhibited by the anti-human mAb, TRFK5 (4.4+/-0.3 versus 0.3+/-0.4 nmol/10(6) cells for 0.5 nM hrIL-5 in the presence of the isotype matched IgG1 control (10 microM) and TRFK5 (10 microM), respectively). TRFK5 also significantly inhibited hrIL-5 induced adherence at concentrations of 0.3 microg/ml and above but had no significant inhibitory effect on either superoxide or adherence caused by eqrIL-5. These results demonstrate that equine IL-5 expressed by CHO cells stimulates equine eosinophils, suggesting that this cytokine could play a role in eosinophil recruitment and activation in equine allergic disease. The anti-human and murine moAb TRFK5 does not appear to recognise the equine protein.

  19. Transcription repressor HANABA TARANU controls flower development by integrating the actions of multiple hormones, floral organ specification genes, and GATA3 family genes in Arabidopsis.

    PubMed

    Zhang, Xiaolan; Zhou, Yun; Ding, Lian; Wu, Zhigang; Liu, Renyi; Meyerowitz, Elliot M

    2013-01-01

    Plant inflorescence meristems and floral meristems possess specific boundary domains that result in proper floral organ separation and specification. HANABA TARANU (HAN) encodes a boundary-expressed GATA3-type transcription factor that regulates shoot meristem organization and flower development in Arabidopsis thaliana, but the underlying mechanism remains unclear. Through time-course microarray analyses following transient overexpression of HAN, we found that HAN represses hundreds of genes, especially genes involved in hormone responses and floral organ specification. Transient overexpression of HAN also represses the expression of HAN and three other GATA3 family genes, HANL2 (HAN-LIKE 2), GNC (GATA, NITRATE-INDUCIBLE, CARBON-METABOLISM-INVOLVED), and GNL (GNC-LIKE), forming a negative regulatory feedback loop. Genetic analysis indicates that HAN and the three GATA3 family genes coordinately regulate floral development, and their expression patterns are partially overlapping. HAN can homodimerize and heterodimerize with the three proteins encoded by these genes, and HAN directly binds to its own promoter and the GNC promoter in vivo. These findings, along with the fact that constitutive overexpression of HAN produces an even stronger phenotype than the loss-of-function mutation, support the hypothesis that HAN functions as a key repressor that regulates floral development via regulatory networks involving genes in the GATA3 family, along with genes involved in hormone action and floral organ specification.

  20. Picroside II Attenuates Airway Inflammation by Downregulating the Transcription Factor GATA3 and Th2-Related Cytokines in a Mouse Model of HDM-Induced Allergic Asthma

    PubMed Central

    Kim, Jin seok; Lee, Jae-Won; Park, Hyun Ah; Ryu, Hyung Won; Lee, Su Ui; Hwang, Kwang Woo; Yun, Won-Kee; Kim, Hyoung-Chin; Ahn, Kyung-Seop; Oh, Sei-Ryang

    2016-01-01

    Picroside II isolated from Pseudolysimachion rotundum var. subintegrum has been used as traditional medicine to treat inflammatory diseases. In this study, we assessed whether picroside II has inhibitory effects on airway inflammation in a mouse model of house dust mite (HDM)-induced asthma. In the HDM-induced asthmatic model, picroside II significantly reduced inflammatory cell counts in the bronchoalveolar lavage fluid (BALF), the levels of total immunoglobulin (Ig) E and HDM-specific IgE and IgG1 in serum, airway inflammation, and mucus hypersecretion in the lung tissues. ELISA analysis showed that picroside II down-regulated the levels of Th2-related cytokines (including IL-4, IL-5, and IL-13) and asthma-related mediators, but it up-regulated Th1-related cytokine, IFNγ in BALF. Picroside II also inhibited the expression of Th2 type cytokine genes and the transcription factor GATA3 in the lung tissues of HDM-induced mice. Finally, we demonstrated that picroside II significantly decreased the expression of GATA3 and Th2 cytokines in developing Th2 cells, consistent with in vivo results. Taken together, these results indicate that picroside II has protective effects on allergic asthma by reducing GATA3 expression and Th2 cytokine bias. PMID:27870920

  1. Insufficient interleukin-12 signalling favours differentiation of human CD4+ and CD8+ T cells into GATA-3+ and GATA-3+ T-bet+ subsets in humanized mice

    PubMed Central

    Billerbeck, Eva; Labitt, Rachael N; Vega, Kevin; Frias-Staheli, Natalia; Dorner, Marcus; Xiao, Jing W; Rice, Charles M; Ploss, Alexander

    2014-01-01

    Differentiation of CD4+ T cells into type 1 or type 2 subsets is mediated by the expression of the opposing lineage defining transcription factors T-bet and GATA-3. However, the existence of GATA-3+ T-bet+ CD4+ T cells in mice suggests functional plasticity of these subsets. Little is known about type 1 and type 2 plasticity of human T-cell subsets in vivo. Here, we show that in the xenogeneic environment of humanized mice, which lacks a functional immune-regulatory network, human CD4+ and, notably, CD8+ T cells preferentially differentiate into interleukin (IL)-4+ GATA-3+ and IL-4+ interferon-γ+ GATA-3+ T-bet+ subsets. Treatment with recombinant human IL-12 or expansion of IL-12-producing human dendritic cells in vivo reverted this phenotype and led to the down-regulation of GATA-3 expression. These changes also correlated with improved antiviral immune responses in humanized mice. In conclusion, our study shows the capacity of human CD4+ and CD8+ T cells for stable co-expression of GATA-3 and T-bet in humanized mice and reveals a critical role for IL-12 in regulating this phenotype. PMID:24766459

  2. Similarity of GATA-3 Expression between Rat and Human Mammary Glands.

    PubMed

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Tsubura, Airo

    2014-07-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans.

  3. Similarity of GATA-3 Expression between Rat and Human Mammary Glands

    PubMed Central

    Kinoshita, Yuichi; Yoshizawa, Katsuhiko; Emoto, Yuko; Yuki, Michiko; Yuri, Takashi; Shikata, Nobuaki; Tsubura, Airo

    2014-01-01

    The GATA family members are zinc finger transcription factors involved in cell differentiation and proliferation. In particular, GATA-3 is necessary for mammary gland maturation and is a useful marker in the characterization of mammary carcinoma in humans. The expression of GATA-3 protein in normal mammary glands, fibroadenomas and carcinomas was immunohistochemically compared in female rats and humans. In normal mammary glands of rats and humans, scattered luminal cells in the acini and whole ductal epithelial cells were positive for GATA-3 in the nuclei. No positive cells were detected in rat or human fibroadenomas. In rat and human mammary carcinomas, the nuclei of proliferating luminal-derived cancer cells expressed GATA-3. Therefore, GATA-3 protein is a candidate marker for mammary carcinoma in rats as well as humans. PMID:25352719

  4. GATA-3 and FOXA1 expression is useful to differentiate breast carcinoma from other carcinomas.

    PubMed

    Davis, Drew G; Siddiqui, Momin T; Oprea-Ilies, Gabriela; Stevens, Keith; Osunkoya, Adeboye O; Cohen, Cynthia; Li, Xiaoxian Bill

    2016-01-01

    GATA-3, a member of the GATA family of zinc-finger DNA binding proteins, and FOXA1, a member of the forkhead transcription factor family, are both associated with estrogen receptor expression. Both GATA-3 and FOXA1 are useful markers for breast carcinoma, but their expression in the different breast cancer subtypes and other neoplasms has not been thoroughly evaluated. We examined the expression of GATA-3 and FOXA1 in estrogen receptor-positive, Her2/neu-positive, and triple-negative breast carcinomas as well as in 10 other common carcinomas, including hepatocellular, colonic, pancreatic, gastric, endometrial (endometrioid), lung, prostatic, renal cell, urothelial, and ovarian serous carcinomas. Primary and metastatic melanomas and mesotheliomas were also evaluated. GATA-3 and FOXA1 staining of estrogen receptor-positive breast carcinomas was seen in 96.6% and 96.2%, respectively. In triple-negative breast carcinomas, GATA-3 and FOXA1 staining was seen in 21.6% and 15.9%, respectively. Among the other tumors, GATA-3 staining was only seen in urothelial carcinoma (70.9%) and FOXA1 staining was only seen in prostatic (87.5%), urothelial (5.1%) carcinomas, and mesotheliomas (40.0%). In conclusion, GATA-3 and FOXA1 are excellent breast carcinoma markers; however, their utility is limited in the triple-negative subtype. The utility of FOXA1 in diagnosing prostatic carcinoma and mesothelioma warrants further investigation.

  5. Interaction between ANXA1 and GATA-3 in Immunosuppression of CD4+ T Cells

    PubMed Central

    Huang, Peng; Zhou, Yuxiang; Liu, Zan

    2016-01-01

    Decreased Th1/Th2 ratio is one of the major characteristics of immunosuppression in sepsis. Both membrane adhesive protein Annexin-A1 (ANXA1) and transcription factor GATA-3 have been reported to play important roles in T cell differentiation. However, the relationship between ANXA1 and GATA-3 in Th1/Th2 shift is unknown. Our study investigated the interaction effects of ANXA1 and GATA-3 to influence T cell differentiation in CD4+ T cells. We found that GATA-3 and ANXA1 were coexpressed on Th0/Th1/Th2 cytoplasm and nuclear. Overexpressed ANXA1 significantly increased the expression of IFNγ and reduced IL-4 expression in T cells, while ANXA1-silenced T cells exhibited decreased production of IFNγ and increased production of IL-4. Knockdown of ANXA1 promoted higher expression level of GATA-3 and low level of T-box transcription factor (T-bet/Tbx21). Further study demonstrated that ANXA1 regulated GATA-3 expression through the formyl peptide receptor like-1 (FPRL-1) downstream signaling pathways ERK and PKB/Akt. These results suggested that ANXA1 modulates GATA-3/T-bet expression induced Th0/Th1 differentiation. Moreover, we found that GATA-3 inhibited ANXA1 expression by binding to its promoter for the first time. It is proposed that the interactions between ANXA1 and GATA-3 may provide clues to understand the immunosuppression and have potential as new therapeutic targets in immunotherapy after sepsis. PMID:27833268

  6. GATA3 Expression in Normal Skin and in Benign and Malignant Epidermal and Cutaneous Adnexal Neoplasms.

    PubMed

    Mertens, Richard B; de Peralta-Venturina, Mariza N; Balzer, Bonnie L; Frishberg, David P

    2015-12-01

    Initial investigations reported GATA3 to be a sensitive and relatively specific marker for mammary and urothelial carcinomas. Recently, GATA3 expression has been described in several other epithelial tumors. However, there has been only limited investigation of GATA3 expression in cutaneous epithelial tumors. The objective of this study was to examine the immunohistochemical expression of GATA3 in a wide variety of cutaneous epithelial neoplasms. GATA3 expression was evaluated in 99 benign and 63 malignant cutaneous epithelial tumors. GATA3 was consistently and usually strongly expressed in clear cell acanthoma, trichofolliculoma, trichoepithelioma, trichilemmoma, sebaceous adenoma, sebaceoma, apocrine hidrocystoma, apocrine tubular papillary adenoma, hidradenoma papilliferum, and syringocystadenoma papilliferum. Hidradenomas exhibited variable positive staining. Most poromas, syringomas, chondroid syringomas, cylindromas, and spiradenomas were negative or only focally and weakly positive. Focal staining was present in all pilomatrixomas. Thirteen of 14 basal cell carcinomas, 21 of 24 squamous carcinomas, and all 6 sebaceous carcinomas exhibited positive staining. The 1 apocrine carcinoma, both mucinous carcinomas, and 2 of 3 microcystic adnexal carcinomas also exhibited positive staining, whereas the 1 eccrine porocarcinoma and the 1 adenoid cystic carcinoma were negative. One of 11 Merkel cell carcinomas exhibited focal weak staining. Our findings demonstrate that GATA3 is expressed in a wide variety of benign and malignant cutaneous epithelial neoplasms. In addition to carcinomas of breast and urothelial origin and other more recently described GATA3-positive tumors, the differential diagnosis of a metastatic tumor of unknown primary origin that expresses GATA3 should also include a carcinoma of cutaneous epithelial origin.

  7. Significance of GATA-3 expression in outcomes of patients with breast cancer who received systemic chemotherapy and/or hormonal therapy and clinicopathologic features of GATA-3-positive tumors.

    PubMed

    Gulbahce, H Evin; Sweeney, Carol; Surowiecka, Maria; Knapp, Dennis; Varghese, Linda; Blair, Cindy K

    2013-11-01

    GATA-3 and estrogen receptor (ER) are involved in a positive cross-regulatory loop and are frequently coexpressed in breast cancers. GATA-3 expression was shown to be an independent predictor of overall and disease-free survival in some studies, whereas others showed no difference. However, the studies used different cutoff values for determining GATA-3 positivity and analyzed outcomes in patients who received systemic therapy together with those who did not. We investigated GATA-3 expression and correlated clinicopathologic findings and outcomes in 516 women who received systemic chemotherapy and/or hormonal therapy. Nuclear staining of 1% or greater was considered positive for GATA-3, ER and progesterone receptor (PR). Of 516 cases, 436 (84.5%) were GATA-3+. GATA-3+ tumors were more likely to be grade 1 or 2, ER+, PR+, non-triple-negative phenotypes (all P < .0001), and higher stage (P = .01). ER-/GATA-3+ tumors, compared with ER-/GATA-3- tumors, had worse breast cancer survival (BCS) (P = .02) and a trend for worse overall survival (OS) (P = .05) in univariate analysis. However, there was no difference in OS and BCS between patients who received chemotherapy and/or hormonal therapy among GATA-3-positive and GATA-3-negative groups. GATA-3+ tumors are correlated with lower grade, ER+, PR+, and non-triple-negative phenotypes. Although there was no difference in OS and BCS between GATA-3-positive and GATA-3-negative groups, there was an adverse effect of GATA-3 expression in the ER-negative subgroup of patients who received systemic therapy.

  8. Dynamic expression of T-bet and GATA3 by regulatory T cells maintains immune tolerance

    PubMed Central

    Yu, Fang; Sharma, Suveena; Edwards, Julie; Feigenbaum, Lionel; Zhu, Jinfang

    2014-01-01

    Regulatory T (Treg) cells can express the transcription factors T-bet and GATA3 but the function of this expression and whether such cells represent stable subsets is still unknown. By using multiple reporter tools, we show that the expression of T-bet and GATA3 in Treg cells is dynamically influenced by the cytokine environment. Treg cell-specific deletion of either Tbx21 or Gata3 genes singly did not result in loss of Treg cell functions; however, mice with combined deficiency of both genes in Treg cells developed severe autoimmune-like diseases. Loss of Treg cell function was correlated with RORγt transcription factor upregulation and reduced Foxp3 expression. Thus, in the steady state, activated Treg cells transiently upregulate either T-bet or GATA3 to maintain T cell homeostasis. PMID:25501630

  9. Differential Expression of T-bet and GATA3 in Egyptian Children with Idiopathic Thrombocytopenic Purpura.

    PubMed

    Hammam, Amira Ahmed; Ezzat, Dina Ahmed; Elwahab, Marwa Hamed Abd

    2016-12-01

    GATA3 and T-box (T-bet) expressed in T-cells are transcriptional factors that play a critical role in development of Th2 and Th1 immunity respectively. GATA3 is expressed during Th2 differentiation and T-bet is expressed exclusively in Th1 cells. Thus, a balance between GATA3 and T-bet is believed to control Th2/Th1 polarization. Therefore, the high expression of T-bet and low expression of GATA3 indicate the existence of Th1 polarization in children with acute immune thrombocytopenic purpura (ITP). This might be related to the regulation of T-bet and GATA3. The objective of this work was to study the expression of transcriptional factors T-bet and GATA3 m RNA in children with idiopathic thrombocytopenic purpura and correlate it with clinical findings, laboratory findings, and outcome of patients. In this study the expression of T-bet and GATA3 genes was analysed in 20 normal healthy individuals and 40 children with ITP (20 acute and 20 persistent) using reverse transcriptase polymerase chain reaction to investigate a possible relation, association or correlation with the type of ITP and prognosis. T-bet was expressed significantly in 60 % of acute ITP children (12/20) (P value 0.001) and not expressed in persistent ITP children (0/20), while GATA3 was expressed in 25 % of persistent ITP patients (5/20) (P value 0.017) and not expressed in acute ITP patients (0/20). Both genes were not detected in healthy controls. We concluded that the high expression of T-bet and the low expression of GATA3 indicate the existence of Th1 polarization in children with acute ITP. This might be related to the regulation of T-bet and GATA3. Intensive studies of abnormal cytokine profiles in ITP have led to cytokine therapies that exploit the effects of IFN-γ on Th2 cells, but such therapies are often ineffective to develop safe and effective therapeutic tools. Targeting specific molecules such as T-bet and GATA3 may be a novel therapeutic tool in ITP.

  10. Lineage-affiliated transcription factors bind the Gata3 Tce1 enhancer to mediate lineage-specific programs

    PubMed Central

    Ohmura, Sakie; Mizuno, Seiya; Oishi, Hisashi; Ku, Chia-Jui; Hermann, Mary; Hosoya, Tomonori; Takahashi, Satoru; Engel, James Douglas

    2016-01-01

    The transcription factor GATA3 is essential for the genesis and maturation of the T cell lineage, and GATA3 dysregulation has pathological consequences. Previous studies have shown that GATA3 function in T cell development is regulated by multiple signaling pathways and that the Notch nuclear effector, RBP-J, binds specifically to the Gata3 promoter. We previously identified a T cell–specific Gata3 enhancer (Tce1) lying 280 kb downstream from the structural gene and demonstrated in transgenic mice that Tce1 promoted T lymphocyte–specific transcription of reporter genes throughout T cell development; however, it was not clear if Tce1 is required for Gata3 transcription in vivo. Here, we determined that the canonical Gata3 promoter is insufficient for Gata3 transcriptional activation in T cells in vivo, precluding the possibility that promoter binding by a host of previously implicated transcription factors alone is responsible for Gata3 expression in T cells. Instead, we demonstrated that multiple lineage-affiliated transcription factors bind to Tce1 and that this enhancer confers T lymphocyte–specific Gata3 activation in vivo, as targeted deletion of Tce1 in a mouse model abrogated critical functions of this T cell–regulatory element. Together, our data show that Tce1 is both necessary and sufficient for critical aspects of Gata3 T cell–specific transcriptional activity. PMID:26808502

  11. Cooperation of Gata3, c-Myc and Notch in malignant transformation of double positive thymocytes.

    PubMed

    van Hamburg, Jan Piet; de Bruijn, Marjolein J W; Dingjan, Gemma M; Beverloo, H Berna; Diepstraten, Hans; Ling, Kam-Wing; Hendriks, Rudi W

    2008-06-01

    Gata transcription factors are critical regulators of proliferation and differentiation implicated in various human cancers, but specific genes activated by Gata proteins remain to be identified. We previously reported that enforced expression of Gata3 during T cell development in CD2-Gata3 transgenic mice induced CD4(+)CD8(+) double-positive (DP) T cell lymphoma. Here, we show that the presence of the DO11.10 T-cell receptor transgene, which directs DP cells towards the CD4 lineage, resulted in enhanced lymphoma development and a dramatic increase in thymocyte cell size in CD2-Gata3 transgenic mice. CD2-Gata3 DP cells expressed high levels of the proto-oncogene c-Myc but the Notch1 signaling pathway, which is known to induce c-Myc, was not activated. Gene expression profiling showed that in CD2-Gata3 lymphoma cells transcription of c-Myc and its target genes was further increased. A substantial fraction of CD2-Gata3 lymphomas had trisomy of chromosome 15, leading to an increased c-Myc gene dose. Interestingly, most lymphomas showed high expression of the Notch targets Deltex1 and Hes1, often due to activating Notch1 PEST domain mutations. Therefore, we conclude that enforced Gata3 expression converts DP thymocytes into a pre-malignant state, characterized by high c-Myc expression, whereby subsequent induction of Notch1 signaling cooperates to establish malignant transformation. The finding that Gata3 regulates c-Myc expression levels, in a direct or indirect fashion, may explain the parallel phenotypes of mice with overexpression or deficiency of either of the two transcription factors.

  12. GATA-3 is down-regulated in patients with clear cell renal carcinoma.

    PubMed

    Yang, F Q; Liu, M; Xu, Y F; Che, J P; Wang, G C; Zheng, J H; Li, X

    2013-09-01

    GATA-3 is a transcription factor involved in human growth and development. Recent studies found its association with breast cancer, however, its expression profile in renal cell carcinoma (RCC) has not been investigated. The study included 35 patients submitted to radical nephrectomy with confirmed pathological diagnosis of RCC. Normal control kidney tissues were obtained from 25 living kidney donors and tissues were biopsied before implantation. The majority of RCC samples were diagnosed as clear cell renal cell carcinoma (94.3%) except for 1 case of papillary RCC and 1 case of collecting duct carcinoma. GATA-3 expression was evaluated by quantitative PCR and Western blotting (WB) in RCC samples and normal kidneys respectively, immunohistochemical staining was performed as well. Meanwhile, the GATA-3 expression in two cancer cell lines (786-O, ACHN) and normal kidney epithelial cells (HK-2) was detected by PCR and WB. In addition, renal cancer cells and HK-2 cells were cultivated and detected by confocal microscopy for the exact intra-cellular localization of GATA-3. Data showed a significant down-regulation of GATA-3 expression present in neoplastic tissues compared with normal tissues; similarly, GATA-3 was significantly attenuated in all renal cancer cell lines compared with normal HK-2 cells. Confocal displayed a strong cytoplasmic immno-fluorescence activity of GATA-3 with peri-nuclear zone in HK-2, whereas the intensity in cancer cells was markedly weaker than that of HK-2. In summary, our present study clarifies that the aberrant expression profile of GATA-3 in human RCC is possibly involved with tumorigenesis, and the complicated mechanism is worthy of further investigation. Copyright © 2012 AEU. Published by Elsevier Espana. All rights reserved.

  13. An NK and T Cell Enhancer Lies 280 Kilobase Pairs 3′ to the Gata3 Structural Gene ▿

    PubMed Central

    Hosoya-Ohmura, Sakie; Lin, Yu-Hsuan; Herrmann, Mary; Kuroha, Takashi; Rao, Arvind; Moriguchi, Takashi; Lim, Kim-Chew; Hosoya, Tomonori; Engel, James Douglas

    2011-01-01

    Transcription factor GATA-3 is vital for multiple stages of T cell and natural killer (NK) cell development, and yet the factors that directly regulate Gata3 transcription during hematopoiesis are only marginally defined. Here, we show that neither of the Gata3 promoters, previously implicated in its tissue-specific regulation, is alone capable of directing Gata3 transcription in T lymphocytes. In contrast, by surveying large swaths of DNA surrounding the Gata3 locus, we located a cis element that can recapitulate aspects of the Gata3-dependent T cell regulatory program in vivo. This element, located 280 kbp 3′ to the structural gene, directs both T cell- and NK cell-specific transcription in vivo but harbors no other tissue activity. This novel, distant element regulates multiple major developmental stages that require GATA-3 activity. PMID:21383068

  14. ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression.

    PubMed

    Shahi, Payam; Wang, Chih-Yang; Lawson, Devon A; Slorach, Euan M; Lu, Angela; Yu, Ying; Lai, Ming-Derg; Gonzalez Velozo, Hugo; Werb, Zena

    2017-03-21

    The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to GATA3 promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for down-regulation of GATA3 via ZPO2. Through this modulation of GATA3 activity, ZPO2 promotes aggressive breast cancer development. Our data provide insight into a mechanism of GATA3 regulation, and identify ZPO2 as a possible candidate gene for future diagnostic and therapeutic strategies.

  15. Usefulness of GATA-3 as a marker of seminal epithelium in prostate biopsies.

    PubMed

    Ortiz-Rey, J A; Chantada-de la Fuente, D; Peteiro-Cancelo, M Á; Gómez-de María, C; San Miguel-Fraile, M P

    2017-04-28

    The incidental presence of seminal vesicle epithelium in prostate needle biopsies is generally recognisable through routine microscopy. However, the biopsy can sometimes be erroneously interpreted as malignant due to its architectural and cytological characteristics, and immunohistochemistry can be useful for correctly identifying the biopsy. Our objective was to analyse the potential usefulness of GATA-3 as a marker of seminal epithelium. Through immunohistochemistry with a monoclonal anti-GATA-3 antibody (clone L50-823), we studied seminal vesicle sections from 20 prostatectomy specimens, 12 prostate needle biopsies that contained seminal vesicle tissue and 68 prostate biopsies without seminal vesicle epithelium, 36 of which showed adenocarcinoma. Staining for GATA-3 was intense in the 20 seminal vesicles of the prostatectomy specimens and in the 12 prostate needle biopsies that contained seminal epithelium. In the 60 biopsies without a seminal vesicle, GATA-3 was positive in the prostate basal cells and even in the secretory cells (57 cases), although with less intensity in 55 of the cases. One of the 36 prostatic adenocarcinomas tested positive for GATA-3. The intense immunohistochemical expression of GATA-3 in the seminal vesicle epithelium can help identify the epithelium in prostate biopsies. This marker is also positive in the basal cells of healthy prostates and, with less intensity, in the secretory cells. Positivity, weak or moderate, is observed on rare occasions in prostatic adenocarcinomas. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

  16. A monoallelic-to-biallelic T-cell transcriptional switch regulates GATA3 abundance

    PubMed Central

    Ku, Chia-Jui; Lim, Kim-Chew; Kalantry, Sundeep; Maillard, Ivan; Engel, James Douglas; Hosoya, Tomonori

    2015-01-01

    Protein abundance must be precisely regulated throughout life, and nowhere is the stringency of this requirement more evident than during T-cell development: A twofold increase in the abundance of transcription factor GATA3 results in thymic lymphoma, while reduced GATA3 leads to diminished T-cell production. GATA3 haploinsufficiency also causes human HDR (hypoparathyroidism, deafness, and renal dysplasia) syndrome, often accompanied by immunodeficiency. Here we show that loss of one Gata3 allele leads to diminished expansion (and compromised development) of immature T cells as well as aberrant induction of myeloid transcription factor PU.1. This effect is at least in part mediated transcriptionally: We discovered that Gata3 is monoallelically expressed in a parent of origin-independent manner in hematopoietic stem cells and early T-cell progenitors. Curiously, half of the developing cells switch to biallelic Gata3 transcription abruptly at midthymopoiesis. We show that the monoallelic-to-biallelic transcriptional switch is stably maintained and therefore is not a stochastic phenomenon. This unique mechanism, if adopted by other regulatory genes, may provide new biological insights into the rather prevalent phenomenon of monoallelic expression of autosomal genes as well as into the variably penetrant pathophysiological spectrum of phenotypes observed in many human syndromes that are due to haploinsufficiency of the affected gene. PMID:26385963

  17. From the cradle to the grave: activities of GATA-3 throughout T cell development and differentiation

    PubMed Central

    Hosoya, Tomonori; Maillard, Ivan; Engel, James Douglas

    2010-01-01

    Summary GATA family transcription factors play multiple vital roles in hematopoiesis in many cell lineages, and in particular, T cells require GATA-3 for execution of several developmental steps. Transcriptional activation of the Gata3 gene is observed throughout T-cell development and differentiation in stage-specific fashion. GATA-3 has been described as a master regulator of T-helper 2 (Th2) cell differentiation in mature CD4+ T cells. During T-cell development in the thymus, its roles in the CD4 vs. CD8 lineage choice and at the β-selection checkpoint are the best characterized. In contrast, its importance prior to β-selection has been obscured both by the developmental heterogeneity of double negative (DN) 1 thymocytes and the paucity of early T-lineage progenitors (ETPs), a subpopulation of DN1 cells that contains the most immature thymic progenitors that retain potent T-lineage developmental potential. By examining multiple lines of in vivo evidence procured through the analysis of Gata3 mutant mice, we have recently demonstrated that GATA-3 is additionally required at the earliest stage of thymopoiesis for the development of the ETP population. Here, we review the characterized functions of GATA-3 at each stage of T-cell development and discuss hypothetical molecular pathways that mediate these functions. PMID:20969588

  18. Gata3 restrains B cell proliferation and cooperates with p18INK4c to repress B cell lymphomagenesis

    PubMed Central

    Liu, Shiqin; Chan, Ho Lam; Bai, Feng; Ma, Jinshan; Scott, Alexandria; Robbins, David J.; Capobianco, Anthony J.; Zhu, Ping; Pei, Xin-Hai

    2016-01-01

    GATA3, a lineage specifier, controls lymphoid cell differentiation and its function in T cell commitment and development has been extensively studied. GATA3 promotes T cell specification by repressing B cell potential in pro T cells and decreased GATA3 expression is essential for early B cell commitment. Inherited genetic variation in GATA3 has been associated with lymphoma susceptibility. However, it remains elusive how the loss of function of GATA3 promotes B cell development and induces B cell lymphomas. In this study, we found that haploid loss of Gata3 by heterozygous germline deletion increased B cell populations in the bone marrow (BM) and spleen, and decreased CD4 T cell populations in the thymus, confirming that Gata3 promotes T and suppresses B cell development. We discovered that haploid loss of Gata3 reduced thymocyte proliferation with induction of p18Ink4c (p18), an inhibitor of CDK4 and CDK6, but enhanced B cell proliferation in the BM and spleen independent of p18. Loss of p18 partially restored Gata3 deficient thymocyte proliferation, but further stimulated Gata3 deficient B cell proliferation in the BM and spleen. Furthermore, we discovered that haploid loss of Gata3 in p18 deficient mice led to the development of B cell lymphomas that were capable of rapidly regenerating tumors when transplanted into immunocompromised mice. These results indicate that Gata3 deficiency promotes B cell differentiation and proliferation, and cooperates with p18 loss to induce B cell lymphomas. This study, for the first time, reveals that Gata3 is a tumor suppressor specifically in B cell lymphomagenesis. PMID:27588406

  19. The GATA3 gene is involved in leprosy susceptibility in Brazilian patients.

    PubMed

    Medeiros, Priscila; da Silva, Weber Laurentino; de Oliveira Gimenez, Bruna Beatriz; Vallezi, Keren Bastos; Moraes, Milton Ozório; de Souza, Vânia Niéto Brito; Latini, Ana Carla Pereira

    2016-04-01

    Leprosy outcome is a complex trait and the host-pathogen-environment interaction defines the emergence of the disease. Host genetic risk factors have been successfully associated to leprosy. The 10p13 chromosomal region was linked to leprosy in familial studies and GATA3 gene is a strong candidate to be part of this association. Here, we tested tag single nucleotide polymorphisms at GATA3 in two case-control samples from Brazil comprising a total of 1633 individuals using stepwise strategy. The A allele of rs10905284 marker was associated with leprosy resistance. Then, a functional analysis was conducted and showed that individuals carrying AA genotype express higher levels of GATA-3 protein in lymphocytes. So, we confirmed that the rs10905284 is a locus associated to leprosy and influences the levels of this transcription factor in the Brazilian population. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Regulation of GATA-3 expression during CD4 lineage differentiation1

    PubMed Central

    Gimferrer, Idoia; Hu, Taishan; Simmons, Amie; Wang, Chi; Souabni, Abdallah; Busslinger, Meinrad; Bender, Timothy P.; Hernandez-Hoyos, Gabriela; Alberola-Ila, José

    2011-01-01

    GATA-3 is necessary for the development of MHC II-restricted CD4 T cells, and its expression is increased during positive selection of these cells. TcR signals drive this upregulation, but the signaling pathways that control this process are not well understood. Using genetic and pharmacological approaches we show that GATA-3 upregulation during thymocyte positive selection is the result of additive inputs from the Ras/MAPK and Calcineurin pathways. This upregulation requires the presence of the transcription factor c-Myb. Furthermore, we show that TH-POK can also upregulate GATA-3 in double positive thymocytes, suggesting the existence of a positive feedback loop that contributes to lock in the initial commitment to the CD4 lineage during differentiation. PMID:21357543

  1. TFE2 and GATA3 Enhance Induction of POU4F3 and Myosin VIIa Positive Cells in Nonsensory Cochlear Epithelium by ATOH1

    PubMed Central

    Masuda, Masatsugu; Pak, Kwang; Chavez, Eduardo; Ryan, Allen F.

    2012-01-01

    Transcription factors (TFs) can regulate different sets of genes to determine specific cell types by means of combinatorial codes. We previously identified closely-spaced TF binding motifs located 8.2-8.5 kb 5′ to the ATG of the murine Pou4f3 gene, a gene required for late hair cell (HC) differentiation and survival. These motifs, 100% conserved among four mammalian species, include a cluster of E-boxes preferred by TCF3/ATOH1 heterodimers as well as motifs for GATA factors and SP1. We hypothesized that these factors might interact to regulate the Pou4f3 gene and possibly induce a HC phenotype in non-sensory cells of the cochlea. Cochlear sensory epithelium explants were prepared from postnatal day 1.5 transgenic mice in which expression of GFP is driven by 8.5 kb of Pou4f3 5′ genomic DNA (Pou4f3/GFP). Electroporation was used to transfect cells of the greater epithelial ridge with multiple plasmids encoding human ATOH1 (hATOH1), hTCF3 (also known as E2A or TEF2), hGATA3, and hSP1. hATOH1 or hTCF3 alone induced Pou4f3/GFP cells but hGATA3 and hSP1 did not. hATOH1 but not hTCF3 induced conversion of greater epithelial ridge cells into Pou4f3/GFP and myosin VIIa double-positive cells. Transfection of hATOH1 in combination with hTCF3 or hGATA3 induced 2-3X more Pou4f3/GFP cells, and similarly enhanced Pou4f3/GFP and myosin VIIa double-positive cells, when compared to hATOH1 alone. Triple or quadruple TF combinations were generally not more effective than double TF combinations except in the middle turn, where co-transfection of hATOH1, hE2A, and hGATA3 was more effective than hATOH1 plus either hTCF3 or hGATA3. The results demonstrate that TFs can cooperate in regulation of the Pou4f3 gene and in the induction of at least one other element of a HC phenotype. Our data further indicate that combinations of TFs can be more effective than individual TFs in the inner ear. PMID:22985730

  2. GATA3 Gene Polymorphisms Associated with Allergic Rhinitis in an Iranian Population

    PubMed Central

    Shirkani, Afshin; Mansouri, Atena; Abbaszadegan, Mohammad Reza; Faridhosseini, Reza; Jabbari Azad, Farahzad; Gholamin, Mehran

    2017-01-01

    Background: The development of allergic rhinitis (AR) is caused by the interaction between genetic predisposition and environmental factors. In this study, the association between GATA3 single nucleotide polymorphisms and AR in an Iranian population was identified. Methods: This case-control study was performed on 86 patients with AR and 86 healthy subjects. This study aimed to evaluate a potential association between two GATA3 SNPs, rs1269486 and rs2229360, and AR. Blood samples were collected and DNA was extracted for the evaluation of these SNPs by RFLP-PCR. Results: A statistically-significant association was found between rs1269486 and AR (P<0.001). The frequencies of the A and GA genotypes were less in patients than in controls. The frequencies of the G allele and the GG genotype were greater in patients than in controls (P < 0.001). Conclusions: SNP rs1269486 of GATA3 was associated with AR and sensitivity to aeroallergens in our population. Because of the significance of this gene in AR, studying the association between GATA3 polymorphisms and AR is recommended for other populations. PMID:28367470

  3. The transcription factor GATA3 actively represses RUNX3 protein-regulated production of interferon-gamma

    USDA-ARS?s Scientific Manuscript database

    The transcription factor GATA3 is crucial for the differentiation of naive CD4+ T cells into T helper 2 (Th2) cells. Here, we show that deletion of Gata3 allowed the appearance of interferon-g (IFN-g)-producing cells in the absence of interleukin-12 (IL-12) and IFN-g. Such IFN-g production was tra...

  4. GATA3 is a master regulator of the transcriptional response to low-dose ionizing radiation in human keratinocytes

    PubMed Central

    Bonin, Florian; Molina, Manuella; Malet, Claude; Ginestet, Chantal; Berthier-Vergnes, Odile; Martin, Michèle T; Lamartine, Jérôme

    2009-01-01

    Background The general population is constantly exposed to low levels of radiation through natural, occupational or medical irradiation. Even if the biological effects of low-level radiation have been intensely debated and investigated, the molecular mechanisms underlying the cellular response to low doses remain largely unknown. Results The present study investigated the role of GATA3 protein in the control of the cellular and molecular response of human keratinocytes exposed to a 1 cGy dose of X-rays. Chromatin immunoprecipitation showed GATA3 to be able to bind the promoter of 4 genes responding to a 1 cGy exposure. To go further into the role of GATA3 after ionizing radiation exposure, we studied the cellular and molecular consequences of radiation in GATA3 knock-down cells. Knock-down was obtained by lentiviral-mediated expression of an shRNA targeting the GATA3 transcript in differentiated keratinocytes. First, radiosensitivity was assessed: the toxicity, in terms of immediate survival (with XTT test), associated with 1 cGy radiation was found to be increased in GATA3 knock-down cells. The impact of GATA3 knock-down on the transcriptome of X-ray irradiated cells was also investigated, using oligonucleotide microarrays to assess changes between 3 h and 72 h post-irradiation in normal vs GATA3 knock-down backgrounds; transcriptome response was found to be completely altered in GATA3 knock-down cells, with a strong induction/repression peak 48 h after irradiation. Functional annotation revealed enrichment in genes known to be involved in chaperone activity, TGFβ signalling and stress response. Conclusion Taken together, these data indicate that GATA3 is an important regulator of the cellular and molecular response of epidermal cells to very low doses of radiation. PMID:19735555

  5. GATA-3 EXPRESSION IN TROPHOBLASTIC TISSUES: An Immunohistochemical Study of 445 Cases, Including Diagnostic Utility

    PubMed Central

    Banet, Natalie; Gown, Allen M.; Shih, Ie-Ming; Li, Qing Kay; Roden, Richard B.S.; Nucci, Marisa R.; Cheng, Liang; Przybycin, Christopher G.; Nasseri-Nik, Niloofar; Wu, Lee-Shu-Fune; Netto, George J.; Ronnett, Brigitte M.; Vang, Russell

    2014-01-01

    Immunohistochemical expression of GATA-3 is seen predominantly in non-neoplastic bladder and breast epithelium and their respective carcinomas; however, data on expression in normal and lesional trophoblastic tissues are limited. Immunohistochemical staining for GATA-3 was assessed in a range of normal/lesional trophoblastic tissues and tumors in the differential diagnosis (n=445), including non-molar products of conceptions/2nd and 3rd trimester placentas/ ectopic pregnancies, hydatidiform moles, placental site nodules, normal/exaggerated implantation sites, choriocarcinomas, epithelioid trophoblastic tumors, placental site trophoblastic tumors, atypical smooth muscle tumors (including leiomyosarcoma), and cervical and pulmonary squamous cell carcinomas. The extent of expression (0 to 4+) and intensity (weak to strong) were recorded. All cases with developing trophoblast/non-neoplastic trophoblastic proliferations and 81% of trophoblastic neoplasms were positive. Of all non-neoplastic trophoblast cell types, expression was observed in cytotrophoblast in 89% of cases, syncytiotrophoblast in 50%, intermediate trophoblast in 100%, and villous trophoblastic columns in 100%. Increasing gestational age was associated with a decrease in extent/intensity of expression in non-neoplastic cytotrophoblast and syncytiotrophoblast while intermediate trophoblast maintained diffuse and strong expression from early to late gestation (p<0.0001). Eighty-nine percent of normal/exaggerated implantation sites showed 3+ or 4+ expression while staining in 55% of placental site nodules was 1+ or 2+. Staining for GATA-3 was present in 78% of choriocarcinomas, 95% of epithelioid trophoblastic tumors, and 71% of placental site trophoblastic tumors. While the number of choriocarcinomas and placental site trophoblastic tumors that showed a spectrum of expression ranging from negative to diffuse was relatively evenly distributed, 81% of epithelioid trophoblastic tumors had 3+ or 4+ staining

  6. A human high affinity interleukin-5 receptor (IL5R) is composed of an IL5-specific alpha chain and a beta chain shared with the receptor for GM-CSF.

    PubMed

    Tavernier, J; Devos, R; Cornelis, S; Tuypens, T; Van der Heyden, J; Fiers, W; Plaetinck, G

    1991-09-20

    cDNA clones encoding two receptor proteins involved in the binding of human interleukin 5 (hIL5) have been isolated. A first class codes for an IL5-specific chain (hIL5R alpha). The major transcript of this receptor gene, as analyzed in both HL-60 eosinophilic cells and eosinophilic myelocytes grown from cord blood, encodes a secreted form of this receptor. This soluble hIL5R alpha has antagonistic properties. A second component of the hIL5R is found to be identical to the beta chain of the human granulocyte-macrophage colony-stimulating factor (GM-CSF) high affinity receptor. The finding that IL5 and GM-CSF share a receptor subunit provides a molecular basis for the observation that these cytokines can partially interfere with each other's binding and have highly overlapping biological activities on eosinophils.

  7. Identification of a novel de novo GATA3 mutation in a patient with HDR syndrome.

    PubMed

    Chen, Liu; Chen, Bing; Leng, Wuilin; Lui, Xiaotian; Wu, Qinan; Ouyang, Xinshou; Liang, Ziwen

    2015-10-01

    We describe the case of a 21-year-old male with hypocalcaemia, hyperphosphataemia, recurrent limb twitch, deafness, proteinuria, increased serum creatinine and urea nitrogen levels, and shrinkage of both kidneys. Brain computed tomography showed intracranial calcifications. The patient was diagnosed with hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) syndrome. DNA sequence analysis of the GATA3 gene showed a novel de novo mutation, c. 529dupC (p. Arg177profs*126), in exon 2, resulting in a frameshift mutation with a premature stop codon after a new 126 amino acid sequence. We provide further evidence that HDR syndrome is caused by haploinsufficiency of GATA3. © The Author(s) 2015.

  8. GATA3 Positivity in Benign Radiated Prostate Glands: A Potential Diagnostic Pitfall.

    PubMed

    Wobker, Sara E; Khararjian, Armen; Epstein, Jonathan I

    2017-04-01

    Histologic changes following radiation therapy to the prostate include multilayering of glands, atrophy, squamous metaplasia, and often marked random nuclear atypia. We have seen multiple consultation cases where the differential diagnosis of these radiated prostate glands included urothelial carcinoma, with multilayered to solid-appearing proliferations that were positive by immunohistochemistry for GATA3. To formally investigate this issue, 30 cases of benign prostate tissue with radiation atypia, from 1990 to 2015, were obtained from our institution. Cases were evaluated by immunohistochemistry for the prostate-specific markers prostate-specific antigen (PSA), P501S (Prostein), and NKX3.1 and urothelial markers GATA3 and uroplakin 2. GATA3 was positive in 100% of cases, with 70% showing moderately strong to strong staining in a mostly patchy manner within a gland. PSA was positive in 93.3% of cases, with 89.2% showing moderately strong to strong staining in a mostly diffuse manner. P501S was positive in 96.7% of cases, with 93.1% showing moderately strong to strong staining in a mostly patchy manner. NKX3.1 was positive in 82.8% of cases, with 33.3% showing moderately strong to strong staining in a mostly patchy manner. Uroplakin 2 was negative in 100% of cases. Our findings highlight that GATA3 is often positive in benign prostate glands with radiation atypia, which along with the morphologic features present a pitfall for the misdiagnosis of urothelial carcinoma. A combination of PSA and P501S is the best prostate-specific panel for use in radiated prostate, with the caveat that they are often patchy and do not stain all radiated glands.

  9. The Adaptor Molecule SAP Regulates IFNγ and IL-4 Production in Vα14 Transgenic NKT cells via Effects on GATA-3 and T-bet Expression1

    PubMed Central

    Cen, Osman; Ueda, Aki; Guzman, Laura; Jain, Jimmy; Bassiri, Hamid; Nichols, Kim E.; Stein, Paul L.

    2008-01-01

    NKT cells comprise a rare regulatory T cell population of limited TCR diversity, with most cells utilizing a Vα14Jα18 TCR. These cells exhibit a critical dependence on the signaling adapter molecule SAP for their ontogeny, an aspect not seen in conventional αβ T cells. Prior studies demonstrate that SAP enhances TCR-induced activation of NF-kB in CD4+ T cells. Since NF-kB is required for NKT cell development, SAP might promote the ontogeny of this lineage by signaling to NF-kB. In this report, we demonstrate that forced expression of the NF-kB target gene, Bcl-xL, or IKKβ, a catalytic subunit of the IkB kinase complex essential for NF-kB activation, fails to restore NKT cell development in sap−/− mice, suggesting that SAP mediates NKT cell development independently of NF-kB. To examine the role of SAP in NKT cell function, we generated NKT cells in sap−/− mice by expressing a transgene encoding the Vα14Jα18 component of the invariant TCR. These cells bound α-GalCer loaded CD1d tetramers, but exhibited a very immature CD24+NK1.1- phenotype. While sap−/− tetramer-reactive cells proliferated in response to TCR activation, they did not produce appreciable levels of IL-4 or IFN-γ. The reduction in cytokine production correlated with the near absence of GATA-3 and T-bet, key transcription factors regulating cytokine expression and maturation of NKT cells. Ectopic expression of GATA-3 partially restored IL-4 production by the NKT cells. Collectively these data suggest that by promoting GATA3 and T-bet expression, SAP exerts control over NKT cell development and mature NKT cell cytokine production. PMID:19155483

  10. Mast cell diversion of T-lineage precursor cells by the essential T-lineage transcription factor GATA-3

    PubMed Central

    Taghon, Tom; Yui, Mary A.; Rothenberg, Ellen V.

    2011-01-01

    GATA-3 is essential for T cell development from the earliest stages. However, highly abundant GATA-3 can drive T-lineage precursors to a non-T fate, depending on Notch signaling and developmental stage. GATA-3 overexpression blocked pro-T cell survival when Notch-Delta signals were present, but enhanced viability in their absence. In double-negative (DN1) and DN2 but not DN3 fetal thymocytes, GATA-3 overexpression rapidly induced mast cell lineage respecification with high frequency by direct transcriptional reprogramming. Normal DN2 thymocytes also displayed mast cell potential, when interleukin 3 and stem cell factor were added in the absence of Notch signaling. Our results suggest a close relationship between the pro-T and mast cell programs and a new role for Notch in T-lineage fidelity. PMID:17603486

  11. GATA3 expression in morphologic subtypes of breast carcinoma: a comparison with gross cystic disease fluid protein 15 and mammaglobin.

    PubMed

    Wendroth, Scott M; Mentrikoski, Mark J; Wick, Mark R

    2015-02-01

    GATA3 is a transcription factor, which is involved in the growth and differentiation of several human tissues. Immunohistochemical staining for this marker has proven to be useful in recognizing a number of tumors, most notably those in the urinary tract and breasts. To date, no study has specifically assessed the distribution of GATA3 among different histomorphologic subtypes of breast carcinoma. The surgical pathology archive at our institution was searched, to retrieve cases of breast carcinomas of the following microscopic types-ductal, lobular, mucinous, metaplastic, medullary, apocrine, signet-ring cell, and micropapillary. Tissue microarrays were created, with four 0.6-mm punch specimens from each case. The tissue microarrays were cut at a 5-μm thickness and stained with monoclonal antibodies to GATA3 (Biocare Medical Inc, Concord, CA), mammaglobin (Dako, Carpinteria, CA), and gross cystic disease fluid protein 15 (Dako). Tumors were considered to be positive for those markers if more than 5% of the cells were labeled. Of 55 ductal adenocarcinomas, 51 (92.7%) expressed GATA3. All 4 GATA3-negative tumors were Nottingham grade III lesions that were also nonreactive for estrogen receptor protein. GATA3 was present in 28 (96.6%) of 29 lobular adenocarcinomas, 10 (90.9%) of 11 apocrine adenocarcinomas, 10 (83.3%) of 12 medullary carcinomas, 5 (55.5%) of 9 metaplastic carcinomas, and 1 of 2 signet-ring cell carcinomas. Mucinous carcinomas (23 cases) and micropapillary carcinomas (12 cases) uniformly and strongly labeled for GATA3. GATA3 equaled or surpassed the sensitivity of mammaglobin and gross cystic disease fluid protein 15 in all histologic subgroups of breast cancer in the study. Although most ductal adenocarcinomas were labeled for GATA3, it was absent in high-grade tumors that also lacked estrogen receptor protein. Favorable prognosis types of breast carcinoma (eg, mucinous carcinoma) and aggressive variants such as micropapillary carcinoma were equally

  12. Critical Role for GATA3 in Mediating Tie2 Expression and Function in Large Vessel Endothelial Cells*

    PubMed Central

    Song, Haihua; Suehiro, Jun-ichi; Kanki, Yasuharu; Kawai, Yoshiko; Inoue, Kenji; Daida, Hiroyuki; Yano, Kiichiro; Ohhashi, Toshio; Oettgen, Peter; Aird, William C.; Kodama, Tatsuhiko; Minami, Takashi

    2009-01-01

    Endothelial phenotypes are highly regulated in space and time by both transcriptional and post-transcriptional mechanisms. There is increasing evidence that the GATA family of transcription factors function as signal transducers, coupling changes in the extracellular environment to changes in downstream target gene expression. Here we show that human primary endothelial cells derived from large blood vessels express GATA2, -3, and -6. Of these factors, GATA3 was expressed at the highest levels. In DNA microarrays of human umbilical vein endothelial cells (HUVEC), small interfering RNA-mediated knockdown of GATA3 resulted in reduced expression of genes associated with angiogenesis, including Tie2. At a functional level, GATA3 knockdown inhibited angiopoietin (Ang)-1-mediated but not vascular endothelial cell growth factor (VEGF)-mediated AKT signaling, cell migration, survival, and tube formation. In electrophoretic gel mobility shift assays and chromatin immunoprecipitation, GATA3 was shown to bind to regulatory regions within the 5′-untranslated region of the Tie2 gene. In co-immunoprecipitation and co-transfection assays, GATA3 and the Ets transcription factor, ELF1, physically interacted and synergized to transactivate the Tie2 promoter. GATA3 knockdown blocked the ability of Ang-1 to attenuate vascular endothelial cell growth factor stimulation of vascular cell adhesion molecule-1 expression and monocytic cell adhesion. Moreover, exposure of human umbilical vein endothelial cells to tumor necrosis factor-α resulted in marked down-regulation of GATA3 expression and reduction in Tie2 expression. Together, these findings suggest that GATA3 is indispensable for Ang-1-Tie2-mediated signaling in large vessel endothelial cells. PMID:19674970

  13. Defects in sensory organ morphogenesis and generation of cochlear hair cells in Gata3-deficient mouse embryos.

    PubMed

    Haugas, Maarja; Lilleväli, Kersti; Salminen, Marjo

    2012-01-01

    The development of the inner ear sensory epithelia involves a complex network of transcription factors and signaling pathways and the whole process is not yet entirely understood. GATA3 is a DNA-binding factor that is necessary for otic morphogenesis and without GATA3 variable defects have been observed already at early stages in mouse embryos. In the less severe phenotypes, one small oval shaped vesicle is formed whereas in the more severe cases, the otic epithelium becomes disrupted and the endolymphatic domain becomes separated from the rest of the otic epithelium. Despite these defects, the early sensory fate specification occurs in Gata3-/- otic epithelium. However, due to the early lethality of Gata3-deficient embryos, the later morphogenesis and sensory development have remained unclear. To gain information of these later processes we produced drug-rescued Gata3-/- embryos that survived up to late gestation. In these older Gata3-/- embryos, a similar variability was observed as earlier. In the more severely affected ears, the development of the separate endolymphatic domain arrested completely whereas the remaining vesicle formed an empty cavity with variable forms, but without any distinguishable otic compartments or morphologically distinct sensory organs. However, the dorsal part of this vesicle was able to adopt a sensory fate and to produce some hair cells. In the less severe cases of Gata3-/- ears, distinct utricular, saccular and cochlear compartments were present and hair cells could be detected in the vestibular sensory epithelia. Although clear cristae and maculae formed, the morphology and size of these sensory areas were abnormal and they remained often un-separated. In contrast to the vestibule, the cochlear sensory compartment remained more immature and no hair or supporting cells could be detected. Our results suggest that GATA3 is critical for normal vestibular and cochlear morphogenesis and that it is especially important for cochlear

  14. Morin promotes prostate cancer cells chemosensitivity to paclitaxel through miR-155/GATA3 axis.

    PubMed

    Li, Bin; Jin, Xunbo; Meng, Huilin; Hu, Bo; Zhang, Tao; Yu, Jiang; Chen, Shaoan; Guo, Xudong; Wang, Weiguo; Jiang, Wei; Wang, Jin

    2017-07-18

    Paclitaxel is a first-line microtubule-stabilizing drug in treating prostate cancer. However, most patients develop resistance and experience relapse. Morin (3,5,7,20,40-pentahydroxyflavone) is an anti-tumor flavonoid in a numerous types of cancer cells including breast, ovarian and lung cancers. We therefore researched the effects of morin as an adjuvant to paclitaxel in in treating DU145 and PC-3 cells in vitro and DU145 derived prostate cancers in nude mice models. The chemosensitivities of these cells to the treatments of morin and paclitaxel were tested through viability assays utilizing cell counting kit 8 (CCK-8) and apoptosis assays through flow cytometry analyses. MicroRNA (miRNA) microarray was employed to determine the changes in miRNA profile of morin treated DU145 cells. The results from microarrays were further certified by quantitative real-time reverse transcription-PCR (qRT-PCR). The underlying targets of miR-155 were verified using luciferase assays followed by Western blot assays. In the results, morin was capable of repressing the cell viabilities in the paclitaxel-treated cells. MiR-155might be an effective target that can be down-regulated in morin-treated cells. We also discovered that GATA binding protein 3 (GATA3) was directly repressed by miR-155, and the treatment of morin reversed the expression of GATA3. In conclusion, morin might be a potential adjuvant of paclitaxel in treating prostate cancer through regulating miR-155/GATA3 axis.

  15. Berberine increases expression of GATA-2 and GATA-3 during inhibition of adipocyte differentiation.

    PubMed

    Hu, Y; Davies, G E

    2009-09-01

    It is known that a number of transcription factors are key regulators in the complex process of adipocyte differentiation including peroxisome proliferator activated receptor gamma (PPARgamma) and the CCAAT enhancer binding protein alpha (C/EBPalpha). Studies have demonstrated that in pre-adipocyte 3T3-L1 cells constitutive expression of the DNA binding proteins GATA-2 and GATA-3 results in protein/protein interactions with C/EBPalpha resulting in down regulation of PPARgamma and subsequent suppressed adipocyte differentiation with cells trapped at the pre-adipocyte stage. Thus it appears that GATA-2 and GATA-3 are of critical importance in regulating adipocyte differentiation through molecular interactions with PPARgamma and C/EBPalpha. Recent reports suggest that berberine, an isoquinoline derivative alkaloid isolated from many medicinal herbs prevents differentiation of 3T3-L1 cells via a down regulation of PPARgamma and C/EBPalpha expression. The aim of this study was to determine the effect of berberine on GATA-2 and 3 gene and protein expression levels during differentiation of 3T3-L1 cells. MTT (Methylthiazolyldiphenyl-tetrazolium bromide) was used to detect the cytotoxic effects of berberine on the viability of 3T3-L1 cells during proliferation and differentiation. Differentiation of 3T3-L1 cells was monitored by Oil Red O staining and RT-PCR of PPARgamma and C/EBPalpha and the expression of GATA-2 and 3 was determined by RT-PCR and Western Blot. Results show that following treatment with 8microM berberine the mRNA and protein expression levels of GATA-2 and 3 were elevated and accompanied by inhibited adipocyte differentiation. These results may lead to the use of berberine to target the induction of specific genes such as GATA-2 and GATA-3 which affect adipocyte differentiation.

  16. Genomic Analysis of the Function of the Transcription Factor gata3 during Development of the Mammalian Inner Ear

    PubMed Central

    Milo, Marta; Cacciabue-Rivolta, Daniela; Kneebone, Adam; Van Doorninck, Hikke; Johnson, Claire; Lawoko-Kerali, Grace; Niranjan, Mahesan; Rivolta, Marcelo; Holley, Matthew

    2009-01-01

    We have studied the function of the zinc finger transcription factor gata3 in auditory system development by analysing temporal profiles of gene expression during differentiation of conditionally immortal cell lines derived to model specific auditory cell types and developmental stages. We tested and applied a novel probabilistic method called the gamma Model for Oligonucleotide Signals to analyse hybridization signals from Affymetrix oligonucleotide arrays. Expression levels estimated by this method correlated closely (p<0.0001) across a 10-fold range with those measured by quantitative RT-PCR for a sample of 61 different genes. In an unbiased list of 26 genes whose temporal profiles clustered most closely with that of gata3 in all cell lines, 10 were linked to Insulin-like Growth Factor signalling, including the serine/threonine kinase Akt/PKB. Knock-down of gata3 in vitro was associated with a decrease in expression of genes linked to IGF-signalling, including IGF1, IGF2 and several IGF-binding proteins. It also led to a small decrease in protein levels of the serine-threonine kinase Akt2/PKBβ, a dramatic increase in Akt1/PKBα protein and relocation of Akt1/PKBα from the nucleus to the cytoplasm. The cyclin-dependent kinase inhibitor p27kip1, a known target of PKB/Akt, simultaneously decreased. In heterozygous gata3 null mice the expression of gata3 correlated with high levels of activated Akt/PKB. This functional relationship could explain the diverse function of gata3 during development, the hearing loss associated with gata3 heterozygous null mice and the broader symptoms of human patients with Hearing-Deafness-Renal anomaly syndrome. PMID:19774072

  17. A Gata3-Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing.

    PubMed

    Yu, Wei-Ming; Appler, Jessica M; Kim, Ye-Hyun; Nishitani, Allison M; Holt, Jeffrey R; Goodrich, Lisa V

    2013-12-10

    Information flow through neural circuits is determined by the nature of the synapses linking the subtypes of neurons. How neurons acquire features distinct to each synapse remains unknown. We show that the transcription factor Mafb drives the formation of auditory ribbon synapses, which are specialized for rapid transmission from hair cells to spiral ganglion neurons (SGNs). Mafb acts in SGNs to drive differentiation of the large postsynaptic density (PSD) characteristic of the ribbon synapse. In Mafb mutant mice, SGNs fail to develop normal PSDs, leading to reduced synapse number and impaired auditory responses. Conversely, increased Mafb accelerates synaptogenesis. Moreover, Mafb is responsible for executing one branch of the SGN differentiation program orchestrated by the Gata3 transcriptional network. Remarkably, restoration of Mafb rescues the synapse defect in Gata3 mutants. Hence, Mafb is a powerful regulator of cell-type specific features of auditory synaptogenesis that offers a new entry point for treating hearing loss. DOI: http://dx.doi.org/10.7554/eLife.01341.001.

  18. GATA3 is a reliable marker for neuroblastoma in limited samples, including FNA Cell Blocks, core biopsies, and touch imprints.

    PubMed

    Wiles, Austin Blackburn; Karrs, Jeremiah Xavier; Pitt, Susan; Almenara, Jorge; Powers, Celeste N; Smith, Steven Christopher

    2017-10-04

    Neuroblastomas (NBs) are the most common solid cancer of childhood and infancy; however, in poorly differentiated forms, they present diagnostic challenges. GATA3 has been implicated functionally in NB differentiation, and limited data support its use as an immunohistochemical biomarker for NBs in resection specimens. GATA3 was tested retrospectively in 30 consecutive archival NB samples, including archival cytopathology needle cores and cell blocks (n = 6), scant surgical biopsy specimens and 2-mm NB tissue cores (n = 16), and air-dried touch imprints (n = 8) to evaluate the utility of this marker. Immunostaining was performed per the institutional standard, Clinical Laboratory Improvement Amendments-compliant automated staining protocol. GATA3 nuclear staining was scored qualitatively for its intensity and proportion of positivity. All 30 NB specimens showed diffuse nuclear positivity with GATA3. Each sample revealed either strong (n = 26) or moderate nuclear staining (n = 4) in more than 75% of NB cells, regardless of the presence or lack of stromata or necrosis or the degree of differentiation. GATA3 is a reliable diagnostic marker for NBs not only in scant/limited surgical specimens but also in cytologic samples, including air-dried touch imprints, which have previously been undescribed for this marker. Cancer (Cancer Cytopathol) 2017. © 2017 American Cancer Society. © 2017 American Cancer Society.

  19. Human GATA-3 trans-activation, DNA-binding, and nuclear localization activities are organized into distinct structural domains.

    PubMed Central

    Yang, Z; Gu, L; Romeo, P H; Bories, D; Motohashi, H; Yamamoto, M; Engel, J D

    1994-01-01

    GATA-3 is a zinc finger transcription factor which is expressed in a highly restricted and strongly conserved tissue distribution pattern in vertebrate organisms, specifically, in a subset of hematopoietic cells, in cells within the central and peripheral nervous systems, in the kidney, and in placental trophoblasts. Tissue-specific cellular genes regulated by GATA-3 have been identified in T lymphocytes and the placenta, while GATA-3-regulated genes in the nervous system and kidney have not yet been defined. We prepared monoclonal antibodies with which we could dissect the biochemical and functional properties of human GATA-3. The results of these experiments show some anticipated phenotypes, for example, the definition of discrete domains required for specific DNA-binding site recognition (amino acids 303 to 348) and trans activation (amino acids 30 to 74). The signaling sequence for nuclear localization of human GATA-3 is a property conferred by sequences within and surrounding the amino finger (amino acids 249 to 311) of the protein, thereby assigning a function to this domain and thus explaining the curious observation that this zinc finger is dispensable for DNA binding by the GATA family of transcription factors. Images PMID:8114750

  20. The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo

    PubMed Central

    Kong, Sun-Young; Kim, Kwang-Soo; Kim, Jiewan; Kim, Min Kyeong; Lee, Ki Hong; Lee, Je-Yong; Oh, Nuri; Park, Ji-In; Park, Ji-Hoon; Heo, Sun-Hee; Shim, Sung Han; Lee, Dong Ryul; Kim, Keun Pil; Park, Kyung-Soon

    2016-01-01

    Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 resulted in extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated. Also, suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells. PMID:27556500

  1. The ELK3-GATA3 axis orchestrates invasion and metastasis of breast cancer cells in vitro and in vivo.

    PubMed

    Kong, Sun-Young; Kim, Kwang-Soo; Kim, Jiewan; Kim, Min Kyeong; Lee, Ki Hong; Lee, Je-Yong; Oh, Nuri; Park, Ji-In; Park, Ji-Hoon; Heo, Sun-Hee; Shim, Sung Han; Lee, Dong Ryul; Kim, Keun Pil; Park, Kyung-Soon

    2016-10-04

    Triple-negative breast cancer is a highly aggressive tumor subtype that lacks effective therapeutic targets. Here, we show that ELK3 is overexpressed in a subset of breast cancers, in particular basal-like and normal-like/claudin-low cell lines. Suppression of ELK3 in MDA-MB-231 cells led to transdifferentiation from an invasive mesenchymal phenotype to a non-invasive epithelial phenotype both in vitro and in vivo. Suppression of ELK3 resulted in extensive changes in genome expression profiles. Among these, GATA3, a master suppressor of metastasis, was epigenetically activated. Also, suppression of GATA3 led to the restoration of migration and invasion. These results suggest that the ELK3-GATA3 axis is a major pathway that promotes metastasis of MDA-MB-231 cells.

  2. Interleukin-5 and IL-5 receptor in health and diseases

    PubMed Central

    TAKATSU, Kiyoshi

    2011-01-01

    While interleukin-5 (IL-5) is initially identified by its ability to support the growth and terminal differentiation of mouse B cells in vitro into antibody-secreting cells, recombinant IL-5 exerts pleiotropic activities on various target cells including B cells, eosinophils, and basophils. IL-5 is produced by both hematopoietic and non-hematopoietic cells including T cells, granulocytes, and natural helper cells. IL-5 exerts its effects for proliferation and differentiation via receptors that comprise an IL-5-specific α and common β-subunit. IL-5Rα expression in activated B cells is regulated by a complex of transcription factors including E12, E47, Sp1, c/EBPβ, and Oct2. IL-5 signals are transduced through JAK–STAT, Btk, and Ras/Raf-ERK signaling pathways and lead to maintenance of survival and functions of B cells and eosinophils. Overexpression of IL-5 in vivo significantly increases eosinophils and B cells in number, while mice lacking a functional gene for IL-5 or IL-5 receptor display a number of developmental and functional impairments in B cells and eosinophil lineages. In humans, the biologic effects of IL-5 are best characterized for eosinophils. The recent expansion in our understanding of eosinophil development and activation and pathogenesis of eosinophil-dependent inflammatory diseases has led to advance in therapeutic options. Intravenous administration of humanized anti-IL-5 monoclonal antibody reduces baseline bronchial mucosal eosinophils in mild asthma; providing important implications for strategies that inhibit the actions of IL-5 to treat asthma and other allergic diseases. PMID:21986312

  3. Release from Th1-type immune tolerance in spleen and enhanced production of IL-5 in Peyer's patch by cholera toxin B induce the glomerular deposition of IgA.

    PubMed

    Yamanaka, Takahiro; Tamauchi, Hidekazu; Suzuki, Yusuke; Suzuki, Hitoshi; Horikoshi, Satoshi; Terashima, Masazumi; Iwabuchi, Kazuya; Habu, Sonoko; Okumura, Ko; Tomino, Yasuhiko

    2016-04-01

    We examined the pathogenesis of glomerular damage in Th2 type-dependent GATA-3 transgenic (GATA-3 Tg) mice with IgA nephropathy (IgAN). GATA-3 Tg mice were immunized orally using OVA plus cholera toxin B (CTB), and measurement of the serum IgA antibody level and histopathological examination were performed. Marked increases in the serum levels of OVA-specific IgA antibody, IgA and IgG, C3 deposits analogous to those seen in IgAN, and expansion of the matrix in association with mesangial cell proliferation were observed. Furthermore, glomerular IgA deposits were co-localized with mannan-binding lectin (MBL) deposits, which might actually have been abnormal IgA deposits. In GATA-3/TCR-Tg mice that had been orally sensitized with CTB plus OVA and were re-stimulated with OVA in vitro, cultured Peyer's patch cells showed the enhanced production of IL-5 and supernatants from cultures of spleen cells showed a reduction of TGF-β production with a simultaneous increase in IL-2 production and the recovery of IFN-γ formation. The amount of TGF-β produced by the spleen cells was found to be correlated with the amount of IFN-γ and IL-IL-2 produced by the cells. Also, the percentage of regulatory T cells (Treg) in the spleens of mice sensitized with OVA plus CTB was lower than that in mice orally sensitized with OVA alone. These results suggest that the increased production of IL-5 from Peyer's patch cells (PPc) and the restored Th1-type immune response might cause the production of abnormal IgA and might induce the deposition of IgA in glomeruli. Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.

  4. Immunohistochemical staining characteristics of nephrogenic adenoma using the PIN-4 cocktail (p63, AMACR, and CK903) and GATA-3.

    PubMed

    McDaniel, Andrew S; Chinnaiyan, Arul M; Siddiqui, Javed; McKenney, Jesse K; Mehra, Rohit

    2014-12-01

    Nephrogenic adenoma (NA) is a benign lesion of the urinary tract associated with injury to the urothelium. The varied morphologic patterns of NA make it a potential diagnostic pitfall, because it can mimic closely prostatic adenocarcinoma and urothelial carcinoma. In current practice, an antibody cocktail comprising p63, CK903, and AMACR (PIN-4 cocktail) is frequently utilized to evaluate foci suspicious for prostatic adenocarcinoma. Although the staining characteristics of the individual components of the PIN-4 cocktail have been reported for NA, no study has described the expression patterns for NA when the stains are applied as a cocktail. GATA-3 is an emerging marker of urothelial carcinoma; however, the GATA-3 staining characteristics of NA have yet to be described. Sixty-three NA specimens (M:F=36:27, average age=51.4 y) from various locations in the urinary tract including urinary bladder (n=40), ureter (n=3), and urethra (n=20) were collected from the archives of 2 institutions. Immunohistochemical analysis with the PIN-4 cocktail and GATA-3 antibodies was performed, and the distribution and intensity of staining was recorded for each antibody in each case. PIN-4 cocktail staining revealed AMACR expression in 56% of cases, CK903 expression in 97%, and rare p63 positivity (in only 2 cases). Only 2 NA cases displayed an overall PIN-4 staining pattern compatible with prostate cancer. GATA-3 expression was noted in 40% of NAs. No correlation between AMACR, CK903, or GATA-3 positivity and histologic pattern or anatomic location was identified. Although heterogenous staining patterns were seen within individual cases, use of the PIN-4 cocktail effectively discriminates NA from prostate cancer because of the high frequency of coexpression of AMACR and CK903 within NA. In addition, GATA-3 is not a useful marker in differentiating between NA and urothelial carcinoma.

  5. IL5 — EDRN Public Portal

    Cancer.gov

    From NCBI Gene: This gene encodes a cytokine that acts as a growth and differentiation factor for both B cells and eosinophils. The encoded cytokine plays a major role in the regulation of eosinophil formation, maturation, recruitment and survival. The increased production of this cytokine may be related to pathogenesis of eosinophil-dependent inflammatory diseases. This cytokine functions by binding to its receptor, which is a heterodimer, whose beta subunit is shared with the receptors for interleukine 3 (IL3) and colony stimulating factor 2 (CSF2/GM-CSF). This gene is located on chromosome 5 within a cytokine gene cluster which includes interleukin 4 (IL4), interleukin 13 (IL13), and CSF2 . This gene, IL4, and IL13 may be regulated coordinately by long-range regulatory elements spread over 120 kilobases on chromosome 5q31. [provided by RefSeq, Jul 2013

  6. Lyn Kinase Controls Basophil GATA-3 Transcription Factor Expression and Induction of Th2 Cell Differentiation

    PubMed Central

    Charles, Nicolas; Watford, Wendy T.; Ramos, Haydeé L.; Hellman, Lars; Oettgen, Hans C.; Gomez, Gregorio; Ryan, John J.; O’Shea, John J.; Rivera, Juan

    2009-01-01

    Summary TH1/TH2 balance is key to host defense and its dysregulation has pathophysiological consequences. Basophils are important in TH2 differentiation. However, the factors controlling the onset and extent of basophil-mediated TH2 differentiation are unknown. Here, we demonstrate that Lyn kinase dampens basophil GATA-3 expression and the initiation and extent of TH2 differentiation. Lyn-null mice had a marked basophilia, a constitutive TH2 skewing that was exacerbated upon in vivo challenge of basophils, produced antibodies to a normally inert antigen, and failed to appropriately respond to a TH1 pathogen. The TH2 skewing was dependent on basophils, IgE and IL-4, but was independent of mast cells. Our findings demonstrate that basophil-expressed Lyn kinase exerts regulatory control on TH2 differentiation and function. PMID:19362019

  7. A novel GATA3 nonsense mutation in a newly diagnosed adult patient of hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome.

    PubMed

    Nanba, Kazutaka; Usui, Takeshi; Nakamura, Michikazu; Toyota, Yuko; Hirota, Keisho; Tamanaha, Tamiko; Kawashima, Sachiko-Tsukamoto; Nakao, Kanako; Yuno, Akiko; Tagami, Tetsuya; Naruse, Mitsuhide; Shimatsu, Akira

    2013-01-01

    Hypoparathyroidism, deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder caused by a GATA3 gene mutation. Here we report a novel mutation of GATA3 in a patient diagnosed with HDR syndrome at the age of 58 with extensive intracranial calcification. A 58-year-old Japanese man showed severe hypocalcemia and marked calcification in the basal ganglia, cerebellum, deep white matter, and gray-white junction on computed tomography (CT). The serum intact parathyroid hormone level was relatively low against low serum calcium concentration. The patient had been diagnosed with bilateral sensorineural deafness in childhood and had a family history of hearing disorders. Imaging studies revealed no renal anomalies. The patient was diagnosed with HDR syndrome, and genetic testing was performed. Genetic analysis of GATA3 showed a novel nonsense mutation at codon 198 (S198X) in exon 3. The S198X mutation leads to a loss of two zinc finger deoxyribonucleic acid (DNA) binding domains and is considered to be responsible for HDR syndrome. We identified a novel nonsense mutation of GATA3 in an adult patient with HDR syndrome who showed extensive intracranial calcification.

  8. Plasma IL-5 concentration and subclinical carotid atherosclerosis

    PubMed Central

    Silveira, Angela; McLeod, Olga; Strawbridge, Rona J.; Gertow, Karl; Sennblad, Bengt; Baldassarre, Damiano; Veglia, Fabrizio; Deleskog, Anna; Persson, Jonas; Leander, Karin; Gigante, Bruna; Kauhanen, Jussi; Rauramaa, Rainer; Smit, Andries J.; Mannarino, Elmo; Giral, Philippe; Gustafsson, Sven; Söderberg, Stefan; Öhrvik, John; Humphries, Steve E.; Tremoli, Elena; de Faire, Ulf; Hamsten, Anders

    2015-01-01

    Objective Genetic variants robustly associated with coronary artery disease were reported in the vicinity of the interleukin (IL)-5 locus, and animal studies suggested a protective role for IL-5 in atherosclerosis. Therefore, we set this work to explore IL-5 as a plasma biomarker for early subclinical atherosclerosis, as determined by measures of baseline severity and change over time of carotid intima-media thickness (cIMT). Methods We used biobank and databases of IMPROVE, a large European prospective cohort study of high-risk individuals (n = 3534) free of clinically overt cardiovascular disease at enrollment, in whom composite and segment-specific measures of cIMT were recorded at baseline and after 15 and 30 months. IL-5 was measured with an immunoassay in plasma samples taken at baseline. Results IL-5 levels were lower in women than in men, lower in the South than in North of Europe, and showed positive correlations with most established risk factors. IL-5 showed significant inverse relationships with cIMT change over time in the common carotid segment in women, but no significant relationships to baseline cIMT in either men or women. Conclusions Our results suggest that IL-5 may be part of protective mechanisms operating in early atherosclerosis, at least in women. However, the relationships are weak and whereas IL-5 has been proposed as a potential molecular target to treat allergies, it is difficult to envisage such a scenario in coronary artery disease. PMID:25587992

  9. Anti-IL5 therapy for asthma and beyond.

    PubMed

    Mukherjee, Manali; Sehmi, Roma; Nair, Parameswaran

    2014-01-01

    Airway inflammation is considered to be the primary component contributing to the heterogeneity and severity of airway disorders. Therapeutic efficacies of diverse novel biologics targeting the inflammatory pathways are under investigation. One such target is IL-5, a type-1 cytokine that is central to the initiation and sustenance of eosinophilic airway inflammation. Over the past decade, anti-IL5 molecules have been documented to have mixed therapeutic benefits in asthmatics. Post hoc analyses of the trials reiterate the importance of identifying the IL-5-responsive patient endotypes. In fact, the currently available anti-IL5 treatments are being considered beyond asthma management; especially in clinical complications with an underlying eosinophilic pathobiology such as hypereosinophilic syndrome (HES) and eosinophilic granulomatosis and polyangitis (EGPA). In addition, closer analyses of the available data indicate alternative mechanisms of tissue eosinophilia that remain uncurbed with the current dosage and delivery platform of the anti-IL5 molecules.

  10. Protective effect of curcumin on acute airway inflammation of allergic asthma in mice through Notch1-GATA3 signaling pathway.

    PubMed

    Chong, Lei; Zhang, Weixi; Nie, Ying; Yu, Gang; Liu, Liu; Lin, Li; Wen, Shunhang; Zhu, Lili; Li, Changchong

    2014-10-01

    Curcumin, a natural product derived from the plant Curcuma longa, has been found to have anti-inflammatory, antineoplastic and antifibrosis effects. It has been reported that curcumin attenuates allergic airway inflammation in mice through inhibiting NF-κB and its downstream transcription factor GATA3. It also has been proved the antineoplastic effect of curcumin through down-regulating Notch1 receptor and its downstream nuclear transcription factor NF-κB levels. In this study, we aimed to investigate the anti-inflammatory effect of curcumin on acute allergic asthma and its underlying mechanisms. 36 male BALB/c mice were randomly divided into four groups (normal, asthma, asthma+budesonide and asthma+curcumin groups). BALF (bronchoalveolar lavage fluid) and lung tissues were analyzed for airway inflammation and the expression of Notch1, Notch2, Notch3, Notch4 and the downstream transcription factor GATA3. Our findings showed that the levels of Notch1 and Notch2 receptors were up-regulated in asthma group, accompanied by the increased expression of GATA3. But the expression of Notch2 receptor was lower than Notch1 receptor. Curcumin pretreatment improved the airway inflammatory cells infiltration and reversed the increasing levels of Notch1/2 receptors and GATA3. Notch3 receptor was not expressed in all of the four groups. Notch4 receptor protein and mRNA expression level in the four groups had no significant differences. The results of the present study suggested that Notch1 and Notch2 receptor, major Notch1 receptor, played an important role in the development of allergic airway inflammation and the inhibition of Notch1-GATA3 signaling pathway by curcumin can prevent the development and deterioration of the allergic airway inflammation. This may be a possible therapeutic option of allergic asthma.

  11. Isolation and characterization of marsupial IL5 genes.

    PubMed

    Hawken, R J; Maccarone, P; Toder, R; Marshall Graves, J A; Maddox, J F

    1999-10-01

    The genomic nucleotide sequence and chromosomal position of the interleukin 5 (IL5) gene has been described for the model marsupial Macropus eugenii (tammar wallaby). A 272 base pair genomic IL5 polymerase chain reaction (PCR) product spanning exon 3, intron 3, and exon 4 was generated using stripe-faced dunnart (Sminthopsis macroura) DNA. This PCR product was used to isolate a genomic lambda clone containing the complete IL5 gene from a tammar wallaby EMBL3 lambda library. Sequencing revealed that the tammar wallaby IL5 gene consists of four exons separated by three introns. Comparison of the marsupial coding sequence with coding sequences from eutherian species revealed 61 to 69% identity at the nucleotide level and 48 to 63% identity at the amino acid (aa) level. A polymorphic complex compound microsatellite was identified within intron 2 of the tammar wallaby IL5 gene. This microsatellite was also found in other marsupials including the swamp wallaby, tree kangaroo, stripe-faced dunnart, South American opossum, brushtail possum, and koala. Fluorescence in situ hybridization using DNA from the IL5 clone on tammar wallaby chromosomes indicated that the IL5 gene is located on Chromosome 1.

  12. Differential signalling for enhanced hexose uptake by interleukin (IL)-3 and IL-5 in male germ cells

    PubMed Central

    2004-01-01

    We studied the expression and function of the IL (interleukin)-3 and IL-5 family of receptors in male germ cells. RT (reverse transcription)-PCR showed expression of mRNAs encoding the α and β subunits of the IL-3 and IL-5 receptors in human testis, and the presence of IL-3 and IL-5 receptors α and β proteins was confirmed by immunoblotting with anti-α and anti-β antibodies. The immunolocalization studies showed expression of these receptors in the germ line in the human testis and in human and bovine ejaculated spermatozoa. Functional studies with bull spermatozoa indicated that IL-3 signalled for increased uptake of hexoses in these cells at picomolar concentrations compatible with expression of functional high-affinity IL-3 receptors in these cells. In contrast, IL-5 failed to induce increased hexose uptake in bull spermatozoa. Experiments using HL-60 eosinophils that express functional IL-3 and IL-5 receptors confirmed that IL-3, but not IL-5, signalled for increased hexose uptake. Our findings suggest that differential signalling for increased hexose uptake by heteromeric high-affinity IL-3 and IL-5 receptors in mammalian spermatozoa is a property that depends on the identity of the α-subunit forming part of the αβ-complex and is not a property specific to the germ cells. PMID:15018615

  13. Clinical significance of T-bet, GATA-3, and Bcl-6 transcription factor expression in bladder carcinoma.

    PubMed

    Bahria-Sediki, Islem Ben; Yousfi, Nadhir; Paul, Catherine; Chebil, Mohamed; Cherif, Mohamed; Zermani, Rachida; El Gaaied, Amel Ben Ammar; Bettaieb, Ali

    2016-05-30

    The aim of this study was to investigate the clinical significance of three immune cell-related transcription factors, T-bet, GATA-3 and Bcl-6 in bladder cancer in Tunisian patients. Expression of T-bet, GATA-3 and Bcl-6 genes was assessed using RT-qPCR in 65 bladder cancers from patients: 32 being diagnosed as low- and medium-grade, 31 as high-grade, 25 as muscle invasive stage and 39 as non-muscle invasive stage. Gene expression was statistically correlated according to the grade, the stage, tobacco consumption, the BCG response and disease severity. T-bet levels in patients with high-grade bladder cancer were significantly elevated compared to patients with low- or medium-grade bladder cancer (p = 0.005). In invasive carcinoma (T2-T4), the T-bet levels were significantly higher than in superficial non-invasive bladder tumors (Tis, Ta, and T1) (p = 0.02). However, T-bet is predictive of the response to BCG. Its expression is high in good responders to BCG (p = 0.02). In contrast, the expression of GATA-3 and Bcl-6 in non-invasive carcinoma (p = 0.008 and p = 0.0003) and in patients with low- and medium-grade cancers (p = 0.001 and p < 0.0001) is significantly higher than in invasive bladder tumors and in patients with high-grade bladder carcinoma, respectively. In addition, heavy smokers, whose tumors express low levels of GATA-3 and Bcl-6, are poor responders to BCG (p = 0.01 and p = 0.03). Finally, better patient survival correlated with GATA-3 (p = 0.04) and Bcl-6 (p = 0.04) but not T-bet expression. Our results suggest that T-bet expression in bladder tumors could be a positive prognostic indicator of BCG therapy, even if high levels are found in high-grade and stage of the disease. However, GATA-3 and Bcl-6 expression could be considered as predictive factors for good patient survival.

  14. Audiometric characteristics of a dutch family with a new mutation in GATA3 causing HDR syndrome.

    PubMed

    van Beelen, E; Leijendeckers, J M; Admiraal, R J C; Huygen, P L M; Hoefsloot, L H; Pennings, R J E; Snik, A F M; Kunst, H P M

    2014-01-01

    We present the case of a Dutch family with a new mutation (c523_528dup) in GATA3 causing HDR syndrome. HDR syndrome is characterised by hypoparathyroidism, deafness and renal defects. In this study, we describe the audiometric characteristics of 5 patients from this family. Their hearing impairment was congenital, bilateral and symmetric. Audiograms showed mild-to-moderate hearing impairment with a flat audiogram configuration. Higher frequencies tended to be affected more strongly. Cross-sectional analyses showed no progression, and a mean audiogram was established. Psychophysical measurements in 3 HDR patients - including speech reception in noise, loudness scaling, gap detection and difference limen for frequency - were obtained to assess hearing function in greater detail. Overall, the results of the psychophysical measurements indicated characteristics of outer hair cell loss. CT scanning showed no anomalies in 3 of the HDR patients. Although 2 patients displayed vestibular symptoms, no anomalies in the vestibular system were found by vestibulo-ocular examination. Our results are in agreement with the theory that outer hair cell malfunctioning can play a major role in HDR syndrome.

  15. GATA3 expression in clinically useful groups of breast carcinoma: a comparison with GCDFP15 and mammaglobin for identifying paired primary and metastatic tumors.

    PubMed

    Yang, Yuqiong; Lu, Shanming; Zeng, Wenqin; Xie, Shoucheng; Xiao, Shengjun

    2017-02-01

    GATA3 has been recognized as the novel marker for identifying primary and metastatic breast carcinomas, consistently showing that GATA3 was significantly more sensitive than traditional markers gross cystic disease fluid protein 15 (GCDFP15) and mammaglobin (MGB). However, clinically useful groups of breast carcinomas status were not identified, which were determining appropriate treatment strategy, affecting the prognosis. In this study, we undertook a comparative study of the marker GATA3 and GCDFP15 and MGB in clinically useful groups of paired primary and metastatic breast cancer. We retrieved 64 cases of matched primary and metastatic breast cancer from the surgical pathology archive at our institution. According to the emerging 2015 St. Gallen Consensus, the clinically useful groups were divided into ER and/or PR (+), HER2 (-), abbreviated as A; ER and/or PR (+), HER2 (+), abbreviated as B; ER and PR (-), HER2 (+), abbreviated as C; ER, PR and HER2 (-), abbreviated as D; each group contained 16 cases (n=16). Tissue microarrays were created, with three 1-mm punch specimens from each case. The tissue microarrays were cut at 4-μm thickness and stained with monoclonal antibodies to GATA3, GCDFP15, and MGB. Staining intensity (0-3+) and extent (0%-100%) were scored with an H-score calculated (range, 0-300). Sensitivities by varying H-score cutoffs (any; ≥50; ≥150) for a positive result in the clinically useful groups of matched primary or metastatic breast cancer among GATA3, GCDFP15, and MGB. GATA3 was significantly more sensitive than GCDFP15 and MGB A and B groups (P<.05) rather than C and D groups (P>.05). However, GATA3 in conjunction with GCDFP15 and MGB detection could improve the sensitivity of C group (P<.05) rather than D group (P>.05). Significantly, good coincidence was observed between primary and metastatic tumor GATA3 expression (κ value = 0.826 >0.75) as compared with the coincidence of GCDFP15 (κ value =0.492 <0.75) and MGB (κ value =0

  16. Unusual Proliferative Glomerulonephritis in a Patient Diagnosed to Have Hypoparathyroidism, Sensorineural Deafness, and Renal Dysplasia (HDR) Syndrome with a Novel Mutation in the GATA3 Gene.

    PubMed

    Kamezaki, Michitsugu; Kusaba, Tetsuro; Adachi, Takaomi; Yamashita, Noriyuki; Nakata, Mayumi; Ota, Noriyoshi; Shiotsu, Yayoi; Ishida, Mami; Usui, Takeshi; Tamagaki, Keiichi

    2017-01-01

    Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is a rare autosomal dominant disease caused by GATA3 mutations. Although several cases with variable renal features have been reported, the presence of histological changes within the glomeruli in adult patients is unclear. We herein report an adult case of HDR syndrome with a novel p.C288W (TGC>TGG) missense mutation in GATA3. His renal histology showed a membranoproliferative glomerulonephritis-like glomerular lesion. Additional renal histological analyses of HDR syndrome patients will be needed to clarify the role of GATA3 in both the developing and adult kidney.

  17. T-cell transcription factor GATA-3 is an immunophenotypic marker of acute leukemias with T-cell differentiation.

    PubMed

    Dorfman, David M; Morgan, Elizabeth A; Pelton, Ashley; Unitt, Christine

    2017-07-01

    T-cell transcription factor GATA-3, known to play a role in early T-cell development and in the development of T-cell neoplasms, is expressed at high levels in fetal and adult thymus, as well as in acute leukemias with T-cell differentiation, including T-lymphoblastic leukemia/lymphoma (22/22 cases), early T-cell precursor lymphoblastic leukemia (11/11 cases), and mixed-phenotype acute leukemia, T/myeloid (4/5 cases), but only rarely in acute myeloid leukemia/myeloid sarcoma (1/36 cases), and not in B-lymphoblastic leukemia (0/16 cases). In contrast, T-bet, the other T-cell transcription factor that controls Th1/Th2 T-cell fate, is not expressed to any significant extent in immature thymocytes or in cases of T-lymphoblastic leukemia or acute myeloid leukemia/myeloid sarcoma, but is expressed in most cases (15/16) of B-lymphoblastic leukemia and in mixed-phenotype acute leukemia, B/myeloid. GATA-3-positive acute leukemias with T-cell differentiation were also found to express proto-oncogene C-MYC, in an average of 52% of neoplastic cells, which, along with GATA-3, may contribute to leukemogenesis, as suggested by transgenic mouse models. We conclude that GATA-3 is a sensitive and specific marker for the diagnosis of acute leukemias with T-cell differentiation and may be a useful addition to the panel of immunophenotypic markers for the diagnostic evaluation of acute leukemias. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma

    PubMed Central

    Kakuki, Takuya; Kurose, Makoto; Takano, Ken-ichi; Kondoh, Atsushi; Obata, Kazufumi; Nomura, Kazuaki; Miyata, Ryo; Kaneko, Yakuto; Konno, Takumi; Takahashi, Syunta; Hatakeyama, Tsubasa; Kohno, Takayuki; Himi, Tetsuo; Kojima, Takashi

    2016-01-01

    Junctional adhesion molecule-A (JAM-A), which belongs to the IgG superfamily, is a tight junction molecule associated with epithelial and endothelial barrier function. Overexpression of JAM-A is also closely associated with invasion and metastasis of cancers such as breast cancer, lung cancer and pancreatic cancer. However, little is known about the mechanism in overexpression of JAM-A in head and neck squamous cell carcinoma (HNSCC). In the present study, we found high expression of JAM-A at the protein and mRNA levels in HNSCC tissues, including those of the oropharynx, larynx, and hypopharynx, together with high protein expression of β-catenin, p63, ΔNp63 and GATA-3. Furthermore, in ELISA, a significant increase of soluble JAM-A in the sera of HNSCC patients was observed compared to healthy subjects. Knockdown of JAM-A by siRNA inhibited cell proliferation, invasion and migration in the HNSCC cell line Detroit562 in vitro. JAM-A expression in Detroit562 was increased via a distinct signal transduction pathway including NF-κB. Expression of JAM-A, β-catenin, p63 and ΔNp63 in Detroit562 was decreased under hypoxia. Knockdown of p63, ΔNp63 or GATA-3 by siRNAs reduced JAM-A expression in Detroit562. In primary cultured HNSCC cells in which CK7, p63, ΔNp63 and GATA-3 were detected, JAM-A expression was decreased by knockdown of p63 or ΔNp63. These results indicate that JAM-A is a biomarker of malignancy in HNSCC and that plasma soluble JAM-A may contribute to serum-based diagnosis of HNSCC. The mechanism of dysregulation of JAM-A via p63/GATA-3 is important in possible molecular targeted therapy for HNSCC. PMID:27036044

  19. Dynamic Expression of Sox2, Gata3, and Prox1 during Primary Auditory Neuron Development in the Mammalian Cochlea

    PubMed Central

    Dabdoub, Alain

    2017-01-01

    Primary auditory neurons (PANs) connect cochlear sensory hair cells in the mammalian inner ear to cochlear nucleus neurons in the brainstem. PANs develop from neuroblasts delaminated from the proneurosensory domain of the otocyst and keep maturing until the onset of hearing after birth. There are two types of PANs: type I, which innervate the inner hair cells (IHCs), and type II, which innervate the outer hair cells (OHCs). Glial cells surrounding these neurons originate from neural crest cells and migrate to the spiral ganglion. Several transcription factors are known to regulate the development and differentiation of PANs. Here we systematically examined the spatiotemporal expression of five transcription factors: Sox2, Sox10, Gata3, Mafb, and Prox1 from early delamination at embryonic day (E) 10.5 to adult. We found that Sox2 and Sox10 were initially expressed in the proneurosensory cells in the otocyst (E10.5). By E12.75 both Sox2 and Sox10 were downregulated in the developing PANs; however, Sox2 expression transiently increased in the neurons around birth. Furthermore, both Sox2 and Sox10 continued to be expressed in spiral ganglion glial cells. We also show that Gata3 and Prox1 were first expressed in all developing neurons, followed by a decrease in expression of Gata3 and Mafb in type I PANs and Prox1 in type II PANs as they matured. Moreover, we describe two subtypes of type II neurons based on Peripherin expression. These results suggest that Sox2, Gata3 and Prox1 play a role during neurogenesis as well as maturation of the PANs. PMID:28118374

  20. Gain- and Loss-of-Function Mutations in the Breast Cancer Gene GATA3 Result in Differential Drug Sensitivity

    PubMed Central

    Kerzendorfer, Claudia; Salic, Sejla; Serra, Violeta; Muellner, Markus K.; Nijman, Sebastian M. B.

    2016-01-01

    Patterns of somatic mutations in cancer genes provide information about their functional role in tumourigenesis, and thus indicate their potential for therapeutic exploitation. Yet, the classical distinction between oncogene and tumour suppressor may not always apply. For instance, TP53 has been simultaneously associated with tumour suppressing and promoting activities. Here, we uncover a similar phenomenon for GATA3, a frequently mutated, yet poorly understood, breast cancer gene. We identify two functional classes of frameshift mutations that are associated with distinct expression profiles in tumours, differential disease-free patient survival and gain- and loss-of-function activities in a cell line model. Furthermore, we find an estrogen receptor-independent synthetic lethal interaction between a GATA3 frameshift mutant with an extended C-terminus and the histone methyltransferases G9A and GLP, indicating perturbed epigenetic regulation. Our findings reveal important insights into mutant GATA3 function and breast cancer, provide the first potential therapeutic strategy and suggest that dual tumour suppressive and oncogenic activities are more widespread than previously appreciated. PMID:27588951

  1. TNF-alpha and Notch signaling regulates the expression of HOXB4 and GATA3 during early T lymphopoiesis.

    PubMed

    Dos Santos Schiavinato, Josiane Lilian; Oliveira, Lucila Habib Bourguignon; Araujo, Amélia Goes; Orellana, Maristela Delgado; de Palma, Patrícia Viana Bonini; Covas, Dimas Tadeu; Zago, Marco Antonio; Panepucci, Rodrigo Alexandre

    2016-10-01

    During the early thymus colonization, Notch signaling activation on hematopoietic progenitor cells (HPCs) drives proliferation and T cell commitment. Although these processes are driven by transcription factors such as HOXB4 and GATA3, there is no evidence that Notch directly regulates their transcription. To evaluate the role of NOTCH and TNF signaling in this process, human CD34(+) HPCs were cocultured with OP9-DL1 cells, in the presence or absence of TNF. The use of a Notch signaling inhibitor and a protein synthesis inhibitor allowed us to distinguish primary effects, mediated by direct signaling downstream Notch and TNF, from secondary effects, mediated by de novo synthesized proteins. A low and physiologically relevant concentration of TNF promoted T lymphopoiesis in OP9-DL1 cocultures. TNF positively modulated the expression of both transcripts in a Notch-dependent manner; however, GATA3 induction was mediated by a direct mechanism, while HOXB4 induction was indirect. Induction of both transcripts was repressed by a GSK3β inhibitor, indicating that activation of canonical Wnt signaling inhibits rather than induces their expression. Our study provides novel evidences of the mechanisms integrating Notch and TNF-alpha signaling in the transcriptional induction of GATA3 and HOXB4. This mechanism has direct implications in the control of self-renewal, proliferation, commitment, and T cell differentiation.

  2. GATA-3 expression identifies a high-risk subset of PTCL, NOS with distinct molecular and clinical features.

    PubMed

    Wang, Tianjiao; Feldman, Andrew L; Wada, David A; Lu, Ye; Polk, Avery; Briski, Robert; Ristow, Kay; Habermann, Thomas M; Thomas, Dafydd; Ziesmer, Steven C; Wellik, Linda E; Lanigan, Thomas M; Witzig, Thomas E; Pittelkow, Mark R; Bailey, Nathanael G; Hristov, Alexandra C; Lim, Megan S; Ansell, Stephen M; Wilcox, Ryan A

    2014-05-08

    The cell of origin and the tumor microenvironment's role remain elusive for the most common peripheral T-cell lymphomas (PTCLs). As macrophages promote the growth and survival of malignant T cells and are abundant constituents of the tumor microenvironment, their functional polarization was examined in T-cell lymphoproliferative disorders. Cytokines that are abundant within the tumor microenvironment, particularly interleukin (IL)-10, were observed to promote alternative macrophage polarization. Macrophage polarization was signal transducer and activator of transcription 3 dependent and was impaired by the Janus kinase inhibitor ruxolitinib. In conventional T cells, the production of T helper (Th)2-associated cytokines and IL-10, both of which promote alternative macrophage polarization, is regulated by the T-cell transcription factor GATA-binding protein 3 (GATA-3). Therefore, its role in the T-cell lymphomas was examined. GATA-3 expression was observed in 45% of PTCLs, not otherwise specified (PTCL, NOS) and was associated with distinct molecular features, including the production of Th2-associated cytokines. In addition, GATA-3 expression identified a subset of PTCL, NOS with distinct clinical features, including inferior progression-free and overall survival. Collectively, these data suggest that further understanding the cell of origin and lymphocyte ontogeny among the T-cell lymphomas may improve our understanding of the tumor microenvironment's pathogenic role in these aggressive lymphomas.

  3. Clinical Auditory Phenotypes Associated with GATA3 Gene Mutations in Familial Hypoparathyroidism-deafness-renal Dysplasia Syndrome

    PubMed Central

    Wang, Li; Lin, Qiong-Fen; Wang, Hong-Yang; Guan, Jing; Lan, Lan; Xie, Lin-Yi; Yu, Lan; Yang, Ju; Zhao, Cui; Liang, Jin-Long; Zhou, Han-Lin; Yang, Huan-Ming; Xiong, Wen-Ping; Zhang, Qiu-Jing; Wang, Da-Yong; Wang, Qiu-Ju

    2017-01-01

    Background: Hypoparathyroidism-deafness-renal dysplasia (HDR) syndrome is an autosomal dominant disorder primarily caused by haploinsufficiency of GATA binding protein 3 (GATA3) gene mutations, and hearing loss is the most frequent phenotypic feature. This study aimed at identifying the causative gene mutation for a three-generation Chinese family with HDR syndrome and analyzing auditory phenotypes in all familial HDR syndrome cases. Methods: Three affected family members underwent otologic examinations, biochemistry tests, and other clinical evaluations. Targeted genes capture combining next-generation sequencing was performed within the family. Sanger sequencing was used to confirm the causative mutation. The auditory phenotypes of all reported familial HDR syndrome cases analyzed were provided. Results: In Chinese family 7121, a heterozygous nonsense mutation c.826C>T (p.R276*) was identified in GATA3. All the three affected members suffered from sensorineural deafness and hypocalcemia; however, renal dysplasia only appeared in the youngest patient. Furthermore, an overview of thirty HDR syndrome families with corresponding GATA3 mutations revealed that hearing impairment occurred earlier in the younger generation in at least nine familial cases (30%) and two thirds of them were found to carry premature stop mutations. Conclusions: This study highlights the phenotypic heterogeneity of HDR and points to a possible genetic anticipation in patients with HDR, which needs to be further investigated. PMID:28303854

  4. Electrostatic study of Alanine mutational effects on transcription: application to GATA-3:DNA interaction complex.

    PubMed

    El-Assaad, Atlal; Dawy, Zaher; Nemer, Georges

    2015-01-01

    Protein-DNA interaction is of fundamental importance in molecular biology, playing roles in functions as diverse as DNA transcription, DNA structure formation, and DNA repair. Protein-DNA association is also important in medicine; understanding Protein-DNA binding kinetics can assist in identifying disease root causes which can contribute to drug development. In this perspective, this work focuses on the transcription process by the GATA Transcription Factor (TF). GATA TF binds to DNA promoter region represented by `G,A,T,A' nucleotides sequence, and initiates transcription of target genes. When proper regulation fails due to some mutations on the GATA TF protein sequence or on the DNA promoter sequence (weak promoter), deregulation of the target genes might lead to various disorders. In this study, we aim to understand the electrostatic mechanism behind GATA TF and DNA promoter interactions, in order to predict Protein-DNA binding in the presence of mutations, while elaborating on non-covalent binding kinetics. To generate a family of mutants for the GATA:DNA complex, we replaced every charged amino acid, one at a time, with a neutral amino acid like Alanine (Ala). We then applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations, for each mutation. These calculations delineate the contribution to binding from each Ala-replaced amino acid in the GATA:DNA interaction. After analyzing the obtained data in view of a two-step model, we are able to identify potential key amino acids in binding. Finally, we applied the model to GATA-3:DNA (crystal structure with PDB-ID: 3DFV) binding complex and validated it against experimental results from the literature.

  5. GATA3 mRNA expression, but not mutation, associates with longer progression-free survival in ER-positive breast cancer patients treated with first-line tamoxifen for recurrent disease.

    PubMed

    Liu, Jingjing; Prager-van der Smissen, Wendy J C; Look, Maxime P; Sieuwerts, Anieta M; Smid, Marcel; Meijer-van Gelder, Marion E; Foekens, John A; Hollestelle, Antoinette; Martens, John W M

    2016-06-28

    In breast cancer, GATA3 mutations have been associated with a favorable prognosis and the response to neoadjuvant aromatase inhibitor treatment. Therefore, we investigated whether GATA3 mutations predict the outcome of tamoxifen treatment in the advanced setting. In a retrospective study consisting of 235 hormone-naive patients with ER-positive breast cancer who received tamoxifen as first-line treatment for recurrent disease, GATA3 mutations (in 14.0% of patients) did not significantly associate with either the overall response rate (ORR) or with the length of progression-free survival (PFS) after the start of tamoxifen therapy. Interestingly, among 148 patients for whom both mutation and mRNA expression data were available, GATA3 mutations associated with an increased expression of GATA3. However, only 23.7% of GATA3 high tumors had a mutation. Evaluation of the clinical significance of GATA3 mRNA revealed that it was associated with prolonged PFS, but not with the ORR, also in multivariate analysis. Thus, GATA3 mRNA expression, but not GATA3 mutation, is an independent predictor of prolonged PFS in ER-positive breast cancer patients who received first-line tamoxifen for recurrent disease. Besides GATA3 mutation, other mechanisms must exist that underlie increased GATA3 levels.

  6. RhIL-11 treatment normalized Th1/Th2 and T-bet/GATA-3 imbalance in in human immune thrombocytopenic purpura (ITP).

    PubMed

    Lin, Ying; Zhou, Xieming; Guo, Wenjian; Li, Qianqian; Pan, Xiahui; Bao, Yunhua; He, Muqing; Zhu, Baoling; Lin, Xiaoji; Jin, Limin; Yao, Rongxin

    2016-09-01

    Immune thrombocytopenia (ITP) is an autoimmune hemorrhagic disorder characterized by reduction in platelet counts. T helper 1 (Th1) cells polarization with an increased shift of Th1/Th2 ratio has been reported in ITP. This shift is associated with transcription factor T-box expressed in T cells (T-bet) upregulation and GATA-binding protein 3 (GATA-3) downregulation, leading to an increased T-bet/GATA-3 ratio. Our previous in vitro study showed that recombinant human interleukin-11 (rhIL-11) could normalize Th1/Th2 imbalance in the peripheral blood mononuclear cells (PBMCs) isolated from adult ITP patients, which co-occurred with T-bet/GATA-3 ratio restoration. In this report, we investigated whether rhIL-11 had therapeutic effect in clinical ITP patients and whether rhIL-11 treatment could normalize Th1/Th2 and T-bet/GATA-3 levels in vivo. We found rhIL-11 treatment had a response rate of 67.7% and significantly decreased Th1 and T-bet levels but increased Th2 and GATA-3 levels in ITP patients who showed good response, normalizing Th1/Th2 and T-bet/GATA-3 ratios similar to that in healthy controls. Thus our study suggested rhIL-11 was effective with tolerable adverse effects in ITP. The treatment strategy warrants further clinical investigation. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Benralizumab: a unique IL-5 inhibitor for severe asthma

    PubMed Central

    Tan, Laren D; Bratt, Jennifer M; Godor, Dorottya; Louie, Samuel; Kenyon, Nicholas J

    2016-01-01

    The presence of eosinophilic inflammation is a characteristic feature of chronic and acute inflammation in asthma. An estimated 5%–10% of the 300 million people worldwide who suffer from asthma have a severe form. Patients with eosinophilic airway inflammation represent approximately 40%–60% of this severe asthmatic population. This form of asthma is often uncontrolled, marked by refractoriness to standard therapy, and shows persistent airway eosinophilia despite glucocorticoid therapy. This paper reviews personalized novel therapies, more specifically benralizumab, a humanized anti-IL-5Rα antibody, while also being the first to provide an algorithm for potential candidates who may benefit from anti-IL-5Rα therapy. PMID:27110133

  8. A core transcriptional network composed of Pax2/8, Gata3 and Lim1 regulates key players of pro/mesonephros morphogenesis.

    PubMed

    Boualia, Sami Kamel; Gaitan, Yaned; Tremblay, Mathieu; Sharma, Richa; Cardin, Julie; Kania, Artur; Bouchard, Maxime

    2013-10-15

    Translating the developmental program encoded in the genome into cellular and morphogenetic functions requires the deployment of elaborate gene regulatory networks (GRNs). GRNs are especially crucial at the onset of organ development where a few regulatory signals establish the different programs required for tissue organization. In the renal system primordium (the pro/mesonephros), important regulators have been identified but their hierarchical and regulatory organization is still elusive. Here, we have performed a detailed analysis of the GRN underlying mouse pro/mesonephros development. We find that a core regulatory subcircuit composed of Pax2/8, Gata3 and Lim1 turns on a deeper layer of transcriptional regulators while activating effector genes responsible for cell signaling and tissue organization. Among the genes directly affected by the core components are the key developmental molecules Nephronectin (Npnt) and Plac8. Hence, the pro/mesonephros GRN links together several essential genes regulating tissue morphogenesis. This renal GRN sheds new light on the disease group Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) in that gene mutations are expected to generate different phenotypic outcomes as a consequence of regulatory network deficiencies rather than threshold effects from single genes.

  9. FOXC1 is involved in ERα silencing by counteracting GATA3 binding and is implicated in endocrine resistance

    PubMed Central

    Yu-Rice, Yi; Jin, Yanli; Han, Bingchen; Qu, Ying; Johnson, Jeffrey; Watanabe, Takaaki; Cheng, Long; Deng, Nan; Tanaka, Hisashi; Gao, Bowen; Liu, Zhenqiu; Sun, Zhijun; Bose, Shikha; Giuliano, Armando E.; Cui, Xiaojiang

    2016-01-01

    Estrogen receptor-α (ERα) mediates the essential biological function of estrogen in breast development and tumorigenesis. Multiple mechanisms, including pioneer factors, coregulators, and epigenetic modifications have been identified as regulators of ERα signaling in breast cancer. However, previous studies of ERα regulation have focused on luminal and HER2-positive subtypes rather than basal-like breast cancer (BLBC), in which ERα is underexpressed. In addition, mechanisms that account for the decrease or loss of ER expression in recurrent tumors after endocrine therapy remain elusive. Here, we demonstrate a novel FOXC1-driven mechanism that suppresses ERα expression in breast cancer. We find that FOXC1 competes with GATA3 for the same binding regions in the cis-regulatory elements (CREs) upstream of the ERα gene and thereby downregulates ERα expression and consequently its transcriptional activity. The forkhead domain of FOXC1 is essential for the competition with GATA3 for DNA binding. Counteracting the action of GATA3 at the ERα promoter region, overexpression of FOXC1 hinders recruitment of RNA polymerase II and increases histone H3K9 trimethylation at ERα promoters. Importantly, ectopic FOXC1 expression in luminal breast cancer cells reduces sensitivity to estrogen and tamoxifen. Furthermore, in breast cancer patients with ER-positive primary tumors who received adjuvant tamoxifen treatment, FOXC1 expression is associated with decreased or undetectable ER expression in recurrent tumors. Our findings highlight a clinically relevant mechanism that contributes to the low or absent ERα expression in BLBC. This study suggests a new paradigm to study ERα regulation during breast cancer progression and indicates a role of FOXC1 in the modulation of cellular response to endocrine treatment. PMID:27041579

  10. Immunohistochemical profile of the penile urethra and differential expression of GATA3 in urothelial versus squamous cell carcinomas of the penile urethra.

    PubMed

    Chaux, Alcides; Han, Jeong S; Lee, Stephen; Gonzalez-Roibon, Nilda; Sharma, Rajni; Burnett, Arthur L; Cubilla, Antonio L; Netto, George J

    2013-12-01

    The penile urethra has a distinctive morphology not yet fully characterized by immunohistochemistry. In addition, both urothelial and squamous cell carcinomas have been reported in the penile urethra, and the distinction between these 2 tumors might be difficult. The purposes of this study are to assess the histology and immunohistochemical profile (CK20, CK7, p63, and GATA3) of the penile urethra and to assess the usefulness of Trans-acting T-cell-specific transcription factor (GATA3) and human papillomavirus detection in distinguishing urothelial versus squamous cell carcinomas. Normal penile urethra was evaluated in 11 total penectomies. The penile urethra was lined by 2 cell layers: a superficial single layer of CK7+, CK20-, and p63- columnar cells and a deep stratified layer of CK7-, CK20-, and p63+ cubical cells. Both layers were GATA3+, supporting urothelial differentiation. In addition, 2 tissue microarrays and 6 surgical specimens of primary tumors of the penile urethra (3 urothelial and 3 squamous cell carcinomas) were evaluated for GATA3 expression. In the tissue microarrays, 22 of 25 upper tract urothelial carcinomas and 0 of 38 penile squamous cell carcinomas were GATA3+. In the surgical specimens, GATA3 was positive in all urothelial carcinomas and negative in all squamous cell carcinomas. Human papillomavirus was detected in 2 of 3 squamous cell carcinomas and in 0 of 3 of the urothelial carcinomas. In conclusion, the penile urethra is covered by epithelial cells that are unique in morphology and immunohistochemical profile. In addition, our study suggests that GATA3 and human papillomavirus detection are useful markers for distinguishing urothelial carcinomas from squamous cell carcinomas of the penile urethra.

  11. A Gata3–Mafb transcriptional network directs post-synaptic differentiation in synapses specialized for hearing

    PubMed Central

    Yu, Wei-Ming; Appler, Jessica M; Kim, Ye-Hyun; Nishitani, Allison M; Holt, Jeffrey R; Goodrich, Lisa V

    2013-01-01

    Information flow through neural circuits is determined by the nature of the synapses linking the subtypes of neurons. How neurons acquire features distinct to each synapse remains unknown. We show that the transcription factor Mafb drives the formation of auditory ribbon synapses, which are specialized for rapid transmission from hair cells to spiral ganglion neurons (SGNs). Mafb acts in SGNs to drive differentiation of the large postsynaptic density (PSD) characteristic of the ribbon synapse. In Mafb mutant mice, SGNs fail to develop normal PSDs, leading to reduced synapse number and impaired auditory responses. Conversely, increased Mafb accelerates synaptogenesis. Moreover, Mafb is responsible for executing one branch of the SGN differentiation program orchestrated by the Gata3 transcriptional network. Remarkably, restoration of Mafb rescues the synapse defect in Gata3 mutants. Hence, Mafb is a powerful regulator of cell-type specific features of auditory synaptogenesis that offers a new entry point for treating hearing loss. DOI: http://dx.doi.org/10.7554/eLife.01341.001 PMID:24327562

  12. Common increase of GATA-3 level in PC-12 cells by three teratogens causing autism spectrum disorders.

    PubMed

    Rout, Ujjwal K; Clausen, Pete

    2009-06-01

    Autism spectrum disorder (ASD) is a disease of neuro-developmental origin of uncertain etiology. The current understanding is that both genetic and environmental factors contribute to the development of ASD. Exposure to valproate, thalidomide and alcohol during gestation are amongst the environmental triggers that are associated with the development of ASD. These teratogens may disturb the ontogeny of the brain by altering the expression pattern of genes that regulate the normal development of the brain. In this study, a neuron-like PC-12 cell model was used to examine the effects of these compounds on the binding potential of 50 different transcription factors to understand the molecular mechanism/s that may be involved in the teratogenesis caused by these agents. Cells in culture were treated with low or high concentrations of teratogens within a range that are reported in the blood of individuals. A pronounced increase in GATA transcription factor binding was observed for all three teratogens. Furthermore, Western blot analysis showed that GATA-3 level in the nuclear fractions was enhanced by each of the three teratogens. Results suggest that altered gene expression pattern due to heightened GATA-3 activities in the fetral brains following exposure to these teratogens may contribute to the development of ASD.

  13. GATA3 induces human T-cell commitment by restraining Notch activity and repressing NK-cell fate

    PubMed Central

    Van de Walle, Inge; Dolens, Anne-Catherine; Durinck, Kaat; De Mulder, Katrien; Van Loocke, Wouter; Damle, Sagar; Waegemans, Els; De Medts, Jelle; Velghe, Imke; De Smedt, Magda; Vandekerckhove, Bart; Kerre, Tessa; Plum, Jean; Leclercq, Georges; Rothenberg, Ellen V.; Van Vlierberghe, Pieter; Speleman, Frank; Taghon, Tom

    2016-01-01

    The gradual reprogramming of haematopoietic precursors into the T-cell fate is characterized by at least two sequential developmental stages. Following Notch1-dependent T-cell lineage specification during which the first T-cell lineage genes are expressed and myeloid and dendritic cell potential is lost, T-cell specific transcription factors subsequently induce T-cell commitment by repressing residual natural killer (NK)-cell potential. How these processes are regulated in human is poorly understood, especially since efficient T-cell lineage commitment requires a reduction in Notch signalling activity following T-cell specification. Here, we show that GATA3, in contrast to TCF1, controls human T-cell lineage commitment through direct regulation of three distinct processes: repression of NK-cell fate, upregulation of T-cell lineage genes to promote further differentiation and restraint of Notch activity. Repression of the Notch1 target gene DTX1 hereby is essential to prevent NK-cell differentiation. Thus, GATA3-mediated positive and negative feedback mechanisms control human T-cell lineage commitment. PMID:27048872

  14. Myocardial Gene Expression of T-bet, GATA-3, Ror-γt, FoxP3, and Hallmark Cytokines in Chronic Chagas Disease Cardiomyopathy: An Essentially Unopposed TH1-Type Response

    PubMed Central

    Nogueira, Luciana Gabriel; Santos, Ronaldo Honorato Barros; Fiorelli, Alfredo Inácio; Mairena, Eliane Conti; Benvenuti, Luiz Alberto; Bocchi, Edimar Alcides; Stolf, Noedir Antonio; Kalil, Jorge; Cunha-Neto, Edecio

    2014-01-01

    Background. Chronic Chagas disease cardiomyopathy (CCC), a late consequence of Trypanosoma cruzi infection, is an inflammatory cardiomyopathy with prognosis worse than those of noninflammatory etiology (NIC). Although the T cell-rich myocarditis is known to play a pathogenetic role, the relative contribution of each of the functional T cell subsets has never been thoroughly investigated. We therefore assessed gene expression of cytokines and transcription factors involved in differentiation and effector function of each functional T cell subset (TH1/TH2/TH17/Treg) in CCC, NIC, and heart donor myocardial samples. Methods and Results. Quantitative PCR showed markedly upregulated expression of IFN-γ and transcription factor T-bet, and minor increases of GATA-3; FoxP3 and CTLA-4; IL-17 and IL-18 in CCC as compared with NIC samples. Conversely, cytokines expressed by TH2 cells (IL-4, IL-5, and IL-13) or associated with Treg (TGF-β and IL-10) were not upregulated in CCC myocardium. Expression of TH1-related genes such as T-bet, IFN-γ, and IL-18 correlated with ventricular dilation, FoxP3, and CTLA-4. Conclusions. Results are consistent with a strong local TH1-mediated response in most samples, possibly associated with pathological myocardial remodeling, and a proportionally smaller FoxP3+CTLA4+ Treg cell population, which is unable to completely curb IFN-γ production in CCC myocardium, therefore fueling inflammation. PMID:25152568

  15. T-bet, GATA-3 and Foxp3 expression and Th1/Th2 cytokine production in the clinical outcome of human infection with Leishmania Viannia species

    PubMed Central

    Díaz, Yira Rosalba; Rojas, Ricardo; Valderrama, Liliana; Saravia, Nancy Gore

    2010-01-01

    Background T cell differentiation determines susceptibility and resistance to experimental cutaneous leishmaniasis, yet mixed T1/Th2 responses characterize the clinical spectrum of human infection with Leishmania Viannia species. Materials and Methods To discern the inter-relationship of T cell differentiation and outcome of human infection, we examined factors that regulate T cell differentiation and Th1/Th2 cytokine responses in asymptomatic infection, active and historical chronic and recurrent cutaneous leishmaniasis. T-bet, GATA-3, Foxp3 and cytokine gene expression were quantified by real time PCR, and correlated with IL-2, IFN-γ, TNF-α, IL-4, IL-13, IL-10 secretion during in vitro response to live L. panamensis. Results Higher GATA-3 than T-bet expression occurred throughout the 15 days of co-culture with promastigotes, however neither transcription nor secretion of IL-4 was detected. Sustained, inverse correlation between GATA-3 expression and secretion of proinflammatory cytokines IFN-γ and TNF-α was observed in asymptomatic infection. In contrast, higher T-bet expression and T-bet:GATA-3 ratio characterized active recurrent disease. Down-regulation of T-bet and GATA-3 expression and increased IL-2 secretion compared to control was directly correlated with Foxp3 expression and IL-13 secretion in chronic disease. Conclusions Regulation of the inflammatory response rather than biased Th1/Th2 response distinguished asymptomatic and recalcitrant outcomes of infection with Leishmnania Viannia species. PMID:20583921

  16. Correlation between the ratio of T-bet/GATA-3 and the levels of IL-4 and IFN-γ in patients with allergic asthma.

    PubMed

    Yong, Ji; Chen, Guo-Qiang; Huang, Bin; Wu, Song

    2011-01-01

    The aim of this study was to investigate the ratio of the transcription factors T-bet/GATA-3 in patients with allergic asthma. Forty-seven individuals with allergic asthma and 47 healthy control individuals provided 5 ml of anticoagulated peripheral venous blood. Lymphocytes in peripheral blood were isolated by Ficoll and treated with phytohemagglutinin (PHA) at a final concentration of 100 mg/l for 48 h. Interferon-γ (IFN-γ) and interleukin-4 (IL-4) levels were detected using an enzyme-linked immunosorbent assay (ELISA), and the mRNA levels of both T-bet and GATA-3 were detected using reverse transcription polymerase chain reaction (RT-PCR). IFN-γ levels in the lymphocytes of asthmatic patients were lower than those of the control group (P<0.05) and were positively correlated with the ratio of T-bet/GATA-3. By contrast, IL-4 levels were significantly higher in asthmatic patients than in the control group (P<0.01) and were negatively correlated with the ratio of T-bet/GATA-3. In conclusion, the ratio of T-bet/GATA-3 can be used as an objective indicator of immune imbalance in patients with allergic asthma.

  17. The Runx1 Transcription Factor Inhibits the Differentiation of Naive CD4+ T Cells into the Th2 Lineage by Repressing GATA3 Expression

    PubMed Central

    Komine, Okiru; Hayashi, Keitaro; Natsume, Waka; Watanabe, Toshio; Seki, Youichi; Seki, Noriyasu; Yagi, Ryoji; Sukzuki, Wataru; Tamauchi, Hidekazu; Hozumi, Katsuto; Habu, Sonoko; Kubo, Masato; Satake, Masanobu

    2003-01-01

    Differentiation of naive CD4+ T cells into helper T (Th) cells is controlled by a combination of several transcriptional factors. In this study, we examined the functional role of the Runx1 transcription factor in Th cell differentiation. Naive T cells from transgenic mice expressing a dominant interfering form of Runx1 exhibited enhanced interleukin 4 production and efficient Th2 differentiation. In contrast, transduction of Runx1 into wild-type T cells caused a complete attenuation of Th2 differentiation and was accompanied by the cessation of GATA3 expression. Furthermore, endogenous expression of Runx1 in naive T cells declined after T cell receptor stimulation, at the same time that expression of GATA3 increased. We conclude that Runx1 plays a novel role as a negative regulator of GATA3 expression, thereby inhibiting the Th2 cell differentiation. PMID:12835475

  18. Detailed analysis of the IL-5-IL-5R alpha interaction: characterization of crucial residues on the ligand and the receptor.

    PubMed Central

    Cornelis, S; Plaetinck, G; Devos, R; Van der Heyden, J; Tavernier, J; Sanderson, C J; Guisez, Y; Fiers, W

    1995-01-01

    The receptor for interleukin-5 (IL-5) is composed of two different subunits. The IL-5 receptor alpha (IL-5R alpha) is required for ligand-specific binding while association with the beta-chain results in increased binding affinity. Murine IL-5 (mIL-5) has similar activity on human and murine cells, whereas human IL-5 (hIL-5) has marginal activity on murine cells. We found that the combined substitution of K84 and N108 on hIL-5 by their respective murine counterpart yields a molecule which is as potent as mIL-5 for growth stimulation of a murine cell line. Since the unidirectional species specificity is due only to the interaction with the IL-5R alpha subunit, we have used chimeric IL-5R alpha molecules to define regions of hIL-5R alpha involved in species-specific hIL-5 ligand binding. We found that this property is largely determined by the NH2-terminal module of hIL-5R alpha, and detailed analysis defined D56 and to a lesser extent E58 as important for binding. Moreover, two additional residues, D55 and Y57, were identified by alanine scanning mutagenesis within the same region. Based on the observed homology between the NH2-terminal module and the membrane proximal (WSXWS-containing) module of hIL-5R alpha we located this stretch of four amino acid residues (D55, D56, Y57 and E58) in the loop region that connects the C and D beta-strands on the proposed tertiary structure of the NH2-terminal module.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:7628440

  19. [Application of immunohistochemistry for p16 and GATA3 and molecular HPV typing in diagnosis of secondary bladder involvement by cervical carcinoma].

    PubMed

    Huang, R F; He, C; Zhu, W F; Li, Y; Chen, G

    2017-06-08

    Objective: To investigate the expression of p16 and GATA3 and the detection of human papillomavirus (HPV) in secondary bladder involvement by cervical carcinomas. Methods: Sixteen cases of cervical carcinoma with bladder involvement diagnosed from December 2008 to March 2016 were collected and evaluated by light microscopy, immunohistochemistry for p16 and GATA3 detection and PCR-reverse dot blot for molecular typing of HPV. Results: The age of the patients ranged from 25 to 76 years with median of 52 years. Morphologically, 14 cases(14/16) showed tumor nests infiltrating lamina propria or muscle bundles of the bladder. By immunohistochemistry, 15 cases (15/16) were found to be diffusely and strongly positive for p16, and 1 showed patchy staining pattern. Seven cases (7/7) of corresponding original cervical cancers were also diffusely and strongly positive for p16. GATA3 staining was negative in 13 cases (13/16), and focal weak to moderate positivity was detected in 3 cases.Three cases (3/7) of corresponding original cervical cancers showed focal weak to moderate positivity of GATA3. Fifteen cases (15/16) showed concordant high risk HPV-positivity, including HPV16 in 8 cases and HPV31 in one case. Five cases showed co-infection of HPV16 and HPV18. One case showed co-infection with HPV18 and HPV45. Conclusion: Differential diagnosis by p16 or GATA3 alone is of limited value. Combination of immunohistochemistry for p16 and GATA3 and molecular typing for HPV detection are useful to distinguish primary bladder carcinoma from the secondary involvement by cervical carcinoma.

  20. Promoter activity 5′ of Dbeta2 is coordinated by E47, Runx1, and GATA-3

    PubMed Central

    McMillan, Ruth E.; Sikes, Michael L.

    2009-01-01

    V(D)J recombination involves the stepwise assembly of B and T cell receptor genes as lymphocytes progress through the early stages of development. While the mechanisms that restrict each step in recombination to its appropriate developmental stage are largely unknown, they share many of the components that regulate transcription. For example, enhancer-dependent modifications in histone acetylation and methylation are essential for both germline transcription and rearrangement of antigen receptor genes. Promoters positioned proximal to individual D and J gene segments in Tcra, Tcrb, Tcrd, IgH, and Igk also contribute to antigen receptor gene assembly, though their effects appear more localized than those of enhancers. Tcrb assembly initiates with D-to-J joining at each of two D-J-C gene segment clusters in DN1/2 thymocytes. DJ joints are fused with Vβ elements to complete Tcrb recombination in DN3 cells. We have previously shown that Dβ2 is flanked by upstream and downstream promoters, with the 5′ promoter being held inactive until D-to-J recombination deletes the NFκB-dependent 3′ promoter. We now report that activity of the 5′ promoter reflects a complex interplay between Runx1, GATA-3, and E47 transcription factors. In particular, while multiple E47 and Runx1 binding sites clustered near the Dβ2 5′RS and overlapping inr elements define the core 5′PDβ2, they act in concert with an array of upstream GATA-3 sites to overcome the inhibitory effects of a 110 bp distal polypurine·polypyrimidine (R·Y) tract. The dependence of 5′PDβ2 on E47 is consistent with the reported role of E proteins in post-DN1 thymocyte development and V-to-DJβ recombination. PMID:19592096

  1. Modulation of growth and differentiation of eosinophils from human peripheral blood CD34+ cells by IL5 and other growth factors.

    PubMed

    Shalit, M; Sekhsaria, S; Malech, H L

    1995-01-01

    independent. Using reverse-transcriptase polymerase chain reaction, the mRNA encoding the eosinophil-specific protein eosinophil peroxidase (EPO) was not detected in Day 0 CD34+ cells, but was demonstrated by Day 3 of culture. We conclude that within 3 days of culture, peripheral blood CD34+ cells can become committed to the eosinophil lineage as demonstrated by responsiveness to IL5 and production of EPO transcripts.

  2. Absent, small or homeotic 2-like protein (ASH2L) enhances the transcription of the estrogen receptor α gene through GATA-binding protein 3 (GATA3).

    PubMed

    Qi, Jin; Huo, Lei; Zhu, Yiwei Tony; Zhu, Yi-Jun

    2014-11-07

    ASH2L is a component of MLL complexes that confer H3K4 trimethylation. The ASH2L gene is located at 8q11-12, which is often amplified in breast cancers. We found that increased ASH2L expression, which can result from gene amplification, is often correlated with increased ERα expression in both breast cancer cell lines and primary breast cancers. Forced expression of ASH2L induced ERα expression in mammary epithelial cells, whereas depletion of ASH2L suppressed ERα expression in breast cancer cells. To understand the mechanism by which ASH2L regulates ERα expression, we identified GATA3 as the binding protein of ASH2L. ASH2L was shown to potentiate the transcriptional activity of GATA3. ASH2L was recruited to the enhancer of the ERα gene through GATA3 to promote ERα transcription. This study established that ASH2L enhances ERα expression as a coactivator of GATA3 in breast cancers. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  3. Tumour-associated changes in intestinal epithelial cells cause local accumulation of KLRG1(+) GATA3(+) regulatory T cells in mice.

    PubMed

    Meinicke, Holger; Bremser, Anna; Brack, Maria; Akeus, Paulina; Pearson, Claire; Bullers, Samuel; Hoffmeyer, Katrin; Stemmler, Marc P; Quiding-Järbrink, Marianne; Izcue, Ana

    2017-09-01

    CD4(+) Foxp3(+) regulatory T (Treg) cells include differentiated populations of effector Treg cells characterized by the expression of specific transcription factors. Tumours, including intestinal malignancies, often present with local accumulation of Treg cells that can prevent tumour clearance, but how tumour progression leads to Treg cell accumulation is incompletely understood. Here using genetically modified mouse models we show that ablation of E-cadherin, a process associated with epithelial to mesenchymal transition and tumour progression, promotes the accumulation of intestinal Treg cells by the specific accumulation of the KLRG1(+) GATA3(+) Treg subset. Epithelial E-cadherin ablation activates the β-catenin pathway, and we find that increasing β-catenin signals in intestinal epithelial cells also boosts Treg cell frequencies through local accumulation of KLRG1(+) GATA3(+) Treg cells. Both E-cadherin ablation and increased β-catenin signals resulted in epithelial cells with higher levels of interleukin-33, a cytokine that preferentially expands KLRG1(+) GATA3(+) Treg cells. Tumours often present reduced E-cadherin expression and increased β-catenin signalling and interleukin-33 production. Accordingly, Treg cell accumulation in intestinal tumours from APC(min/+) mice was exclusively due to the increase in KLRG1(+) GATA3(+) Treg cells. Our data identify a novel axis through which epithelial cells control local Treg cell subsets, which may be activated during intestinal tumorigenesis. © 2017 John Wiley & Sons Ltd.

  4. T cell factor 1 initiates the T helper type 2 fate by inducing the transcription factor GATA-3 and repressing interferon-γ

    PubMed Central

    Yu, Qing; Sharma, Archna; Oh, Sun Young; Moon, Hyung-Geun; Hossain, M Zulfiquer; Salay, Theresa M; Leeds, Karen E; Du, Hansen; Wu, Beibei; Waterman, Marian L; Zhu, Zhou; Sen, Jyoti Misra

    2010-01-01

    The differentiation of activated CD4+ T cells into the T helper type 1 (TH1) or TH2 fate is regulated by cytokines and the transcription factors T-bet and GATA-3. Whereas interleukin 12 (IL-12) produced by antigen-presenting cells initiates the TH1 fate, signals that initiate the TH2 fate are not completely characterized. Here we show that early GATA-3 expression, required for TH2 differentiation, was induced by T cell factor 1 (TCF-1) and its cofactor β-catenin, mainly from the proximal Gata3 promoter upstream of exon 1b. This activity was induced after T cell antigen receptor (TCR) stimulation and was independent of IL-4 receptor signaling through the transcription factor STAT6. Furthermore, TCF-1 blocked TH1 fate by negatively regulating interferon-γ (IFN-γ) expression independently of β-catenin. Thus, TCF-1 initiates TH2 differentiation of activated CD4+ T cells by promoting GATA-3 expression and suppressing IFN-γ expression. PMID:19648923

  5. Simultaneous carcinomas of the breast and ovary: utility of Pax-8, WT-1, and GATA3 for distinguishing independent primary tumors from metastases.

    PubMed

    Espinosa, Inigo; Gallardo, Alberto; D'Angelo, Emanuela; Mozos, Ana; Lerma, Enrique; Prat, Jaime

    2015-05-01

    Breast carcinomas rarely metastasize to the ovary and are even more rarely present clinically as primary ovarian tumors. However, patients with breast cancer not infrequently develop independent primary ovarian carcinomas. In these cases, distinction between independent primaries and metastatic tumors is crucial. Several comparative immunohistochemical studies have been reported, but few included significant clinicopathologic data and none investigated cases of ovarian and breast carcinomas from the same patients. In this study, we compared 18 cases of patients with bona fide independent breast and ovarian carcinomas (15 high-grade serous and 3 clear cell carcinomas), with 9 cases of patients with known mammary carcinomas (7 lobular and 2 ductal carcinomas) metastatic to the ovary. Immunohistochemical stains for Pax-8, WT-1, and GATA3 were carried out on tissue microarrays (TMA). Most primary ovarian carcinomas were larger than the metastatic tumors (P=0.001) and were diagnosed at an advanced stage. All primary ovarian tumors showed marked nuclear pleomorphism, whereas only 2 metastatic breast carcinomas had Grade 3 nuclei (P=0.000). The vast majority of ovarian metastases (7/9) showed the typical pattern of lobular breast carcinoma. Pax-8 and WT-1 expression were found in 16 of 18 (88%) and 13 of 18 (72%) primary ovarian carcinomas, respectively. In contrast, all primary ovarian carcinomas were negative for GATA3. The 2 Pax-8-negative ovarian carcinomas were also negative for WT-1. With the exception of 3 triple-negative carcinomas, all primary breast carcinomas were positive for GATA3. All metastatic breast carcinomas were positive for GATA3 and negative for Pax-8. WT-1 expression was seen in only 1 of 9 metastatic breast carcinomas (11%). Patients with ovarian metastases had worse prognosis than patients with independent breast and ovarian carcinomas (P=0.000). Pax-8, WT-1, and GATA3 immunoreactions are useful in the distinction between independent primaries and

  6. Solanum paniculatum L. decreases levels of inflammatory cytokines by reducing NFKB, TBET and GATA3 gene expression in vitro.

    PubMed

    Rios, Raimon; Silva, Hugo Bernardino Ferreira da; Carneiro, Norma Vilany Queiroz; Pires, Anaque de Oliveira; Carneiro, Tamires Cana Brasil; Costa, Ryan Dos Santos; Marques, Cintia Rodrigues; Machado, Marta Santos Serafim; Velozo, Eudes da Silva; Silva, Telma M G da; Silva, Tania M S da; Conceição, Adilva de Souza; Alcântara-Neves, Neuza Maria; Figueiredo, Camila Alexandrina

    2017-09-14

    Solanum paniculatum L., popularly known as jurubeba, is a common subtropical plant from Brazil, Paraguay, Bolivia and Argentina, that is used in folk medicine for the treatment of anemia, gastrointestinal disorders and inflammatory conditions in general. In addition to that, an ethnobotanical survey in "Todos os Santos" Bay have pointed out S. paniculatum as an herb to treat asthma. Previous publications have shown that S. paniculatum possesses antibiotic, antioxidant and modulatory effects on gastric acid secretion; however, its anti-inflammatory potential remains unexplored. Herein, we analyzed the S. paniculatum fruits hexane extract (SpE) for the presence of stigmasterol and β-sitosterol and investigated the anti-inflammatory effect of SpE in vitro. SpE was subjected to high-performance liquid chromatography (HPLC) for standardization and quantification of stigmasterol and β-sitosterol. Spleen cells from BALB/c mice were cultivated and stimulated with pokeweed mitogen and also exposed to 15, 30 and 60µg/mL of SpE. Following treatment, levels of IFN-γ, IL-4 and IL-10 in the culture supernatants were assessed by ELISA. We also evaluated nitric oxide (NO) production by murine LPS-stimulated peritoneal macrophages using the Griess technique. In addition, the ability of SpE to stabilize membranes was assessed using a model of hemolysis induced by heat on murine erythrocytes. Gene expression of Th1-cell-specific Tbx21 transcription factor (TBET), zinc-finger transcription factor-3 (GATA3), and nuclear factor-κB (NFKB) in murine spleen cells were assessed by quantitative Polymerase Chain Reaction (qRT-PCR). SpE at 15, 30 and 60µg/mL significantly attenuated cell proliferation, decreased IL-4 release, reduced NO production and improved erythrocyte membrane stabilization in a concentration-dependent manner. SpE was also able to decrease the release of IFN-γ without altering IL-10 levels. The mechanism whereby SpE decreased inflammatory markers may be related to

  7. Biodistribution of the GATA-3-specific DNAzyme hgd40 after inhalative exposure in mice, rats and dogs

    SciTech Connect

    Turowska, Agnieszka; Librizzi, Damiano; Baumgartl, Nadja; Kuhlmann, Jens; Dicke, Tanja; Merkel, Olivia; Homburg, Ursula; Höffken, Helmut; Renz, Harald; Garn, Holger

    2013-10-15

    The DNAzyme hgd40 was shown to effectively reduce expression of the transcription factor GATA-3 RNA which plays an important role in the regulation of Th2-mediated immune mechanisms such as in allergic bronchial asthma. However, uptake, biodistribution and pharmacokinetics of hgd40 have not been investigated yet. We examined local and systemic distribution of hgd40 in naive mice and mice suffering from experimental asthma. Furthermore, we evaluated the pharmacokinetics as a function of dose following single and repeated administration in rats and dogs. Using intranasal administration of fluorescently labeled hgd40 we demonstrated that the DNAzyme was evenly distributed in inflamed asthmatic mouse lungs within minutes after single dose application. Systemic distribution was investigated in mice using radioactive labeled hgd40. After intratracheal application, highest amounts of hgd40 were detected in the lungs. High amounts were also detected in the bladder indicating urinary excretion as a major elimination pathway. In serum, low systemic hgd40 levels were detected already at 5 min post application (p.a.), subsequently decreasing over time to non-detectable levels at 2 h p.a. As revealed by Single Photon Emission Computed Tomography, trace amounts of hgd40 were detectable in lungs up to 7 days p.a. Also in the toxicologically relevant rats and dogs, hgd40 was detectable in blood only shortly after inhalative application. The plasma pharmacokinetic profile was dose and time dependent. Repeated administration did not lead to drug accumulation in plasma of dogs and rats. These pharmacokinetic of hgd40 provide guidance for clinical development, and support an infrequent and convenient dose administration regimen. - Highlights: • Local and systemic distribution of GATA-3-specific DNAzyme hgd40 was investigated. • Pharmacokinetics of hgd40 was tested in rats and dogs. • hgd40 dissolved in PBS was easily taken up into the lungs after local application. • No

  8. Florfenicol inhibits allergic airway inflammation in mice by p38 MAPK-mediated phosphorylation of GATA 3.

    PubMed

    Xinxin, Ci; Chi, Chen; Xiao, Chu; Xue, Xu; Yongjun, Yang; Junqing, Cui; Xuming, Deng

    2011-02-01

    Florfenicol has been shown to possess anti-inflammatory activity. However, its possible use for asthma has not yet been studied. First we investigated the anti-inflammatory properties of florfenicol using mice asthma model. BALB/c mice were immunized and challenged by ovalbumin. Treatment with florfenicol caused a marked reduction in inflammatory cells and three Th2 type cytokines in the bronchoalveolar lavage fluids of mice. The levels of ovalbumin-specific IgE and airway hyperresponsiveness were significantly altered after treatment with florfenicol. Histological studies using H&E and AB-PAS staining demonstrate that florfenicol substantially inhibited ovalbumin-induced inflammatory cells infiltration in lung tissue and goblet cell hyperplasia in the airway. These results were similar to those obtained with dexamethasone treatment. We then investigated which signal transduction mechanisms could be implicated in florfenicol activity. Our results suggested that the protective effect of florfenicol was mediated by the inhibition of the p38 MAPK-mediated phosphorylation of GATA 3.

  9. Infection of IL5 transgenic mice with Mesocestoides corti induces very high levels of IL5 but depressed production of eosinophils.

    PubMed

    Strath, M; Dent, L; Sanderson, C

    1992-02-01

    Transgenic mice expressing interleukin 5 (IL5) have been demonstrated to show a lifelong high level eosinophilia. These mice were produced using a construct in which the dominant control region (DCR) of the human CD2 gene was ligated to a 10-kb fragment containing the mouse IL5 gene. The construct allows the expression of the IL5 gene under the control of its own promoter, but the DCR ensures constitutive expression by all T cells. Infection of these transgenic mice with Mesocestoides corti, which is itself a potent inducer of eosinophilia, increases serum IL5 to very high levels. This demonstrates that the transgenes retain inducibility, which is a feature of the endogenous gene. However, despite the high levels of IL5, the numbers of eosinophils in the blood, marrow, and spleen decrease during the period 1-4 weeks after infection. Furthermore, there is a decrease in eosinophil precursors, as assessed by the capacity of bone marrow to produce eosinophils in culture. After this decrease eosinophils return to their previous high levels, although the levels of IL5 remain high. These results suggest that a control mechanism is operating to limit the numbers of eosinophils produced. This control appears to act at the level of the precursor production and may not be directly related to the high levels of IL5.

  10. Biosensor analysis of dynamics of interleukin 5 receptor subunit beta(c) interaction with IL5:IL5R(alpha) complexes.

    PubMed

    Scibek, Jeffery J; Evergren, Emma; Zahn, Stefan; Canziani, Gabriela A; Van Ryk, Donald; Chaiken, Irwin M

    2002-08-15

    To gain insight into IL5 receptor subunit recruitment mechanism, and in particular the experimentally elusive pathway for assembly of signaling subunit beta(c), we constructed a soluble beta(c) ectodomain (s(beta)(c)) and developed an optical biosensor assay to measure its binding kinetics. Functionally active s(beta)(c) was anchored via a C-terminal His tag to immobilized anti-His monoclonal antibodies on the sensor surface. Using this surface, we quantitated for the first time direct binding of s(beta)(c) to IL5R(alpha) complexed to either wild-type or single-chain IL5. Binding was much weaker if at all with either R(alpha) or IL5 alone. Kinetic evaluation revealed a moderate affinity (0.2-1 microM) and relatively fast off rate for the s(beta)(c) interaction with IL5:R(alpha) complexes. The data support a model in which beta(c) recruitment occurs with preformed IL5:R(alpha) complex. Dissociation kinetics analysis suggests that the IL5-alpha-beta(c) complex is relatively short-lived. Overall, this study solidifies a model of sequential recruitment of receptor subunits by IL5, provides a novel biosensor binding assay of beta(c) recruitment dynamics, and sets the stage for more advanced characterization of the roles of structural elements within R(alpha), beta(c), and cytokines of the IL5/IL3/GM-CSF family in receptor recruitment and activation.

  11. The effect of synthetic salidroside on cytokines and airway inflammation of asthma induced by diisocyanate (TDI) in mice by regulating GATA3/T-bet.

    PubMed

    Wang, Jing; Xiao, Lu; Zhu, Lingpeng; Hu, Mei; Wang, Qiujuan; Yan, Tianhua

    2015-04-01

    This study was conducted to explore the anti-asthma effects of synthetic salidroside on cytokines and airway inflammation of asthma induced by diisocyanate (TDI) in mice. The experiment was carried out 60 female BALB/C mice which were randomly assigned to six experimental groups: control, vehicle, model, dexamethasone (2 mg/kg), and salidroside (24 and 48 mg/kg). After the experiment, histological studies were evaluated by the hematoxylin and eosin staining, the bronchoalveolar lavage fluid (BALF) and blood were collected from the animals, and the composition of the induced inflammatory cells, and the concentrations of certain cytokines (IL-4, INF-γ) were evaluated. GATA3 and T-bet mRNAs were evaluated by QPCR. Our study demonstrated that salidroside inhibited TDI-induced increases in eosinophil count; IL-4 and INF-γ were recovered. Histological studies demonstrated that salidroside substantially inhibited TDI-induced eosinophilia in lung tissue. Salidroside can improve T-bet mRNA and reduce GATA3 mRNA in lung. These findings suggest that salidroside may effectively ameliorate the progression of asthma and could be used as a therapy for patients with allergic asthma by regulating GATA3/T-bet balance.

  12. GATA3 rs3824662 gene polymorphism as possible risk factor in a cohort of Egyptian patients with pediatric acute lymphoblastic leukemia and its prognostic impact.

    PubMed

    Mosaad, Youssef M; Elashery, Rasha; Darwish, Ahmad; Sharaf Eldein, Omar A; Barakat, Tarek; Marouf, Samy; Abou El-Khier, Noha T; Youssef, Laila F; Fawzy, Iman M

    2017-03-01

    To investigate the possible role of GATA3 rs3824662 polymorphism as risk factor for the development of acute lymphoblastic leukemia (ALL) in a cohort of Egyptian children and to evaluate its prognostic role. Typing of GATA3 rs3824662 polymorphism was done using real-time PCR for 116 patients with ALL and 273 healthy controls. The A allele and AA genotype were significantly higher in ALL patients (p = .015 and .016, respectively) especially B-ALL (p = .014 and .01, respectively). The AA genotype was associated with shorter disease free survival (DFS) in univariate (p = .017) and multivariate cox regression analysis (p = .028), increased incidence of relapse (p = .008) and poor prognosis (p = .028) in pediatric ALL. The GATA3 rs3824662 A allele and AA genotype may be risk factors for the development of pediatric ALL especially B-ALL in the studied cohort of Egyptian patients. The AA genotype is associated with shorter DSF, increased incidence of relapse and poor prognosis in pediatric ALL.

  13. The conserved lymphokine element-0 in the IL5 promoter binds to a high mobility group-1 protein.

    PubMed

    Marrugo, J; Marsh, D G; Ghosh, B

    1996-10-01

    The conserved lymphokine elements-0 (CLE0) in the IL5 promoter is essential for the expression of IL-5. Here, we report the cloning and expression of a cDNA encoding a novel CLE0-binding protein, CLEBP-1 from a mouse Th2 clone, D10.G4.1. Interestingly, it was found that the CLEBP1 cDNA sequence was almost identical to the sequences of known high mobility group-1 (HMG1) cDNAs. When expressed as a recombinant fusion protein in Escherichia coli, CLEBP-1 was shown to bind to the IL5-CLE0 element in electrophoretic mobility-shift assays (EMSA) and southwestern blot analysis. The CLEBP-1 fusion protein cross-reacts with and-HMG-1/2 in Western blot analysis. It also binds to the CLE0 elements of IL4, GMCSF and GCSF genes. CLEBP-1 and closely related HMG-1 and HMG-2 proteins may play key roles in facilitating the expression of the lymphokine genes that contain CLE0 elements.

  14. Sequence and expression analysis of two T helper master transcription factors, T-bet and GATA3, in rainbow trout Oncorhynchus mykiss and analysis of their expression during bacterial and parasitic infection.

    PubMed

    Wang, Tiehui; Holland, Jason W; Martin, Sam A M; Secombes, Christopher J

    2010-11-01

    The polarization of naïve CD4+ T cells to T helper (Th)1 or Th2 cells is specified by two master transcription factors, T-bet and GATA3, and is an essential feature of mammalian adaptive immune responses to pathogens and the development of long-lasting immunity. We report here the cloning of rainbow trout Oncorhynchus mykiss T-bet and GATA3, to allow the future evaluation of the existence of Th1 and Th2 cells in salmonid fish. The trout T-bet translation shares high amino acid identities to other fish T-bet molecules (71-72%) but low identities to mammalian T-bet genes (41-42%), although the middle T-box DNA binding domain is highly conserved among all the T-bet proteins from fish and mammals. The trout GATA3 has high amino acid sequence identities (73-88%) to all known vertebrate molecules, with two highly conserved zinc finger motifs. The identity of the trout T-bet and GATA3 molecules was confirmed by phylogenetic tree analysis. A comparable expression level of T-bet and GATA3 was seen in the spleen, head kidney and muscle in healthy trout, but a higher expression level of GATA3 was seen in the gills, brain, skin and intestine relative to that of T-bet. T-bet and GATA3 expression was modulated by different stimulants. The T cell stimulant PHA up-regulated the expression of both T-bet and GATA3 in splenocytes, suggesting that they may be mainly expressed by activated T cells. The expression of T-bet and GATA3 in the spleen was increased by acute stress, but their expression was inhibited by bacterial (Yersinia ruckeri) infection. In a parasitic infection model, Tetracapsuloides bryosalmonae infection induced a biased gene expression profile where a large increase in the expression of T-bet, IFN-gamma and IL-2 was seen, suggesting that a Th1-like response is likely induced by this disease. A better understanding of pathogen modulated expression of T-bet and GATA3, and the potential underlying host immune responses elicited as a consequence of their expression

  15. [Effects of garlicin on the expression of transcription factor T-bet and GATA-3 in blood lymph cells in rats with allergic rhinitis].

    PubMed

    Chen, Dong; Li, Yu-xiao; Li, Tian-ying; Wen, Wei-ping; Shi, Jian-bo; He, Xiao-guang

    2010-02-01

    To investigate the effects of garlicin on the expression of transcription factors T-bet and GATA-3 in blood lymph cells of experimental rats with allergic rhinitis. Thirty healthy SD rats were randomly divided into 3 groups, with 10 rats for each. Ten rats (pharmacological group) were sensitized and intranasally challenged by ovalbumin (OVA), aluminium hydroxide hydrate gel and Bordetella pertussis (B. pertussis) inactive microorganism suspension adjuvants, as the allergic rhinitis models, and then injection of garlicin (0.4 ml) intraperitoneally per day for 10 days. Ten rats in the control group were immunized as the pharmacological group, and then injection of physiological saline as equal volume as garlicin. Ten rats in the negative control group were investigated using physiological saline only. Plasma and lymph cells were separated from 2 ml blood which was extracted from rat heart. Enzyme linked immunosorbent assay (ELISA) was utilized to detect the levels of plasma IL-4 and IFN-γ, and RT-PCR was utilized to detect the expression of T-bet and GATA-3. The levels of IL-4 (x(-) ± s) were (6.292 ± 1.734), (14.252 ± 1.971), (4.916 ± 0.600) pg/ml, respectively, and the levels of IFN-γ were (24.338 ± 2.375), (12.364 ± 1.749), (16.136 ± 2.012) pg/ml, respectively, among the pharmacological, control and negative control groups. The plasma level of IL-4 in the pharmacological group rats was lower than that of control group rats (t = 4.23, P < 0.05), while there was no significant difference between the pharmacological and negative control group rats (t = 1.01, P > 0.05). The plasma level of IFN-γ was increased significantly in the pharmacological group rats when compared with the value of control group rats (t = 4.61, P < 0.05) and with the negative control group (t = 5.79, P < 0.05), respectively. There was no significant difference (t = 1.17, P > 0.05) in plasma level of IFN-γ in the control group rats when compared with the negative control group

  16. HSP70/CD80 DNA vaccine inhibits airway remodeling by regulating the transcription factors T-bet and GATA-3 in a murine model of chronic asthma

    PubMed Central

    Yan, Li; Xiao-Ling, Shi; Zheng-Yan, Cheng; Guo-Ping, Li; Sen, Zhong

    2013-01-01

    Introduction Airway remodeling is an important pathologic feature of chronic asthma. T-bet and GATA-3, the key transcription factors for differentiation toward Th1 and Th2 cells, play an important role in the pathogenesis of airway inflammation, airway hyperresponsiveness and airway remodeling. Previous studies showed that HSP70/CD80 DNA vaccine can reduce airway hyperresponsiveness and airway inflammation in acute asthmatic mice. The present study was designed to determine the effect of HSP70/CD80 DNA vaccine on airway remodeling through regulating the development of Th1/Th2. Material and methods Before being sensitized and challenged by ovalbumin, the BALB/c mice were immunized with DNA vaccine. Lung tissues were assessed by histological examinations. Interferon-γ (IFN-γ)/interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid were determined by ELISA and expressions of IFN-γ, IL-4, T-bet and GATA-3 in spleen were evaluated by real-time polymerase chain reaction. Results Chronic asthmatic mice had higher airway hyperresponsiveness, a thicker airway wall, more PAS-positive goblet cells, more subepithelial extracellular matrix deposition and more proliferating airway smooth muscle (ASM)-like cells than control mice (p < 0.05). Compared with the chronic asthmatic mice, the treatment with HSP70/CD80 DNA vaccine could reduce airway hyperreactivity, mucus secretion, subepithelial collagen deposition, and smooth muscle cell proliferation (p < 0.05). DNA vaccination also increased levels of IFN-γ/IL-4 in BAL fluid (p < 0.05), and expression of T-bet/GATA-3 in the spleen (p < 0.05). Conclusions HSP70/CD80 DNA vaccine can inhibit airway remodeling through regulating the development of Th1/Th2 subsets in asthmatic mice. PMID:24273578

  17. Treating asthma with anti-IgE or anti-IL5.

    PubMed

    Lötvall, J; Pullerits, T

    1999-10-01

    In the last decades, several key mechanisms driving asthma pathophysiooogy have been discovered. These include the role of IgE in allergic disease, and the role of IL-5 in eosinophilic inflammation. In the last few years, tools to block each of these have been developed. At this time, early clinical studies with neutralizing antibodies against both IgE and IL-5 have been performed in asthma patients, with promising results, and larger studies are underway. The mechanisms of, and possible role of, both anti-IgE and anti-IL-5 treatment in asthma are discussed in this review article.

  18. FOXA1, GATA3 and PPARɣ Cooperate to Drive Luminal Subtype in Bladder Cancer: A Molecular Analysis of Established Human Cell Lines

    PubMed Central

    Warrick, Joshua I.; Walter, Vonn; Yamashita, Hironobu; Chung, Eunah; Shuman, Lauren; Amponsa, Vasty Osei; Zheng, Zongyu; Chan, Wilson; Whitcomb, Tiffany L.; Yue, Feng; Iyyanki, Tejaswi; Kawasawa, Yuka I.; Kaag, Matthew; Guo, Wansong; Raman, Jay D.; Park, Joo-Seop; DeGraff, David J.

    2016-01-01

    Discrete bladder cancer molecular subtypes exhibit differential clinical aggressiveness and therapeutic response, which may have significant implications for identifying novel treatments for this common malignancy. However, research is hindered by the lack of suitable models to study each subtype. To address this limitation, we classified bladder cancer cell lines into molecular subtypes using publically available data in the Cancer Cell Line Encyclopedia (CCLE), guided by genomic characterization of bladder cancer by The Cancer Genome Atlas (TCGA). This identified a panel of bladder cancer cell lines which exhibit genetic alterations and gene expression patterns consistent with luminal and basal molecular subtypes of human disease. A subset of bladder cancer cell lines exhibit in vivo histomorphologic patterns consistent with luminal and basal subtypes, including papillary architecture and squamous differentiation. Using the molecular subtype assignments, and our own RNA-seq analysis, we found overexpression of GATA3 and FOXA1 cooperate with PPARɣ activation to drive transdifferentiation of a basal bladder cancer cells to a luminial phenotype. In summary, our analysis identified a set of human cell lines suitable for the study of molecular subtypes in bladder cancer, and furthermore indicates a cooperative regulatory network consisting of GATA3, FOXA1, and PPARɣ drive luminal cell fate. PMID:27924948

  19. Plasmacytoid Urothelial Carcinoma of the Urinary Bladder Metastatic to the Duodenum: A Case Report—Diagnostic Relevance of GATA3 Immunohistochemistry

    PubMed Central

    2017-01-01

    Plasmacytoid urothelial carcinoma (PUC) of the urinary bladder is a rare and aggressive subtype of urothelial carcinoma. Its deceptive morphology is characterized by a discohesive growth of cells with plasmacytoid morphology. Since this tumor might be confused with plasmacytoma, lymphoma, or carcinoma variants, appropriate diagnosis in small biopsy samples could be challenging. This study reports the case of a 53-year-old man who presented with frequent nocturnal urgency, without hematuria. A transurethral bladder and a prostate resection specimen displayed infiltration of neoplastic cells in a spray-like discohesive pattern with occasional formation of small irregular nests and cord-like arrangements. The basic morphology of the tumor cells was plasmacytoid, with eccentric nuclei and eosinophilic cytoplasm. Tumor cells grew through the lamina muscularis mucosae, with splintering of the bladder wall musculature and infiltration of prostatic tissue. They displayed strong and diffuse nuclear reactivity for p53 and GATA3. Eight months after surgery, the patient experienced upper abdominal discomfort. A duodenal biopsy showed infiltration of plasmacytoid atypical cells strongly immunoreactive for GATA3, consistent with the previously diagnosed PUC. The patient died eleven months after the primary diagnosis of his PUC of tumor cachexia losing about 50% of his original body weight, furthermore, with ascites and intraperitoneal tumor spread. PMID:28255490

  20. Nephric duct insertion is a crucial step in urinary tract maturation that is regulated by a Gata3-Raldh2-Ret molecular network in mice

    PubMed Central

    Chia, Ian; Grote, David; Marcotte, Michael; Batourina, Ekaterina; Mendelsohn, Cathy; Bouchard, Maxime

    2011-01-01

    Urinary tract development depends on a complex series of events in which the ureter moves from its initial branch point on the nephric duct (ND) to its final insertion site in the cloaca (the primitive bladder and urethra). Defects in this maturation process can result in malpositioned ureters and hydronephrosis, a common cause of renal disease in children. Here, we report that insertion of the ND into the cloaca is an unrecognized but crucial step that is required for proper positioning of the ureter and that depends on Ret signaling. Analysis of Ret mutant mice at birth reveals hydronephrosis and defective ureter maturation, abnormalities that our results suggest are caused, at least in part, by delayed insertion of the ND. We find a similar set of malformations in mutants lacking either Gata3 or Raldh2. We show that these factors act in parallel to regulate ND insertion via Ret. Morphological analysis of ND extension in wild-type embryos reveals elaborate cellular protrusions at ND tips that are not detected in Ret, Gata3 or Raldh2 mutant embryos, suggesting that these protrusions may normally be important for fusion with the cloaca. Together, our studies reveal a novel Ret-dependent event, ND insertion, that, when abnormal, can cause obstruction and hydronephrosis at birth; whether ND defects underlie similar types of urinary tract abnormalities in humans is an interesting possibility. PMID:21521737

  1. Evaluating the utility of trefoil factor 1 as a mammary-specific immunostain compared and in conjunction with GATA-3 and mammaglobin in the distinction between carcinoma of breast and lung.

    PubMed

    Wells, Justin M; Ginter, Paula S; Liu, Yifang; Chen, Zhengming; Narula, Navneet; Shin, Sandra J

    2015-09-01

    The distinction between metastatic breast carcinomas (BCs) and primary lung carcinomas (PLCs) can be difficult. This study tested the utility of trefoil factor 1 (TFF1) for this purpose and compared it with mammaglobin and GATA protein binding 3 (GATA-3). Tissue microarrays containing 365 BCs and 338 PLCs were stained with TFF1, mammaglobin, and GATA-3, and an H-score was calculated. Sensitivity, specificity, and accuracy were calculated, and logistical regression analysis was performed. Accuracy of correctly classifying the tumor type was 81.9%, 71.3%, and 64.0% for GATA-3, mammaglobin, and TFF1, respectively. Odds ratios for selecting BCs were 25.69, 93.15, and 4.17, respectively, with P values less than .001. With a single exception, the best immunopanel included GATA-3 and mammaglobin in all comparisons. TFF1 demonstrated breast specificity but was inferior to mammaglobin and GATA-3. Therefore, its routine clinical use may not be justified. TFF1 showed little benefit when added to an immunopanel. Copyright© by the American Society for Clinical Pathology.

  2. Circulating, but not local lung, IL-5 is required for the development of antigen-induced airways eosinophilia.

    PubMed Central

    Wang, J; Palmer, K; Lŏtvall, J; Milan, S; Lei, X F; Matthaei, K I; Gauldie, J; Inman, M D; Jordana, M; Xing, Z

    1998-01-01

    IL-5 is induced locally in the lung and systemically in the circulation during allergic airways eosinophilic inflammation both in humans and experimental animals. However, the precise role of local and systemic IL-5 in the development of allergic airways eosinophilia remains to be elucidated. In our current study, we demonstrate that compared with their IL-5(+/+) counterparts, IL-5(-/-) mice lacked an IL-5 response both in the lung and peripheral blood, yet they released similar amounts of IL-4, eotaxin, and MIP-1alpha in the lung after ovalbumin (OVA) sensitization and challenge. At cellular levels, these mice failed to develop peripheral blood and airways eosinophilia while the responses of lymphocytes, neutrophils, and macrophages remained similar to those in IL-5(+/+) mice. To dissect the relative role of local and systemic IL-5 in this model, we constructed a gene transfer vector expressing murine IL-5. Intramuscular IL-5 gene transfer to OVA-sensitized IL-5(-/-) mice led to raised levels of IL-5 compartmentalized to the circulation and completely reconstituted airways eosinophilia upon OVA challenge, which was associated with reconstitution of eosinophilia in the bone marrow and peripheral blood. Significant airways eosinophilia was observed for at least 7 d in these mice. In contrast, intranasal IL-5 gene transfer, when rendered to give rise to a significant but compartmentalized level of transgene protein IL-5 in the lung, was unable to reconstitute airways eosinophilia in OVA-sensitized IL-5(-/-) mice upon OVA-challenge, which was associated with a lack of eosinophilic responses in bone marrow and peripheral blood. Our findings thus provide unequivocal evidence that circulating but not local lung IL-5 is critically required for the development of allergic airways eosinophilia. These findings also provide the rationale for developing strategies to target circulating IL-5 and/or its receptors in bone marrow to effectively control asthmatic airways

  3. Prolonged activation of IL-5–producing ILC2 causes pulmonary arterial hypertrophy

    PubMed Central

    Tsuneyama, Koichi; Kawaguchi, Makoto; Fukuoka, Junya; Kudo, Fujimi; Nakae, Susumu; Arita, Makoto; Nagai, Yoshinori; Takaki, Satoshi; Takatsu, Kiyoshi

    2017-01-01

    IL-33 is one of the critical cytokines that activates group 2 innate lymphoid cells (ILC2s) and mediates allergic reactions. Accumulating evidence suggests that IL-33 is also involved in the pathogenesis of several chronic inflammatory diseases. Previously, we generated an IL-5 reporter mouse and revealed that lung IL-5–producing ILC2s played essential roles in regulating eosinophil biology. In this study, we evaluated the consequences of IL-33 administration over a long period, and we observed significant expansion of ILC2s and eosinophils surrounding pulmonary arteries. Unexpectedly, pulmonary arteries showed severe occlusive hypertrophy that was ameliorated in IL-5– or eosinophil-deficient mice, but not in Rag2-deficient mice. This indicates that IL-5–producing ILC2s and eosinophils play pivotal roles in pulmonary arterial hypertrophy. Administration of a clinically used vasodilator was effective in reducing IL-33–induced hypertrophy and repressed the expansion of ILC2s and eosinophils. Taken together, these observations demonstrate a previously unrecognized mechanism in the development of pulmonary arterial hypertrophy and the causative roles of ILC2 in the process. PMID:28405615

  4. Successful TB treatment induces B-cells expressing FASL and IL5RA mRNA.

    PubMed

    van Rensburg, Ilana C; Wagman, Chandre; Stanley, Kim; Beltran, Caroline; Ronacher, Katharina; Walzl, Gerhard; Loxton, Andre G

    2017-01-10

    Activated B-cells increase T-cell behaviour during autoimmune disease and other infections by means of cytokine production and antigen-presentation. Functional studies in experimental autoimmune encephalomyelitis (EAE) indicate that B-cell deficiencies, and a lack of IL10 and IL35 leads to a poor prognosis. We hypothesised that B-cells play a role during tuberculosis. We evaluated B-cell mRNA expression using real-time PCR from healthy community controls, individuals with other lung diseases and newly diagnosed untreated pulmonary TB patients at three different time points (diagnosis, month 2 and 6 of treatment).We show that FASLG, IL5RA, CD38 and IL4 expression was lower in B-cells from TB cases compared to healthy controls. The changes in expression levels of CD38 may be due to a reduced activation of B-cells from TB cases at diagnosis. By month 2 of treatment, there was a significant increase in the expression of APRIL and IL5RA in TB cases. Furthermore, after 6 months of treatment, APRIL, FASLG, IL5RA and CD19 were upregulated in B-cells from TB cases. The increase in the expression of APRIL and CD19 suggests that there may be restored activation of B-cells following anti-TB treatment. The upregulation of FASLG and IL5RA indicates that B-cells expressing regulatory genes may play an important role in the protective immunity against M.tb infection. Our results show that increased activation of B-cells is present following successful TB treatment, and that the expression of FASLG and IL5RA could potentially be utilised as a signature to monitor treatment response.

  5. Association of functional polymorphisms in promoter regions of IL5, IL6 and IL13 genes with development and prognosis of autoimmune thyroid diseases.

    PubMed

    Inoue, N; Watanabe, M; Morita, M; Tatusmi, K; Hidaka, Y; Akamizu, T; Iwatani, Y

    2011-03-01

    To clarify the association of genetic producibility of interleukin (IL)-5, IL-6 and IL-13, which are secreted by T helper type 2 (Th2), with the development and prognosis of autoimmune thyroid disease (AITD), we genotyped IL5-746C/T, IL6-572C/G and IL13-1112C/T polymorphisms, which are functional polymorphisms in the promoter regions of the genes regulating these cytokines. Fifty-seven patients with intractable Graves' disease (GD), 52 with GD in remission, 52 with severe Hashimoto's disease (HD), 56 with mild HD and 91 healthy controls were examined in this study. The IL13-1112T allele, which correlates with higher producibility of IL-13, was more frequent in patients with GD in remission than in those with intractable GD [P=0·009, odds ratio (OR)=3·52]. The IL5-746T allele, which may correlate with lower levels of IL-5, was more frequent in patients with GD in remission than controls (P=0·029, OR=2·00). The IL6-572G allele carriers (CG and GG genotypes), which have higher producibility of IL-6, were more frequent in AITD patients (P=0·033, OR=1·75), especially in GD in remission (P=0·031, OR=2·16) and severe HD (P=0·031, OR=2·16) than in controls. Interestingly, both allele and genotype frequencies of Th2 cytokine genes were similar between GD and HD patients. In conclusion, functional polymorphisms in the genes encoding Th2 cytokines are associated differently with the development and prognosis of AITD from each other.

  6. Cooperative Action of Multiple cis-Acting Elements Is Required for N-myc Expression in Branchial Arches: Specific Contribution of GATA3

    PubMed Central

    Potvin, Éric; Beuret, Laurent; Cadrin-Girard, Jean-François; Carter, Marcelle; Roy, Sophie; Tremblay, Michel; Charron, Jean

    2010-01-01

    The precise expression of the N-myc proto-oncogene is essential for normal mammalian development, whereas altered N-myc gene regulation is known to be a determinant factor in tumor formation. Using transgenic mouse embryos, we show that N-myc sequences from kb −8.7 to kb +7.2 are sufficient to reproduce the N-myc embryonic expression profile in developing branchial arches and limb buds. These sequences encompass several regulatory elements dispersed throughout the N-myc locus, including an upstream limb bud enhancer, a downstream somite enhancer, a branchial arch enhancer in the second intron, and a negative regulatory element in the first intron. N-myc expression in the limb buds is under the dominant control of the limb bud enhancer. The expression in the branchial arches necessitates the interplay of three regulatory domains. The branchial arch enhancer cooperates with the somite enhancer region to prevent an inhibitory activity contained in the first intron. The characterization of the branchial arch enhancer has revealed a specific role of the transcription factor GATA3 in the regulation of N-myc expression. Together, these data demonstrate that correct N-myc developmental expression is achieved via cooperation of multiple positive and negative regulatory elements. PMID:20855530

  7. Selective regulation of T cell IL-5 synthesis by OM-01, JTE-711 and p38 MAP kinase inhibitor: independent control of Th2 cytokines, IL-4 and IL-5.

    PubMed

    Mori, A; Okudaira, H; Kobayashi, N; Akiyama, K

    2001-01-01

    Helper T cells are involved in chronic eosinophilic inflammation. Control of cytokine production seems to be an effective management. The effect of nonactin, SB203580, a p38 MAP kinase inhibitor, and JTE-711 on the cytokine production of allergen-specific T cell clones was determined. The effect of nonactin on the airway eosinophilia was investigated using murine asthma model. Nonactin suppressed IL-5 synthesis by human Th cells in a dose-dependent manner without affecting IL-2 or IL-4 synthesis, and still significantly suppressed murine airway eosinophilia induced by the antigen inhalation. SB203580 and JTE-711 also selectively inhibited IL-5 synthesis in vitro. Synthesis of IL-5 by human Th cells can be differentially regulated from that of other major T cell cytokines. The in vivo effects of selective IL-5 synthesis inhibitors suggest that IL-5 is the reasonable target for the regulation of allergic disorders accompanied by eosinophilic inflammation. Copyright 2001 S. Karger AG, Basel

  8. EP300-ZNF384 fusion gene product up-regulates GATA3 gene expression and induces hematopoietic stem cell gene expression signature in B-cell precursor acute lymphoblastic leukemia cells.

    PubMed

    Yaguchi, Akinori; Ishibashi, Takeshi; Terada, Kazuki; Ueno-Yokohata, Hitomi; Saito, Yuya; Fujimura, Junya; Shimizu, Toshiaki; Ohki, Kentaro; Manabe, Atsushi; Kiyokawa, Nobutaka

    2017-04-04

    ZNF384-related fusion genes are associated with a distinct subgroup of B-cell precursor acute lymphoblastic leukemias in childhood, with a frequency of approximately 3-4%. We previously identified a novel EP300-ZNF384 fusion gene. Patients with the ZNF384-related fusion gene exhibit a hematopoietic stem cell (HSC) gene expression signature and characteristic immunophenotype with negative or low expression of CD10 and aberrant expression of myeloid antigens, such as CD33 and CD13. However, the molecular basis of this pathogenesis remains completely unknown. In the present study, we examined the biological effects of EP300-ZNF384 expression induced by retrovirus-mediated gene transduction in an REH B-cell precursor acute lymphoblastic leukemia cell line, and observed the acquisition of the HSC gene expression signature and an up-regulation of GATA3 gene expression, as assessed by microarray analysis. In contrast, the gene expression profile induced by wild-type ZNF384 in REH cells was significantly different from that by EP300-ZNF384 expression. Together with the results of reporter assays, which revealed the enhancement of GATA3-promoter activity by EP300-ZNF384 expression, these findings suggest that EP300-ZNF384 mediates GATA3 gene expression and may be involved in the acquisition of the HSC gene expression signature and characteristic immunophenotype in B-cell precursor acute lymphoblastic leukemia cells.

  9. Anti-IL5 decreases the number of eosinophils but not the severity of dermatitis in Sharpin-deficient mice.

    PubMed

    Renninger, Matthew L; Seymour, Rosemarie E; Whiteley, Laurence O; Sundberg, John P; Hogenesch, Harm

    2010-03-01

    Sharpin-deficient (Sharpin(cpdm)) mutant mice develop a chronic eosinophilic dermatitis. To determine the efficacy of eosinophil-depletion in chronic inflammation, Sharpin(cpdm) mice were treated with anti-IL5 antibodies. Mice treated with anti-IL5 had a 90% reduction of circulating eosinophils and a 50% decrease in cutaneous eosinophils after 10 days compared with sham-treated littermates. Reducing the number of eosinophils resulted in increased severity of alopecia and erythema and a significant increase in epidermal thickness. Skin homogenates from mice treated with anti-IL5 had decreased mRNA expression of arylsulfatase B (Arsb), diamine oxidase (amiloride-binding protein 1, also called histaminase; Abp1) and Il10, which are mediators that eosinophils may release to quench inflammation. Skin homogenates from mice treated with anti-IL5 also had decreased mRNA expression of Il4, Il5, Ccl11, kit ligand (Kitl) and Tgfa; and increased mRNA expression of Tgfb1, Mmp12 and tenascin C (Tnc). In order to further decrease the accumulation of eosinophils, Sharpin(cpdm) mice were crossed with IL5 null mice. Il5(-/-), Sharpin(cpdm)/Sharpin(cpdm) mice had a 98% reduction of circulating eosinophils and a 95% decrease in cutaneous eosinophils compared with IL5-sufficient Sharpin(cpdm) mice. The severity of the lesions was similar between IL5-sufficient and IL5-deficient mice. Double mutant mice had a significant decrease in Abp1, and a significant increase in Tgfb1, Mmp12 and Tnc mRNA compared with controls. These data indicate that eosinophils are not essential for the development of dermatitis in Sharpin(cpdm) mice and suggest that eosinophils have both pro-inflammatory and anti-inflammatory roles in the skin of these mice.

  10. Adenosine A2A receptor signaling affects IL-21/IL-22 cytokines and GATA3/T-bet transcription factor expression in CD4(+) T cells from a BTBR T(+) Itpr3tf/J mouse model of autism.

    PubMed

    Ahmad, Sheikh F; Ansari, Mushtaq A; Nadeem, Ahmed; Bakheet, Saleh A; Almutairi, Mashal M; Attia, Sabry M

    2017-10-15

    Autism is a complex heterogeneous neurodevelopmental disorder; previous studies have identified altered immune responses among individuals diagnosed with autism. An imbalance in the production of pro- and anti-inflammatory cytokines and transcription factors plays a role in neurodevelopmental behavioral and autism disorders. BTBR T(+) Itpr3tf/J (BTBR) mice are used as a model for autism, as they exhibit social deficits, communication deficits, and repetitive behaviors compared with C57BL/6J (B6) mice. The adenosine A2A receptor (A2AR) appears to be a potential target for the improvement of behavioral, inflammatory, immune, and neurological disorders. We investigated the effects of the A2AR antagonist SCH 5826 (SCH) and agonist CGS 21680 (CGS) on IL-21, IL-22, T-bet, T-box transcription factor (T-bet), GATA3 (GATA Binding Protein 3), and CD152 (CTLA-4) expression in BTBR mice. Our results showed that BTBR mice treated with SCH had increased CD4(+)IL-21(+), CD4(+)IL-22(+), CD4(+)GATA3(+), and CD4(+)T-bet(+) and decreased CD4(+)CTLA-4(+) expression in spleen cells compared with BTBR control mice. Moreover, CGS efficiently decreased CD4(+)IL-21(+), CD4(+)IL-22(+), CD4(+)GATA3(+), and CD4(+)T-bet(+) and increased CD4(+)CTLA-4 production in spleen cells compared with SCH-treated and BTBR control mice. Additionally, SCH treatment significantly increased the mRNA and protein expression levels of IL-21, IL-22, GATA3, and T-bet in brain tissue compared with CGS-treated and BTBR control mice. The augmented levels of IL-21/IL-22 and GATA3/T-bet could be due to altered A2AR signaling. Our results indicate that A2AR agonists may represent a new class of compounds that can be developed for use in the treatment of autistic and neuroimmune dysfunctions. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Simvastatin Inhibits IL-5-Induced Chemotaxis and CCR3 Expression of HL-60-Derived and Human Primary Eosinophils.

    PubMed

    Fu, Chia-Hsiang; Tsai, Wan-Chun; Lee, Ta-Jen; Huang, Chi-Che; Chang, Po-Hung; Su Pang, Jong-Hwei

    2016-01-01

    IL-5-induced chemotaxis of eosinophils is an important feature of allergic airway inflammatory diseases. Simvastatin, a lipid lowering agent, has been shown to exhibit anti-inflammatory and anti-allergic effects. Our aim was to investigate the effect of simvastatin on IL-5-induced eosinophil chemotaxis and its regulatory mechanisms. Eosinophils were derived by treating HL-60 clone 15 (HC15) cells with butyric acid (BA) in an alkaline condition or through direct isolation from human peripheral blood. The expressions of CC chemokine receptor 3 (CCR3) and interleukin (IL)-5 receptors (IL5Rα and β) were analyzed using RT/real-time PCR. The granular proteins were stained using fast green. Eotaxin-induced chemotaxis was measured using a transwell migration assay. CCR3 protein expression was revealed by immunocytochemistry. An animal model of allergic rhinitis was established by challenging Sprague-Dawley® rats repeatedly with ovalbumin. Butyric acid significantly increased the expression of IL5Rα and IL5Rβ, CCR3 and granular proteins in HC15 cells, indicating the maturation of eosinophils (BA-E cells). IL-5 further enhanced the CCR3 expression at both the mRNA and protein levels and the eotaxin-induced chemotaxis of BA-E cells. Simvastatin inhibited the effects of IL-5 on BA-E cells, but not in the presence of mevalonate. Similar results were also exhibited in human primary eosinophils. In vivo animal studies further confirmed that oral simvastatin could significantly suppress the infiltration of eosinophils into turbinate tissues of allergic rats. Therefore, simvastatin was demonstrated to inhibit IL-5-induced CCR3 expression and chemotaxis of eosinophils mediated via the mevalonate pathway. We confirmed that simvastatin also reduced eosinophilic infiltration in allergic rhinitis.

  12. STAT4-mediated transcriptional repression of the IL5 gene in human memory Th2 cells.

    PubMed

    Gonzales-van Horn, Sarah R; Estrada, Leonardo D; van Oers, Nicolai S C; Farrar, J David

    2016-06-01

    Type I interferon (IFN-α/β) plays a critical role in suppressing viral replication by driving the transcription of hundreds of interferon-sensitive genes (ISGs). While many ISGs are transcriptionally activated by the ISGF3 complex, the significance of other signaling intermediates in IFN-α/β-mediated gene regulation remains elusive, particularly in rare cases of gene silencing. In human Th2 cells, IFN-α/β signaling suppressed IL5 and IL13 mRNA expression during recall responses to T-cell receptor (TCR) activation. This suppression occurred through a rapid reduction in the rate of nascent transcription, independent of de novo expression of ISGs. Further, IFN-α/β-mediated STAT4 activation was required for repressing the human IL5 gene, and disrupting STAT4 dimerization reversed this effect. This is the first demonstration of STAT4 acting as a transcriptional repressor in response to IFN-α/β signaling and highlights the unique activity of this cytokine to acutely block the expression of an inflammatory cytokine in human T cells.

  13. Semaphorin 7A is expressed on airway eosinophils and upregulated by IL-5 family cytokines.

    PubMed

    Esnault, Stephane; Kelly, Elizabeth A; Johansson, Mats W; Liu, Lin Ying; Han, Shih-Tsung; Akhtar, Moneeb; Sandbo, Nathan; Mosher, Deane F; Denlinger, Loren C; Mathur, Sameer K; Malter, James S; Jarjour, Nizar N

    2014-01-01

    Semaphorin 7A (sema7a) plays a major role in TGF-β1-induced lung fibrosis. Based on the accumulating evidence that eosinophils contribute to fibrosis/remodeling in the airway, we hypothesized that airway eosinophils may be a significant source of sema7a. In vivo, sema7a was expressed on the surface of circulating eosinophils and upregulated on bronchoalveolar lavage eosinophils obtained after segmental bronchoprovocation with allergen. Based on mRNA levels in unfractionated and isolated bronchoalveolar cells, eosinophils are the predominant source of sema7a. In vitro, among the members of the IL-5-family cytokines, sema7a protein on the surface of blood eosinophils was increased more by IL-3 than by GM-CSF or IL-5. Cytokine-induced expression of cell surface sema7a required translation of newly synthesized protein. Finally, a recombinant sema7a induced alpha-smooth muscle actin production in human bronchial fibroblasts. semaphorin 7A is a potentially important modulator of eosinophil profibrotic functions in the airway remodeling of patients with chronic asthma.

  14. Chromosome mapping of the owl monkey CSF1R and IL5 genes.

    PubMed

    Ma, N S; Lin, K C

    1992-08-01

    We mapped the owl monkey colony-stimulating factor 1 receptor (CSF1R) locus to the proximal region of chromosome 3q of karyotype VI(K-VI) and karyotype V(K-V) and the interleukin 5 (IL5) locus to the mid-region of chromosome 3q(K-VI) and 19q(K-IV) using a combination of Southern hybridization of somatic cells and in situ chromosomal hybridization methodologies. The findings support the proposed evolution of owl monkey chromosome 3(K-VI) from a fusion of two smaller structures, the homologs of chromosomes 6 and 19 (K-IV). The data also indicate genomic conservation of the HSA 5q23-q35 segment in the higher primates.

  15. Severe asthma: anti-IgE or anti-IL-5?

    PubMed Central

    Papathanassiou, Evgenia; Loukides, Stelios; Bakakos, Petros

    2016-01-01

    Severe asthma is a discrete clinical entity characterised by recurrent exacerbations, reduced quality of life and poor asthma control as ordinary treatment regimens remain inadequate. Difficulty in managing severe asthma derives partly from the multiple existing phenotypes and our inability to recognise them. Though the exact pathogenetic pathway of severe allergic asthma remains unclear, it is known that numerous inflammatory cells and cytokines are involved, and eosinophils represent a key inflammatory cell mediator. Anti-IgE (omalizumab) and anti-IL-5 (mepolizumab) antibodies are biological agents that interfere in different steps of the Th2 inflammatory cascade and are licensed in severe asthma. Both exhibit a favourable clinical outcome as they reduce exacerbation rate and improve asthma control and quality of life, while mepolizumab also induces an oral steroid sparing effect. Nevertheless, it is still questionable which agent is more suitable in the management of severe allergic asthma since no comparable studies have been conducted. Omalizumab's established effectiveness in clinical practice over a long period is complemented by a beneficial effect on airway remodelling process mediated mainly through its impact on eosinophils and other parameters strongly related to eosinophilic inflammation. However, it is possible that mepolizumab through nearly depleting eosinophils could have a similar effect on airway remodelling. Moreover, to date, markers indicative of the patient population responding to each treatment are unavailable although baseline eosinophils and exacerbation rate in the previous year demonstrate a predictive value regarding anti-IL-5 therapy effectiveness. On the other hand, a better therapeutic response for omalizumab has been observed when low forced expiratory volume in 1 sec, high-dose inhaled corticosteroids and increased IgE concentrations are present. Consequently, conclusions are not yet safe to be drawn based on existing knowledge

  16. Effects of β-d-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients.

    PubMed

    Barati, Anis; Jamshidi, Ahmad Reza; Ahmadi, Hossein; Aghazadeh, Zahra; Mirshafiey, Abbas

    2017-01-01

    Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier: IRCT2014011213739N2).

  17. Effects of β-d-mannuronic acid, as a novel non-steroidal anti-inflammatory medication within immunosuppressive properties, on IL17, RORγt, IL4 and GATA3 gene expressions in rheumatoid arthritis patients

    PubMed Central

    Barati, Anis; Jamshidi, Ahmad Reza; Ahmadi, Hossein; Aghazadeh, Zahra; Mirshafiey, Abbas

    2017-01-01

    Rheumatoid arthritis (RA) is the most common form of chronic inflammatory arthritis characterized by pain, swelling and destruction of joints, with a resultant disability. Disease-modifying anti-rheumatic drugs (DMARDs) and biological drugs can interfere with the disease process. In this study, the effect of β-d-mannuronic acid (M2000) as a novel non-steroidal anti-inflammatory drug (NSAID) with immunosuppressive and anti-inflammatory effects together with antioxidant effects was evaluated on IL17, RORγt, IL4 and GATA3 gene expression in 12 RA patients. Previously, M2000 driven from sodium alginate (natural product; patented, DEU: 102016113018.4) has shown a notable efficacy in experimental models of multiple sclerosis, RA and nephrotic syndrome. This study was performed on 12 patients with RA who had an inadequate response to conventional treatments. During this trial, patients were permitted to continue the conventional therapy excluding NSAIDs. M2000 was administered orally at a dose of 500 mg twice daily for 12 weeks. The peripheral blood mononuclear cells (PBMCs) were collected before and after treatment to evaluate the expression levels of IL4, GATA3, IL17 and RORγt. The gene expression results showed that M2000 has a potent efficacy, so that it could not only significantly decrease IL17 and RORγt levels but also increase IL4 and GATA3 levels after 12 weeks of treatment. Moreover, the gene expression results were in accordance with the clinical and preclinical assessments. In conclusion, M2000 as a natural novel agent has therapeutic and immunosuppressive properties on RA patients (identifier: IRCT2014011213739N2). PMID:28408801

  18. Local hypersensitivity reaction in transgenic mice with squamous epithelial IL-5 overexpression provides a novel model of eosinophilic oesophagitis.

    PubMed

    Masterson, Joanne C; McNamee, Eóin N; Hosford, Lindsay; Capocelli, Kelley E; Ruybal, Joseph; Fillon, Sophie A; Doyle, Alfred D; Eltzschig, Holger K; Rustgi, Anil K; Protheroe, Cheryl A; Lee, Nancy A; Lee, James J; Furuta, Glenn T

    2014-01-01

    Eosinophilic oesophagitis (EoE) is a chronic inflammatory condition of the oesophagus with limited treatment options. No previous transgenic model has specifically targeted the oesophageal mucosa to induce oesophageal eosinophilia. We developed a mouse model that closely resembles EoE by utilising oxazolone haptenation in mice with transgenic overexpression of an eosinophil poietic and survival factor (interleukin (IL)-5) in resident squamous oesophageal epithelia. Overexpression of IL-5 in the healthy oesophagus was achieved in transgenic mice (L2-IL5) using the squamous epithelial promoter Epstein-Barr virus ED-L2. Oxazolone-challenged L2-IL5 mice developed dose-dependent pan-oesophageal eosinophilia, including eosinophil microabscess formation and degranulation as well as basal cell hyperplasia. Moreover, oesophagi expressed increased IL-13 and the eosinophil agonist chemokine eotaxin-1. Treatment of these mice with corticosteroids significantly reduced eosinophilia and epithelial inflammation. L2-IL5 mice provide a novel experimental model that can potentially be used in preclinical testing of EoE-related therapeutics and mechanistic studies identifying pathogenetic features associated with mucosal eosinophilia.

  19. Identification of residues involved in binding of IL5 to betacom using betaIL3 and betacom chimeras.

    PubMed

    Czabotar, P E; Holland, J; Sanderson, C J

    1999-10-22

    In mice there are two forms of the beta chain used in the IL3 receptor system, betacom and betaIL3. betacom is used by the IL3, IL5 and GM-CSF receptors whereas betaIL3 is only used in the IL3 receptor. In this work an assay was developed to identify residues of beta1L3 that restrict IL5 activity. It was found that such residues reside within the 2nd CRM of the molecule. Furthermore, when residues in the betaIL3 B'-C' loop were replaced with betacom sequence a form of betaIL3 was produced that was able to respond to IL5. This region is also responsible for IL3 binding to betaIL3 in the absence of alpha chain. It is therefore an important structural motif of betacom and betaIL3 responsible for both ligand interaction and specificity.

  20. Relationship between IL-4 and IL-5 mRNA expression and disease severity in atopic asthma.

    PubMed

    Humbert, M; Corrigan, C J; Kimmitt, P; Till, S J; Kay, A B; Durham, S R

    1997-09-01

    Atopic asthma is characterized by chronic inflammation of the bronchial mucosa in which eosinophil- and immunoglobulin E (IgE)-dependent mechanisms are believed to be prominent. Therefore, specific proeosinophilic mediators such as interleukin (IL)-5 and essential cofactors for IgE switching in B-lymphocytes such as IL-4 could play a pivotal role in asthma. However, the exact role that individual inflammatory mediators play in the development of the disease in humans is still unknown. Using semiquantitative reverse transcriptase-polymerase chain reaction amplification in bronchial biopsies from 10 atopic asthmatics, we have tested the hypothesis that IL-4 and IL-5 mRNA expression relative to beta-actin mRNA correlates with validated indicators of disease severity. IL-4 and IL-5 mRNA copies relative to beta-actin mRNA were detected in bronchial biopsies from atopic asthmatics. The numbers of IL-5 mRNA copies relative to beta-actin mRNA correlated with disease severity assessed by the Aas asthma score (r = 0.70, p = 0.01), baseline FEV1 (r = -0.94, p = 0.001), baseline peak expiratory flow rate (r = -0.77, p = 0.01), peak expiratory flow rate variability over 2 wk (r = 0.69, p = 0.028), and the histamine PC20 (r = -0.72, p = 0.018). Conversely, the numbers of IL-4 mRNA copies relative to beta-actin mRNA did not correlate with asthma severity, but they positively correlated with total serum IgE concentrations (r = -0.90, p = 0.001). Our present results support the concept that IL-5 may determine asthma clinical expression and severity, and by inference they support the development of IL-5 targeted therapies.

  1. Effects of Reactive Oxygen and Nitrogen Metabolites on RANTES- and IL-5-Induced Eosinophil Chemotactic Activity in Vitro

    PubMed Central

    Sato, Etsuro; Simpson, Keith L.; Grisham, Matthew B.; Koyama, Sekiya; Robbins, Richard A.

    1999-01-01

    Eosinophils and increased production of nitric oxide (NO) and superoxide, components of peroxynitrite, have been implicated in the pathogenesis of a number of allergic disorders including asthma. Peroxynitrite induced protein nitration may compromise enzyme and protein function. We hypothesized that peroxynitrite may modulate eosinophil migration by modulating chemotactic cytokines. To test this hypothesis, the eosinophil chemotactic responses of regulated on activation, normal T cell expressed and secreted (RANTES) and interleukin (IL)-5 incubated with and without peroxynitrite were evaluated. Peroxynitrite-attenuated RANTES and IL-5 induced eosinophil chemotactic activity (ECA) in a dose-dependent manner (P < 0.05) but did not attenuate leukotriene B4 or complement-activated serum ECA. The reducing agents deferoxamine and dithiothreitol reversed the ECA inhibition by peroxynitrite, and exogenous L-tyrosine abrogated the inhibition by peroxynitrite. PAPA-NONOate, a NO donor, or superoxide generated by lumazine or xanthine and xanthine oxidase, did not show an inhibitory effect on ECA. The peroxynitrite generator, 3-morpholinosydnonimine, caused a concentration-dependent inhibition of ECA. Peroxynitrite reduced RANTES and IL-5 binding to eosinophils and resulted in nitrotyrosine formation. These findings are consistent with nitration of tyrosine by peroxynitrite with subsequent inhibition of RANTES and IL-5 binding to eosinophils and suggest that peroxynitrite may play a role in regulation of eosinophil chemotaxis. PMID:10433951

  2. Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF.

    PubMed

    Quail, Daniela F; Olson, Oakley C; Bhardwaj, Priya; Walsh, Logan A; Akkari, Leila; Quick, Marsha L; Chen, I-Chun; Wendel, Nils; Ben-Chetrit, Nir; Walker, Jeanne; Holt, Peter R; Dannenberg, Andrew J; Joyce, Johanna A

    2017-08-01

    Obesity is associated with chronic, low-grade inflammation, which can disrupt homeostasis within tissue microenvironments. Given the correlation between obesity and relative risk of death from cancer, we investigated whether obesity-associated inflammation promotes metastatic progression. We demonstrate that obesity causes lung neutrophilia in otherwise normal mice, which is further exacerbated by the presence of a primary tumour. The increase in lung neutrophils translates to increased breast cancer metastasis to this site, in a GM-CSF- and IL5-dependent manner. Importantly, weight loss is sufficient to reverse this effect, and reduce serum levels of GM-CSF and IL5 in both mouse models and humans. Our data indicate that special consideration of the obese patient population is critical for effective management of cancer progression.

  3. IL-5 links adaptive and natural immunity specific for epitopes of oxidized LDL and protects from atherosclerosis

    PubMed Central

    Binder, Christoph J.; Hartvigsen, Karsten; Chang, Mi-Kyung; Miller, Marina; Broide, David; Palinski, Wulf; Curtiss, Linda K.; Corr, Maripat; Witztum, Joseph L.

    2004-01-01

    During atherogenesis, LDL is oxidized, generating various oxidation-specific neoepitopes, such as malondialdehyde-modified (MDA-modified) LDL (MDA-LDL) or the phosphorylcholine (PC) headgroup of oxidized phospholipids (OxPLs). These epitopes are recognized by both adaptive T cell–dependent (TD) and innate T cell–independent type 2 (TI-2) immune responses. We previously showed that immunization of mice with MDA-LDL induces a TD response and atheroprotection. In addition, a PC-based immunization strategy that leads to a TI-2 expansion of innate B-1 cells and secretion of T15/EO6 clonotype natural IgM antibodies, which bind the PC of OxPLs within oxidized LDL (OxLDL), also reduces atherogenesis. T15/EO6 antibodies inhibit OxLDL uptake by macrophages. We now report that immunization with MDA-LDL, which does not contain OxPL, unexpectedly led to the expansion of T15/EO6 antibodies. MDA-LDL immunization caused a preferential expansion of MDA-LDL–specific Th2 cells that prominently secreted IL-5. In turn, IL-5 provided noncognate stimulation to innate B-1 cells, leading to increased secretion of T15/EO6 IgM. Using a bone marrow transplant model, we also demonstrated that IL-5 deficiency led to decreased titers of T15/EO6 and accelerated atherosclerosis. Thus, IL-5 links adaptive and natural immunity specific to epitopes of OxLDL and protects from atherosclerosis, in part by stimulating the expansion of atheroprotective natural IgM specific for OxLDL. PMID:15286809

  4. PPAR-γ signaling and IL-5 inhibition together prevent chronic rejection of MHC Class II-mismatched cardiac grafts.

    PubMed

    Chen, Yan; Li, Daxu; Tsang, Julia Yuen Shan; Niu, Na; Peng, Jiao; Zhu, Jiang; Hui, Kenneth; Xu, Aimin; Lui, Vincent Chi Hang; Lamb, Jonathan Robert; Tam, Paul Kwong Hang

    2011-06-01

    Chronic rejection can prevent long-term survival of organ transplants. Although the beneficial effects of peroxisome proliferator-activated receptor-gamma (PPAR-γ) in reducing graft rejection have been reported, the details of the underlying mechanisms remain unclear, especially in the context of modulating cellular infiltration and preventing vasculopathy and interstitial fibrosis. The therapeutic effects of the PPAR-γ agonist, rosiglitazone, combined with anti-interleukin-5 are explored in a mouse model of MHC Class II-histoincompatible cardiac transplantation. Rosiglitazone treatment alone marginally increased long-term survival and reduced CD8 T-cell infiltration and vasculopathy in the grafts. However, there was no reduction in collagen deposition and interleukin (IL)-4, IL-5 and eosinophil infiltration were increased. Anti-IL-5 antibody treatment alone reduced eosinophil infiltration and collagen deposition, but had no effect on CD8 T-cell infiltration or vasculopathy. Combined treatment with anti-IL-5 antibody and rosiglitazone prevented graft rejection. Furthermore, rosiglitazone treatment increased adiponectin receptor II expression in grafts and on dendritic cells and T cells in vitro. Graft survival correlated with increased expression in grafts of the inhibitory molecule PD-L1. The findings obtained increase the knowledge on the mode of action of rosiglitazone in promoting the survival of MHC Class II-mismatched cardiac transplants in which the CD8 T cells and eosinophils play key roles. PPAR-γ signaling combined with IL-5 blockade prevents graft rejection. Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.

  5. IL5RA polymorphisms, smoking and eczema in Japanese women: the Kyushu Okinawa Maternal and Child Health Study.

    PubMed

    Miyake, Y; Tanaka, K; Arakawa, M

    2015-02-01

    The present case-control study examined the relationship between IL5RA SNPs and eczema in young adult Japanese women. Cases and control subjects were selected from pregnant women who participated in the baseline survey of the Kyushu Okinawa Maternal and Child Health Study, which is an ongoing prebirth cohort study. Cases comprised 188 women with eczema in the previous 12 months as defined according to the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC), regardless of the presence of a doctor's diagnosis of atopic eczema. Control subjects comprised 1130 women without eczema as defined according to the ISAAC criteria who also had not been diagnosed with atopic eczema by a doctor. Compared with the AA genotype of IL5RA SNP rs17881144, the AT genotype, but not the TT genotype, was significantly associated with a decreased risk of eczema. The ATTAGA haplotype and the GTAGCA haplotype of rs17882210, rs3804797, rs334809, rs9831572, rs6771148 and rs17881144 were significantly associated with an increased risk of eczema. In contrast, the GCTGCA haplotype was significantly related to a decreased risk of eczema. Multiplicative interactions between IL5RA SNPs rs334809 and rs17881144 and smoking with respect to eczema were marginally significant (P = 0.07 and 0.07, respectively). This is the first study to show significant associations between IL5RA SNP rs17881144, the ATTAGA haplotype, the GTAGCA haplotype, and the GCTGCA haplotype and eczema. Smoking may modify the relationships between SNPs rs334809 and rs17881144 and eczema.

  6. Effect of lipoteichoic acid on IL-2 and IL-5 release from T lymphocytes in asthma and COPD.

    PubMed

    Mat, Zeynep; Grensemann, Barbara; Yakin, Yakup; Knobloch, Jürgen; Koch, Andrea

    2012-07-01

    Susceptibility to infections with gram-positive bacteria, which are an important trigger of exacerbations, is increased in COPD and asthma. Unraveling the underlying mechanisms may help developing therapeutic strategies to reduce exacerbation rates. The aim of this study was to evaluate the effects of lipoteichoic acid (LTA), a danger signal from gram-positive bacteria, on T cell cytokines related to bacterial infection defense in COPD and asthma. T cell populations within peripheral blood mononuclear cells (PBMCs) were ex-vivo activated towards T(H)2/T(C)2 subtypes and subsequently stimulated with LTA. IL-2 and IL-5 concentrations in cell culture supernatants were measured by ELISA comparative between non-smokers (NS), current smokers without airflow limitation (S), smokers with moderate to severe COPD and mild to moderate asthmatics (A) (each n=10). IL-2 and IL-5 baseline levels were without differences between the cohorts. After T cell activation, IL-2 and IL-5 releases were increased in all cohorts, however, for IL-2 this increase was significantly higher in S and by trend in COPD compared to the other groups. LTA time-dependently suppressed IL-2 release in NS, S and COPD but not in A. LTA reduced IL-5 release in COPD and A but not in NS and S. Summarized, LTA reduces T(H)2/T(C)2 cytokines indicating immunosuppressive effects, which are dysregulated in COPD and asthma. This implies a misguided response to gram-positive bacterial infections, which might help to explain the increased susceptibility to bacterial infections in COPD and asthma. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. The retinoic acid receptor-α modulators ATRA and Ro415253 reciprocally regulate human IL-5+ Th2 cell proliferation and cytokine expression

    PubMed Central

    2013-01-01

    Background Th2 cytokine responses are enhanced by all trans retinoic acid (ATRA), the bioavailable form of vitamin A. Retinoic acid receptor alpha (RARα) is the high affinity receptor for ATRA that mediates these pro-Th2 effects. We have previously characterized two major human Th2 subpopulations: IL-5- Th2 (IL-5-, IL-4+, IL-13+) and IL-5+ Th2 cells (IL-5+, IL-4+, IL-13+), which represent less and more highly differentiated Th2 cells, respectively. We hypothesized that the pro-Th2 effects of ATRA may differentially affect these Th2 subpopulations. Methods Specific cytokine producing Th2 subpopulations were identified using intracellular cytokine staining. Proliferation was measured using the Cell Trace Violet proliferation tracking dye. Apoptotic cells were identified using either annexin-V or active caspase 3 staining. Th2 gene expression was measured using quantitative polymerase chain reaction. Results ATRA increased the output of Th2 cells from house dust mite allergen (HDM) specific short-term cell lines, and this enhancement was limited to the IL-5+ Th2 subpopulation. Conversely, the RARα antagonist Ro415253 decreased Th2 cell output from these cultures, and this effect was again limited to the IL-5+ Th2 subpopulation. ATRA and Ro415253 respectively augmented and inhibited Th2 cell proliferation, and this affect was more pronounced for the IL-5+ vs. IL-5- Th2 subpopulation. ATRA and Ro415253 respectively augmented and inhibited the expression of IL5 in a significant manner, which was not found for IL4 or IL13. Conclusions We report that the reciprocal regulation of Th2 cytokine expression and proliferation by RARα modulators are largely limited to modulation of IL-5 gene expression and to proliferation of the highly differentiated IL-5+ Th2 subpopulation. These results suggest that RARα antagonism is a potential means to therapeutically target allergic inflammation. Trial registration Clinicaltrials.gov identifier: NCT01212016 PMID:24314292

  8. A novel small compound SH-2251 suppresses Th2 cell-dependent airway inflammation through selective modulation of chromatin status at the Il5 gene locus.

    PubMed

    Suzuki, Junpei; Kuwahara, Makoto; Tofukuji, Soichi; Imamura, Masashi; Kato, Fuminori; Nakayama, Toshinori; Ohara, Osamu; Yamashita, Masakatsu

    2013-01-01

    IL-5 is a key cytokine that plays an important role in the development of pathological conditions in allergic inflammation. Identifying strategies to inhibit IL-5 production is important in order to establish new therapies for treating allergic inflammation. We found that SH-2251, a novel thioamide-related small compound, selectively inhibits the differentiation of IL-5-producing Th2 cells. SH-2251 inhibited the induction of active histone marks at the Il5 gene locus during Th2 cell differentiation. The recruitment of RNA polymerase II, and following expression of the Th2 cell-specific intergenic transcripts around the Il5 gene locus was also inhibited. Furthermore, Th2 cell-dependent airway inflammation in mice was suppressed by the oral administration of SH-2251. Gfi1, a transcriptional repressor, was identified as a downstream target molecule of SH-2251 using a DNA microarray analysis. The Gfi1 expression dramatically decreased in SH-2251-treated Th2 cells, and the SH-2251-mediated inhibition of IL-5-producing Th2 cell differentiation was restored by transduction of Gfi1. Therefore, our study unearthed SH-2251 as a novel therapeutic candidate for allergic inflammation that selectively inhibits active histone marks at the Il5 gene locus.

  9. Slow-dissociation effect of common signaling subunit beta c on IL5 and GM-CSF receptor assembly.

    PubMed

    Ishino, Tetsuya; Harrington, Adrian E; Zaks-Zilberman, Meirav; Scibek, Jeffery J; Chaiken, Irwin

    2008-05-01

    Receptor activation by IL5 and GM-CSF is a sequential process that depends on their interaction with a cytokine-specific subunit alpha and recruitment of a common signaling subunit beta (betac). In order to elucidate the assembly dynamics of these receptor subunits, we performed kinetic interaction analysis of the cytokine-receptor complex formation by a surface plasmon resonance biosensor. Using the extracellular domains of receptor fused with C-terminal V5-tag, we developed an assay method to co-anchor alpha and betac subunits on the biosensor surface. We demonstrated that dissociation of the cytokine-receptor complexes was slower when both subunits were co-anchored on the biosensor surface than when alpha subunit alone was anchored. The slow-dissociation effect of betac had a similar impact on GM-CSF receptor stabilization to that of IL5. The effects were abolished by alanine replacement of either Tyr18 or Tyr344 residue in betac, which together constitute key parts of a cytokine binding epitope. The data argue that betac plays an important role in preventing the ligand-receptor complexes from rapidly dissociating. This slow-dissociation effect of betac explains how, when multiple betac cytokine receptor alpha subunits are present on the same cell surface, selective betac usage can be controlled by sequestration in stabilized cytokine-alpha-betac complexes.

  10. LZTFL1 Upregulated by All-trans Retinoic Acid during CD4+ T Cell Activation Enhances IL-5 Production

    PubMed Central

    Jiang, Hong; Promchan, Kanyarat; Lin, Bor-Ruei; Lockett, Stephen; Chen, De; Marshall, Heather; Badralmaa, Yunden; Natarajan, Ven

    2015-01-01

    Retinoic acids (RAs), which are metabolites of vitamin A, have been shown to be involved in multiple T cell effector responses through their binding to the retinoic acid receptor, a ligand-activated transcription factor. Since the molecular mechanism of regulation by RA is still not fully uncovered, we investigated the gene expression profile of all-trans retinoic acid (ATRA)–treated human CD4+ T cells. Leucine zipper transcription factor-like 1 (LZTFL1) was upregulated by ATRA in a dose- and time-dependent manner. The expression of LZTFL1 depended on both ATRA and TCR signaling. LZTFL1 accumulated in the plasma membrane compartment of human CD4+ T cells, and during immunological synapse (IS) formation, it transiently redistributed to the T cell and APC contact zone, indicating its role in T cell activation. Live cell imaging demonstrates that at the initial stage of IS formation, LZTFL1 is concentrated at the APC contact site, and during later stages, it relocates to the distal pole. Knockdown of LZTFL1 reduced the basal- and ATRA-induced levels of IL-5 in CD4+ T cells, and overexpression of LZTFL1 enhanced the TCR-mediated NFAT signaling, suggesting that LZTFL1 is an important regulator of ATRA-induced T cell response. Together, these data indicate that LZTFL1 modulates T cell activation and IL-5 levels. PMID:26700766

  11. Antigen-induced recruitment of eosinophils: importance of CD4+ T cells, IL5, and mast cells.

    PubMed

    Hom, J T; Estridge, T

    1994-12-01

    Eosinophils of sensitized mice readily recruit to the site of antigen challenge. In the present study, experiments were performed to determine the involvement of different cell types in the antigen-induced recruitment of eosinophils. We demonstrated that a single treatment with anti-L3T4 monoclonal antibody (mAb) on the day of allergen challenge significantly decreased antigen-induced recruitment of eosinophils. Treatments with anti-L3T4 mAb during the sensitization period also caused a substantial reduction in the migration of eosinophils into the site of challenge with antigen. Thus, it appears that both stages of eosinophil recruitment, sensitization and antigen-challenge, are dependent upon the presence of L3T4+ T cells. Moreover, while treatments with anti-IL5 mAb blocked eosinophil migration, anti-IL2 mAb failed to alter the antigen-induced recruitment of eosinophils. In addition, significant numbers of eosinophils from the mast-cell-deficient mice were found to migrate into the peritoneal cavities upon allergen challenge. Eosinophil migration was also observed in several mouse strains of different H-2 haplotypes. The present findings suggest that CD4+ T cells and IL5 but not IL2 may play important roles in modulating the recruitment of eosinophils. Moreover, the involvement of mast cells does not appear to be essential for eosinophil migration. Finally, the development of antigen-induced recruitment of eosinophils is probably not under the immunogenetic regulation by genes within the H-2 complex.

  12. The FIP1L1-PDGFRA fusion gene cooperates with IL-5 to induce murine hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL)-like disease.

    PubMed

    Yamada, Yoshiyuki; Rothenberg, Marc E; Lee, Andrew W; Akei, Hiroko Saito; Brandt, Eric B; Williams, David A; Cancelas, Jose A

    2006-05-15

    Dysregulated tyrosine kinase activity by the Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) fusion gene has been identified as a cause of clonal hypereosinophilic syndrome (HES), called F/P-positive chronic eosinophilic leukemia (CEL) in humans. However, transplantation of F/P-transduced hematopoietic stem cells/progenitors (F/P(+) HSCs/Ps) into mice results in a chronic myelogenous leukemia-like disease, which does not resemble HES. Because a subgroup of patients with HES show T-cell-dependent interleukin-5 (IL-5) overexpression, we determined if expression of the F/P fusion gene in the presence of transgenic T-cell IL-5 overexpression in mice induces HES-like disease. Mice that received a transplant of CD2-IL-5-transgenic F/P(+) HSC/Ps (IL-5Tg-F/P) developed intense leukocytosis, strikingly high eosinophilia, and eosinophilic infiltration of nonhematopoietic as well as hematopoietic tissues, a phenotype resembling human HES. The disease phenotype was transferable to secondary transplant recipients of a high cell dose, suggesting involvement of a short-term repopulating stem cell or an early myeloid progenitor. Induction of significant eosinophilia was specific for F/P since expression of another fusion oncogene, p210-BCR/ABL, in the presence of IL-5 overexpression was characterized by a significantly lower eosinophilia than IL-5Tg-F/P recipients. These results suggest that F/P is not sufficient to induce a HES/CEL-like disease but requires a second event associated with IL-5 overexpression.

  13. Identification of a fourth ancient member of the IL-3/IL-5/GM-CSF cytokine family, KK34, in many mammals.

    PubMed

    Yamaguchi, Takuya; Schares, Susann; Fischer, Uwe; Dijkstra, Johannes M

    2016-12-01

    The related cytokine genes IL-3, IL-5 and GM-CSF map to the (extended) TH2 cytokine locus of the mammalian genome. For chicken an additional related cytokine gene, KK34, was reported downstream of the IL-3 plus GM-CSF cluster, but hitherto it was believed that mammalian genomes lack this gene. However, the present study identifies an intact orthologue of chicken KK34 gene in many mammals like cattle and pig, while remnants of KK34 can be found in human and mouse. Bovine KK34 was found to be transcribed, and its recombinant protein could induce STAT5 phosphorylation and proliferation of lymphocytes upon incubation with bovine PBMCs. This concludes that KK34 is a fourth functional cytokine of the IL-3/IL-5/GM-CSF/KK34-family (alias IL-5 family) in mammals. While analyzing KK34, the present study also made new identifications of cytokine genes in the extended TH2 cytokine loci for reptiles, birds and marsupials. This includes a hitherto unknown cytokine gene in birds and reptiles which we designated "IL-5famE". Other newly identified genes are KK34, GM-CSF(-like), IL-5, and IL-13 in reptiles, and IL-3 in marsupials.

  14. Expansion of CD3+CD4-CD8- T cell population expressing high levels of IL-5 in Omenn's syndrome.

    PubMed Central

    Melamed, I; Cohen, A; Roifman, C M

    1994-01-01

    Omenn's syndrome is a fatal, autosomal-recessive combined immune deficiency characterized by several erythematous exfoliative eruptions, lymphadenopathy, hepatosplenomegaly, and elevated eosinophil count. In some of these patients an expansion of CD3+CD4-CD8- double negative (DN) T cell population was observed. We show here that the DN population represents a clonal expansion of T cells which preferentially use V beta 14 in their T cell receptor complex. Using polymerase chain reaction, we show that patient's DN cells express spontaneously high levels of IL-5, thus possibly explaining the abundance of eosinophils in this disorder. The increase of IgE observed in patients with Omenn's syndrome is unlikely to be related to IL-4 production, as IL-4 levels in patient samples were low. However, patient's low expression of interferon-gamma (IFN-gamma), which has been reported to inhibit IgE production, may explain the elevated levels of IgE in this patient. The results thus highlight the importance of the inhibitory effect of IFN-gamma on regulation of IgE production. Images Fig. 4 Fig. 5 Fig. 6 PMID:8287598

  15. Interaction between endothelial cells and the secreted cytokine drives the fate of an IL4- or an IL5-transduced tumour.

    PubMed

    Di Carlo, E; Modesti, A; Coletti, A; Colombo, M P; Giovarelli, M; Forni, G; Diodoro, M G; Musiani, P

    1998-12-01

    Injection of interleukin-4 (IL4) gene-transduced tumour cells into syngeneic immunocompetent mice resulted in tumour rejection in which a key role for eosinophils was suggested. To evaluate whether IL5 inhibits tumour growth by selectively inducing eosinophil recruitment and activation, a poorly differentiated mammary adenocarcinoma cell line (TSA) was transfected with the IL5 gene and the cells secreting IL5 (TSA-IL5) were injected subcutaneously (s.c.) in syngeneic mice. The oncogenicity of TSA-IL5 was compared with that exhibited by TSA cells transfected with the IL4 gene (TSA-IL4) and with the neomycin resistance gene only (TSA-neo). At progressive times after subcutaneous challenge, tumour growth areas were studied histologically, ultrastructurally, and immunohistochemically to identify the reactive cells, visualize tumour vessels, and detect the cytokines and chemokines involved in the anti-tumour reaction. Both the morphological and the functional data showed that TSA-IL5, despite the large eosinophil infiltrate, grew progressively like TSA-neo, suggesting that eosinophils per se do not play a crucial role in TSA tumour rejection. Furthermore, our data indicate that the rejection of TSA-IL4 depends on the IL4-induced expression of VCAM-1 and MCP-1 by endothelial cells. MCP-1 together with VCAM-1 results in recruitment and activation of basophils, mast cells, and macrophages, and hence a pro-inflammatory cytokine cascade that initially favours the influx and activation of neutrophils and finally tumour rejection. In this context, the rejection of TSA-IL4 seems to involve a variety of reactive cells and rests on a continuous cross-talk between basophils, mast cells, macrophages, CD8-positive lymphocytes, and granulocyte subsets, mostly neutrophils.

  16. Recombinant Mycobacterium bovis BCG producing IL-18 reduces IL-5 production and bronchoalveolar eosinophilia induced by an allergic reaction.

    PubMed

    Biet, F; Duez, C; Kremer, L; Marquillies, P; Amniai, L; Tonnel, A-B; Locht, C; Pestel, J

    2005-08-01

    Allergic reactions occur through the exacerbated induction of a Th2 cell type expression profile and can be prevented by agents favoring a Th1 profile. Bacillus Calmette-Guérin (BCG) is able to induce high IFN-gamma levels and has been shown to decrease experimentally induced allergy. The induction of IFN-gamma is mediated by interleukin (IL)-12 known to be secreted upon mycobacterial infections and can be enhanced by IL-18 acting in synergy with IL-12. We evaluated the ability of a recombinant BCG strain producing IL-18 (rBCG) to modify the Th2 type responses in a murine model of ovalbumin (OVA)-dependent allergic reaction. Mice were injected intraperitoneally or intranasally with OVA at days 0 and 15 and exposed to an OVA aerosol challenge at days 29, 30, 31 and 34. At days 0 and 15, two additional groups of mice received OVA together with 5 x 10(6) colony forming units of either rBCG or nonrecombinant BCG. A time-course analysis of OVA-specific immunoglobulin (Ig)E, IgG1 and IgG2a levels indicated no significant difference between the three groups of mice. However, following in vitro stimulation with OVA, lymph node cells from rBCG-treated mice produced less IL-5 and more IFN-gamma than those of mice injected with nonrecombinant BCG. In addition, 48 h after the last OVA challenge, a strong reduction of bronchoalveolar eosinophilia was found in the rBCG-injected mice compared to the nontreated or nonrecombinant BCG-treated groups. These results indicate that the production of IL-18 by rBCG may enhance the immunomodulatory properties of BCG that suppress pulmonary Th2 responses and, in particular, decrease airway eosinophilia.

  17. Transcriptional regulation of the human IL5 gene by ionizing radiation in Jurkat T cells: evidence for repression by an NF-AT-like element.

    PubMed

    Lu-Hesselmann, J; Messer, G; van Beuningen, D; Kind, P; Peter, R U

    1997-12-01

    Eosinophilia is often observed in patients with parasitic infections and atopic diseases like allergic asthma and atopic dermatitis. Additionally, it is a typical feature of the inflammatory reaction after therapeutic and accidental exposure to ionizing radiation. This uniquely specific phenomenon regulated by the cytokine interleukin 5 (IL-5) suggests specific control for IL5 gene expression. In this study, we generated promoter-CAT constructs containing different human IL-5 promoter regions spanning from positions -507 to +43. Transfection experiments in Jurkat T cells revealed that the promoter sequence from -57 to +43 was required for constitutive and inducible IL-5 promoter activity. Low baseline CAT activity could be enhanced by treatment with phenylmercuric acetate (PMA) or the combination of PMA and calcium ionophore. The promoter region between positions -97 and +43 showed responsiveness to low-dose X rays. Electrophoretic mobility shift assays demonstrated that the region from -117 to -97 was responsive to irradiation. Transcription factors specifically bound to this sequence showed a dose-dependent response to single doses of X rays between 1 and 8 Gy. Competition analysis indicated that the protein-DNA complexes at this region were related to the nuclear factor of activated T cells (NF-AT). Further confirmation was obtained by the addition of specific antibodies into protein-DNA reactions. For the first time, we have demonstrated that specific DNA binding of NF-ATp at the promoter region from -117 to -97 is involved in transcriptional regulation of the human IL5 gene in response to ionizing radiation.

  18. Lyn mediates FIP1L1-PDGFRA signal pathway facilitating IL- 5RA intracellular signal through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex in CEL.

    PubMed

    Li, Bin; Zhang, Guangsen; Li, Cui; Li, Ruijuan; Lu, Jingchen; He, Zhengxi; Wang, Quan; Peng, Zhenzi; Wang, Jun; Dong, Yeping; Zhang, Chunfang; Tan, Jie Qiong; Bahri, Nacef; Wang, Yuexiang; Duan, Chaojun

    2016-08-19

    The Fip1-like1 (FIP1L1)-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) oncogene can cause chronic eosinophilic leukemia (CEL), but requires IL-5 cytokine participation. In this study, we investigate the mechanism of F/P in collaboration with IL-5 in CEL. The results showed that Lyn, a key effector in the IL-5-motivated eosinophil production, is extensively activated in F/P-positive CEL cells. Lyn can associate and phosphorylate IL-5 receptor α (IL-5RA) in F/P-positive cells. Moreover, the activation of Lyn and IL-5R kinase were strengthened when the cells were stimulated by IL-5. Lyn inhibition in F/P-positive CEL cells attenuated cellular proliferation, induced apoptosis, and blocked cell migration and major basic protein (MBP) release. We identified the FIP1L1-PDGFRA/JAK2/Lyn/Akt complex in the F/P-expressing cells which can be disrupted by dual inhibition of JAK2 and Lyn, repressing cell proliferation in both EOL-1(F/P-positive human eosinophilic cell line) and imatinib-resistance (IR) cells. Altogether, our data demonstrate that Lyn is a vital downstream kinase activated by F/P converged with IL-5 signals in CEL cells. Lyn activate and expand IL-5RA intracellular signaling through FIP1L1-PDGFRA/JAK2/Lyn/Akt network complex, provoking eosinophils proliferation and exaggerated activation manifested as CEL.

  19. A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6.

    PubMed

    De León-Nava, Marco A; Álvarez-Delgado, Carolina; Donis-Maturano, Luis; Hernández-Ruiz, Joselin; Manjarrez-Reyna, Aaron N; Cruz-Avilés, Edgar; Leon-Cabrera, Sonia; Morales-Montor, Jorge; Fragoso, José M; Escobedo, Galileo

    2016-12-01

    We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients.

  20. A non-hepatotropic parasite infection increases mortality in the acetaminophen-induced acute liver failure murine model: possible roles for IL-5 and IL-6

    PubMed Central

    De León-Nava, Marco A; Álvarez-Delgado, Carolina; Donis-Maturano, Luis; Hernández-Ruiz, Joselin; Manjarrez-Reyna, Aaron N; Cruz-Avilés, Edgar; Leon-Cabrera, Sonia; Morales-Montor, Jorge; Fragoso, José M; Escobedo, Galileo

    2016-01-01

    We evaluated the effects of a non-hepatotropic parasite infection (Taenia crassiceps) on the outcome of acetaminophen-induced acute liver failure in mice. Uninfected and T. crassiceps infected mice orally received either 300 mg/kg acetaminophen or water as vehicle (n = 5 per group). Survival analysis, hepatocyte necrosis, alanine aminotransferase (ALT) levels, CYP2E1 protein, interleukin (IL-) 5, and IL-6 were assessed for all groups. All infected mice died within 16 h after exposure to acetaminophen (Tc+APAP group), whereas only one-third of uninfected animals exposed to acetaminophen (APAP group) died. Uninfected (Control group) and infected (Tc group) mice that received the vehicle showed no liver damage. Tc+APAP mice exhibited massive liver necrosis characterised by marked balloning degeneration of hepatocytes and higher serum ALT compared to Control, Tc, and APAP animals. Liver tissue from Tc+APAP mice also displayed increased expression of CYP2E1 protein and higher mRNA and protein levels of IL-5 and IL-6 compared to the other groups. These findings suggest that non-hepatotropic parasite infections may increase mortality following acute liver failure by promoting hepatocyte necrosis via IL-5 and IL-6-dependent CYP2E1 overproduction. This study identifies new potential risk factors associated with severe acute liver failure in patients. PMID:27812602

  1. IL-2 absorption affects IFN-gamma and IL-5, but not IL-4 producing memory T cells in double color cytokine ELISPOT assays.

    PubMed

    Quast, Stefan; Zhang, Wenji; Shive, Carey; Kovalovski, Damian; Ott, Patrick A; Herzog, Bernhard A; Boehm, Bernhard O; Tary-Lehmann, Magdalena; Karulin, Alexey Y; Lehmann, Paul V

    2005-09-01

    Cytokine assays are gaining increasing importance for human immune monitoring because they reliably detect antigen-specific T cells in primary PBMC, even at low clonal sizes. Double color ELISPOT assays permit the simultaneous visualization of cells producing two different cytokines. Permitting the simultaneous assessment of type 1 and 2 immunity and due to the limited numbers of PBMC available from human study subjects, double color assays should be particularly attractive for clinical trials. Since the performance of double color assays has not yet been validated, we set out to compare them to single color measurements. Testing the recall antigen-induced cytokine response of PBMC, we found that double color assays regularly provided lower numbers of IFN-gamma and IL-5 spots than single color measurements when IL-2 detection was part of the double color assay. We showed that the inhibitory effect resulted from IL-2 absorption and could be overcome by either antibody free preactivation cultures or by inclusion of anti-CD28 antibody. In contrast, the simultaneous detection of IL-2 did not affect the numbers of IL-4 spots. Therefore, unlike IL-2/IL-4 and IFN-gamma/IL-5 assays, IL-2/IFN-gamma, and IL-2/IL-5 assays require compensation for the IL-2 capture to provide accurate numbers for the frequencies of cytokine producing memory T cells.

  2. Association of polymorphisms in the human IL4 and IL5 genes with atopic bronchial asthma and severity of the disease.

    PubMed

    Freidin, Maxim B; Kobyakova, Olga S; Ogorodova, Ludmila M; Puzyrev, Valery P

    2003-01-01

    Two polymorphisms in the IL4 (G/C 3'-UTR) and IL5 (C-703T) genes were studied in a sample of families whose probands had atopic bronchial asthma (BA) (66 families, n = 183) and in a group of non-cognate individuals with the severe form of the disease (n = 34). The samples were collected from the Russian population in the city of Tomsk (Russia). Using the transmission/disequilibrium test (TDT), a significant association of allele C-703 IL5 with BA was established (TDT = 4.923, p = 0.007 +/- 0.0007). The analysis of 40 individuals with mild asthma and 49 patients with the severe form of the disease revealed a negative association of genotype GG IL4 (OR = 0.39, 95% CI = 0.15-0.99, p = 0.035), and also a trend towards a positive association of the GC IL4 genotype (OR = 2.52, 95% CI = 0.98-6.57, p = 0.052) with mild BA. There was a concordance of the clinical classification of BA severity with the 'genotype' (McNemar's chi(2) test with continuity correction constituted 0.03, d.f. = 1, p = 0.859). These results suggest that polymorphisms in the IL4 and IL5 genes contribute to the susceptibility to atopic BA and could determine the clinical course of the disease.

  3. The acquisition of cytokine responsiveness by murine B cells: a role for antigen and IL-5 in the induction of IL-2 receptors.

    PubMed Central

    Poudrier, J; Owens, T

    1994-01-01

    The mechanism whereby small resting (high buoyant density) murine B cells are induced to express interleukin-2 receptors (IL-2R) and to respond to IL-2 was addressed by staining with anti-IL-2R alpha and -IL-2R beta monoclonal antibodies (mAb), and using receptor-specific cDNA probes. Resting B cells expressed undetectable levels of both IL-2R alpha and beta chains on their surface and did not respond to IL-2, even at supra-physiological concentrations. Sepharose-coupled, but not streptavidin-cross-linked, plastic-adsorbed or soluble, anti-mu up-regulated the expression of IL-2R alpha and beta chains and mRNA to levels comparable to those seen in activated T cells. Anti-mu-stimulated B cells responded to IL-2 by incorporation of [3H]thymidine and high rate immunoglobulin (Ig) secretion. Both IL-5 (at optimal concentration) and suboptimal lipopolysaccharide (LPS; 20 ng/ml) induced surface expression of IL-2R alpha. The level of expression induced by IL-5 was equivalent to that on anti-Ig-activated B cells. Neither stimulus induced detectable expression of IL-2R beta, and neither induced B cells to respond to IL-2. IL-2R alpha expression was strongly enhanced, and low levels of IL-2R beta staining and mRNA were induced by the combination of LPS plus IL-5. LPS+IL-5-treated B cells responded to IL-2 by Ig secretion. This indicates that B cells regulate their responsiveness to IL-2 similarly to T cells, via the combined level of expression of IL-2R beta and IL-2R alpha. The synergy between IL-5 and LPS for B-cell responses shows a requirement for complementary stimuli such as would be provided by cytokines, and either cellular interaction or antigen recognition in regulation of B-cell responsiveness to IL-2. Images Figure 4 Figure 5 PMID:8206511

  4. Sequential mutations in the interleukin-3 (IL3)/granulocyte-macrophage colony-stimulating factor/IL5 receptor beta-subunit genes are necessary for the complete conversion to growth autonomy mediated by a truncated beta C subunit.

    PubMed

    Hannemann, J; Hara, T; Kawai, M; Miyajima, A; Ostertag, W; Stocking, C

    1995-05-01

    An amino-terminally truncated beta C receptor (beta C-R) subunit of the interleukin-3 (IL3)/granulocyte-macrophage colony-stimulating factor/IL5 receptor complex mediates factor-independent and tumorigenic growth in two spontaneous mutants of a promyelocytic cell line. The constitutive activation of the JAK2 protein kinase in these mutants confirms that signaling occurs through the truncated receptor protein. Noteworthily, in addition to a 10-kb deletion in the beta C-R subunit gene encoding the truncated receptor, several secondary and independent mutations that result in the deletion or functional inactivation of the allelic beta C-R subunit and the closely related beta IL3-R subunit genes were observed in both mutants, suggesting that such mutations are necessary for the full oncogenic penetrance of the truncated beta C-R subunit. Reversion of these mutations by the expression of the wild-type beta C-R in the two mutants resulted in a fivefold decrease in cloning efficiency of the mutants in the absence of IL3, confirming a functional interaction between the wild-type and truncated proteins. Furthermore, expression of the truncated beta C-R subunit in factor-dependent myeloid cells did not immediately render the cells autonomous but increased the spontaneous frequency to factor-independent growth by 4 orders of magnitude. Implications for both leukemogenic progression and receptor-subunit interaction and signaling are discussed.

  5. The allergen-induced airway hyperresponsiveness in a human-mouse chimera model of asthma is T cell and IL-4 and IL-5 dependent.

    PubMed

    Tournoy, K G; Kips, J C; Pauwels, R A

    2001-06-01

    The cellular and molecular mechanisms involved in the airway hyperresponsiveness (AHR) of patients with allergic asthma remain unclear. A role for Th2 inflammatory cells was suggested based on murine asthma models. No direct evidence exists on the role of these cells in human asthma. The development of a mouse-human chimera might be useful, allowing the in vivo study of the components of the human immune system relevant to asthma. We investigated the role of allergen-reactive T lymphocytes in a human-mouse SCID model. SCID mice were reconstituted intratracheally with human PBMC from healthy, nonallergic, nonasthmatic donors and exposed to an aerosol of house dust mite allergen after i.p. injection with Dermatophagoides pteronyssinus I Ag and alum. The donor T lymphocytes had a Th1 cytokine phenotype. The reconstituted and allergen-challenged mice developed AHR to carbachol. The mouse airways and lungs were infiltrated with human T lymphocytes. No eosinophils or increases in human IgE were observed. The intrapulmonary human T lymphocytes demonstrated an increase in intracytoplasmic IL-4 and IL-5 and a decrease in IFN-gamma after exposure to allergen adjuvant. Antagonizing human IL-4/IL-13 or IL-5 resulted in a normalization of the airway responsiveness, despite a sustained intracellular Th2 cytokine production. These results provide evidence that the activated human allergen-reactive Th2 cells producing IL-4 or IL-5 are pivotal in the induction of AHR, whereas no critical role for eosinophils or IgE could be demonstrated. They also demonstrate that human allergen-specific Th1 lymphocytes can be driven to a Th2 phenotype.

  6. Evidence for multiple promoters of the human IL-5 receptor alpha subunit gene: a novel 6-base pair element determines cell-specific promoter function.

    PubMed

    Zhang, J; Kuvelkar, R; Cheewatrakoolpong, B; Williams, S; Egan, R W; Billah, M M

    1997-12-01

    In addition to a previously characterized promoter (P1), we now show the existence of a second promoter for the human IL-5Ralpha gene. Initially, a genomic region (P2) 5' upstream of human IL-5Ralpha exon 2 was cloned by an inverted PCR. The transcriptional start site was then mapped to a deoxycytidine (C) residue within P2 by analyzing cellular mRNA with both the 5' rapid amplification of cDNA end-PCR and S1 nuclease protection assays. Transfection of eosinophilic HL-60 cells with reporter gene constructs in which either P1 or P2 was linked to the bacterial chloramphenicol acetyltransferase (CAT) gene resulted in CAT expression; little or no CAT expression occurred in other myeloid and nonmyeloid cell lines. Deletion studies showed that a 66-bp region, ranging from -31 to +35, was sufficient to promote CAT expression in eosinophilic HL-60 cells. Analysis of linker-scanning mutants identified a novel 6-bp element (5' CTAATT 3') spanning -19 to -14 that was essential for P2 promoter activity. In electrophoretic mobility shift assays, a P2 region from -31 to +1 containing the unique 6-bp element, when used as a probe, formed a complex with a protein(s) that was found only in the eosinophilic cell line. This binding activity was lost upon replacement of the 6-bp element with a 6-bp linker, suggesting that this element likely serves as the binding site for an eosinophilic HL-60 cell-specific transcription factor(s). Together, these data suggest an important role for P2 promoter in the regulation of eosinophil-specific expression of the human IL-5 receptor alpha gene.

  7. Endogenous IL-10 regulates IFN-gamma and IL-5 cytokine production and the granulomatous response in Schistosomiasis mansoni-infected mice.

    PubMed Central

    Boros, D L; Whitfield, J R

    1998-01-01

    In murine Schistosomiasis mansoni circumovum, granuloma formation is regulated by pro- and anti-inflammatory cytokines. Among the latter, interleukin-10 (IL-10) has been shown to regulate the inflammatory response. In this study we examined the role of endogenously produced IL-10 in T-helper 1 (Th1)- and Th2-type cytokine production and granuloma formation. The dynamics of IL-10 production through the course of the infection were different in granuloma versus splenic cells. In the former, production peaked during the early developmental stage (6 weeks of infection) of the granuloma and then declined. In splenocytes production peaked at 12 weeks, before down-modulation of the granuloma response. In the developing granuloma both macrophages and T cells secreted IL-10. In anti-IL-10 monoclonal antibody (mAb)-supplemented granuloma cell cultures endogenous IL-10-mediated regulation of interferon-gamma (IFN-gamma) was manifest only at 6 weeks; that of IL-2 continued throughout the infection (6-20 weeks). IL-4 production was unaffected, but IL-5 production was regulated at the 6 and 8 weeks time point. Splenocytes showed regulation of IFN-gamma and IL-2 production at the peak of the granulomatous response (8 weeks). IL-4 production was not regulated, whereas IL-5 production was regulated only at 6 weeks. Repeated injections of anti-IL-10 mAb given to mice at 6, 12 or 20 weeks of the infection significantly enhanced liver and lung granuloma growth, tissue eosinophilia, and IFN-gamma, IL-5 production at the early developmental phase (6 weeks) of the lesions. Thus, in schistosome-infected mice endogenous IL-10 is shown to regulate Th1- and Th2-type cytokine production and granuloma formation during the early Th0/Th1 phase of the immune response. PMID:9767435

  8. Histamine reverses IL-5-afforded human eosinophil survival by inducing apoptosis: pharmacological evidence for a novel mechanism of action of histamine.

    PubMed

    Hasala, Hannele; Giembycz, Mark A; Janka-Junttila, Mirkka; Moilanen, Eeva; Kankaanranta, Hannu

    2008-01-01

    Eosinophils are essential inflammatory cells in the pathogenesis of asthma and atopic conditions. Histamine, released from mast cells and basophils in response to allergen exposure, is a critical mediator in the allergic response. Histamine exerts its effects via four unequivocally characterized histamine receptors, H(1-4). Several functions of eosinophils have previously been shown to be stimulated by histamine. However, its effects on eosinophil apoptosis are unknown. The aim of the present study was to resolve the effects of histamine on constitutive apoptosis of human eosinophils and on the survival-enhancing action of interleukin (IL)-5. Additional experiments were conducted to elucidate the histamine receptor(s) involved in any response seen and the associated signal transduction cascade. Human isolated peripheral blood eosinophils were cultured in the absence or presence of histamine, IL-5 and receptor antagonists/agonists or mediator inhibitors/analogues. Apoptosis was assessed by measuring the relative DNA content of propidium iodide (PI)-stained cells and the effects were confirmed by morphological analysis with bright field microscopy. Caspase activities were assessed by using commercial Caspase-Glo 3/7, 8 and 9 luminescence assays. Histamine (10-100 microM) partially reversed IL-5-induced human eosinophil survival by enhancing apoptosis as assessed by measuring the relative DNA content of PI-stained cells. This effect was not mediated through any of the known histamine receptors or through non-specific activation of 5-hydroxytryptamine receptors or alpha-adrenoceptors. Moreover, the reversal of IL-5-inhibited eosinophil apoptosis by histamine seemed not to utilize the conventional intracellular second-messenger pathways including cyclic AMP, protein kinase A or phospholipase C. Inhibition of caspase 6 and caspases 1, 10 or 12 reversed the effects of histamine but also inhibited apoptosis in general. In conclusion, the data presented herein indicate that

  9. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study.

    PubMed

    Goines, Paula E; Croen, Lisa A; Braunschweig, Daniel; Yoshida, Cathleen K; Grether, Judith; Hansen, Robin; Kharrazi, Martin; Ashwood, Paul; Van de Water, Judy

    2011-08-02

    Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders. Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (n = 84), (2) a developmental delay (DD) but not autism (n = 49) or (3) no known developmental disability (general population (GP); n = 159). ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis. Elevated concentrations of IFN-γ, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism. The profile of elevated serum IFN-γ, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment.

  10. Crucial role of IL-4/STAT6 in T cell-mediated hepatitis: up-regulating eotaxins and IL-5 and recruiting leukocytes.

    PubMed

    Jaruga, Barbara; Hong, Feng; Sun, Rui; Radaeva, Svetlana; Gao, Bin

    2003-09-15

    T cell-mediated immune responses are implicated in the pathogenesis of a variety of liver disorders; however, the underlying mechanism remains obscure. Con A injection is a widely accepted mouse model to study T cell-mediated liver injury, in which STAT6 is rapidly activated. Disruption of the IL-4 and STAT6 gene by way of genetic knockout abolishes Con A-mediated liver injury without affecting IFN-gamma/STAT1, IL-6/STAT3, or TNF-alpha/NF-kappaB signaling or affecting NKT cell activation. Infiltration of neutrophils and eosinophils in Con A-induced hepatitis is markedly suppressed in IL-4 (-/-) and STAT6(-/-) mice compared with wild-type mice. IL-4 treatment induces expression of eotaxins in hepatocytes and sinusoidal endothelial cells isolated from wild-type mice but not from STAT6(-/-) mice. Con A injection induces expression of eotaxins in the liver and elevates serum levels of IL-5 and eotaxins; such induction is markedly attenuated in IL-4(-/-) and STAT6(-/-) mice. Finally, eotaxin blockade attenuates Con A-induced liver injury and leukocyte infiltration. Taken together, these findings suggest that IL-4/STAT6 plays a critical role in Con A-induced hepatitis, via enhancing expression of eotaxins in hepatocytes and sinusoidal endothelial cells, and induces IL-5 expression, thereby facilitating recruitment of eosinophils and neutrophils into the liver and resulting in hepatitis.

  11. Expression of TSLP and Downstream Molecules IL-4, IL-5, and IL-13 on the Eye Surface of Patients with Various Types of Allergic Conjunctivitis

    PubMed Central

    2016-01-01

    Background. The pathogenesis of allergic conjunctivitis has not been clearly established. Moreover, previous studies fail to consider human models of allergic conjunctivitis. This study investigated the expression of thymic stromal lymphopoiet in TSLP and its downstream molecules in conjunctival scrappings and tear. Methods. This cross-sectional study compares patients with vernal keratoconjunctivitis (VKC), seasonal allergic conjunctivitis (SAC), and perennial allergic conjunctivitis (PAC) with normal controls. There are 80 people recorded in Shanxi Eye Hospital. Increasingly, 20 are with VKC, 20 are with SAC, 20 are with PAC, and the remaining 20 are normal controls. Conjunctiva were harvested for total RNA extraction and gene expression by real-time polymerase chain reaction. Epithelial cells were collected to make pathological sections for immunohistochemical staining. Human tears were evaluated by Luminex microbead assay. A P value less than 0.05 from Dunnett's post hoc test in SPSS means a statistical significant distinction. Results. Positive expression in conjunctival cells of patients with allergic conjunctivitis. The expression of TSLP and IL-4, IL-5, and IL-13 mRNA shows a statistically significant difference (P < 0.05). TSLP and IL-4, IL-5, and IL-13 concentrations show a statistically significant difference (P < 0.01). Conclusions. This study suggests that TSLP and downstream molecules are expressed in patients with various types of allergic conjunctivitis. PMID:27504196

  12. Mistletoe treatment induces GM-CSF- and IL-5 production by PBMC and increases blood granulocyte- and eosinophil counts: a placebo controlled randomized study in healthy subjects.

    PubMed

    Huber, Roman; Rostock, M; Goedl, R; Lüdtke, R; Urech, K; Buck, S; Klein, R

    2005-10-18

    Various immunological effects have been reported during application of mistletoe preparations. Because these data are heterogeneous, we performed a placebo controlled study to investigate (1) effects on peripheral granulocyte and eosinophil counts, (2) related cytokine levels and (3) whether effects are related to mistletoe lectin (ML). 43 volunteers were randomized to receive the mistletoe plant extract Iscador Quercus spezial (IQ), purified ML, IQ which was depleted from ML, or placebo subcutaneously twice per week for 8 weeks. Weekly, differential blood count and every four weeks spontaneous and IQ- and ML-induced cytokine production by peripheral blood mononuclear cells (PBMC) were analyzed. Leukocyte-, granulocyte-, and eosinophil counts were significantly higher during treatment in the IQ- and ML-groups than in the placebo group. Furthermore, a significant increase of antigen-induced production of GM-CSF, IL-5 and IFNgamma by PBMC was observed in the IQ- and ML-group but not in the groups receiving ML-depleted IQ or placebo. Severe side effects did not occur in any of the subjects. Treatment with IQ or ML stimulates the production of GM-CSF, IL-5 and IFNgamma by PBMC, and this is accompanied by an increase of eosinophil- and granulocyte-counts. These observations may, therefore, open rational therapeutic indications for mistletoe extracts.

  13. Increased midgestational IFN-γ, IL-4 and IL-5 in women bearing a child with autism: A case-control study

    PubMed Central

    2011-01-01

    Background Immune anomalies have been documented in individuals with autism spectrum disorders (ASDs) and their family members. It is unknown whether the maternal immune profile during pregnancy is associated with the risk of bearing a child with ASD or other neurodevelopmental disorders. Methods Using Luminex technology, levels of 17 cytokines and chemokines were measured in banked serum collected from women at 15 to 19 weeks of gestation who gave birth to a child ultimately diagnosed with (1) ASD (n = 84), (2) a developmental delay (DD) but not autism (n = 49) or (3) no known developmental disability (general population (GP); n = 159). ASD and DD risk associated with maternal cytokine and chemokine levels was estimated by using multivariable logistic regression analysis. Results Elevated concentrations of IFN-γ, IL-4 and IL-5 in midgestation maternal serum were significantly associated with a 50% increased risk of ASD, regardless of ASD onset type and the presence of intellectual disability. By contrast, elevated concentrations of IL-2, IL-4 and IL-6 were significantly associated with an increased risk of DD without autism. Conclusion The profile of elevated serum IFN-γ, IL-4 and IL-5 was more common in women who gave birth to a child subsequently diagnosed with ASD. An alternative profile of increased IL-2, IL-4 and IL-6 was more common for women who gave birth to a child subsequently diagnosed with DD without autism. Further investigation is needed to characterize the relationship between these divergent maternal immunological phenotypes and to evaluate their effect on neurodevelopment. PMID:21810230

  14. Intracellular IL-4, IL-5, and IFN-γ as the main characteristic of CD4+CD30+ T cells after allergen stimulation in patients with vernal keratoconjunctivitis

    PubMed Central

    Magaña, Diana; Aguilar, Gustavo; Linares, Marisela; Ayala-Balboa, Julio; Santacruz, Concepción; Chávez, Raúl; Estrada-Parra, Sergio; Garfias, Yonathan; Lascurain, Ricardo; Jiménez-Martínez, Maria C.

    2015-01-01

    Background Vernal keratoconjunctivitis (VKC) is a severe form of allergic conjunctivitis, in which inflammatory infiltrates of the conjunctiva are characterized by CD3+ and CD30+ cells. Until today, the functional involvement of CD30+ T cells in VKC was unclear. Our aim was to evaluate the functional characteristics of CD30+ T cells after allergen stimulation in peripheral blood mononuclear cells obtained from patients with VKC. Methods Seventeen consecutive patients at the Institute of Ophthalmology with active forms of VKC were included. Results After allergen stimulation, we observed the frequency of CD30+ T cells increased compared with non-stimulated cells (p<0.0001). The CD30+ T cells responded to the specific allergen-inducing expression of intracellular interleukin-4 (IL-4), IL-5, and interferon-gamma (IFN-γ) compared with the CD30- T cells (p<0.0001). Increased early secretion of soluble CD30 was observed in the supernatant of the cultured cells from patients with keratoconjunctivitis, compared with healthy controls (p=0.03). Blockage with IL-4 significantly diminished CD30 frequency in the allergen-stimulated cells. Conclusions Our results suggest that after allergenic stimulation, CD4+CD30+ cells are the most important source of IL-4, IL-5, and IFN-γ. IL-4 acts as an activation loop that increases CD30 expression on T cells after specific stimulation. These findings suggest that CD4+CD30+ T cells are effector cells and play a significant role in the immune pathogenic response in patients with vernal keratoconjunctivitis. PMID:25999672

  15. Chromosome 5q candidate genes in coeliac disease: genetic variation at IL4, IL5, IL9, IL13, IL17B and NR3C1.

    PubMed

    Ryan, A W; Thornton, J M; Brophy, K; Daly, J S; McLoughlin, R M; O'Morain, C; Abuzakouk, M; Kennedy, N P; Stevens, F M; Feighery, C; Kelleher, D; McManus, R

    2005-02-01

    Genetic predisposition to coeliac disease (CD) is determined primarily by alleles at the HLA-DQB locus, and evidence exists implicating other major histocompatibility complex-linked genes (6p21) and the CTLA4 locus on chromosome 2q33. In addition, extensive family studies have provided strong, reproducible evidence for a susceptibility locus on chromosome 5q (CELIAC2). However, the gene responsible has not been identified. We have assayed genetic variation at the IL4, IL5, IL9, IL13, IL17B and NR3C1 (GR) loci, all of which are present on chromosome 5q and have potential or demonstrated involvement in autoimmune and/or inflammatory disease, in a sample of 409 CD cases and 355 controls. Thirteen single nucleotide polymorphisms were chosen on the basis of functional relevance, prior disease association and, where possible, prior knowledge of the haplotype variation present in European populations. There were no statistically significant allele or haplotype frequency differences between cases and controls. Therefore, these results provide no evidence that these loci are associated with CD in this sample population.

  16. Naive helper T cells from BCG-vaccinated volunteers produce IFN-gamma and IL-5 to mycobacterial antigen-pulsed dendritic cells.

    PubMed

    Kowalewicz-Kulbat, Magdalena; Kaźmierczak, Dominik; Donevski, Stefan; Biet, Franck; Pestel, Joël; Rudnicka, Wiesława

    2008-01-01

    Mycobacterium bovis bacillus Calmette-Guérin (BCG) is a live vaccine that has been used in routine vaccination against tuberculosis for nearly 80 years. However, its efficacy is controversial. The failure of BCG vaccination may be at least partially explained by the induction of poor or inappropriate host responses. Dendritic cells (DCs) are likely to play a key role in the induction of immune response to mycobacteria by polarizing the reactivity of T lymphocytes toward a Th1 profile, contributing to the generation of protective cellular immunity against mycobacteria. In this study we aimed to investigate the production of Th1 and Th2 cytokines by naive CD4+ T cells to mycobacterial antigen-pulsed DCs in the group of young, healthy BCG vaccinated volunteers. The response of naive helper T cells was compared with the response of total blood lymphocytes. Our present results clearly showed that circulating naive CD45RA+CD4+ lymphocytes from BCG-vaccinated subjects can become effector helper cells producing IFN-gamma and IL-5 under the stimulation by autologous dendritic cells presenting mycobacterial protein antigen-PPD or infected with live M. bovis BCG bacilli.

  17. TNF-alpha from inflammatory dendritic cells (DCs) regulates lung IL-17A/IL-5 levels and neutrophilia versus eosinophilia during persistent fungal infection.

    PubMed

    Fei, Mingjian; Bhatia, Shikha; Oriss, Timothy B; Yarlagadda, Manohar; Khare, Anupriya; Akira, Shizuo; Saijo, Shinobu; Iwakura, Yoichiro; Fallert Junecko, Beth A; Reinhart, Todd A; Foreman, Oded; Ray, Prabir; Kolls, Jay; Ray, Anuradha

    2011-03-29

    Aspergillus fumigatus is commonly associated with allergic bronchopulmonary aspergillosis in patients with severe asthma in which chronic airway neutrophilia predicts a poor outcome. We were able to recapitulate fungus-induced neutrophilic airway inflammation in a mouse model in our efforts to understand the underlying mechanisms. However, neutrophilia occurred in a mouse strain-selective fashion, providing us with an opportunity to perform a comparative study to elucidate the mechanisms involved. Here we show that TNF-α, largely produced by Ly6c(+)CD11b(+) dendritic cells (DCs), plays a central role in promoting IL-17A from CD4(+) T cells and collaborating with it to induce airway neutrophilia. Compared with C57BL/6 mice, BALB/c mice displayed significantly more TNF-α-producing DCs and macrophages in the lung. Lung TNF-α levels were drastically reduced in CD11c-DTR BALB/c mice depleted of CD11c+ cells, and TNF-α-producing Ly6c(+)CD11b(+) cells were abolished in Dectin-1(-/-) and MyD88(-/-) BALB/c mice. TNF-α deficiency itself blunted accumulation of inflammatory Ly6c(+)CD11b(+) DCs. Also, lack of TNF-α decreased IL-17A but promoted IL-5 levels, switching inflammation from a neutrophil to eosinophil bias resembling that in C57BL/6 mice. The TNF-α(low) DCs in C57BL/6 mice contained more NF-κB p50 homodimers, which are strong repressors of TNF-α transcription. Functionally, collaboration between TNF-α and IL-17A triggered significantly higher levels of the neutrophil chemoattractants keratinocyte cytokine and macrophage inflammatory protein 2 in BALB/c mice. Our study identifies TNF-α as a molecular switch that orchestrates a sequence of events in DCs and CD4 T cells that promote neutrophilic airway inflammation.

  18. Conjugates of ovalbumin and monomethoxypolyethylene glycol abolish late allergic responses and decrease IL-4 and IL-5 mRNA expression in the rat.

    PubMed

    Lavoie, J-P; Maghni, K; Taha, R; Yang, X-X; Lang, G M; Sehon, A H; Hamid, Q A; Martin, J G

    2003-01-01

    The purpose of this study was to test the therapeutic potential of monomethoxypolyethylene glycol (mPEG) conjugated-allergen using a rodent model of allergic asthma. Previously, this conjugate has been shown to possess the dual capacity of inducing long-term ovalbumin (OA)-specific suppression of the antibody response and inactivating rat mast cells that have been sensitized with murine IgE to OA. Ovalbumin sensitized and challenged Brown Norway rats were studied. Fourteen days after sensitization, a test group of six rats received mPEG-OA solution intratracheally and were challenged 30 min later with aerosolized OA. Another group of seven sensitized rats was similarly challenged with OA 30 min after intratracheal administration of normal saline. A group of six sensitized rats received mPEG-OA solution intratracheally but were challenged with normal saline. Another group of seven sensitized rats received mPEG-BSA solution intratracheally and were challenged 30 min later with aerosolized OA. A final group of five unsensitized rats were neither challenged nor medicated intratracheally. Pulmonary resistance was measured before and for 8 h following inhalation challenge. mPEG-OA treatment had an inhibitory effect on the allergic late airway response, but the early response was not significantly altered. Both mPEG-OA and mPEG-BSA reduced the total cells, eosinophils and neutrophils, in bronchoalveolar lavage and decreased the expression of IL-4, IL-5 and IFN-gamma mRNA. In conclusion, mPEG-OA can prevent the development of allergen-induced late airway responses and reduce airway Th2-type cytokine expression whereas mPEG conjugated to an irrelevant antigen (BSA) is anti-inflammatory but does not affect the late response.

  19. Peptide insertions in domain 4 of hbeta(c), the shared signalling receptor subunit for GM-CSF, IL3 and IL5, induce ligand-independent activation.

    PubMed

    Jones, K L; Bagley, C J; Butcher, C; Barry, S C; Vadas, M A; D'Andrea, R J

    2001-06-21

    A mutant form of the common beta-subunit of the GM-CSF, interleukin-3 (IL3) and IL5 receptors is activated by a 37 residue duplicated segment which includes the WSXWS motif and an adjacent, highly conserved, aliphatic/basic element. Haemopoietic expression of this mutant, hbeta(c)FIDelta, in mice leads to myeloproliferative disease. To examine the mechanism of activation of this mutant we targetted the two conserved motifs in each repeat for mutagenesis. Here we show that this mutant exhibits constitutive activity in BaF-B03 cells in the presence of mouse or human GM-CSF receptor alpha-subunit (GMRalpha) and this activity is disrupted by mutations of the conserved motifs in the first repeat. In the presence of these mutations the receptor reverts to an alternative conformation which retains responsiveness to human IL3 in a CTLL cell line co-expressing the human IL3 receptor alpha-subunit (hIL3Ralpha). Remarkably, the activated conformation is maintained in the presence of substitutions, deletions or replacement of the second repeat. This suggests that activation occurs due to insertion of extra sequence after the WSXWS motif and is not dependent on the length or specific sequence of the insertion. Thus hbeta(c) displays an ability to fold into functional receptor conformations given insertion of up to 37 residues in the membrane-proximal region. Constitutive activation most likely results from a specific conformational change which alters a dormant, inactive receptor complex, permitting functional association with GMRalpha and ligand-independent mitogenic signalling.

  20. Interleukin-Encoding Adenoviral Vectors as Genetic Adjuvant for Vaccination against Retroviral Infection

    PubMed Central

    Ohs, Inga; Windmann, Sonja; Wildner, Oliver; Dittmer, Ulf; Bayer, Wibke

    2013-01-01

    Interleukins (IL) are cytokines with stimulatory and modulatory functions in the immune system. In this study, we have chosen interleukins which are involved in the enhancement of TH2 responses and B cell functions to analyze their potential to improve a prophylactic adenovirus-based anti-retroviral vaccine with regard to antibody and virus-specific CD4+ T cell responses. Mice were vaccinated with an adenoviral vector which encodes and displays the Friend Virus (FV) surface envelope protein gp70 (Ad.pIXgp70) in combination with adenoviral vectors encoding the interleukins IL4, IL5, IL6, IL7 or IL23. Co-application of Ad.pIXgp70 with Ad.IL5, Ad.IL6 or Ad.IL23 resulted in improved protection with high control over FV-induced splenomegaly and reduced viral loads. Mice co-immunized with adenoviral vectors encoding IL5 or IL23 showed increased neutralizing antibody responses while mice co-immunized with Ad.IL6 or Ad.IL23 showed improved FV-specific CD4+ T cell responses compared to mice immunized with Ad.pIXgp70 alone. We show that the co-application of adenoviral vectors encoding specific interleukins is suitable to improve the vaccination efficacy of an anti-retroviral vaccine. Improved protection correlated with improved CD4+ T cell responses and especially with higher neutralizing antibody titers. The co-application of selected interleukin-encoding adenoviral vectors is a valuable tool for vaccination with regard to enhancement of antibody mediated immunity. PMID:24349306

  1. Interleukin-encoding adenoviral vectors as genetic adjuvant for vaccination against retroviral infection.

    PubMed

    Ohs, Inga; Windmann, Sonja; Wildner, Oliver; Dittmer, Ulf; Bayer, Wibke

    2013-01-01

    Interleukins (IL) are cytokines with stimulatory and modulatory functions in the immune system. In this study, we have chosen interleukins which are involved in the enhancement of TH2 responses and B cell functions to analyze their potential to improve a prophylactic adenovirus-based anti-retroviral vaccine with regard to antibody and virus-specific CD4(+) T cell responses. Mice were vaccinated with an adenoviral vector which encodes and displays the Friend Virus (FV) surface envelope protein gp70 (Ad.pIXgp70) in combination with adenoviral vectors encoding the interleukins IL4, IL5, IL6, IL7 or IL23. Co-application of Ad.pIXgp70 with Ad.IL5, Ad.IL6 or Ad.IL23 resulted in improved protection with high control over FV-induced splenomegaly and reduced viral loads. Mice co-immunized with adenoviral vectors encoding IL5 or IL23 showed increased neutralizing antibody responses while mice co-immunized with Ad.IL6 or Ad.IL23 showed improved FV-specific CD4(+) T cell responses compared to mice immunized with Ad.pIXgp70 alone. We show that the co-application of adenoviral vectors encoding specific interleukins is suitable to improve the vaccination efficacy of an anti-retroviral vaccine. Improved protection correlated with improved CD4(+) T cell responses and especially with higher neutralizing antibody titers. The co-application of selected interleukin-encoding adenoviral vectors is a valuable tool for vaccination with regard to enhancement of antibody mediated immunity.

  2. 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

  3. 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.

  4. 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.

  5. The synthesis of Rantes, G-CSF, IL-4, IL-5, IL-6, IL-12 and IL-13 in human whole-blood cultures is modulated by an extract from Eleutherococcus senticosus L. roots.

    PubMed

    Schmolz, M W; Sacher, F; Aicher, B

    2001-05-01

    An ethanol extract derived from the roots of Eleutherococcus senticosus was found to influence markedly the cytokine synthesis of activated whole blood cultures of ten healthy volunteers. Whereas the synthesis of Rantes was increased over a wide range of concentrations, the release of IL-4, IL-5 and IL-12 was significantly inhibited. An inhibition at higher concentrations, switching to a stimulation at lower doses of the extract was seen with G-CSF, IL-6 and IL-13. From these particular immuno-pharmacological effects of Eleutherococcus senticosus we suggest this herbal preparation possesses immuno-modulatory potency, rather than just being immuno-suppressive or -stimulating.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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}

  12. Combined Analysis of IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT Supernatant Is Useful for Distinguishing Active Tuberculosis from Latent Infection.

    PubMed

    Suzukawa, Maho; Akashi, Shunsuke; Nagai, Hideaki; Nagase, Hiroyuki; Nakamura, Hiroyuki; Matsui, Hirotoshi; Hebisawa, Akira; Ohta, Ken

    2016-01-01

    The QuantiFERON®-TB Gold In-Tube test (QFT), an interferon-γ release assay, is used to diagnose Mycobacterium tuberculosis, but its inaccuracy in distinguishing active tuberculosis from latent infection is a major concern. There is thus a need for an easy and accurate tool for achieving that goal in daily clinical settings. This study aimed to identify candidate cytokines for specifically differentiating active tuberculosis from latent infection. Our study population consisted of 31 active TB (tuberculosis) patients, 29 LTBI (latent tuberculosis infection) patients and 10 healthy control subjects. We assayed for 27 cytokines in QFT supernatants of both specific antigen-stimulated blood samples (TBAg) and negative-control samples (Nil). We analyzed their specificities and sensitivities by creating receiver operating characteristic (ROC) curves and measuring the area under those curves (AUCs). In TBAg-Nil supernatants, IL-10, IFN-γ, MCP-1 and IL-1RA showed high AUCs of 0.8120, 0.7842, 0.7419 and 0.7375, respectively. Compared with each cytokine alone, combined assay for these top four cytokines showed positive rates in diagnosing active TB, and GDA analysis revealed that MCP-1 and IL-5 are potent in distinguishing active TB from LTBI, with Wilk's lambda = 0.718 (p < 0.001). Furthermore, utilizing the unique characteristic of IL-2 that its TBAg-Nil supernatant levels are higher in LTBI compared to active TB, the difference between IFN-γ and IL-2 showed a large AUC of 0.8910. In summary, besides IFN-γ, IL-2, IL-5, IL-10, IL-1RA and MCP-1 in QFT supernatants may be useful for distinguishing active TB from LTBI. Those cytokines may also help us understand the difference in pathogenesis between active TB and LTBI.

  13. CSL311, a novel, potent, therapeutic monoclonal antibody for the treatment of diseases mediated by the common β chain of the IL-3, GM-CSF and IL-5 receptors

    PubMed Central

    Panousis, Con; Dhagat, Urmi; Edwards, Kirsten M.; Rayzman, Veronika; Hardy, Matthew P.; Braley, Hal; Gauvreau, Gail M.; Hercus, Timothy R.; Smith, Steven; Sehmi, Roma; McMillan, Laura; Dottore, Mara; McClure, Barbara J.; Fabri, Louis J.; Vairo, Gino; Lopez, Angel F; Parker, Michael W.; Nash, Andrew D.; Wilson, Nicholas J.; Wilson, Michael J.; Owczarek, Catherine M.

    2016-01-01

    ABSTRACT The β common-signaling cytokines interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-5 stimulate pro-inflammatory activities of haematopoietic cells via a receptor complex incorporating cytokine-specific α and shared β common (βc, CD131) receptor. Evidence from animal models and recent clinical trials demonstrate that these cytokines are critical mediators of the pathogenesis of inflammatory airway disease such as asthma. However, no therapeutic agents, other than steroids, that specifically and effectively target inflammation mediated by all 3 of these cytokines exist. We employed phage display technology to identify and optimize a novel, human monoclonal antibody (CSL311) that binds to a unique epitope that is specific to the cytokine-binding site of the human βc receptor. The binding epitope of CSL311 on the βc receptor was defined by X-ray crystallography and site-directed mutagenesis. CSL311 has picomolar binding affinity for the human βc receptor, and at therapeutic concentrations is a highly potent antagonist of the combined activities of IL-3, GM-CSF and IL-5 on primary eosinophil survival in vitro. Importantly, CSL311 inhibited the survival of inflammatory cells present in induced sputum from human allergic asthmatic subjects undergoing allergen bronchoprovocation. Due to its high potency and ability to simultaneously suppress the activity of all 3 β common cytokines, CSL311 may provide a new strategy for the treatment of chronic inflammatory diseases where the human βc receptor is central to pathogenesis. The coordinates for the βc/CSL311 Fab complex structure have been deposited with the RCSB Protein Data Bank (PDB 5DWU). PMID:26651396

  14. CSL311, a novel, potent, therapeutic monoclonal antibody for the treatment of diseases mediated by the common β chain of the IL-3, GM-CSF and IL-5 receptors.

    PubMed

    Panousis, Con; Dhagat, Urmi; Edwards, Kirsten M; Rayzman, Veronika; Hardy, Matthew P; Braley, Hal; Gauvreau, Gail M; Hercus, Timothy R; Smith, Steven; Sehmi, Roma; McMillan, Laura; Dottore, Mara; McClure, Barbara J; Fabri, Louis J; Vairo, Gino; Lopez, Angel F; Parker, Michael W; Nash, Andrew D; Wilson, Nicholas J; Wilson, Michael J; Owczarek, Catherine M

    2016-01-01

    The β common-signaling cytokines interleukin (IL)-3, granulocyte-macrophage colony stimulating factor (GM-CSF) and IL-5 stimulate pro-inflammatory activities of haematopoietic cells via a receptor complex incorporating cytokine-specific α and shared β common (βc, CD131) receptor. Evidence from animal models and recent clinical trials demonstrate that these cytokines are critical mediators of the pathogenesis of inflammatory airway disease such as asthma. However, no therapeutic agents, other than steroids, that specifically and effectively target inflammation mediated by all 3 of these cytokines exist. We employed phage display technology to identify and optimize a novel, human monoclonal antibody (CSL311) that binds to a unique epitope that is specific to the cytokine-binding site of the human βc receptor. The binding epitope of CSL311 on the βc receptor was defined by X-ray crystallography and site-directed mutagenesis. CSL311 has picomolar binding affinity for the human βc receptor, and at therapeutic concentrations is a highly potent antagonist of the combined activities of IL-3, GM-CSF and IL-5 on primary eosinophil survival in vitro. Importantly, CSL311 inhibited the survival of inflammatory cells present in induced sputum from human allergic asthmatic subjects undergoing allergen bronchoprovocation. Due to its high potency and ability to simultaneously suppress the activity of all 3 β common cytokines, CSL311 may provide a new strategy for the treatment of chronic inflammatory diseases where the human βc receptor is central to pathogenesis. The coordinates for the βc/CSL311 Fab complex structure have been deposited with the RCSB Protein Data Bank (PDB 5DWU).

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Interleukin-5 receptor alpha subunit gene regulation in human eosinophil development: identification of a unique cis-element that acts lie an enhancer in regulating activity of the IL-5R alpha promoter.

    PubMed

    Sun, Z; Yergeau, D A; Wong, I C; Tuypens, T; Tavernier, J; Paul, C C; Baumann, M A; Auron, P E; Tenen, D G; Ackerman, S J

    1996-01-01

    Further functional and biochemical characterization of the nuclear factor(s) which interacts with the EOS1 enhancer-like element in the IL-5R alpha promoter is currently in progress. Since different transcription factors recognize and interact with DNA in distinct fashions and with distinct structural motifs, we have modeled potential binding of the EOS1 factor to its cis-element based upon its methylation interference pattern (Fig. 2), using a cylindrical DNA helical projection (Fig. 6). Over a length of two helical turns, all nuclear protein contacts indicated by methylation interference map to one side of the DNA helix, suggesting that EOS1 binds in the major groove, across the minor groove, and on only one side of the helix. Further review of the model also reveals a potential diad symmetry for the binding site, suggestive of binding by a homodimer and consistent with the formation of the two DNA-protein complexes in our electrophoretic mobility shift experiments that could represent interactions with monomer versus dimer. Comparison of the EOS1 binding motif to similar models for the binding of other transcription factor families for which structural crystallographic and/or binding data is available suggests a similarity of the EOS1 complex to that of the bacterial helix-turn-helix phage lambda and 434 repressor-operator complexes, and the Cys4 zinc finger glucocorticoid response element (GRE) DNA-binding motifs, all of which show similar diad symmetry and binding in the major groove on one side of the DNA. The possibility that EOS1 functions as a GRE is being investigated, especially since there is a consensus AP-1 site at bp -440 to -432 of the IL-5R alpha promoter, immediately adjacent to the EOS1 binding site (see Fig. 5 in reference [36]) and AP-1/GRE interactions have been identified for composite response elements in the regulation of a number of different genes. The identification or cloning of EOS1, a potentially novel and eosinophil lineage

  1. 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).

  2. 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.

  3. Activating point mutations in the common beta subunit of the human GM-CSF, IL-3 and IL-5 receptors suggest the involvement of beta subunit dimerization and cell type-specific molecules in signalling.

    PubMed Central

    Jenkins, B J; D'Andrea, R; Gonda, T J

    1995-01-01

    We have combined retroviral expression cloning with random mutagenesis to identify two activating point mutations in the common signal-transducing subunit (h beta c) of the receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3 and IL-5 by virtue of their ability to confer factor independence on the haemopoietic cell line, FDC-P1. One mutation (V449E) is located within the transmembrane domain and, by analogy with a similar mutation in the neu oncogene, may act by inducing dimerization of h beta c. The other mutation (I374N) lies in the extracellular, membrane-proximal portion of h beta c. Neither of these mutants, nor a previously described mutant of h beta c (FI delta, which has a small duplication in the extracellular region), was capable of inducing factor independence in CTLL-2 cells, while only V449E could induce factor independence in BAF-B03 cells. These results imply that the extracellular and transmembrane mutations act by different mechanisms. Furthermore, they imply that the mutants, and hence also wild-type h beta c, interact with cell type-specific signalling molecules. Models are presented which illustrate how these mutations may act and predict some of the characteristics of the putative receptor-associated signalling molecules. Images PMID:7556069

  4. 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…

  5. 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…

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. A novel approach to understanding the role of polymorphic forms of the NR3C1 and TGF-β1 genes in the modulation of the expression of IL-5 and IL-15 mRNA in asthmatic inflammation.

    PubMed

    Panek, Michał; Jonakowski, Mateusz; Zioło, Jan; Wieteska, Łukasz; Małachowska, Beata; Pietras, Tadeusz; Szemraj, Janusz; Kuna, Piotr

    2016-06-01

    The aim of the present study was to identify polymorphic forms of the nuclear receptor subfamily 3, group C, member 1 (NR3C1) and transforming growth factor β1 (TGF-β1) genes and evaluate their impact on the expression levels of interleukin (IL)-5 and IL‑15 in asthma. The study was conducted on a control group consisting of 91 people (54 women and 37 men). The patient group consisted of 130 participants (86 women and 44 men). Genotyping was performed by polymerase chain reaction‑restriction fragment length polymorphism (PCR‑RFLP) and PCR‑high resolution melting (HRM) methods. Interleukin expression was measured by reverse transcription‑quantitative polymerase chain reaction. The frequency of the polymorphic forms in the analyzed group were observed to be: Tth111I (rs10052957) controls AA 0.0440, AG 0.5714, GG 0.3846, patients AA 0.1538/AG 0.4692, GG 0.3769; ER22/23EK (rs6189 /rs6190) controls AG 0.0556, GG 0.9444, patients AG 0.0385, GG 0.9615; N363S (rs6195) controls AA 0.6444, AG 0.2667, GG 0.0889, patients AA 0.7846, AG 0.1385, GG 0.0769; BclI (rs41423247) controls CC 0.0879, CG 0.5604, GG 0.3516, patients CC 0.1008, CG 0.5736, GG 0.3256; C‑509T (rs1800469) controls TT 0.0805, CT 0.6322, CC 0.2874, patients TT 0.1102, CT 0.5669, CC 0.3228. The results indicated that the C‑509T single nucleotide polymorphism (SNP) of the TGF-β1 gene contributed to an increase in the IL‑5 mRNA expression levels. The GG genotype of the N363S SNP of the NR3C1 gene was observed to result in an increase in the expression levels of IL‑15. The present study indicated that the selected SNPs of the NR3C1 and TGF‑β1 genes demonstrate a regulatory effect on the expression of IL‑5 and IL‑15. Therefore, genetic variation affects inflammation in asthma and the clinical course of the disease.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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…

  17. 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…

  18. 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.

  19. 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

  20. Different effect of prostaglandin E2 on B-cell activation by two distinct B-cell differentiation factors, B151-TRF1/IL-5 and B151-TRF2: selective inhibition of B151-TRF2-induced antibody response through increases in intracellular cyclic AMP levels

    PubMed Central

    Ishihara, K.; Ono, S.; Takahama, Y.; Hirayama, F.; Hirano, H.; Itoh, K.; Dobashi, K.; Murakami, S.; Katoh, Y.; Yamaguchi, M.; Hamaoka, T.

    1989-01-01

    Effects of prostaglandin E2 (PGE2) on murine B-cell activation induced by two distinct B-cell differentiation factors, B151-TRF1/IL-5 and B151-TRF2, were examined. A final differentiation of unprimed B cells into IgM-producing cells induced by B151-TRF2 was markedly inhibited by PGE2 at physiological concentrations (around 10-8 M), whereas B151-TRF1/IL-5-induced antibody responses of unprimed as well as activated B cells were not affected by PGE2, even at 10-6 M. B-cell responses induced by B151-TRF2-like factors from autoimmune-prone MRL/1pr mice were also inhibited by PGE2. Biphasic increases in intracellular cyclic AMP (cAMP) levels were induced by culturing B cells with 10-6 or 10-8 M PGE2: rapid increases within 8 min and delayed increases around 16 hr. The direct addition of dibutyryl cAMP to cultures of B cells resulted in marked inhibition of antibody responses when stimulated with B151-TRF2 but not with B151-TRF1/IL-5. The B151-TRF2-induced antibody responses were also inhibited by cAMP-elevating reagents such as forskolin, cholera toxin and theophyline. Furthermore, 2′, 5′-dideoxyadenosine, which is an inhibitor of adenylate cyclase, prevented the PGE2-mediated cAMP accumulation in unprimed B cells as well as the PGE2-mediated inhibition of B151-TRF2-induced B-cell responses when added at the initiation of culture. These results suggest that PGE2 inhibits B151-TRF2-induced antibody responses through the activation of adenylate cyclase and subsequent accumulation of intracellular cAMP, whereas B151-TRF1/IL-5-responsive B cells are resistant to the inhibitory effect of PGE2 and cAMP. PMID:2553585

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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…

  9. [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.

  10. 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.

  11. 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.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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…

  8. 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.

  9. 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.

  10. 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…

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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…

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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).

  2. 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.

  3. 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.

  4. 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

  5. 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).

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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…

  10. 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…

  11. 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…

  12. 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.

  13. 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

  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. 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.

  16. 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.

  17. 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,…

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. Young Children's Automatic Encoding of Social Categories

    ERIC Educational Resources Information Center

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

    2015-01-01

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

  4. 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...

  5. 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...

  6. 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...

  7. 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

  8. 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

  9. 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

  10. 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…

  11. 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.

  12. 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

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Virus-encoded microRNAs

    PubMed Central

    Grundhoff, Adam; Sullivan, Christopher S.

    2011-01-01

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

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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}

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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.…

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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

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

    NASA Astrophysics Data System (ADS)

    Kosyakov, B. P.

    2005-08-01

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

  6. 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.

  7. 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.

  8. 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.

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. 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…

  14. Multiple channel secure communication using chaotic system encoding

    SciTech Connect

    Miller, S.L.

    1996-12-31

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

  15. 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.…

  16. 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.

  17. A VLSI architecture for high performance CABAC encoding

    NASA Astrophysics Data System (ADS)

    Shojania, Hassan; Sudharsanan, Subramania

    2005-07-01

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

  18. 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…

  19. 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…

  20. 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.

  1. 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…

  2. 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…

  3. 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…

  4. 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…

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. 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…

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. A User's Guide to the Encyclopedia of DNA Elements (ENCODE)

    PubMed Central

    2011-01-01

    The mission of the Encyclopedia of DNA Elements (ENCODE) Project is to enable the scientific and medical communities to interpret the human genome sequence and apply it to understand human biology and improve health. The ENCODE Consortium is integrating multiple technologies and approaches in a collective effort to discover and define the functional elements encoded in the human genome, including genes, transcripts, and transcriptional regulatory regions, together with their attendant chromatin states and DNA methylation patterns. In the process, standards to ensure high-quality data have been implemented, and novel algorithms have been developed to facilitate analysis. Data and derived results are made available through a freely accessible database. Here we provide an overview of the project and the resources it is generating and illustrate the application of ENCODE data to interpret the human genome. PMID:21526222

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.