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Sample records for 6-sulfo sialyl lewis

  1. A novel, high endothelial venule-specific sulfotransferase expresses 6-sulfo sialyl Lewis(x), an L-selectin ligand displayed by CD34.

    PubMed

    Hiraoka, N; Petryniak, B; Nakayama, J; Tsuboi, S; Suzuki, M; Yeh, J C; Izawa, D; Tanaka, T; Miyasaka, M; Lowe, J B; Fukuda, M

    1999-07-01

    L-selectin mediates lymphocyte homing by facilitating lymphocyte adhesion to unique carbohydrate ligands, sulfated sialyl Lewis(x), which are expressed on high endothelial venules (HEV) in secondary lymphoid organs. The nature of the sulfotransferase(s) that contribute to sulfation of such L-selectin counterreceptors has been uncertain. We herein describe a novel L-selectin ligand sulfotransferase, termed LSST, that directs the synthesis of the 6-sulfo sialyl Lewis(x) on L-selectin counterreceptors CD34, GlyCAM-1, and MAdCAM-1. LSST is predominantly expressed in HEV and exhibits striking catalytic preference for core 2-branched mucin-type O-glycans as found in natural L-selectin counterreceptors. LSST enhances L-selectin-mediated adhesion under shear compared to nonsulfated controls. LSST therefore corresponds to an HEV-specific sulfotransferase that contributes to the biosynthesis of L-selectin ligands required for lymphocyte homing. PMID:10435581

  2. Langerhans' cell expression of the selectin ligand, sialyl Lewis x.

    PubMed Central

    Ross, E L; Barker, J N; Allen, M H; Chu, A C; Groves, R W; MacDonald, D M

    1994-01-01

    Cellular adhesion molecules play a central role in leucocyte migration through peripheral blood and tissues. A crucial stage in these events in selectin-mediated adhesion involving E-selectin expressed on activated endothelium interacting with a range of carbohydrate ligands expressed by specific subpopulations of leucocytes. As such mechanisms may be relevant to bone marrow-derived dendritic epidermal Langerhans' cell (LC) migration, expression of these carbohydrate ligands was assessed immunocytochemically in whole skin biopsies and in epidermal cell suspensions obtained from adult humans. Double-labelling experiments revealed that sialyl Lewis x, recognized by the monoclonal antibody CSLEX1, was expressed on epidermal LC (n = 9). Furthermore, expression was enhanced at 24 hr following epicutaneous application of antigen and in the inflammatory disorder psoriasis (n = 10). E-selectin was concomitantly strongly expressed on dermal endothelium in psoriasis and allergic contact dermatitis. Intradermal injection of the T-cell-derived cytokine interferon-gamma (IFN-gamma) led to increased LC expression of sialyl Lewis x. In epidermal cell suspensions, in contrast to keratinocytes, CD1a+ cells expressed sialyl Lewis x, intensity of which was enhanced after 4 days in culture. CSLEX1 staining could be abolished and CD15 (non-sialated Lewis x) expression induced by saponification and treatment with neuraminidase. Expression of other selectin ligands was also examined. While the cutaneous lymphocyte antigen defined by the monoclonal antibody HECA-452 reacted with a small minority of LC, sialyl Lewis a and sulphatide were not expressed under any experimental conditions. These studies indicate that E-selectin-sialyl Lewis x interactions are potentially important in LC migration, both into and out of skin. Images Figure 2 Figure 3 Figure 5 Figure 6 PMID:7512530

  3. Prominent expression of sialyl Lewis X-capped core 2-branched O-glycans on high endothelial venule-like vessels in gastric MALT lymphoma

    PubMed Central

    Kobayashi, Motohiro; Mitoma, Junya; Hoshino, Hitomi; Yu, Shin-Yi; Shimojo, Yasuyo; Suzawa, Kenichi; Khoo, Kay-Hooi; Fukuda, Minoru; Nakayama, Jun

    2011-01-01

    High endothelial venule (HEV)-like vessels have been observed in gastric B-cell lymphoma of mucosa-associated lymphoid tissue type (MALT lymphoma), as well as in its preceding lesion, chronic Helicobacter pylori gastritis. Previously we reported that glycans on HEV-like vessels in the latter lesion served as L-selectin ligands. However, the biochemical and functional nature of glycans on HEV-like vessels in gastric MALT lymphoma remained to be determined. In this study, we performed immunohistochemical analysis for sialyl Lewis X (sLeX)-related glycoepitopes using three monoclonal antibodies MECA-79, HECA-452, and NCC-ST-439, and found that MECA-79−/HECA-452+/NCC-ST-439+ HEV-like vessels preferentially appears in gastric MALT lymphoma compared to chronic H. pylori gastritis, suggesting that appearance of MECA-79−/HECA-452+/NCC-ST-439+ HEV-like vessels marks gastric MALT lymphoma. We then constructed a set of CHO cell lines expressing possible MECA-79−/HECA-452+/NCC-ST-439+ glycans, as well as other sLeX-type glycans, on CD34, and evaluated L-selectin binding to those cells using L-selectin•IgM chimera binding and lymphocyte adhesion assays. L-selectin•IgM chimeras bound to CHO cells expressing 6-sulfo sLeX attached to core 2-branched O-glycans with or without 6-sulfo sLeX attached to extended core 1 O-glycans but only marginally to other CHO cell lines. On the other hand, CHO cells expressing 6-sulfo sLeX attached to extended core 1 and/or core 2-branched O-glycans, and also non-sulfated sLeX attached to core 2-branched O-glycans showed substantial lymphocyte binding, while binding was negligible on cell lines expressing 6-sulfo and non-sulfated sLeX attached to N-glycans and non-sulfated sLeX attached to extended core 1 O-glycans. These results indicate that MECA-79−/HECA-452+/NCC-ST-439+ glycans, namely 6-sulfo and non-sulfated sLeXs attached to core 2-branched O-glycans, expressed on HEV-like vessels in gastric MALT lymphoma, function as L

  4. Novel Antibodies Reactive with Sialyl Lewis X in Both Humans and Mice Define Its Critical Role in Leukocyte Trafficking and Contact Hypersensitivity Responses*

    PubMed Central

    Matsumura, Ryuji; Hirakawa, Jotaro; Sato, Kaori; Ikeda, Toshiaki; Nagai, Motoe; Fukuda, Minoru; Imai, Yasuyuki; Kawashima, Hiroto

    2015-01-01

    Sialyl Lewis X (sLex) antigen functions as a common carbohydrate determinant recognized by all three members of the selectin family. However, its expression and function in mice remain undefined due to the poor reactivity of conventional anti-sLex monoclonal antibodies (mAbs) with mouse tissues. Here, we developed novel anti-sLex mAbs, termed F1 and F2, which react well with both human and mouse sLex, by immunizing fucosyltransferase (FucT)-IV and FucT-VII doubly deficient mice with 6-sulfo-sLex-expressing cells transiently transfected with an expression vector encoding CMP-N-acetylneuraminic acid hydroxylase. F1 and F2 specifically bound both the N-acetyl and the N-glycolyl forms of sLex as well as 6-sulfo-sLex, a major ligand for L-selectin expressed in high endothelial venules, and efficiently blocked physiological lymphocyte homing to lymph nodes in mice. Importantly, both of the mAbs inhibited contact hypersensitivity responses not only when administered in the L-selectin-dependent sensitization phase but also when administered in the elicitation phase in mice. When administered in the latter phase, F1 and F2 efficiently blocked rolling of mouse leukocytes along blood vessels expressing P- and E-selectin in the auricular skin in vivo. Consistent with these findings, the mAbs blocked P- and E-selectin-dependent leukocyte rolling in a flow chamber assay. Taken together, these results indicate that novel anti-sLex mAbs reactive with both human and mouse tissues, with the blocking ability against leukocyte trafficking mediated by all three selectins, have been established. These mAbs should be useful in determining the role of sLex antigen under physiological and pathological conditions. PMID:25944902

  5. Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl-Lewis(x) to increase binding to airway epithelial cells.

    PubMed

    Jeffries, J L; Jia, J; Choi, W; Choe, S; Miao, J; Xu, Y; Powell, R; Lin, J; Kuang, Z; Gaskins, H R; Lau, G W

    2016-07-01

    Cystic fibrosis (CF) patients battle life-long pulmonary infections with the respiratory pathogen Pseudomonas aeruginosa (PA). An overabundance of mucus in CF airways provides a favorable niche for PA growth. When compared with that of non-CF individuals, mucus of CF airways is enriched in sialyl-Lewis(x), a preferred binding receptor for PA. Notably, the levels of sialyl-Lewis(x) directly correlate with infection severity in CF patients. However, the mechanism by which PA causes increased sialylation remains uncharacterized. In this study, we examined the ability of PA virulence factors to modulate sialyl-Lewis(x) modification in airway mucins. We found pyocyanin (PCN) to be a potent inducer of sialyl-Lewis(x) in both mouse airways and in primary and immortalized CF and non-CF human airway epithelial cells. PCN increased the expression of C2/4GnT and ST3Gal-IV, two of the glycosyltransferases responsible for the stepwise biosynthesis of sialyl-Lewis(x), through a tumor necrosis factor (TNF)-α-mediated phosphoinositol-specific phospholipase C (PI-PLC)-dependent pathway. Furthermore, PA bound more efficiently to airway epithelial cells pre-exposed to PCN in a flagellar cap-dependent manner. Importantly, antibodies against sialyl-Lewis(x) and anti-TNF-α attenuated PA binding. These results indicate that PA secretes PCN to induce a favorable environment for chronic colonization of CF lungs by increasing the glycosylation of airway mucins with sialyl-Lewis(x). PMID:26555707

  6. Heterogeneity in Lewis-X and sialyl-Lewis-X antigen expression on monocytes in whole blood: relation to stimulus-induced oxidative burst.

    PubMed Central

    Elbim, C.; Hakim, J.; Gougerot-Pocidalo, M. A.

    1998-01-01

    By using flow cytometric analysis of cells in whole blood expressing high levels of CD14, we found a subpopulation of monocytes (8% of total) with higher scatter parameters, high capacity to produce reactive oxygen species (ROS), stronger expression of Lewis-X (CD15), sialyl-Lewis-X, CD11b and CD18 antigens, as well as an increased polymerized actin content. The size of this subpopulation increased after stimulation with lipopolysaccharide at the expense of the remaining monocytes, suggesting that its features were inducible. The membrane increase in Lewis-X and sialyl-Lewis-X expression observed during this conversion was largely due to the translocation of these carbohydrate structures from intracellular pools. Moreover, this subpopulation behaved as a primed monocyte subpopulation producing large amounts of H2O2 in response to N-formyl-methionyl-leucyl-phenylalanine. Increased H2O2 production was inhibited not only by anti-CD14 but also by anti-CD15 and anti-sialyl-Lewis-X monoclonal antibodies when added before lipopolysaccharide. These results show that lipopolysaccharide priming is regulated, at least in part, by Lewis-X and sialyl-Lewis-X structures expressed on the monocyte membrane. All together, this highly reactive and inducible subpopulation of monocytes, which share phenotypic and functional characteristics with neutrophils, might play an important role in host defenses and inflammatory responses. PMID:9546369

  7. Glycan Motif Profiling Reveals Plasma Sialyl-Lewis X Elevations in Pancreatic Cancers That Are Negative for Sialyl-Lewis A*

    PubMed Central

    Tang, Huiyuan; Singh, Sudhir; Partyka, Katie; Kletter, Doron; Hsueh, Peter; Yadav, Jessica; Ensink, Elliot; Bern, Marshall; Hostetter, Galen; Hartman, Douglas; Huang, Ying; Brand, Randall E.; Haab, Brian B.

    2015-01-01

    The sialyl-Lewis A (sLeA) glycan forms the basis of the CA19–9 assay and is the current best biomarker for pancreatic cancer, but because it is not elevated in ∼25% of pancreatic cancers, it is not useful for early diagnosis. We hypothesized that sLeA-low tumors secrete glycans that are related to sLeA but not detectable by CA19–9 antibodies. We used a method called motif profiling to predict that a structural isomer of sLeA called sialyl-Lewis X (sLeX) is elevated in the plasma of some sLeA-low cancers. We corroborated this prediction in a set of 48 plasma samples and in a blinded set of 200 samples. An antibody sandwich assay formed by the capture and detection of sLeX was elevated in 13 of 69 cancers that were not elevated in sLeA, and a novel hybrid assay of sLeA capture and sLeX detected 24 of 69 sLeA-low cancers. A two-marker panel based on combined sLeA and sLeX detection differentiated 109 pancreatic cancers from 91 benign pancreatic diseases with 79% accuracy (74% sensitivity and 78% specificity), significantly better than sLeA alone, which yielded 68% accuracy (65% sensitivity and 71% specificity). Furthermore, sLeX staining was evident in tumors that do not elevate plasma sLeA, including those with poorly differentiated ductal adenocarcinoma. Thus, glycan-based biomarkers could characterize distinct subgroups of patients. In addition, the combined use of sLeA and sLeX, or related glycans, could lead to a biomarker panel that is useful in the clinical diagnosis of pancreatic cancer. Précis: This paper shows that a structural isomer of the current best biomarker for pancreatic cancer, CA19–9, is elevated in the plasma of patients who are low in CA19–9, potentially enabling more comprehensive detection and classification of pancreatic cancers. PMID:25733690

  8. Solution structure of sialyl Lewis X mimics studied by two-dimensional NMR

    NASA Astrophysics Data System (ADS)

    Demura, Makoto; Noda, Masatoshi; Kajimoto, Tetsuya; Uchiyama, Taketo; Umemoto, Kimiko; Wong, Chi-Huey; Asakura, Tetsuo

    2002-01-01

    A structure of the peptidic mimic of sialyl Lewis X (Sle X) (α- N-acetyl-neuraminyl-(2,3)-β- D-galactopyranosyl-(1,4)-[α- L-fucopyranosyl-(1,3)-β- D- N-acetyl-glucosamine]) in an aqueous solution was studied using two-dimensional 1H NMR spectroscopy. Complete assignments of 1H NMR chemical shift of the SLe X mimic have been performed. The presence of three conformers of the SLe X mimic in a solution was proposed by using distance geometry calculation based on NOE constraints, which were obtained from NOESY experiments. In addition, intermolecular interaction between the mimic and the crystal structure of E-selectin was refined using molecular dynamics. This suggested the conformational rearrangement of the functional groups of the conformers to the active sites of E-selectin. The relationship between the binding activities toward E-selectin and the three-dimensional structures of other mimics was also discussed.

  9. False sugar sequence ions in electrospray tandem mass spectrometry of underivatized sialyl-Lewis-type oligosaccharides

    NASA Astrophysics Data System (ADS)

    Ernst, Beat; Müller, Dieter R.; Richter, Wilhelm J.

    1997-01-01

    Formation of "false" sugar sequence ions from branched tetrasaccharides of the sialyl-Lewis-type by migration of fucose towards sialic acid residues is shown to occur in [M + H]+ and [M + NH4]+ ions produced by electrospray ionization and subjected to low energy collision induced dissociation (CID). For the verification of their composition and sequence, such irregular ions were produced in the orifice region of the ion source, mass selected in Q1, and subjected to a second CID step in Q2 of a triple quadrupole analyser. When produced and analysed in the same "double CID" fashion, the branched B3 ions still containing all four sugar subunits show such migration to only a minor extent. The analysis of Bn fragment ions with high numbers for n may thus have advantages over the analysis of M-like species

  10. O-linked oligosaccharides from salivary agglutinin: Helicobacter pylori binding sialyl-Lewis x and Lewis b are terminating moieties on hyperfucosylated oligo-N-acetyllactosamine.

    PubMed

    Issa, Samah; Moran, Anthony P; Ustinov, Sergey N; Lin, Jack Han-Hsing; Ligtenberg, Antoon J; Karlsson, Niclas G

    2010-08-01

    Salivary agglutinin plays a vital biological role modulating the protective effect in the oral cavity by interacting with a broad range of oral pathogens. Here, we describe the first characterization of the O-linked oligosaccharides of salivary agglutinin identified by negative ion liquid chromatography-mass spectrometry. The dominating structures were neutral or monosialylated core 1 (Galbeta1-3GalNAcalpha1-Ser/Thr) and core 2 (Galbeta1-3(GlcNAcbeta1-6)GalNAcalpha1-Ser/Thr) structures extended by fucosylated oligo-N-acetyllactosamine units. Oligosaccharides detected as [M-H](-) or [M-2H](2)(-) ions ranged from the disaccharide Galbeta1-3GalNAcol up to structures of almost 4000 Da, corresponding to core 1/2 structures with five N-acetyllactosamine units and 11 fucoses. Fucose was found either as terminal or internal blood group H structures in type 1 (Galbeta1-3GlcNAcbeta1-R), type 2 (Galbeta1-4GlcNAcbeta1-R) and type 3 (Galbeta1-3GalNAcalpha1-Ser/Thr) units, where the chains also could be fucosylated on GlcNAc yielding repeated Lewis a/b or Lewis x/y structures. Sialylation was located either at the non-reducing end of the N-acetyllactosamine chains as sialyl-Lewis x or as sialyl-T (NeuAcalpha2-3Galbeta1-3GalNAcalpha1-Ser/Thr) type structures with or without further extension of the C-6 branch of GalNAc with neutral fucosylated N-acetyllactosamine chains. The data indicated that sialylation, fucosylation and type 1 N-acetyllactosamine termination are important regulatory elements for controlling the oligosaccharide chain length. Furthermore, it was shown that these regulatory oligosaccharide elements could be utilized by the pathogen Helicobacter pylori to colonize the oral cavity, reside in dental plaque and serve as a reservoir for reinfection after successful clearance of H. pylori gastric infection. PMID:20466654

  11. Clinicopathological and prognostic significance of sialyl Lewis X overexpression in patients with cancer: a meta-analysis

    PubMed Central

    Liang, Jin-xiao; Liang, Yong; Gao, Wei

    2016-01-01

    Many studies have shown that sialyl Lewis X (sLeX) is related to cancer prognosis and clinicopathology, but failed to provide conclusive results. We conducted the present meta-analysis to identify the association between sLeX overexpression and cancer prognosis. We searched studies in PubMed and Embase databases. Relative risk or hazard ratio with 95% confidence intervals were estimated with the Mantel–Haenszel random-effect method and 29 studies were included. Our meta-analysis showed that sLeX overexpression is significantly related to lymphatic invasion, venous invasion, T stage, N stage, M stage, tumor stage, recurrence, and overall survival. In subgroup analysis, we found that cancer type and ethnicity might be two major contributing factors to the possible presence of heterogeneity among the studies. In conclusion, sLeX overexpression is associated with tumor metastasis, recurrence, and overall survival in cancer patients, it plays an important role in cancer prognosis. PMID:27307752

  12. alpha 4 Integrins and sialyl Lewis x modulation in chronic Chagas disease: further evidence of persistent immune activation.

    PubMed

    Laucella, S A; Riarte, A; Prado, N; Zapata, J; Segura, E L

    2001-05-01

    We have previously shown that titers of soluble platelet selectin (s-P-selectin) and soluble vascular cell adhesion molecule-1 (s-VCAM-1) were increased in sera of patients with chronic Trypanosoma cruzi infection. In this study, we analyzed the expression of CD49d-integrins, that bind to VCAM-1, and sialyl Lewis x (SLe(x)), which binds selectins, in peripheral blood lymphocytes of 27 patients with Chagas' disease at different levels of disease severity. Patients with a mild form of Chagas' disease showed a lower number of CD49d(+) cells, in comparison with those with severe chronic cardiopathy. Decreased levels of CD49d(+) cells were detected in CD3(-) cell populations. Conversely, SLe(x) expression was found to be decreased in patients with severe Chagas' disease. Levels of soluble platelet endothelial cell adhesion molecule-1 (s-PECAM-1) were significantly increased in the plasma of patients with severe Chagas' disease while unaltered levels of MCP-1 were recorded. These data show that VCAM-1 and P-Selectin ligands are differentially expressed during the chronic phase of the Trypanosoma cruzi infection. These findings also reinforce a role of the P-selectin/SLe(x) adhesion pathway rather than very late antigen-4 (VLA-4)/VCAM-1, in the pathogenesis of Chagas' disease. PMID:11309161

  13. Amyloid-β peptide on sialyl-Lewis(X)-selectin-mediated membrane tether mechanics at the cerebral endothelial cell surface.

    PubMed

    Askarova, Sholpan; Sun, Zhe; Sun, Grace Y; Meininger, Gerald A; Lee, James C-M

    2013-01-01

    Increased deposition of amyloid-β peptide (Aβ) at the cerebral endothelial cell (CEC) surface has been implicated in enhancement of transmigration of monocytes across the brain blood barrier (BBB) in Alzheimer's disease (AD). In this study, quantitative immunofluorescence microscopy (QIM) and atomic force microscopy (AFM) with cantilevers biofunctionalized by sialyl-Lewis(x) (sLe(x)) were employed to investigate Aβ-altered mechanics of membrane tethers formed by bonding between sLe(x) and p-selectin at the CEC surface, the initial mechanical step governing the transmigration of monocytes. QIM results indicated the ability for Aβ to increase p-selectin expression at the cell surface and promote actin polymerization in both bEND3 cells (immortalized mouse CECs) and human primary CECs. AFM data also showed the ability for Aβ to increase cell stiffness and adhesion probability in bEND3 cells. On the contrary, Aβ lowered the overall force of membrane tether formation (Fmtf ), and produced a bimodal population of Fmtf , suggesting subcellular mechanical alterations in membrane tethering. The lower Fmtf population was similar to the results obtained from cells treated with an F-actin-disrupting drug, latrunculin A. Indeed, AFM results also showed that both Aβ and latrunculin A decreased membrane stiffness, suggesting a lower membrane-cytoskeleton adhesion, a factor resulting in lower Fmtf . In addition, these cerebral endothelial alterations induced by Aβ were abrogated by lovastatin, consistent with its anti-inflammatory effects. In sum, these results demonstrated the ability for Aβ to enhance p-selectin expression at the CEC surface and induce cytoskeleton reorganization, which in turn, resulted in changes in membrane-cytoskeleton adhesion and membrane tethering, mechanical factors important in transmigration of monocytes through the BBB. PMID:23593361

  14. Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3high regulatory T cells in humans

    PubMed Central

    Miyara, Makoto; Chader, Driss; Sage, Edouard; Sugiyama, Daisuke; Nishikawa, Hiroyoshi; Bouvry, Diane; Claër, Laetitia; Hingorani, Ravi; Balderas, Robert; Rohrer, Jurg; Warner, Noel; Chapelier, Alain; Valeyre, Dominique; Kannagi, Reiji; Sakaguchi, Shimon; Amoura, Zahir; Gorochov, Guy

    2015-01-01

    CD4+ regulatory T (Treg) cells expressing CD25 and the transcription factor forkhead box P3 (FOXP3) are indispensable for immunological self-tolerance and homeostasis. FOXP3+CD25+CD4+ T cells in humans, however, are heterogeneous in function and differentiation status, including suppressive or nonsuppressive cells as well as resting or activated Treg cells. We have searched for cell surface markers specific for suppression-competent Treg cells by using a panel of currently available monoclonal antibodies reactive with human T cells. We found that CD15s (sialyl Lewis x) was highly specific for activated, terminally differentiated, and most suppressive FOXP3high effector Treg (eTreg) cells and able to differentiate them in various clinical settings from nonsuppressive FOXP3+ T cells secreting inflammatory cytokines. For example, CD15s+FOXP3+ eTreg cells were increased in sarcoidosis, whereas it was nonsuppressive CD15s−FOXP3+ T cells that were expanded in lupus flares. FOXP3+ cells induced from conventional CD4+ T cells by T-cell receptor stimulation hardly expressed CD15s. CD15s+CD4+ T-cell depletion was sufficient to evoke and enhance in vitro immune responses against tumor or viral antigens. Collectively, we have identified CD15s as a biomarker instrumental in both phenotypic and functional analysis of FOXP3+CD4+ T-cell subpopulations in health and disease. It allows specific targeting of eTreg cells, rather than whole FOXP3+CD4+ T cells, in controlling immune responses. PMID:26015572

  15. Sialyl Lewis x (CD15s) identifies highly differentiated and most suppressive FOXP3high regulatory T cells in humans.

    PubMed

    Miyara, Makoto; Chader, Driss; Sage, Edouard; Sugiyama, Daisuke; Nishikawa, Hiroyoshi; Bouvry, Diane; Claër, Laetitia; Hingorani, Ravi; Balderas, Robert; Rohrer, Jurg; Warner, Noel; Chapelier, Alain; Valeyre, Dominique; Kannagi, Reiji; Sakaguchi, Shimon; Amoura, Zahir; Gorochov, Guy

    2015-06-01

    CD4(+) regulatory T (Treg) cells expressing CD25 and the transcription factor forkhead box P3 (FOXP3) are indispensable for immunological self-tolerance and homeostasis. FOXP3(+)CD25(+)CD4(+) T cells in humans, however, are heterogeneous in function and differentiation status, including suppressive or nonsuppressive cells as well as resting or activated Treg cells. We have searched for cell surface markers specific for suppression-competent Treg cells by using a panel of currently available monoclonal antibodies reactive with human T cells. We found that CD15s (sialyl Lewis x) was highly specific for activated, terminally differentiated, and most suppressive FOXP3(high) effector Treg (eTreg) cells and able to differentiate them in various clinical settings from nonsuppressive FOXP3(+) T cells secreting inflammatory cytokines. For example, CD15s(+)FOXP3(+) eTreg cells were increased in sarcoidosis, whereas it was nonsuppressive CD15s(-)FOXP3(+) T cells that were expanded in lupus flares. FOXP3(+) cells induced from conventional CD4(+) T cells by T-cell receptor stimulation hardly expressed CD15s. CD15s(+)CD4(+) T-cell depletion was sufficient to evoke and enhance in vitro immune responses against tumor or viral antigens. Collectively, we have identified CD15s as a biomarker instrumental in both phenotypic and functional analysis of FOXP3(+)CD4(+) T-cell subpopulations in health and disease. It allows specific targeting of eTreg cells, rather than whole FOXP3(+)CD4(+) T cells, in controlling immune responses. PMID:26015572

  16. Eosinophil-Selective Binding and Proapoptotic Effect in Vitro of a Synthetic Siglec-8 Ligand, Polymeric 6′-Sulfated Sialyl Lewis X

    PubMed Central

    Hudson, Sherry A.; Bovin, Nicolai V.; Schnaar, Ronald L.; Crocker, Paul R.; Bochner, Bruce S.

    2009-01-01

    The lectin Siglec-8 (sialic acid-binding, immunoglobulin-like lectin), which is selectively expressed on eosinophil surfaces and regulates eosinophil survival, preferentially binds to the glycan 6′-sulfo-sialyl Lewis X (6′-sulfo-sLex). Antibody engagement of Siglec-8 on eosinophils causes their apoptosis, suggesting that engagement of Siglec-8 with its natural glycan ligands in vivo may control allergic inflammation. We report that a soluble synthetic polymer displaying 6′-sulfo-sLex glycan selectively binds to human eosinophils and human embryonic kidney 293 cells expressing Siglec-8. Binding was inhibited by anti-Siglec-8 antibody. In whole blood, eosinophils were the only leukocyte subtype to detectably bind polymeric 6′-sulfo-sLex. Interleukin-5-primed eosinophils underwent apoptosis when incubated with either anti-Siglec-8 monoclonal antibody or polymeric 6′-sulfo-sLex, although the glycan polymer was less effective. These data demonstrate that a soluble, multivalent glycan selectively binds to human eosinophils and induces their apoptosis in vitro and provide proof-of-concept that such a reagent could be used to selectively target eosinophils. PMID:19458105

  17. Amyloid-β Peptide on Sialyl-LewisX-Selectin-Mediated Membrane Tether Mechanics at the Cerebral Endothelial Cell Surface

    PubMed Central

    Askarova, Sholpan; Sun, Zhe; Sun, Grace Y.; Meininger, Gerald A.; Lee, James C-M.

    2013-01-01

    Increased deposition of amyloid-β peptide (Aβ) at the cerebral endothelial cell (CEC) surface has been implicated in enhancement of transmigration of monocytes across the brain blood barrier (BBB) in Alzheimer's disease (AD). In this study, quantitative immunofluorescence microscopy (QIM) and atomic force microscopy (AFM) with cantilevers biofunctionalized by sialyl-Lewisx (sLex) were employed to investigate Aβ-altered mechanics of membrane tethers formed by bonding between sLex and p-selectin at the CEC surface, the initial mechanical step governing the transmigration of monocytes. QIM results indicated the ability for Aβ to increase p-selectin expression at the cell surface and promote actin polymerization in both bEND3 cells (immortalized mouse CECs) and human primary CECs. AFM data also showed the ability for Aβ to increase cell stiffness and adhesion probability in bEND3 cells. On the contrary, Aβ lowered the overall force of membrane tether formation (Fmtf), and produced a bimodal population of Fmtf, suggesting subcellular mechanical alterations in membrane tethering. The lower Fmtf population was similar to the results obtained from cells treated with an F-actin-disrupting drug, latrunculin A. Indeed, AFM results also showed that both Aβ and latrunculin A decreased membrane stiffness, suggesting a lower membrane-cytoskeleton adhesion, a factor resulting in lower Fmtf. In addition, these cerebral endothelial alterations induced by Aβ were abrogated by lovastatin, consistent with its anti-inflammatory effects. In sum, these results demonstrated the ability for Aβ to enhance p-selectin expression at the CEC surface and induce cytoskeleton reorganization, which in turn, resulted in changes in membrane-cytoskeleton adhesion and membrane tethering, mechanical factors important in transmigration of monocytes through the BBB. PMID:23593361

  18. Synthesis and structural analysis using 2-D NMR of Sialyl Lewis X (SLe{sup x}) and Lewis X (Le{sup x}) oligosaccharides: Ligands related to E-selectin [ELAM-1] binding

    SciTech Connect

    Ball, G.E.; Nagy, J.O.; Brown, E.G.

    1992-06-17

    The sialyl Lewis X (SLe{sup x}) determinant (NeuAc-{alpha}-2,3-Gal-{beta}-1,4-[Fuc-{alpha}-1,3]-GlcNAc), compound 1, is a ligand for E-selectin (endothelial leucocyte adhesion molecule 1, or ELAM-1), a member of the selectin family of cell adhesion molecules. Interactions between E-selectin and leucocyte-bound SLe{sup x} or closely related oligosaccharides are thought to be important early events in the inflammation process. Binding analysis has shown that the sialic acid (NeuAc) and the fucose (Fuc) moieties are essential for high affinity. The related desialylated trisaccharide Le{sup x} (Gas-{beta}-1,4-[Fuc-{alpha}-1,3]-GlcNAc), for example, is not a high-affinity ligand for E-selectin. In this communication, the authors describe the syntheses of SLe{sup x} 1 and the {beta}-O-allyl glycoside of Le{sup x} 2 using a cloned fucosyltransferase and their complete NMR spectral assignments including ROESY and NOESY experiments in order to investigate the conformation of these compounds in solution. 25 refs., 2 figs.

  19. Rapidly Self-Renewing Human Multipotent Marrow Stromal Cells (hMSC) Express Sialyl Lewis X and Actively Adhere to Arterial Endothelium in a Chick Embryo Model System

    PubMed Central

    McFerrin, Harris E.; Olson, Scott D.; Gutschow, Miriam V.; Semon, Julie A.; Sullivan, Deborah E.; Prockop, Darwin J.

    2014-01-01

    Background There have been conflicting observations regarding the receptors utilized by human multipotent mesenchymal bone marrow stromal cells (hMSC) to adhere to endothelial cells (EC). To address the discrepancies, we performed experiments with cells prepared with a standardized, low-density protocol preserving a sub-population of small cells that are rapidly self-renewing. Methods Sialyl Lewis X (SLeX) and α4 integrin expression were determined by flow cytometry. Fucosyltransferase expression was determined by quantitative realtime RT-PCR. Cell adhesion assays were carried out with a panel of endothelial cells from arteries, veins and the microvasculature in vitro. In vivo experiments were performed to determine single cell interactions in the chick embryo chorioallantoic membrane (CAM). The CAM is a well-characterized respiratory organ allowing for time-lapse image acquisition of large numbers of cells treated with blocking antibodies against adhesion molecules expressed on hMSC. Results hMSC expressed α4 integrin, SLeX and fucosyltransferase 4 and adhered to human EC from arteries, veins and the microvasculature under static conditions in vitro. In vivo, hMSC rolled on and adhered to arterioles in the chick embryo CAM, whereas control melanoma cells embolized. Inhibition of α4 integrin and/or SLeX with blocking antibodies reduced rolling and adhesion in arterioles and increased embolism of hMSC. Conclusions The results demonstrated that rapidly self-renewing hMSC were retained in the CAM because they rolled on and adhered to respiratory arteriolar EC in an α4 integrin- and SLeX-dependent manner. It is therefore important to select cells based on their cell adhesion receptor profile as well as size depending on the intended target of the cell and the injection route. PMID:25144321

  20. Effect of ST3GAL 4 and FUT 7 on sialyl Lewis X synthesis and multidrug resistance in human acute myeloid leukemia.

    PubMed

    Ma, Hongye; Zhou, Huimin; Li, Peng; Song, Xiaobo; Miao, Xiaoyan; Li, Yanping; Jia, Li

    2014-09-01

    Sialyl Lewis X (sLe X, CD15s) is a key antigen produced on tumor cell surfaces during multidrug resistance (MDR) development. The present study investigated the effect of α1, 3 fucosyltransferase VII (FucT VII) and α2, 3 sialyltransferase IV (ST3Gal IV) on sLe X oligosaccharides synthesis as well as their impact on MDR development in acute myeloid leukemia cells (AML). FUT7 and ST3GAL4 were overexpressed in three AML MDR cells and bone marrow mononuclear cells (BMMC) of AML patients with MDR by real-time polymerase chain reaction (PCR). A close association was found between the expression levels of FUT7 and ST3GAL4 and the amount of sLe X oligosaccharides, as well as the phenotypic variation of MDR of HL60 and HL60/ADR cells both in vitro and in vivo. Manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway, thereby regulating the proportionally mutative expression of P-glycoprotein (P-gp) and multidrug resistance related protein 1 (MRP1), both of which are known to be involved in MDR. Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or Akt short hairpin RNA (shRNA) resulted in the reduced MDR of HL60/ADR cells. This study indicated that sLe X involved in the development of MDR of AML cells probably through FUT7 and ST3GAL4 regulating the activity of PI3K/Akt signaling pathway and the expression of P-gp and MRP1. PMID:24953795

  1. Directed evolution of lectins with sugar-binding specificity for 6-sulfo-galactose.

    PubMed

    Hu, Dan; Tateno, Hiroaki; Kuno, Atsushi; Yabe, Rikio; Hirabayashi, Jun

    2012-06-01

    6-sulfo-galactose (6S-Gal) is a prevalent motif observed in highly sulfated keratan sulfate, which is closely associated with the glioblastoma malignancy while acting as a critical determinant for endogenous lectins. However, facile detection of this unique glycoepitope is greatly hampered because of a lack of appropriate probes. We have previously reported tailoring an α2-6-linked sialic acid-binding lectin from a ricin-B chain-like galactose-binding protein, EW29Ch, by a reinforced ribosome display system following an error-prone PCR. In this study, we challenged the creation of novel lectins to recognize 6S-Gal-terminated glycans by incorporating a high-throughput screening system with a glycoconjugate microarray. After two rounds of selection procedures, 20 mutants were obtained and 12 were then successfully expressed in Escherichia coli, 8 of which showed a significant affinity for 6'-Sulfo-LN (6-O-sulfo-Galβ1-4GlcNAc), which the parental EW29Ch lacked. Analysis of two representative mutants by frontal affinity chromatography revealed a substantial affinity (K(d) ∼3 μm) for a 6S-Gal-terminated glycan. On the basis of the observation that all eight mutants have a common mutation at Glu-20 to Lys, site-directed mutagenesis experiments were performed focusing on this aspect. The results clearly indicated that the E20K mutation is necessary and sufficient to acquire the specificity for 6S-Gal. We also confirmed a difference in binding between E20K and EW29Ch to CHO cells, in which enzymes to catalyze the synthesis of 6S-Gal were overexpressed. The results clearly demonstrate that these mutants have potential to distinguish between cells containing different amounts of 6S-Gal-terminated glycans. This new technology will be used to provide novel tools essential for sulfoglycomics. PMID:22493425

  2. Accumulation and therapeutic modulation of 6-sulfo LacNAc+ dendritic cells in multiple sclerosis

    PubMed Central

    Thomas, Katja; Dietze, Kristin; Wehner, Rebekka; Metz, Imke; Tumani, Hayrettin; Schultheiß, Thorsten; Günther, Claudia; Schäkel, Knut; Reichmann, Heinz; Brück, Wolfgang; Schmitz, Marc

    2014-01-01

    Objective: To examine the potential role of 6-sulfo LacNAc+ (slan) dendritic cells (DCs) displaying pronounced proinflammatory properties in the pathogenesis of multiple sclerosis (MS). Methods: We determined the presence of slanDCs in demyelinated brain lesions and CSF samples of patients with MS. In addition, we explored the impact of methylprednisolone, interferon-β, glatiramer acetate, or natalizumab on the frequency of blood-circulating slanDCs in patients with MS. We also evaluated whether interferon-β modulates important proinflammatory capabilities of slanDCs. Results: SlanDCs accumulate in highly inflammatory brain lesions and are present in the majority of CSF samples of patients with MS. Short-term methylprednisolone administration reduces the percentage of slanDCs in blood of patients with MS and the proportion of tumor necrosis factor-α– or CD150-expressing slanDCs. Long-term interferon-β treatment decreases the percentage of blood-circulating slanDCs in contrast to glatiramer acetate or natalizumab. Furthermore, interferon-β inhibits the secretion of proinflammatory cytokines by slanDCs and their capacity to promote proliferation and differentiation of T cells. Conclusion: Accumulation of slanDCs in highly inflammatory brain lesions and their presence in CSF indicate that slanDCs may play an important role in the immunopathogenesis of MS. The reduction of blood-circulating slanDCs and the inhibition of their proinflammatory properties by methylprednisolone and interferon-β may contribute to the therapeutic efficiency of these drugs in patients with MS. PMID:25340085

  3. Global Metabolic Inhibitors of Sialyl- and Fucosyltransferases

    PubMed Central

    Rillahan, Cory D.; Antonopoulos, Aristotelis; Lefort, Craig T.; Sonon, Roberto; Azadi, Parastoo; Ley, Klaus; Dell, Anne; Haslam, Stuart M.; Paulson, James C.

    2012-01-01

    Despite the fundamental roles of sialyl- and fucosyltransferases in mammalian physiology, there are few pharmacological tools to manipulate their function in a cellular setting. Although fluorinated analogs of the donor substrates are well-established transition state inhibitors of these enzymes, they are not membrane permeable. By exploiting promiscuous monosaccharide salvage pathways, we show that fluorinated analogs of sialic acid and fucose can be taken up and metabolized to the desired donor substrate-based inhibitors inside the cell. Due to the existence of metabolic feedback loops, they also act to prevent the de novo synthesis of the natural substrates, resulting in a global, family-wide shutdown of sialyl- and/or fucosyltransferases and remodeling of cell surface glycans. As an example of the functional consequences, the inhibitors drastically reduce expression of the sialylated and fucosylated ligand Sialyl Lewis X on myeloid cells, resulting in loss of binding to selectins and impaired leukocyte rolling. PMID:22683610

  4. Crystal Structures of the Staphylococcal Toxin SSL5 in Complex With Sialyl-Lewis X Reveal a Conserved Binding Site That Shares Common Features With Viral And Bacterial Sialic Acid-Binding Proteins

    SciTech Connect

    Baker, H.M.; Basu, I.; Chung, M.C.; Caradoc-Davies, T.; Fraser, J.D.; Baker, E.N.

    2009-06-02

    Staphylococcus aureus is a significant human pathogen. Among its large repertoire of secreted toxins is a group of staphylococcal superantigen-like proteins (SSLs). These are homologous to superantigens but do not have the same activity. SSL5 is shown here to bind to human granulocytes and to the cell surface receptors for human IgA (Fc alphaRI) and P-selectin [P-selectin glycoprotein ligand-1 (PSGL-1)] in a sialic acid (Sia)-dependent manner. Co-crystallization of SSL5 with the tetrasaccharide sialyl Lewis X (sLe(X)), a key determinant of PSGL-1 binding to P-selectin, led to crystal structures of the SSL5-sLe(X) complex at resolutions of 1.65 and 2.75 A for crystals at two pH values. In both structures, sLe(X) bound to a specific site on the surface of the C-terminal domain of SSL5 in a conformation identical with that bound by P-selectin. Conservation of the key carbohydrate binding residues indicates that this ability to bind human glycans is shared by a substantial subgroup of the SSLs, including SSL2, SSL3, SSL4, SSL5, SSL6, and SSL11. This indicates that the ability to target human glycans is an important property of this group of toxins. Structural comparisons also showed that the Sia binding site in SSL5 contains a substructure that is shared by other Sia binding proteins from bacteria as well as viruses and represents a common binding motif.

  5. Selective α-Sialylation

    NASA Astrophysics Data System (ADS)

    Ando, Hiromune; Kiso, Makoto

    Chemical construction of a α-glycoside of sialic acid is a demanding subject due to the structural disadvantages of sialic acid: the carboxylate group at C1, the deoxy moiety adjacent to the anomeric center, and the glycerol branch from C6. This chapter will provide an overview of sialic acid chemistry and show how the disadvantages can be surmounted and it will also cover the cutting-edge methodology used for α-selective sialylation. In this chapter, the forty-year history of sialylation is compartmentalized into three periods. The first period represents the use of 2-halogeno sialy donors. The second period covers the use of C3-appended sialyl donors and a set of thioglycoside donors, including also the acetonitrile effect, and third is the period of C5-modified sialy donors. While following this division, the chemistry of α-selective sialylation is discussed, and some examples of the stereoselective syntheses of sialyl oligosaccharides are described. Furthermore, the synthesis of the homopolymer of sialic acid and artificial sialyl S- and C-glycosides is discussed.

  6. A Novel Type of Macrothrombocytopenia Associated with a Defect in α2,3-Sialylation

    PubMed Central

    Jones, Claire; Denecke, Jonas; Sträter, Ronald; Stölting, Torsten; Schunicht, Yvonne; Zeuschner, Dagmar; Klumperman, Judith; Lefeber, Dirk J.; Spelten, Oliver; Zarbock, Alexander; Kelm, Sørge; Strenge, Karen; Haslam, Stuart M.; Lühn, Kerstin; Stahl, Dorothea; Gentile, Luca; Schreiter, Thomas; Hilgard, Philip; Beck-Sickinger, Annette G.; Marquardt, Thorsten; Wild, Martin K.

    2011-01-01

    We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to α2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of α2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected. PMID:21864493

  7. A novel type of macrothrombocytopenia associated with a defect in α2,3-sialylation.

    PubMed

    Jones, Claire; Denecke, Jonas; Sträter, Ronald; Stölting, Torsten; Schunicht, Yvonne; Zeuschner, Dagmar; Klumperman, Judith; Lefeber, Dirk J; Spelten, Oliver; Zarbock, Alexander; Kelm, Sørge; Strenge, Karen; Haslam, Stuart M; Lühn, Kerstin; Stahl, Dorothea; Gentile, Luca; Schreiter, Thomas; Hilgard, Philip; Beck-Sickinger, Annette G; Marquardt, Thorsten; Wild, Martin K

    2011-10-01

    We describe a novel type of human thrombocytopenia characterized by the appearance of giant platelets and variable neutropenia. Searching for the molecular defect, we found that neutrophils had strongly reduced sialyl-Lewis X and increased Lewis X surface expression, pointing to a deficiency in sialylation. We show that the glycosylation defect is restricted to α2,3-sialylation and can be detected in platelets, neutrophils, and monocytes. Platelets exhibited a distorted structure of the open canalicular system, indicating defective platelet generation. Importantly, patient platelets, but not normal platelets, bound to the asialoglycoprotein receptor (ASGP-R), a liver cell-surface protein that removes desialylated thrombocytes from the circulation in mice. Taken together, this is the first type of human thrombocytopenia in which a specific defect of α2,3-sialylation and an induction of platelet binding to the liver ASGP-R could be detected. PMID:21864493

  8. Lipopolysaccharide structures of Helicobacter pylori genomic strains 26695 and J99, mouse model H. pylori Sydney strain, H. pylori P466 carrying sialyl Lewis X, and H. pylori UA915 expressing Lewis B classification of H. pylori lipopolysaccharides into glycotype families.

    PubMed

    Monteiro, M A; Appelmelk, B J; Rasko, D A; Moran, A P; Hynes, S O; MacLean, L L; Chan, K H; Michael, F S; Logan, S M; O'Rourke, J; Lee, A; Taylor, D E; Perry, M B

    2000-01-01

    This study describes the molecular makeup of the cell-wall lipopolysaccharides (LPSs) (O-chain polysaccharide-->core oligosaccharide-->lipid A) from five Helicobacter pylori strains: H. pylori 26695 and J99, the complete genome sequences of which have been published, the established mouse model Sydney strain (SS1), and the symptomatic strains P466 and UA915. All chemical and serological experiments were performed on the intact LPSs. H. pylori 26695 and SS1 possessed either a low-Mr semi-rough-form LPS carrying mostly a single Ley type-2 blood-group determinant in the O-chain region covalently attached to the core oligosaccharide or a high-Mr smooth-form LPS, as did strain J99, with an elongated partially fucosylated type-2 N-acetyllactosamine (polyLacNAc) O-chain polymer, terminated mainly by a Lex blood-group determinant, connected to the core oligosaccharide. In the midst of semi-rough-form LPS glycoforms, H. pylori 26695 and SS1 also expressed in the O-chain region a difucosylated antigen, alpha-L-Fucp(1-3)-alpha-L-Fucp(1-4)-beta-D-GlcpNAc, and the cancer-cell-related type-1 or type-2 linear B-blood-group antigen, alpha-D-Galp(1-3)-beta-D-Galp(1-3 or 4)-beta-D-GlcpNAc. The LPS of H. pylori strain P466 carried the cancer-associated type-2 sialyl Lex blood-group antigen, and the LPS from strain UA915 expressed a type-1 Leb blood-group unit. These findings should aid investigations that focus on identifying and characterizing genes responsible for LPS biosynthesis in genomic strains 26695 and J99, and in understanding the role of H. pylori LPS in animal model studies. The LPSs from the H. pylori strains studied to date were grouped into specific glycotype families. PMID:10632700

  9. Multifaceted Role of Sialylation in Prion Diseases

    PubMed Central

    Baskakov, Ilia V.; Katorcha, Elizaveta

    2016-01-01

    Mammalian prion or PrPSc is a proteinaceous infectious agent that consists of a misfolded, self-replicating state of a sialoglycoprotein called the prion protein, or PrPC. Sialylation of the prion protein N-linked glycans was discovered more than 30 years ago, yet the role of sialylation in prion pathogenesis remains poorly understood. Recent years have witnessed extraordinary growth in interest in sialylation and established a critical role for sialic acids in host invasion and host-pathogen interactions. This review article summarizes current knowledge on the role of sialylation of the prion protein in prion diseases. First, we discuss the correlation between sialylation of PrPSc glycans and prion infectivity and describe the factors that control sialylation of PrPSc. Second, we explain how glycan sialylation contributes to the prion replication barrier, defines strain-specific glycoform ratios, and imposes constraints for PrPSc structure. Third, several topics, including a possible role for sialylation in animal-to-human prion transmission, prion lymphotropism, toxicity, strain interference, and normal function of PrPC, are critically reviewed. Finally, a metabolic hypothesis on the role of sialylation in the etiology of sporadic prion diseases is proposed. PMID:27551257

  10. Multifaceted Role of Sialylation in Prion Diseases.

    PubMed

    Baskakov, Ilia V; Katorcha, Elizaveta

    2016-01-01

    Mammalian prion or PrP(Sc) is a proteinaceous infectious agent that consists of a misfolded, self-replicating state of a sialoglycoprotein called the prion protein, or PrP(C). Sialylation of the prion protein N-linked glycans was discovered more than 30 years ago, yet the role of sialylation in prion pathogenesis remains poorly understood. Recent years have witnessed extraordinary growth in interest in sialylation and established a critical role for sialic acids in host invasion and host-pathogen interactions. This review article summarizes current knowledge on the role of sialylation of the prion protein in prion diseases. First, we discuss the correlation between sialylation of PrP(Sc) glycans and prion infectivity and describe the factors that control sialylation of PrP(Sc). Second, we explain how glycan sialylation contributes to the prion replication barrier, defines strain-specific glycoform ratios, and imposes constraints for PrP(Sc) structure. Third, several topics, including a possible role for sialylation in animal-to-human prion transmission, prion lymphotropism, toxicity, strain interference, and normal function of PrP(C), are critically reviewed. Finally, a metabolic hypothesis on the role of sialylation in the etiology of sporadic prion diseases is proposed. PMID:27551257

  11. Sialylation: an Avenue to Target Cancer Cells.

    PubMed

    Vajaria, Bhairavi N; Patel, Kinjal R; Begum, Rasheedunnisa; Patel, Prabhudas S

    2016-07-01

    Tumorigenesis and metastasis are frequently associated with altered structure and expression of oligosaccharides on cell surface glycoproteins and glycolipids. The expression of sialylated glycoconjugates has been shown to change during development, differentiation, disease and oncogenic transformation. Abnormal sialylation in cancer cell is a distinctive feature associated with malignant properties including invasiveness and metastatic potential. The alterations in sialylation is accompanied by changes in sialic acid, sialidase activity, sialyltransferase (ST) activity or sialoproteins. The present review summarizes the reports on alterations of sialic acid, linkage specific STs and sialoproteins, sialidase activity together with different subtypes of ST and sialidases mRNA expressions in various cancers like lung, breast, oral, cervical, ovarian, pancreatic etc. Sialic acids are widely distributed in nature as terminal sugars of oligosaccharides attached to proteins or lipids. The increase shedding of sialic acid observed in malignant tumors may be due to different types of sialidases. The amount of sialic acid is governed by levels of sialidases and STs. Various types of STs are also involved in formation of different types sialylated tumor associated carbohydrate antigens which plays important role in metastasis. The alterations associated with sialylation aids in early diagnosis, prognosis and post treatment monitoring in various cancers. Recently newer drugs targeting different interplays of sialylation have been developed, which might have profound effect in inhibiting sialylation and thus cancer metastasis and infiltration. PMID:26685886

  12. One-pot multienzyme synthesis of Lewis x and sialyl Lewis x antigens

    PubMed Central

    Yu, Hai; Lau, Kam; Li, Yanhong; Sugiarto, Go; Chen, Xi

    2012-01-01

    L-Fucose has been found abundantly in human milk oligosaccharides, bacterial lipopolysaccharides, glycolipids, and many N- and O-linked glycans produced by mammalian cells. Fucose-containing carbohydrates have important biological functions. Alterations in the expression of fucosylated oligosaccharides have been observed in several pathological processes such as cancer and atherosclerosis. Chemical formation of fucosidic bonds is challenging due to its acid lability. Enzymatic construction of fucosidic bonds by fucosyltransferases is highly efficient and selective but requires the expensive sugar nucleotide donor guanosine 5′- diphosphate-L-fucose (GDP-Fuc). Here, we describe a protocol for applying a one-pot three-enzyme system in synthesizing structurally defined fucose-containing oligosaccharides from free L-fucose. In this system, GDP-Fuc is generated from L-fucose, adenosine 5′-triphosphate (ATP), and guanosine 5′-triphosphate (GTP) by a bifunctional L-fucokinase/GDP-fucose pyrophosphorylase (FKP). An inorganic pyrophosphatase (PpA) is used to degrade the by-product pyrophosphate (PPi) to drive the reaction towards the formation of GDP-Fuc. In situ generated GDP-Fuc is then used by a suitable fucosyltransferase for the formation of fucosides. The three-enzyme reactions are carried out in one pot without the need for high cost sugar nucleotide or isolation of intermediates. The time for the synthesis is 4–24 hours. Purification and characterization of products can be completed in 2–3 days. PMID:25000293

  13. Engineering of complex protein sialylation in plants.

    PubMed

    Kallolimath, Somanath; Castilho, Alexandra; Strasser, Richard; Grünwald-Gruber, Clemens; Altmann, Friedrich; Strubl, Sebastian; Galuska, Christina Elisabeth; Zlatina, Kristina; Galuska, Sebastian Peter; Werner, Stefan; Thiesler, Hauke; Werneburg, Sebastian; Hildebrandt, Herbert; Gerardy-Schahn, Rita; Steinkellner, Herta

    2016-08-23

    Sialic acids (Sias) are abundant terminal modifications of protein-linked glycans. A unique feature of Sia, compared with other monosaccharides, is the formation of linear homo-polymers, with its most complex form polysialic acid (polySia). Sia and polySia mediate diverse biological functions and have great potential for therapeutic use. However, technological hurdles in producing defined protein sialylation due to the enormous structural diversity render their precise investigation a challenge. Here, we describe a plant-based expression platform that enables the controlled in vivo synthesis of sialylated structures with different interlinkages and degree of polymerization (DP). The approach relies on a combination of stably transformed plants with transient expression modules. By the introduction of multigene vectors carrying the human sialylation pathway into glycosylation-destructed mutants, transgenic plants that sialylate glycoproteins in α2,6- or α2,3-linkage were generated. Moreover, by the transient coexpression of human α2,8-polysialyltransferases, polySia structures with a DP >40 were synthesized in these plants. Importantly, plant-derived polySia are functionally active, as demonstrated by a cell-based cytotoxicity assay and inhibition of microglia activation. This pathway engineering approach enables experimental investigations of defined sialylation and facilitates a rational design of glycan structures with optimized biotechnological functions. PMID:27444013

  14. Engineering of complex protein sialylation in plants

    PubMed Central

    Kallolimath, Somanath; Castilho, Alexandra; Strasser, Richard; Grünwald-Gruber, Clemens; Altmann, Friedrich; Strubl, Sebastian; Galuska, Christina Elisabeth; Zlatina, Kristina; Galuska, Sebastian Peter; Werner, Stefan; Thiesler, Hauke; Werneburg, Sebastian; Hildebrandt, Herbert; Gerardy-Schahn, Rita; Steinkellner, Herta

    2016-01-01

    Sialic acids (Sias) are abundant terminal modifications of protein-linked glycans. A unique feature of Sia, compared with other monosaccharides, is the formation of linear homo-polymers, with its most complex form polysialic acid (polySia). Sia and polySia mediate diverse biological functions and have great potential for therapeutic use. However, technological hurdles in producing defined protein sialylation due to the enormous structural diversity render their precise investigation a challenge. Here, we describe a plant-based expression platform that enables the controlled in vivo synthesis of sialylated structures with different interlinkages and degree of polymerization (DP). The approach relies on a combination of stably transformed plants with transient expression modules. By the introduction of multigene vectors carrying the human sialylation pathway into glycosylation-destructed mutants, transgenic plants that sialylate glycoproteins in α2,6- or α2,3-linkage were generated. Moreover, by the transient coexpression of human α2,8-polysialyltransferases, polySia structures with a DP >40 were synthesized in these plants. Importantly, plant-derived polySia are functionally active, as demonstrated by a cell-based cytotoxicity assay and inhibition of microglia activation. This pathway engineering approach enables experimental investigations of defined sialylation and facilitates a rational design of glycan structures with optimized biotechnological functions. PMID:27444013

  15. Regulation of the metastatic cell phenotype by sialylated glycans

    PubMed Central

    Schultz, Matthew J.; Swindall, Amanda F.

    2014-01-01

    Tumor cells exhibit striking changes in cell surface glycosylation as a consequence of dysregulated glycosyltransferases and glycosidases. In particular, an increase in the expression of certain sialylated glycans is a prominent feature of many transformed cells. Altered sialylation has long been associated with metastatic cell behaviors including invasion and enhanced cell survival; however, there is limited information regarding the molecular details of how distinct sialylated structures or sialylated carrier proteins regulate cell signaling to control responses such as adhesion/migration or resistance to specific apoptotic pathways. The goal of this review is to highlight selected examples of sialylated glycans for which there is some knowledge of molecular mechanisms linking aberrant sialylation to critical processes involved in metastasis. PMID:22699311

  16. Lewy Body Disease

    MedlinePlus

    Lewy body disease is one of the most common causes of dementia in the elderly. Dementia is the loss of mental ... to affect normal activities and relationships. Lewy body disease happens when abnormal structures, called Lewy bodies, build ...

  17. Lewy Body Dementia Research

    MedlinePlus

    ... Alzheimer's when Lewy Bodies are present Lewy body pathology is found in up to 50% of cases ... between people who have autopsy-verified Alzheimer’s disease pathology alone versus those who have both Alzheimer’s and ...

  18. Lewy Body Dementia Diagnosis

    MedlinePlus

    ... individuals, it may also be due to the natural course of the disease. All Rights Reserved Lewy Body Dementia Association, Inc. 912 Killian Hill Road S.W., Lilburn, GA 30047 © 2016 Lewy Body Dementia Association, Inc. Connect ...

  19. Post-conversion sialylation of prions in lymphoid tissues

    PubMed Central

    Srivastava, Saurabh; Makarava, Natallia; Katorcha, Elizaveta; Savtchenko, Regina; Brossmer, Reinhard; Baskakov, Ilia V.

    2015-01-01

    Sialylated glycans on the surface of mammalian cells act as part of a “self-associated molecular pattern,” helping the immune system to recognize “self” from “altered self” or “nonself.” To escape the host immune system, some bacterial pathogens have evolved biosynthetic pathways for host-like sialic acids, whereas others recruited host sialic acids for decorating their surfaces. Prions lack nucleic acids and are not conventional pathogens. Nevertheless, prions might use a similar strategy for invading and colonizing the lymphoreticular system. Here we show that the sialylation status of the infectious, disease-associated state of the prion protein (PrPSc) changes with colonization of secondary lymphoid organs (SLOs). As a result, spleen-derived PrPSc is more sialylated than brain-derived PrPSc. Enhanced sialylation of PrPSc is recapitulated in vitro by incubating brain-derived PrPSc with primary splenocytes or cultured macrophage RAW 264.7 cells. General inhibitors of sialyltranserases (STs), the enzymes that transfer sialic acid residues onto terminal positions of glycans, suppressed extrasialylation of PrPSc. A fluorescently labeled precursor of sialic acid revealed ST activity associated with RAW macrophages. This study illustrates that, upon colonization of SLOs, the sialylation status of prions changes by host STs. We propose that this mechanism is responsible for camouflaging prions in SLOs and has broad implications. PMID:26627256

  20. Human Synovial Lubricin Expresses Sialyl Lewis x Determinant and Has L-selectin Ligand Activity*

    PubMed Central

    Jin, Chunsheng; Ekwall, Anna-Karin Hultgård; Bylund, Johan; Björkman, Lena; Estrella, Ruby P.; Whitelock, John M.; Eisler, Thomas; Bokarewa, Maria; Karlsson, Niclas G.

    2012-01-01

    Lubricin (or proteoglycan 4 (PRG4)) is an abundant mucin-like glycoprotein in synovial fluid (SF) and a major component responsible for joint lubrication. In this study, it was shown that O-linked core 2 oligosaccharides (Galβ1–3(GlcNAcβ1–6)GalNAcα1-Thr/Ser) on lubricin isolated from rheumatoid arthritis SF contained both sulfate and fucose residues, and SF lubricin was capable of binding to recombinant L-selectin in a glycosylation-dependent manner. Using resting human polymorphonuclear granulocytes (PMN) from peripheral blood, confocal microscopy showed that lubricin coated circulating PMN and that it partly co-localized with L-selectin expressed by these cells. In agreement with this, activation-induced shedding of L-selectin also mediated decreased lubricin binding to PMN. It was also found that PMN recruited to inflamed synovial area and fluid in rheumatoid arthritis patients kept a coat of lubricin. These observations suggest that lubricin is able to bind to PMN via an L-selectin-dependent and -independent manner and may play a role in PMN-mediated inflammation. PMID:22930755

  1. Discovering Lewis and Clark

    ERIC Educational Resources Information Center

    Olsen, Ken

    2006-01-01

    Writer and historian Bernard DeVoto observed more than 50 years ago that a dismaying amount of American history has been written without regards to the Indians. Such disregard is glaring in many mainstream stories of Meriwether Lewis and William Clark. Lewis and Clark began preparing for their historic journey in 1803 and officially launched the…

  2. Dynamic Sialylation in Transforming Growth Factor-β (TGF-β)-induced Epithelial to Mesenchymal Transition*

    PubMed Central

    Du, Jun; Hong, Senlian; Dong, Lu; Cheng, Bo; Lin, Liang; Zhao, Bing; Chen, Ye-Guang; Chen, Xing

    2015-01-01

    Epithelial-mesenchymal transition (EMT) is a fundamental process in embryonic development and organ formation. Aberrant regulation of EMT often leads to tumor progression. Changes in cell surface sialylation have recently been implicated in mediating EMT. Herein we report the visualization of dynamic changes of sialylation and glycoproteomic analysis of newly synthesized sialylated proteins in EMT by metabolic labeling of sialylated glycans with azides, followed by click labeling with fluorophores or affinity tags. We discovered that sialylation was down-regulated during EMT but then reverted and up-regulated in the mesenchymal state after EMT, accompanied by mRNA expression level changes of genes involved in the sialic acid biosynthesis. Quantitative proteomic analysis identified a list of sialylated proteins whose biosynthesis was dynamically regulated during EMT. Sialylation of cell surface adherent receptor integrin β4 was found to be down-regulated, which may regulate integrin functions during EMT. Furthermore, a global sialylation inhibitor was used to probe the functional role of sialylation during EMT. We found that inhibition of sialylation promoted EMT. Taken together, our findings suggest the important role of sialylation in regulating EMT and imply its possible function in related pathophysiological events, such as cancer metastasis. PMID:25809486

  3. B-cell-independent sialylation of IgG.

    PubMed

    Jones, Mark B; Oswald, Douglas M; Joshi, Smita; Whiteheart, Sidney W; Orlando, Ron; Cobb, Brian A

    2016-06-28

    IgG carrying terminal α2,6-linked sialic acids added to conserved N-glycans within the Fc domain by the sialyltransferase ST6Gal1 accounts for the anti-inflammatory effects of large-dose i.v. Ig (IVIg) in autoimmunity. Here, B-cell-specific ablation of ST6Gal1 in mice revealed that IgG sialylation can occur in the extracellular environment of the bloodstream independently of the B-cell secretory pathway. We also discovered that secreted ST6Gal1 is produced by cells lining central veins in the liver and that IgG sialylation is powered by serum-localized nucleotide sugar donor CMP-sialic acid that is at least partially derived from degranulating platelets. Thus, antibody-secreting cells do not exclusively control the sialylation-dependent anti-inflammatory function of IgG. Rather, IgG sialylation can be regulated by the liver and platelets through the corresponding release of enzyme and sugar donor into the cardiovascular circulation. PMID:27303031

  4. Lewy Body Disease

    MedlinePlus

    ... of symptoms, including Changes in alertness and attention Hallucinations Problems with movement and posture Muscle stiffness Confusion Loss of memory Lewy body disease can be hard to diagnose, because Parkinson's ...

  5. Globally profiling sialylation status of macrophages upon statin treatment.

    PubMed

    Wang, Dan; Nie, Huan; Ozhegov, Evgeny; Wang, Lin; Zhou, Aimin; Li, Yu; Sun, Xue-Long

    2015-09-01

    Sialic acids (SAs) are widely expressed on immune cells and their levels and linkages named as sialylation status vary upon cellular environment changes related to both physiological and pathological processes. In this study, we performed a global profiling of the sialylation status of macrophages and their release of SAs in the cell culture medium by using flow cytometry, confocal microscopy and liquid chromatography tandem mass spectrometry (LC-MS/MS). Both flow cytometry and confocal microscopy results showed that cell surface α-2,3-linked SAs were predominant in the normal culture condition and changed slightly upon treatment with atorvastatin for 24 h, whereas α-2,6-linked SAs were negligible in the normal culture condition but significantly increased after treatment. Meanwhile, the amount of total cellular SAs increased about three times (from 369 ± 29 to 1080 ± 50 ng/mL) upon treatment as determined by the LC-MS/MS method. On the other hand, there was no significant change for secreted free SAs and conjugated SAs in the medium. These results indicated that the cell surface α-2,6 sialylation status of macrophages changes distinctly upon atorvastatin stimulation, which may reflect on the biological functions of the cells. PMID:26033937

  6. Globally profiling sialylation status of macrophages upon statin treatment

    PubMed Central

    Wang, Dan; Nie, Huan; Ozhegov, Evgeny; Wang, Lin; Zhou, Aimin; Li, Yu; Sun, Xue-Long

    2015-01-01

    Sialic acids (SAs) are widely expressed on immune cells and their levels and linkages named as sialylation status vary upon cellular environment changes related to both physiological and pathological processes. In this study, we performed a global profiling of the sialylation status of macrophages and their release of SAs in the cell culture medium by using flow cytometry, confocal microscopy and liquid chromatography tandem mass spectrometry (LC-MS/MS). Both flow cytometry and confocal microscopy results showed that cell surface α-2,3-linked SAs were predominant in the normal culture condition and changed slightly upon treatment with atorvastatin for 24 h, whereas α-2,6-linked SAs were negligible in the normal culture condition but significantly increased after treatment. Meanwhile, the amount of total cellular SAs increased about three times (from 369 ± 29 to 1080 ± 50 ng/mL) upon treatment as determined by the LC-MS/MS method. On the other hand, there was no significant change for secreted free SAs and conjugated SAs in the medium. These results indicated that the cell surface α-2,6 sialylation status of macrophages changes distinctly upon atorvastatin stimulation, which may reflect on the biological functions of the cells. PMID:26033937

  7. Reversible off and on switching of prion infectivity via removing and reinstalling prion sialylation.

    PubMed

    Katorcha, Elizaveta; Daus, Martin L; Gonzalez-Montalban, Nuria; Makarava, Natallia; Lasch, Peter; Beekes, Michael; Baskakov, Ilia V

    2016-01-01

    The innate immune system provides the first line of defense against pathogens. To recognize pathogens, this system detects a number of molecular features that discriminate pathogens from host cells, including terminal sialylation of cell surface glycans. Mammalian cell surfaces, but generally not microbial cell surfaces, have sialylated glycans. Prions or PrP(Sc) are proteinaceous pathogens that lack coding nucleic acids but do possess sialylated glycans. We proposed that sialylation of PrP(Sc) is essential for evading innate immunity and infecting a host. In this study, the sialylation status of PrP(Sc) was reduced by replicating PrP(Sc) in serial Protein Misfolding Cyclic Amplification using sialidase-treated PrP(C) substrate and then restored to original levels by replication using non-treated substrate. Upon intracerebral administration, all animals that received PrP(Sc) with original or restored sialylation levels were infected, whereas none of the animals that received PrP(Sc) with reduced sialylation were infected. Moreover, brains and spleens of animals from the latter group were completely cleared of prions. The current work established that the ability of prions to infect the host via intracerebral administration depends on PrP(Sc) sialylation status. Remarkably, PrP(Sc) infectivity could be switched off and on in a reversible manner by first removing and then restoring PrP(Sc) sialylation. PMID:27609323

  8. Reversible off and on switching of prion infectivity via removing and reinstalling prion sialylation

    PubMed Central

    Katorcha, Elizaveta; Daus, Martin L.; Gonzalez-Montalban, Nuria; Makarava, Natallia; Lasch, Peter; Beekes, Michael; Baskakov, Ilia V.

    2016-01-01

    The innate immune system provides the first line of defense against pathogens. To recognize pathogens, this system detects a number of molecular features that discriminate pathogens from host cells, including terminal sialylation of cell surface glycans. Mammalian cell surfaces, but generally not microbial cell surfaces, have sialylated glycans. Prions or PrPSc are proteinaceous pathogens that lack coding nucleic acids but do possess sialylated glycans. We proposed that sialylation of PrPSc is essential for evading innate immunity and infecting a host. In this study, the sialylation status of PrPSc was reduced by replicating PrPSc in serial Protein Misfolding Cyclic Amplification using sialidase-treated PrPC substrate and then restored to original levels by replication using non-treated substrate. Upon intracerebral administration, all animals that received PrPSc with original or restored sialylation levels were infected, whereas none of the animals that received PrPSc with reduced sialylation were infected. Moreover, brains and spleens of animals from the latter group were completely cleared of prions. The current work established that the ability of prions to infect the host via intracerebral administration depends on PrPSc sialylation status. Remarkably, PrPSc infectivity could be switched off and on in a reversible manner by first removing and then restoring PrPSc sialylation. PMID:27609323

  9. Dementia with lewy bodies.

    PubMed

    Posner, H; Chin, S; Marder, K

    2001-10-17

    In this case study, we describe the symptoms, neuropsychological testing, and brain pathology of a man with dementia with Lewy bodies. Dementia with Lewy bodies might be the second most common form of degenerative dementia in the elderly. Progressive cognitive decline, well-formed visual hallucinations, and parkinsonism are core features of this disease. This case was marked by preserved verbal expression despite impairment in memory, visuospatial skills, and attention span. Development of visual symptoms and parkinsonism occurred very early in the course of the disease. PMID:14602963

  10. Symptoms of Lewy Body Dementia

    MedlinePlus

    ... of the environment or personal interactions, and the natural progression of the disease. All Rights Reserved Lewy Body Dementia Association, Inc. 912 Killian Hill Road S.W., Lilburn, GA 30047 © 2016 Lewy Body Dementia Association, Inc. Connect ...

  11. Lewy body dementias.

    PubMed

    Walker, Zuzana; Possin, Katherine L; Boeve, Bradley F; Aarsland, Dag

    2015-10-24

    The broad importance of dementia is undisputed, with Alzheimer's disease justifiably getting the most attention. However, dementia with Lewy bodies and Parkinson's disease dementia, now called Lewy body dementias, are the second most common type of degenerative dementia in patients older than 65 years. Despite this, Lewy body dementias receive little attention and patients are often misdiagnosed, leading to less than ideal management. Over the past 10 years, considerable effort has gone into improving diagnostic accuracy by refining diagnostic criteria and using imaging and other biomarkers. Dementia with Lewy bodies and Parkinson's disease dementia share the same pathophysiology, and effective treatments will depend not only on successful treatment of symptoms but also on targeting the pathological mechanisms of disease, ideally before symptoms and clinical signs develop. We summarise the most pertinent progress from the past 10 years, outlining some of the challenges for the future, which will require refinement of diagnosis and clarification of the pathogenesis, leading to disease-modifying treatments. PMID:26595642

  12. Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis.

    PubMed

    Ohmi, Yuhsuke; Ise, Wataru; Harazono, Akira; Takakura, Daisuke; Fukuyama, Hidehiro; Baba, Yoshihiro; Narazaki, Masashi; Shoda, Hirofumi; Takahashi, Nobunori; Ohkawa, Yuki; Ji, Shuting; Sugiyama, Fumihiro; Fujio, Keishi; Kumanogoh, Atsushi; Yamamoto, Kazuhiko; Kawasaki, Nana; Kurosaki, Tomohiro; Takahashi, Yoshimasa; Furukawa, Koichi

    2016-01-01

    Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy. PMID:27046227

  13. Sialylation converts arthritogenic IgG into inhibitors of collagen-induced arthritis

    PubMed Central

    Ohmi, Yuhsuke; Ise, Wataru; Harazono, Akira; Takakura, Daisuke; Fukuyama, Hidehiro; Baba, Yoshihiro; Narazaki, Masashi; Shoda, Hirofumi; Takahashi, Nobunori; Ohkawa, Yuki; Ji, Shuting; Sugiyama, Fumihiro; Fujio, Keishi; Kumanogoh, Atsushi; Yamamoto, Kazuhiko; Kawasaki, Nana; Kurosaki, Tomohiro; Takahashi, Yoshimasa; Furukawa, Koichi

    2016-01-01

    Rheumatoid arthritis (RA)-associated IgG antibodies such as anti-citrullinated protein antibodies (ACPAs) have diverse glycosylation variants; however, key sugar chains modulating the arthritogenic activity of IgG remain to be clarified. Here, we show that reduced sialylation is a common feature of RA-associated IgG in humans and in mouse models of arthritis. Genetically blocking sialylation in activated B cells results in exacerbation of joint inflammation in a collagen-induced arthritis (CIA) model. On the other hand, artificial sialylation of anti-type II collagen antibodies, including ACPAs, not only attenuates arthritogenic activity, but also suppresses the development of CIA in the antibody-infused mice, whereas sialylation of other IgG does not prevent CIA. Thus, our data demonstrate that sialylation levels control the arthritogenicity of RA-associated IgG, presenting a potential target for antigen-specific immunotherapy. PMID:27046227

  14. N-acetyl-5-N,4-O-oxazolidinone-protected sialyl sulfoxide: an α-selective sialyl donor with Tf2O/(Tol)2SO in dichloromethane.

    PubMed

    Gu, Zhen-yuan; Zhang, Jia-xin; Xing, Guo-wen

    2012-06-01

    Sweet as sugar: Sialyl sulfoxide protected by N-acetyl-5-N,4-O-oxazolidinone was readily prepared, and its coupling to various sugar acceptors was investigated. When the reaction was promoted by Tf(2)O/(Tol)(2)SO, efficient and highly α-selective sialylation yielded α(2,6), α(2,3), and α(2,4) glycosidic linkages between sialic acid and glucose/glacotose. PMID:22488903

  15. Dementia with Lewy bodies

    PubMed Central

    Ferman, Tanis J.; Boeve, Bradley F.

    2009-01-01

    Synopsis The advent of new immunostains have improved our ability to detect limbic and cortical Lewy bodies, and it is now evident that Dementa with Lewy bodies (DLB) is the second most common neurodegenerative dementia, after Alzheimer’s disease (AD). Distinguishing DLB from AD has important implications for treatment, in terms of substances that may worsen symptoms (i.e., anticholinergic and certain neuroleptic medications) and those that may improve them (i.e., cholinesterase inhibitors, carbidopa-levodopa). Neurocognitive patterns, psychiatric features, extrapyramidal signs and sleep disturbance are helpful in differentiating DLB from AD early in the disease course. Differences in the severity of cholinergic depletion as well as type and distribution of neuropathology contribute to these clinical differences, though DLB patients with a high density of co-occuring AD pathology are less clinical distinguishable from AD. PMID:17659188

  16. Expression of functionally active sialylated human erythropoietin in plants

    PubMed Central

    Jez, Jakub; Castilho, Alexandra; Grass, Josephine; Vorauer-Uhl, Karola; Sterovsky, Thomas; Altmann, Friedrich; Steinkellner, Herta

    2013-01-01

    Recombinant human erythropoietin (rhEPO), a glycohormone, is one of the leading biopharmaceutical products. The production of rhEPO is currently restricted to mammalian cell expression systems because of rhEPO's highly complex glycosylation pattern, which is a major determinant for drug-efficacy. Here we evaluate the ability of plants to produce different glycoforms of rhEPO. cDNA constructs were delivered to Nicotiana benthamiana (N. benthamiana) and transiently expressed by a viral based expression system. Expression levels up to 85 mg rhEPO/kg fresh leaf material were achieved. Moreover, co-expression of rhEPO with six mammalian genes required for in planta protein sialylation resulted in the synthesis of rhEPO decorated mainly with bisialylated N-glycans (NaNa), the most abundant glycoform of circulating hEPO in patients with anemia. A newly established peptide tag (ELDKWA) fused to hEPO was particularly well-suited for purification of the recombinant hormone based on immunoaffinity. Subsequent lectin chromatography allowed enrichment of exclusively sialylated rhEPO. All plant-derived glycoforms exhibited high biological activity as determined by a cell-based receptor-binding assay. The generation of rhEPO carrying largely homogeneous glycosylation profiles (GnGnXF, GnGn, and NaNa) will facilitate further investigation of functionalities with potential implications for medical applications. PMID:23325672

  17. Frustrated Lewis Pairs.

    PubMed

    Stephan, Douglas W

    2015-08-19

    The articulation of the notion of "frustrated Lewis pairs" (FLPs), which emerged from the discovery that H2 can be reversibly activated by combinations of sterically encumbered Lewis acids and bases, has prompted a great deal of recent activity. Perhaps the most remarkable consequence has been the development of FLP catalysts for the hydrogenation of a range of organic substrates. In the past 9 years, the substrate scope has evolved from bulky polar species to include a wide range of unsaturated organic molecules. In addition, effective stereoselective metal-free hydrogenation catalysts have begun to emerge. The mechanism of this activation of H2 has been explored, and the nature and range of Lewis acid/base combinations capable of effecting such activation have also expanded to include a variety of non-metal species. The reactivity of FLPs with a variety of other small molecules, including olefins, alkynes, and a range of element oxides, has also been developed. Although much of this latter chemistry has uncovered unique stoichiometric transformations, metal-free catalytic hydroamination, CO2 reduction chemistry, and applications in polymerization have also been achieved. The concept is also beginning to find applications in bioinorganic and materials chemistry as well as heterogeneous catalysis. This Perspective highlights many of these developments and discusses the relationship between FLPs and established chemistry. Some of the directions and developments that are likely to emerge from FLP chemistry in the future are also presented. PMID:26214241

  18. [Diffuse Lewy body disease].

    PubMed

    Kosaka, K

    1995-12-01

    Diffuse Lewy body disease (DLBD), which we have proposed since 1976, has received great attention among both researchers and clinicians. Recently, it was reported by some English and American research groups that DLBD is the second most frequent dementing illness in the elderly, following Alzheimer-type dementia (ATD). Our recent research of 79 autopsied dementia cases in a hospital disclosed that DLBD (15.4%) was the second most common degenerative dementia, following ATD (43.6%). In 1980 we proposed Lewy body disease, and classified it into three types: brain stem type, transitional type, and diffuse type. Diffuse type of LBD is now called DLBD. In 1990 we divided DLBD into two forms: common form and pure form. The common form of DLBD has more or less Alzheimer pathology, and pure form has none. Very recently, we proposed the cerebral type of LBD, in which numerous Lewy bodies are found in the cerebral cortex and amygdala, but no PD pathology is present in the brain stem. Therefore, LBD is now classified as follows: [table: see text] PMID:8752428

  19. Edwin W. Lewis, Jr.

    NASA Technical Reports Server (NTRS)

    1999-01-01

    Edwin W. Lewis Jr. is a research pilot in the Airborne Science program, Flight Crew Branch, Dryden Flight Research Center, Edwards, California. He currently flies the DC-8, F/A-18, Lear Jet 24, King Air, and T-34C in support of Dryden's flight operations and is mentor pilot for the King Air and the Lear Jet. Prior to accepting this assignment Lewis was a pilot for eight years at NASA's Ames Research Center, Moffett Field, California, flying 10 different aircraft - C-130B, DC-8-72, UH-1, SH-3, King Air, Lear 24, T-38A, T-39G and YO-3A - in support of NASA flight missions. Lewis also flew the Kuiper Airborne Observatory (a modified civilian version of the Lockheed C-141 Starlifter). He was project pilot for Ames' 747 and T-38 programs. Lewis was born in New York City on May 19, 1936, and began flight training as a Civil Air Patrol cadet in 1951, ultimately earning his commercial pilot's certificate in 1958. He received a bachelor of arts degree in biology from Hobart College, Geneva, N.Y., and entered the U.S. Air Force through the Reserve Officer Training Corps. Following pilot training he was assigned to Moody Air Force Base, Ga., as an instructor pilot, for both the T-33 and T-37 aircraft. He served in Vietnam in 1965 and 1966, where he was a forward air controller, instructor and standardization/evaluation pilot, flying more than 1,000 hours in the O-1 'Bird Dog.' Lewis separated from the regular Air Force and joined Pan American World Airways and the 129th Air Commando Group, California Air National Guard (ANG) based in Hayward, California. During his 18-year career with the California ANG he flew the U-6, U-10, C-119, HC-130 aircraft and the HH-3 helicopter. He retired as commander, 129th Air Rescue and Recovery Group, a composite combat rescue group, in the grade of colonel. During his 22 years as an airline pilot, he flew the Boeing 707, 727 and 747. He took early retirement from Pan American in 1989 to become a pilot with NASA.

  20. Effect of sialylation on EGFR phosphorylation and resistance to tyrosine kinase inhibition.

    PubMed

    Yen, Hsin-Yung; Liu, Ying-Chih; Chen, Nai-Yu; Tsai, Chia-Feng; Wang, Yi-Ting; Chen, Yu-Ju; Hsu, Tsui-Ling; Yang, Pan-Chyr; Wong, Chi-Huey

    2015-06-01

    Epidermal growth factor receptor (EGFR) is a heavily glycosylated transmembrane receptor tyrosine kinase. Upon EGF-binding, EGFR undergoes conformational changes to dimerize, resulting in kinase activation and autophosphorylation and downstream signaling. Tyrosine kinase inhibitors (TKIs) have been used to treat lung cancer by inhibiting EGFR phosphorylation. Previously, we demonstrated that EGFR sialylation suppresses its dimerization and phosphorylation. In this report, we further investigated the effect of sialylation on the phosphorylation profile of EGFR in TKI-sensitive and TKI-resistant cells. Sialylation was induced in cancer progression to inhibit the association of EGFR with EGF and the subsequent autophosphorylation. In the absence of EGF the TKI-resistant EGFR mutant (L858R/T790M) had a higher degree of sialylation and phosphorylation at Y1068, Y1086, and Y1173 than the TKI-sensitive EGFR. In addition, although sialylation in the TKI-resistant mutants suppresses EGFR tyrosine phosphorylation, with the most significant effect on the Y1173 site, the sialylation effect is not strong enough to stop cancer progression by inhibiting the phosphorylation of these three sites. These findings were supported further by the observation that the L858R/T790M EGFR mutant, when treated with sialidase or sialyltransferase inhibitor, showed an increase in tyrosine phosphorylation, and the sensitivity of the corresponding resistant lung cancer cells to gefitinib was reduced by desialylation and was enhanced by sialylation. PMID:25971727

  1. Lewis Incubator for Technology (LIFT)

    NASA Technical Reports Server (NTRS)

    Zeman, Wayne P.; King, Joseph B.; Jankura, Richard E., Jr.

    2004-01-01

    This report summarizes the work done to operate the Lewis Incubator for Technology for the period October 2000 through September 2004. The Lewis Incubator helped the startup and growth of technology based businesses with the potential to incorporate technology from the NASA Glenn Research Center.

  2. Investigation of ovarian cancer associated sialylation changes in N-linked glycopeptides by quantitative proteomics

    PubMed Central

    2012-01-01

    Background In approximately 80% of patients, ovarian cancer is diagnosed when the patient is already in the advanced stages of the disease. CA125 is currently used as the marker for ovarian cancer; however, it lacks specificity and sensitivity for detecting early stage disease. There is a critical unmet need for sensitive and specific routine screening tests for early diagnosis that can reduce ovarian cancer lethality by reliably detecting the disease at its earliest and treatable stages. Results In this study, we investigated the N-linked sialylated glycopeptides in serum samples from healthy and ovarian cancer patients using Lectin-directed Tandem Labeling (LTL) and iTRAQ quantitative proteomics methods. We identified 45 N-linked sialylated glycopeptides containing 46 glycosylation sites. Among those, ten sialylated glycopeptides were significantly up-regulated in ovarian cancer patients’ serum samples. LC-MS/MS analysis of the non-glycosylated peptides from the same samples, western blot data using lectin enriched glycoproteins of various ovarian cancer type samples, and PNGase F (+/−) treatment confirmed the sialylation changes in the ovarian cancer samples. Conclusion Herein, we demonstrated that several proteins are aberrantly sialylated in N-linked glycopeptides in ovarian cancer and detection of glycopeptides with abnormal sialylation changes may have the potential to serve as biomarkers for ovarian cancer. PMID:22856521

  3. [Dementia with Lewy bodies].

    PubMed

    Orimo, Satoshi

    2016-03-01

    It is important to differentiate dementia with Lewy bodies (DLB) and other dementia, especially Alzheimer disease (AD), because the medical treatment, management, and the prognosis of these diseases are different. In regard to clinical features, DLB patients have relatively mild memory disturbance, fluctuating cognition, more severe disturbances of attention, executive function, visuospacial function, visual hallucination, depression, autonomic symptoms, REM sleep behavior disorder, and idiopathic parkinsonism compared to AD patients. In regard to imaging tools, DLB patients have milder atrophy of medial temporal lobe by brain MRI, reduced occipital activity by SPECT or PET, reduced MIBG uptake by MIBG cardiac scintigraphy, and low dopamine transporter activity in the basal ganglia by SPECT or PET. PMID:27025091

  4. Expression of α2,6-sialic acid-containing and Lewis-active glycolipids in several types of human ovarian carcinomas

    PubMed Central

    TANAKA, KYOKO; MIKAMI, MIKIO; AOKI, DAISUKE; KIGUCHI, KAZUSHIGE; ISHIWATA, ISAMU; IWAMORI, MASAO

    2010-01-01

    To identify glycolipid antigens associated with histologically defined types of ovarian carcinomas, we determined the amounts of α2,6-sialyl and Lewis-active glycolipids, the specific activities of the α2,3- and α2,6-sialyltransferases, and the gene expression of sugar transferases in mucinous and serous cystadenocarcinoma, clear cell adenocarcinoma and endometrioid carcinoma tissues and cell lines derived from them. α2,6-sialyl glycolipid IV6NeuAcα-nLc4Cer detected with a newly developed monoclonal antibody, Y916, was present in 5/7 serous cystadenocarcinoma cases in relatively higher amounts than those in the other carcinoma tissues. On the other hand, the amounts of Lewis-active glycolipids in serous cystadenocarcinoma tissues were lower than those in the other carcinoma tissues. No correlation was observed between the structures of Lewis glycolipids and the histological classification. The gene expression of α2,3- and α2,6-sialyltransferases and α1,3/4-fucosyltransferase for the synthesis of Lewis-active glycolipids was not positively correlated with the amounts of the respective glycolipids, probably due to the epigenetic regulation of transferases in the overall metabolic pathways for lacto-series glycolipids. However, the amounts of GM3 and GD3 with short carbohydrate chains correlated with the relative intensities of GM3 and GD3 synthase gene expression, respectively. Among ovarian carcinoma-derived cell lines, the serous cystadenocarcinoma-derived ones exhibited a lower frequency of Lewis-active glycolipid expression than the other carcinoma-derived ones, which was similar to that in the respective tissues. Thus, malignancy-related Lewis-active glycolipids were shown to be regulated in different modes in ovarian serous cystadenocarcinomas and the other carcinomas. PMID:22870113

  5. Lewy body disease and dementia with Lewy bodies

    PubMed Central

    KOSAKA, Kenji

    2014-01-01

    In 1976 we reported our first autopsied case with diffuse Lewy body disease (DLBD), the term of which we proposed in 1984. We also proposed the term “Lewy body disease” (LBD) in1980. Subsequently, we classified LBD into three types according to the distribution pattern of Lewy bodies: a brain stem type, a transitional type and a diffuse type. Later, we added the cerebral type. As we have proposed since 1980, LBD has recently been used as a generic term to include Parkinson’s disease (PD), Parkinson’s disease with dementia (PDD) and dementia with Lewy bodies (DLB), which was proposed in 1996 on the basis of our reports of DLBD. DLB is now known to be the second most frequent dementia following Alzheimer’s disease (AD). In this paper we introduce our studies of DLBD and LBD. PMID:25311140

  6. A novel sialyl LeX expression score as a potential prognostic tool in colorectal cancer

    PubMed Central

    2012-01-01

    Background Treatment decisions in colorectal cancer subsequent to surgery are based mainly on the TNM system. There is a need to establish novel prognostic markers based on the molecular characterization of tumor cells. Evidence exists that sialyl LeX expression is correlated with an unfavorable outcome in colorectal cancer. The aim of this study was to establish a simple sialyl LeX staining score and to determine a potential correlation with the prognosis in a series of advanced colorectal carcinoma patients. Methods In order to implement routine use of sialyl LeX immunohistology, we established a new, easily reproducible score and defined a cutoff which discriminated groups with better or worse outcome, respectively. We then correlated sialyl LeX expression of 215 UICC stage III and IV patients with disease-free and cancer-related survival. Results A five-stage score could be established based on automated immunohistochemical stainings. Using a statistical model, we calculated a cutoff to discriminate between weak and strong staining positivity of sialyl LeX. Patients with strong positive specimens had a worse cancer-related survival (P = 0.004) but no difference was observed for disease-free survival (P = 0.352). Conclusions These results demonstrate a strong correlation between high sialyl LeX-expression in colorectal carcinomas and cancer-related survival. Our highly standardized and easy-to-use staining score is suitable for routine use and hence it could be recommended to evaluate sialyl LeX-expression as part of the standard histopathological analysis of colorectal carcinomas and to validate the score prospectively based on a larger population. PMID:22621806

  7. The Role of Sialyl-Tn in Cancer

    PubMed Central

    Munkley, Jennifer

    2016-01-01

    Activation of an aberrant glycosylation pathway in cancer cells can lead to expression of the onco-foetal sialyl-Tn (sTn) antigen. STn is a truncated O-glycan containing a sialic acid α-2,6 linked to GalNAc α-O-Ser/Thr and is associated with an adverse outcome and poor prognosis in cancer patients. The biosynthesis of the sTn antigen has been linked to the expression of the sialytransferase ST6GalNAc1, and also to mutations in and loss of heterozygosity of the COSMC gene. sTn neo- or over-expression occurs in many types of epithelial cancer including gastric, colon, breast, lung, oesophageal, prostate and endometrial cancer. sTn is believed to be carried by a variety of glycoproteins and may influence protein function and be involved in tumour development. This review discusses how the role of sTn in cancer development and tumour cell invasiveness might be organ specific and occur through different mechanisms depending on each cancer type or subtype. As the sTn-antigen is expressed early in carcinogenesis targeting sTn in cancer may enable the targeting of tumours from the earliest stage. PMID:26927062

  8. Capillary electrophoresis of sialylated oligosaccharides in milk from different species.

    PubMed

    Monti, Lucia; Cattaneo, Tiziana Maria Piera; Orlandi, Mario; Curadi, Maria Claudia

    2015-08-28

    Oligosaccharides are relevant components of human milk, which have been quite well studied for their pre-biotic effect and their capacity in stimulating the immune system. Since oligosaccharides from milk of non-human mammals received so far less attention, the aim of this work was the application of capillary electrophoresis (CE) for the analysis of sialylated oligosaccharides in cow, goat and equine (mare and donkey) milk to possibly identify potential sources of oligosaccharides to use as health promoting ingredients in functional foods. Human milk was used as reference milk. A recent CE technique was applied to resolve and quantify 3-sialyllactose (3-SL), 6-sialyllactose (6-SL) and disialyl-lacto-N-tetraose (DSLNT). Analysis of non-human milk samples confirmed differences among species and individuals: DSLNT, which was the most abundant compound in human milk (455-805μg/mL) was missing in most of the samples. In most cases, 3-SL showed to be the most concentrated of the quantified analytes, with values ranging from 12 to 77μg/mL. PMID:26228851

  9. An interview with Lewis Wolpert.

    PubMed

    Wolpert, Lewis; Vicente, Catarina

    2015-08-01

    Lewis Wolpert is a retired developmental biologist who, over his long career, has made many important contributions to the field, from his French Flag model and the concept of positional information to the famous quote that it is "not birth, marriage or death, but gastrulation which is truly the most important time in your life." In addition to his scientific contributions, Lewis is also a prolific writer, from the textbook 'Developmental Biology' to books about popular science, religion and his battle with depression. Although born in South Africa, it was in the United Kingdom that Lewis spent most of his scientific career. We met Lewis at the Spring Meeting of the British Society for Developmental Biology, where he was awarded the Waddington Medal. PMID:26243866

  10. Significance of Lewis phenotyping using saliva and gastric tissue: comparison with the Lewis phenotype inferred from Lewis and secretor genotypes.

    PubMed

    Hong, Yun Ji; Hwang, Sang Mee; Kim, Taek Soo; Song, Eun Young; Park, Kyoung Un; Song, Junghan; Han, Kyou-Sup

    2014-01-01

    Lewis phenotypes using various types of specimen were compared with the Lewis phenotype predicted from Lewis and Secretor genotypes. This is the first logical step in explaining the association between the Lewis expression and Helicobacter pylori. We performed a study of the followings on 209 patients who underwent routine gastroscopy: erythrocyte and saliva Lewis phenotyping, gastric Lewis phenotyping by the tissue array, and the Lewis and Secretor genes genotyping. The results of phenotyping were as follows [Le(a-b-), Le(a+b-), Le(a-b+), and Le(a+b+), respectively, in order]: erythrocyte (12.4%, 25.8%, 61.2%, and 0.5%); saliva (2.4%, 27.3%, 70.3%, and 0.0%); gastric mucosa (8.1%, 6.7%, 45.5%, and 39.7%). The frequency of Le, le (59/508) , le (59/1067) , and le (59) alleles was 74.6%, 21.3%, 3.1%, and 1.0%, respectively, among 418 alleles. The saliva Lewis phenotype was completely consistent with the Lewis phenotype inferred from Lewis and Secretor genotypes, but that of gastric mucosa could not be predicted from genotypes. Lewis phenotyping using erythrocytes is only adequate for transfusion needs. Saliva testing for the Lewis phenotype is a more reliable method for determining the peripheral Lewis phenotype of an individual and the gastric Lewis phenotype must be used for the study on the association between Helicobacter pylori and the Lewis phenotype. PMID:24783214

  11. Dementia with Lewy bodies

    PubMed Central

    Graff-Radford, Jonathan; Murray, Melissa E.; Lowe, Val J.; Boeve, Bradley F.; Ferman, Tanis J.; Przybelski, Scott A.; Lesnick, Timothy G.; Senjem, Matthew L.; Gunter, Jeffrey L.; Smith, Glenn E.; Knopman, David S.; Jack, Clifford R.; Dickson, Dennis W.; Petersen, Ronald C.

    2014-01-01

    Objectives: To investigate clinical, imaging, and pathologic associations of the cingulate island sign (CIS) in dementia with Lewy bodies (DLB). Methods: We retrospectively identified and compared patients with a clinical diagnosis of DLB (n = 39); patients with Alzheimer disease (AD) matched by age, sex, and education (n = 39); and cognitively normal controls (n = 78) who underwent 18F-fluorodeoxyglucose (FDG) and C11 Pittsburgh compound B (PiB)-PET scans. Among these patients, we studied those who came to autopsy and underwent Braak neurofibrillary tangle (NFT) staging (n = 10). Results: Patients with a clinical diagnosis of DLB had a higher ratio of posterior cingulate to precuneus plus cuneus metabolism, cingulate island sign (CIS), on FDG-PET than patients with AD (p < 0.001), a finding independent of β-amyloid load on PiB-PET (p = 0.56). Patients with CIS positivity on visual assessment of FDG-PET fit into the group of high- or intermediate-probability DLB pathology and received clinical diagnosis of DLB, not AD. Higher CIS ratio correlated with lower Braak NFT stage (r = −0.96; p < 0.001). Conclusions: Our study found that CIS on FDG-PET is not associated with fibrillar β-amyloid deposition but indicates lower Braak NFT stage in patients with DLB. Identifying biomarkers that measure relative contributions of underlying pathologies to dementia is critical as neurotherapeutics move toward targeted treatments. PMID:25056580

  12. Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity.

    PubMed

    Quast, Isaak; Keller, Christian W; Maurer, Michael A; Giddens, John P; Tackenberg, Björn; Wang, Lai-Xi; Münz, Christian; Nimmerjahn, Falk; Dalakas, Marinos C; Lünemann, Jan D

    2015-11-01

    IgG molecules exert both pro- and antiinflammatory effector functions based on the composition of the fragment crystallizable (Fc) domain glycan. Sialylated IgG Fc domains have antiinflammatory properties that are attributed to their ability to increase the activation threshold of innate effector cells to immune complexes by stimulating the upregulation of the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we report that IgG Fc sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity (CDC). Fc sialylation of a CD20-targeting antibody had no impact on antibody-dependent cellular cytotoxicity and did not change the affinity of the antibody for activating Fcγ receptors. In contrast, the presence of sialic acid abrogated the increased binding of C1q to Fc-galactosylated IgG1 and resulted in decreased levels of C3b deposition on the cell surface. Similar to monoclonal antibodies, sialic acid inhibited the increased C1q binding to galactosylated Fc fragments in human polyclonal IgG. In sera derived from patients with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system in which humoral immune responses mediate tissue damage, induction of IgG Fc sialylation was associated with clinical disease remission. Thus, impairment of CDC represents an FcγR-independent mechanism by which Fc-sialylated glycovariants might limit proinflammatory IgG effector functions. PMID:26436649

  13. Sialylation of IgG Fc domain impairs complement-dependent cytotoxicity

    PubMed Central

    Quast, Isaak; Keller, Christian W.; Maurer, Michael A.; Giddens, John P.; Tackenberg, Björn; Wang, Lai-Xi; Münz, Christian; Nimmerjahn, Falk; Dalakas, Marinos C.; Lünemann, Jan D.

    2015-01-01

    IgG molecules exert both pro- and antiinflammatory effector functions based on the composition of the fragment crystallizable (Fc) domain glycan. Sialylated IgG Fc domains have antiinflammatory properties that are attributed to their ability to increase the activation threshold of innate effector cells to immune complexes by stimulating the upregulation of the inhibitory Fcγ receptor IIB (FcγRIIB). Here, we report that IgG Fc sialylation of human monoclonal IgG1 molecules impairs their efficacy to induce complement-mediated cytotoxicity (CDC). Fc sialylation of a CD20-targeting antibody had no impact on antibody-dependent cellular cytotoxicity and did not change the affinity of the antibody for activating Fcγ receptors. In contrast, the presence of sialic acid abrogated the increased binding of C1q to Fc-galactosylated IgG1 and resulted in decreased levels of C3b deposition on the cell surface. Similar to monoclonal antibodies, sialic acid inhibited the increased C1q binding to galactosylated Fc fragments in human polyclonal IgG. In sera derived from patients with chronic inflammatory demyelinating polyneuropathy, an autoimmune disease of the peripheral nervous system in which humoral immune responses mediate tissue damage, induction of IgG Fc sialylation was associated with clinical disease remission. Thus, impairment of CDC represents an FcγR-independent mechanism by which Fc-sialylated glycovariants might limit proinflammatory IgG effector functions. PMID:26436649

  14. Sialylation of Integrin beta1 is Involved in Radiation-Induced Adhesion and Migration in Human Colon Cancer Cells

    SciTech Connect

    Lee, Minyoung; Lee, Hae-June; Seo, Woo Duck; Park, Ki Hun; Lee, Yun-Sil

    2010-04-15

    Purpose: Previously, we reported that radiation-induced ST6 Gal I gene expression was responsible for an increase of integrin beta1 sialylation. In this study, we have further investigated the function of radiation-mediated integrin beta1 sialylation in colon cancer cells. Methods and Materials: We performed Western blotting and lectin affinity assay to analyze the expression and level of sialylated integrin beta1. After exposure to ionizing radiation (IR), adhesion and migration of cells were measured by in vitro adhesion and migration assay. Results: IR increased sialylation of integrin beta1 responsible for its increased protein stability and adhesion and migration of colon cancer cells. However, for cells with an N-glycosylation site mutant of integrin beta1 located on the I-like domain (Mu3), these effects were dramatically inhibited. In addition, integrin beta1-mediated radioresistance was not observed in cells containing this mutant. When sialylation of integrin beta1 was targeted with a sulfonamide chalcone compound, inhibition of radiation-induced sialylation of integrin beta1 and inhibition of radiation-induced adhesion and migration occurred. Conclusion: The increase of integrin beta1 sialylation by ST6 Gal I is critically involved in radiation-mediated adhesion and migration of colon cancer cells. From these findings, integrin beta1 sialylation may be a novel target for overcoming radiation-induced survival, especially radiation-induced adhesion and migration.

  15. Pseudomonas aeruginosa pyocyanin modulates mucin glycosylation with sialyl-Lewisx to increase binding to airway epithelial cells

    PubMed Central

    Choi, Woosuk; Choe, Shawn; Miao, Jinfeng; Xu, Ying; Powell, Rebecca; Lin, Jingjun; Kuang, Zhizhou; Gaskins, H Rex; Lau, Gee W.

    2015-01-01

    Cystic fibrosis (CF) patients battle life-long pulmonary infections with the respiratory pathogen Pseudomonas aeruginosa (PA). An overabundance of mucus in CF airways provides a favorable niche for PA growth. When compared to that of non-CF individuals, mucus of CF airways is enriched in sialyl-Lewisx, a preferred binding receptor for PA. Notably, the levels of sialyl-Lewisx directly correlate with infection severity in CF patients. However, the mechanism by which PA causes increased sialylation remains uncharacterized. In this study, we examined the ability of PA virulence factors to modulate sialyl-Lewisx modification in airway mucins. We found pyocyanin (PCN) to be a potent inducer of sialyl-Lewisx in both mouse airways and in primary and immortalized CF and non-CF human airway epithelial cells. PCN increased the expression of C2/4GnT and ST3Gal-IV, two of the glycosyltransferases responsible for the stepwise biosynthesis of sialyl-Lewisx, through a TNF-α-mediated phosphoinositol-specific phospholipase C (PI-PLC) dependent pathway. Furthermore, PA bound more efficiently to airway epithelial cells pre-exposed to PCN through a flagellar cap-dependent manner. Importantly, antibodies against sialyl-Lewisx and anti-TNF-α attenuated PA binding. These results indicate that PCN secretes PCN to induce a favorable environment for chronic colonization of CF lungs by increasing the glycosylation of airway mucins with sialyl-Lewisx. PMID:26555707

  16. Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity

    PubMed Central

    2016-01-01

    Many mechanisms have been proposed for how heightened aerobic glycolytic metabolism fuels cancer pathogenicity, but there are still many unexplored pathways. Here, we have performed metabolomic profiling to map glucose incorporation into metabolic pathways upon transformation of mammary epithelial cells by 11 commonly mutated human oncogenes. We show that transformation of mammary epithelial cells by oncogenic stimuli commonly shunts glucose-derived carbons into synthesis of sialic acid, a hexosamine pathway metabolite that is converted to CMP-sialic acid by cytidine monophosphate N-acetylneuraminic acid synthase (CMAS) as a precursor to glycoprotein and glycolipid sialylation. We show that CMAS knockdown leads to elevations in intracellular sialic acid levels, a depletion of cellular sialylation, and alterations in the expression of many cancer-relevant genes to impair breast cancer pathogenicity. Our study reveals the heretofore unrecognized role of sialic acid metabolism and protein sialylation in regulating the expression of genes that maintain breast cancer pathogenicity. PMID:27380425

  17. Protein Sialylation Regulates a Gene Expression Signature that Promotes Breast Cancer Cell Pathogenicity.

    PubMed

    Kohnz, Rebecca A; Roberts, Lindsay S; DeTomaso, David; Bideyan, Lara; Yan, Peter; Bandyopadhyay, Sourav; Goga, Andrei; Yosef, Nir; Nomura, Daniel K

    2016-08-19

    Many mechanisms have been proposed for how heightened aerobic glycolytic metabolism fuels cancer pathogenicity, but there are still many unexplored pathways. Here, we have performed metabolomic profiling to map glucose incorporation into metabolic pathways upon transformation of mammary epithelial cells by 11 commonly mutated human oncogenes. We show that transformation of mammary epithelial cells by oncogenic stimuli commonly shunts glucose-derived carbons into synthesis of sialic acid, a hexosamine pathway metabolite that is converted to CMP-sialic acid by cytidine monophosphate N-acetylneuraminic acid synthase (CMAS) as a precursor to glycoprotein and glycolipid sialylation. We show that CMAS knockdown leads to elevations in intracellular sialic acid levels, a depletion of cellular sialylation, and alterations in the expression of many cancer-relevant genes to impair breast cancer pathogenicity. Our study reveals the heretofore unrecognized role of sialic acid metabolism and protein sialylation in regulating the expression of genes that maintain breast cancer pathogenicity. PMID:27380425

  18. 100 years of Lewy pathology.

    PubMed

    Goedert, Michel; Spillantini, Maria Grazia; Del Tredici, Kelly; Braak, Heiko

    2013-01-01

    In 1817, James Parkinson described the symptoms of the shaking palsy, a disease that was subsequently defined in greater detail, and named after Parkinson, by Jean-Martin Charcot. Parkinson expected that the publication of his monograph would lead to a rapid elucidation of the anatomical substrate of the shaking palsy; in the event, this process took almost a century. In 1912, Fritz Heinrich Lewy identified the protein aggregates that define Parkinson disease (PD) in some brain regions outside the substantia nigra. In 1919, Konstantin Nikolaevich Tretiakoff found similar aggregates in the substantia nigra and named them after Lewy. In the 1990s, α-synuclein was identified as the main constituent of the Lewy pathology, and its aggregation was shown to be central to PD, dementia with Lewy bodies, and multiple system atrophy. In 2003, a staging scheme for idiopathic PD was introduced, according to which α-synuclein pathology originates in the dorsal motor nucleus of the vagal nerve and progresses from there to other brain regions, including the substantia nigra. In this article, we review the relevance of Lewy's discovery 100 years ago for the current understanding of PD and related disorders. PMID:23183883

  19. Humoral response against sialyl-Le(a) glycosylated protein species in esophageal cancer: Insights for immunoproteomic studies.

    PubMed

    Fernandes, Elisabete; Peixoto, Andreia; Neves, Manuel; Afonso, Luís Pedro; Santos, Lúcio Lara; Ferreira, José Alexandre

    2015-12-01

    Esophageal cancers (ECs) show poor prognosis and decreased overall survival due to late diagnosis and ineffective therapeutics, urging the introduction of novel biomarkers to aid disease management. The levels of sialyl-Lewis(a) antigen (sLe(a) ) are frequently increased in digestive tumours, which has been explored in serological non-invasive prognostication (CA19-9 test); however, with low sensitivity and specificity. Autoantibodies against cancer antigens are considered the next generation biomarkers, as they are present in circulation long before tumour-associated proteins. Based on these observations we have mined the serum of EC patients (n = 7) for antibodies against sLe(a) -glycosylated protein species. All EC were positive for sLe(a) , irrespectively of their histological nature but only two patients showed elevated CA19-9. Moreover, IgG titers, with emphasis on IgG1, were elevated in EC patients in comparison to the control group. SLe(a) -glycoproteins were then extracted from tumours of patients with negative CA19-9, isolated by immunoprecipitation and blotted with patients IgG. Autoantibodies against sLe(a) -glycosylated proteins were detected in all cases. Different SLe(a) -glycoproteins were observed for tumours of distinct histological natures, which now require identification and validation in larger patient sets. This preliminary data suggests that antoantibodies against sLe(a) glycosylated proteins hold potential for non-invasive diagnosis in CA19-9 negative cases and sets the rational for future immunoproteomic studies envisaging highly specific EC biomarkers. PMID:26333169

  20. Sialylation of vitronectin regulates stress fiber formation and cell spreading of dermal fibroblasts via a heparin-binding site.

    PubMed

    Miyamoto, Yasunori; Tanabe, Mio; Date, Kimie; Sakuda, Kanoko; Sano, Kotone; Ogawa, Haruko

    2016-04-01

    Vitronectin (VN) plays an important role in tissue regeneration. We previously reported that VN from partial hepatectomized (PH) rats results in a decrease of sialylation of VN and de-sialylation of VN decreases the cell spreading of hepatic stellate cells. In this study, we analyzed the mechanism how sialylation of VN regulates the properties of mouse primary cultured dermal fibroblasts (MDF) and a dermal fibroblast cell line, Swiss 3T3 cells. At first, we confirmed that VN from PH rats or de-sialylated VN also decreased cell spreading in MDF and Swiss 3T3 cells. The de-sialylation suppressed stress fiber formation in Swiss 3T3 cells. Next, we analyzed the effect of the de-sialylation of VN on stress fiber formation in Swiss 3T3 cells. RGD peptide, an inhibitor for a cell binding site of VN, did not affect the cell attachment of Swiss 3T3 cells on untreated VN but significantly decreased it on de-sialylated VN, suggesting that the de-sialylation attenuates the binding activity of an RGD-independent binding site in VN. To analyze a candidate RGD-independent binding site, an inhibition experiment of stress fiber formation for a heparin binding site was performed. The addition of heparin and treatment of cells with heparinase decreased stress fiber formation in Swiss 3T3 cells. Furthermore, de-sialylation increased the binding activity of VN to heparin, as detected by surface plasmon resonance (SPR). These results demonstrate that sialylation of VN glycans regulates stress fiber formation and cell spreading of dermal fibroblast cells via a heparin binding site. PMID:26979432

  1. Sialylated immunoglobulin G can neutralize influenza virus infection through receptor mimicry

    PubMed Central

    Zhao, Conghui; Liu, Xingmu; Zhang, Zaiping; Li, Tongfei; Sun, Ruiman; Gu, Huan; Gu, Jiang

    2016-01-01

    Influenza viruses possess a great threat to human health, but there is still no effective drug to deal with the outbreak of possible new influenza subtypes. In this study, we first fractionated sialylated immunoglobulin G (IgG), mainly Fab sialylated fraction, with sambucus nigra agglutinin affinity chromatography. We then demonstrated that sialylated IgG possessed more effective neutralizing activity against 2009 A (H1N1) subtype than that of IgG mixture, and sialosides on the Fab is crucial in this neutralization reaction as when such residues were removed with neuraminidase A digestion the blocking effect was significantly reduced. It appears that sialic acid residues attached to Fab could serve as binding moieties to receptor binding site of influenza virus. These findings indicate that sialylated IgG probably is an effective anti-influenza broad-spectrum drug utilizing its receptor mimicry to competitively inhibit the attachment of influenza viruses with sialic acid receptors on target cells. This property would be particularly useful if it can be applied to prevent newly emerged influenza virus strain infections in future epidemics. PMID:26870994

  2. T cell–independent B cell activation induces immunosuppressive sialylated IgG antibodies

    PubMed Central

    Hess, Constanze; Winkler, André; Lorenz, Alexandra K.; Holecska, Vivien; Blanchard, Véronique; Eiglmeier, Susanne; Schoen, Anna-Lena; Bitterling, Josephine; Stoehr, Alexander D.; Petzold, Dominique; Schommartz, Tim; Mertes, Maria M.M.; Schoen, Carolin T.; Tiburzy, Ben; Herrmann, Anne; Köhl, Jörg; Manz, Rudolf A.; Madaio, Michael P.; Berger, Markus; Wardemann, Hedda; Ehlers, Marc

    2013-01-01

    Antigen-specific Abs are able to enhance or suppress immune responses depending on the receptors that they bind on immune cells. Recent studies have shown that pro- or antiinflammatory effector functions of IgG Abs are also regulated through their Fc N-linked glycosylation patterns. IgG Abs that are agalactosylated (non-galactosylated) and asialylated are proinflammatory and induced by the combination of T cell–dependent (TD) protein antigens and proinflammatory costimulation. Sialylated IgG Abs, which are immunosuppressive, and Tregs are produced in the presence of TD antigens under tolerance conditions. T cell–independent (TI) B cell activation via B cell receptor (BCR) crosslinking through polysaccharides or via BCR and TLR costimulation also induces IgG Abs, but the Fc glycosylation state of these Abs is unknown. We found in mouse experiments that TI immune responses induced suppressive sialylated IgGs, in contrast to TD proinflammatory Th1 and Th17 immune responses, which induced agalactosylated and asialylated IgGs. Transfer of low amounts of antigen-specific sialylated IgG Abs was sufficient to inhibit B cell activation and pathogenic immune reactions. These findings suggest an immune regulatory function for TI immune responses through the generation of immunosuppressive sialylated IgGs and may provide insight on the role of TI immune responses during infection, vaccination, and autoimmunity. PMID:23979161

  3. Synthesis of oxime-linked mucin mimics containing thetumor-related TN and sialyl TN antigens

    SciTech Connect

    Marcaurelle, Lisa A.; Shin, Youngsook; Goon, Scarlett; Bertozzi,Carolyn R.

    2001-08-21

    The synthesis of oxime-linked mucin mimics was accomplished via the incorporation of multiple ketone residues into a peptide followed by reaction with aminooxy sugars corresponding to the tumor-related T{sub N} and sialyl T{sub N} (ST{sub N}) antigens.

  4. Sialylated immunoglobulin G can neutralize influenza virus infection through receptor mimicry.

    PubMed

    Huang, Tao; Chen, Xueling; Zhao, Conghui; Liu, Xingmu; Zhang, Zaiping; Li, Tongfei; Sun, Ruiman; Gu, Huan; Gu, Jiang

    2016-03-29

    Influenza viruses possess a great threat to human health, but there is still no effective drug to deal with the outbreak of possible new influenza subtypes. In this study, we first fractionated sialylated immunoglobulin G (IgG), mainly Fab sialylated fraction, with sambucus nigra agglutinin affinity chromatography. We then demonstrated that sialylated IgG possessed more effective neutralizing activity against 2009 A (H1N1) subtype than that of IgG mixture, and sialosides on the Fab is crucial in this neutralization reaction as when such residues were removed with neuraminidase A digestion the blocking effect was significantly reduced. It appears that sialic acid residues attached to Fab could serve as binding moieties to receptor binding site of influenza virus. These findings indicate that sialylated IgG probably is an effective anti-influenza broad-spectrum drug utilizing its receptor mimicry to competitively inhibit the attachment of influenza viruses with sialic acid receptors on target cells. This property would be particularly useful if it can be applied to prevent newly emerged influenza virus strain infections in future epidemics. PMID:26870994

  5. Sialylation Facilitates the Maturation of Mammalian Sperm and Affects Its Survival in Female Uterus.

    PubMed

    Ma, Xue; Pan, Qian; Feng, Ying; Choudhury, Biswa P; Ma, Qianhong; Gagneux, Pascal; Ma, Fang

    2016-06-01

    Establishment of adequate levels of sialylation is crucial for sperm survival and function after insemination; however, the mechanism for the addition of the sperm sialome has not been identified. Here, we report evidence for several different mechanisms that contribute to the establishment of the mature sperm sialome. Directly quantifying the source of the nucleotide sugar CMP-beta-N-acetylneuraminic acid in epididymal fluid indicates that transsialylation occurs in the upper epididymis. Western blots for the low-molecular-mass sialoglycoprotein (around 20-50 kDa) in C57BL/6 mice epididymal fluid reflect that additional sialome could be obtained by glycosylphosphatidylinositol-anchored sialoglycopeptide incorporation during epididymal transit in the caput of the epididymis. Additionally, we found that in Cmah (CMP-N-acetylneuraminic acid hydroxylase)-/- transgenic mice, epididymal sperm obtained sialylated-CD52 from seminal vesicle fluid (SVF). Finally, we used Gfp (green fluorescent protein)+/+ mouse sperm to test the role of sialylation on sperm for protection from female leukocyte attack. There is very low phagocytosis of the epididymal sperm when compared to that of sperm coincubated with SVF. Treating sperm with Arthrobacter ureafaciens sialidase (AUS) increased phagocytosis even further. Our results highlight the different mechanisms of increasing sialylation, which lead to the formation of the mature sperm sialome, as well as reveal the sialome's function in sperm survival within the female genital tract. PMID:27075617

  6. Sialylation of anti-histone immunoglobulin G autoantibodies determines their capabilities to participate in the clearance of late apoptotic cells.

    PubMed

    Magorivska, I; Muñoz, L E; Janko, C; Dumych, T; Rech, J; Schett, G; Nimmerjahn, F; Bilyy, R; Herrmann, M

    2016-04-01

    The Fc portion of immunoglobulin (Ig)G harbours a single glycosylation site. Glycan sialylation is critical for structure and for certain effector functions of IgG. Anti-histone IgG of patients with systemic lupus erythematosus is reportedly responsible for the recruitment of polymorphonuclear cells (PMN) to the clearance of apoptotic cells. Autoantibodies decorating secondary necrotic cells (SNEC) induce proinflammatory responses after activation of blood-borne phagocytes. Analysing the sialylation status of affinity-purified anti-histone IgG in patients with systemic lupus erythematosus (SLE), we demonstrated that the anti-histone IgG was contained preferentially in the non-sialylated fraction. In functional ex-vivo phagocytosis studies, non-sialylated anti-SNEC IgG directed SNEC preferentially into PMN but did not change their cytokine secretion profiles. In contrast, sialylated IgG reduced the phagocytosis by monocytes of SNEC. Moreover, the sialylated anti-SNEC IgG was not simply anti-inflammatory, but switched the cytokine secretion profiles from interleukin (IL)-6/IL-8 to tumour necrosis factor (TNF)-α/IL-1β. Here we describe how different sialylation statuses of IgG autoantibodies contribute to the complex inflammatory network that regulates chronic inflammation. PMID:26618514

  7. Lewis & Clark: An Interdisciplinary Expedition

    ERIC Educational Resources Information Center

    Brugar, Kristy

    2004-01-01

    On January 18, 1803 President Thomas Jefferson asked Congress to fund an expedition to the source of the Missouri River. This expedition would become known as the Corps of Discovery, which would spend twenty-eight months exploring, studying, and documenting the wonders of the western frontier. Led by Captains Meriwether Lewis and William Clark,…

  8. Lewis and Clark as Naturalists.

    ERIC Educational Resources Information Center

    Smithsonian Institution, Washington, DC. National Museum of Natural History.

    Intended for use in elementary and high school education, this Web site includes a teacher's guide and three lesson plans. The site contains images of museum specimens, scientific drawings, and field photos of the plant and animal species observed by Meriwether Lewis and William Clark, along with journal excerpts, historical notes, and references…

  9. Sialylation of Outer Membrane Porin Protein D: A Mechanistic Basis of Antibiotic Uptake in Pseudomonas aeruginosa*

    PubMed Central

    Khatua, Biswajit; Vleet, Jeremy Van; Choudhury, Biswa Pronab; Chaudhry, Rama; Mandal, Chitra

    2014-01-01

    Pseudomonas aeruginosa (PA) is an environmentally ubiquitous, extracellular, opportunistic pathogen, associated with severe infections of immune-compromised host. We demonstrated earlier the presence of both α2,3- and α2,6-linked sialic acids (Sias) on PA (PA+Sias) and normal human serum is their source of Sias. PA+Sias showed decreased complement deposition and exhibited enhanced association with immune-cells through sialic acid binding immunoglobulin like lectins (Siglecs). Such Sias-siglec-9 interaction between PA+Sias and neutrophils helped to subvert host immunity. Additionally, PA+Sias showed more resistant to β-lactam antibiotics as reflected in their minimum inhibitory concentration required to inhibit the growth of 50% than PA−Sias. Accordingly, we have affinity purified sialoglycoproteins of PA+Sias. They were electrophoresed and identified by matrix-assisted laser desorption-ionization time-of-flight/time-of-flight mass spectrometry analysis. Sequence study indicated the presence of a few α2,6-linked, α2,3-linked, and both α2,3- and α2,6-linked sialylated proteins in PA. The outer membrane porin protein D (OprD), a specialized channel-forming protein, responsible for uptake of β-lactam antibiotics, is one such identified sialoglycoprotein. Accordingly, sialylated (OprD+Sias) and non-sialylated (OprD−Sias) porin proteins were separately purified by using anion exchange chromatography. Sialylation of purified OprD+Sias was confirmed by several analytical and biochemical procedures. Profiling of glycan structures revealed three sialylated N-glycans and two sialylated O-glycans in OprD+Sias. In contrast, OprD−Sias exhibit only one sialylated N-glycans. OprD−Sias interacts with β-lactam antibiotics more than OprD+Sias as demonstrated by surface plasmon resonance study. Lyposome-swelling assay further exhibited that antibiotics have more capability to penetrate through OprD−Sias purified from four clinical isolates of PA. Taken together, it

  10. Inhibition of Chemokine (C-C Motif) Receptor 7 Sialylation Suppresses CCL19-Stimulated Proliferation, Invasion and Anti-Anoikis

    PubMed Central

    Su, Mei-Lin; Chang, Tsung-Ming; Chiang, Chi-Hsiang; Chang, Han-Chen; Hou, Ming-Feng; Li, Wen-Shan; Hung, Wen-Chun

    2014-01-01

    Chemokine (C-C motif) receptor 7 (CCR7) is involved in lymph-node homing of naive and regulatory T cells and lymphatic metastasis of cancer cells. Sialic acids comprise a group of monosaccharide units that are added to the terminal position of the oligosaccharide chain of glycoproteins by sialyation. Recent studies suggest that aberrant sialylation of receptor proteins contributes to proliferation, motility, and drug resistance of cancer cells. In this study, we addressed whether CCR7 is a sialylated receptor protein and tried to elucidate the effect of sialylation in the regulation of signal transduction and biological function of CCR7. Our results demonstrated that α-2, 3-sialyltransferase which catalyze sialylation reaction in vivo was overexpressed in breast tumor tissues and cell lines. Lectin blot analysis clearly demonstrated that CCR7 receptor was sialyated in breast cancer cells. Chemokine (C-C motif) ligand 19 (CCL19), the cognate ligand for CCR7, induced the activation of extracellular signal-regulated kinase (ERK) and AKT signaling and increased the expression of cell cycle regulatory proteins and proliferation of breast cancer cells. When cells were pre-treated with a sialyltransferase inhibitor AL10 or sialidase, CCL19-induced cell growth was significantly suppressed. CCL19 also increased invasion and prevented anoikis by up-regulating pro-survival proteins Bcl-2 and Bcl-xL. Inhibition of sialylation by AL10 totally abolished these effects. Finally, we showed that AL10 inhibited tumorigenicity of breast cancer in experimental animals. Taken together, we demonstrate for the first time that CCR7 receptor is a sialylated protein and sialylation is important for the paracrine stimulation by its endogenous ligand CCL19. In addition, inhibition of aberrant sialylation of CCR7 suppresses proliferation and invasion and triggers anoikis in breast cancer cells. Targeting of sialylation enzymes may be a novel strategy for breast cancer treatment. PMID:24915301

  11. Understanding and Controlling Sialylation in a CHO Fc-Fusion Process

    PubMed Central

    Lewis, Amanda M.; Croughan, William D.; Aranibar, Nelly; Lee, Alison G.; Warrack, Bethanne; Abu-Absi, Nicholas R.; Patel, Rutva; Drew, Barry; Borys, Michael C.; Reily, Michael D.; Li, Zheng Jian

    2016-01-01

    A Chinese hamster ovary (CHO) bioprocess, where the product is a sialylated Fc-fusion protein, was operated at pilot and manufacturing scale and significant variation of sialylation level was observed. In order to more tightly control glycosylation profiles, we sought to identify the cause of variability. Untargeted metabolomics and transcriptomics methods were applied to select samples from the large scale runs. Lower sialylation was correlated with elevated mannose levels, a shift in glucose metabolism, and increased oxidative stress response. Using a 5-L scale model operated with a reduced dissolved oxygen set point, we were able to reproduce the phenotypic profiles observed at manufacturing scale including lower sialylation, higher lactate and lower ammonia levels. Targeted transcriptomics and metabolomics confirmed that reduced oxygen levels resulted in increased mannose levels, a shift towards glycolysis, and increased oxidative stress response similar to the manufacturing scale. Finally, we propose a biological mechanism linking large scale operation and sialylation variation. Oxidative stress results from gas transfer limitations at large scale and the presence of oxygen dead-zones inducing upregulation of glycolysis and mannose biosynthesis, and downregulation of hexosamine biosynthesis and acetyl-CoA formation. The lower flux through the hexosamine pathway and reduced intracellular pools of acetyl-CoA led to reduced formation of N-acetylglucosamine and N-acetylneuraminic acid, both key building blocks of N-glycan structures. This study reports for the first time a link between oxidative stress and mammalian protein sialyation. In this study, process, analytical, metabolomic, and transcriptomic data at manufacturing, pilot, and laboratory scales were taken together to develop a systems level understanding of the process and identify oxygen limitation as the root cause of glycosylation variability. PMID:27310468

  12. Modification of sialylation is associated with multidrug resistance in human acute myeloid leukemia.

    PubMed

    Ma, H; Zhou, H; Song, X; Shi, S; Zhang, J; Jia, L

    2015-02-01

    Aberrant cell surface sialylation patterns have been shown to correlate with tumor progression and metastasis. However, the role of sialylation regulation of cancer multidrug resistance (MDR) remains poorly understood. This study investigated sialylation in modification on MDR in acute myeloid leukemia (AML). Using mass spectrometry (MS) analysis, the composition profiling of sialylated N-glycans differed in three pairs of AML cell lines. Real-time PCR showed the differential expressional profiles of 20 sialyltransferase (ST) genes in the both AML cell lines and bone marrow mononuclear cells (BMMCs) of AML patients. The expression levels of ST3GAL5 and ST8SIA4 were detected, which were overexpressed in HL60 and HL60/adriamycin-resistant (ADR) cells. The altered levels of ST3GAL5 and ST8SIA4 were found in close association with the MDR phenotype changing of HL60 and HL60/ADR cells both in vitro and in vivo. Further data demonstrated that manipulation of these two genes' expression modulated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway and its downstream target thus regulated the proportionally mutative expression of P-glycoprotein (P-gp) and MDR-related protein 1 (MRP1), both of which are known to be involved in MDR. Blocking the PI3K/Akt pathway by its specific inhibitor LY294002 or by Akt small interfering RNA resulted in the reduced chemosensitivity of HL60/ADR cells. Therefore, this study indicated that sialylation involved in the development of MDR of AML cells probably through ST3GAL5 or ST8SIA4 regulating the activity of PI3K/Akt signaling and the expression of P-gp and MRP1. PMID:24531716

  13. Understanding and Controlling Sialylation in a CHO Fc-Fusion Process.

    PubMed

    Lewis, Amanda M; Croughan, William D; Aranibar, Nelly; Lee, Alison G; Warrack, Bethanne; Abu-Absi, Nicholas R; Patel, Rutva; Drew, Barry; Borys, Michael C; Reily, Michael D; Li, Zheng Jian

    2016-01-01

    A Chinese hamster ovary (CHO) bioprocess, where the product is a sialylated Fc-fusion protein, was operated at pilot and manufacturing scale and significant variation of sialylation level was observed. In order to more tightly control glycosylation profiles, we sought to identify the cause of variability. Untargeted metabolomics and transcriptomics methods were applied to select samples from the large scale runs. Lower sialylation was correlated with elevated mannose levels, a shift in glucose metabolism, and increased oxidative stress response. Using a 5-L scale model operated with a reduced dissolved oxygen set point, we were able to reproduce the phenotypic profiles observed at manufacturing scale including lower sialylation, higher lactate and lower ammonia levels. Targeted transcriptomics and metabolomics confirmed that reduced oxygen levels resulted in increased mannose levels, a shift towards glycolysis, and increased oxidative stress response similar to the manufacturing scale. Finally, we propose a biological mechanism linking large scale operation and sialylation variation. Oxidative stress results from gas transfer limitations at large scale and the presence of oxygen dead-zones inducing upregulation of glycolysis and mannose biosynthesis, and downregulation of hexosamine biosynthesis and acetyl-CoA formation. The lower flux through the hexosamine pathway and reduced intracellular pools of acetyl-CoA led to reduced formation of N-acetylglucosamine and N-acetylneuraminic acid, both key building blocks of N-glycan structures. This study reports for the first time a link between oxidative stress and mammalian protein sialyation. In this study, process, analytical, metabolomic, and transcriptomic data at manufacturing, pilot, and laboratory scales were taken together to develop a systems level understanding of the process and identify oxygen limitation as the root cause of glycosylation variability. PMID:27310468

  14. Analysis and Functional Consequences of Increased Fab-Sialylation of Intravenous Immunoglobulin (IVIG) after Lectin Fractionation

    PubMed Central

    Käsermann, Fabian; Boerema, David J.; Rüegsegger, Monika; Hofmann, Andreas; Wymann, Sandra; Zuercher, Adrian W.; Miescher, Sylvia

    2012-01-01

    It has been proposed that the anti-inflammatory effects of intravenous immunoglobulin (IVIG) might be due to the small fraction of Fc-sialylated IgG. In this study we biochemically and functionally characterized sialic acid-enriched IgG obtained by Sambucus nigra agglutinin (SNA) lectin fractionation. Two main IgG fractions isolated by elution with lactose (E1) or acidified lactose (E2) were analyzed for total IgG, F(ab’)2 and Fc-specific sialic acid content, their pattern of specific antibodies and anti-inflammatory potential in a human in vitro inflammation system based on LPS- or PHA-stimulated whole blood. HPLC and LC-MS testing revealed an increase of sialylated IgG in E1 and more substantially in the E2 fraction. Significantly, the increased amount of sialic acid residues was primarily found in the Fab region whereas only a minor increase was observed in the Fc region. This indicates preferential binding of the Fab sialic acid to SNA. ELISA analyses of a representative range of pathogen and auto-antigens indicated a skewed antibody pattern of the sialylated IVIG fractions. Finally, the E2 fraction exerted a more profound anti-inflammatory effect compared to E1 or IVIG, evidenced by reduced CD54 expression on monocytes and reduced secretion of MCP-1 (CCL2); again these effects were Fab- but not Fc-dependent. Our results show that SNA fractionation of IVIG yields a minor fraction (approx. 10%) of highly sialylated IgG, wherein the sialic acid is mainly found in the Fab region. The tested anti-inflammatory activity was associated with Fab not Fc sialylation. PMID:22675478

  15. Characterization of the specificities of human blood group H gene-specified alpha 1,2-L-fucosyltransferase toward sulfated/sialylated/fucosylated acceptors: evidence for an inverse relationship between alpha 1,2-L-fucosylation of Gal and alpha 1,6-L-fucosylation of asparagine-linked GlcNAc.

    PubMed

    Chandrasekaran, E V; Jain, R K; Larsen, R D; Wlasichuk, K; Matta, K L

    1996-07-01

    The assembly of complex structures bearing the H determinant was examined by characterizing the specificities of a cloned blood group H gene-specified alpha 1,2-L-fucosyltransferase (FT) toward a variety of sulfated, sialylated, or fucosylated Gal beta 1,3/4GlcNAc beta- or Gal beta 1,3GalNAc alpha-based acceptor structures. (a) As compared to the basic type 2, Gal beta 1,4GlcNAc beta-(K(m) = 1.67 mM), the basic type 1 was 137% active (K(m) = 0.83 mM). (b) On C-6 sulfation of Gal, type 1 became 142.1% active and type 2 became 223.0% active (K(m) = 0.45 mM). (c) On C-6 sulfation of GlcNAc, type 2 showed 33.7% activity. (d) On C-3 or C-4 fucosylation of GlcNAc, both types 1 and 2 lost activity. (e) Type 1 showed 70.8% and 5.8% activity, respectively, on C-6 and C-4 O-methylation of GlcNAc. (f) Type 1 retained 18.8% activity on alpha 2,6-sialylation of GlcNAc. (g) Terminal type 1 or 2 of extended chain had lower activity. (h) With Gal in place of GlcNAc in type 1, the activity became 43.2%. (i) Compounds with terminal alpha 1,3-linked Gal were inactive. (j) Gal beta 1,3GalNAc alpha- (the T-hapten) was approximately 0.4-fold as active as Gal beta 1,4GlcNAc beta-. (k) C-6 sulfation of Gal on the T-hapten did not affect the acceptor activity. (l) C-6 sulfation of GalNAc decreased the activity to 70%, whereas on C-6 sulfation of both Gal and GalNAc the T-hapten lost the acceptor ability. (m) C-6 sialylation of GalNAc also led to inactivity. (n) beta 1,6 branching from GalNAc of the T-hapten by a GlcNAc residue or by units such as Gal beta 1, 4GlcNAc-, Gal beta 1,4(Fuc alpha 1,3)GlcNAc-, or 3-sulfoGal beta 1,4GlcNAc- resulted in 111.9%, 282.8%, 48.3%, and 75.3% activities, respectively. (o) The enhancement of enzyme affinity by a sulfo group on C-6 of Gal was demonstrated by an increase (approximately 5-fold) in the K(m) for Gal beta 1,4GlcNAc beta 1,6(Gal beta 1,3)GalNAc alpha-O-Bn in presence of 6-sulfoGal beta 1,- 4GlcNAc beta-O-Me (3.0 mM). (p) Among the two sites in

  16. Lectin-dependent inhibition of antigen-antibody reaction: application for measuring α2,6-sialylated glycoforms of transferrin.

    PubMed

    Hoshi, Kyoka; Kariya, Yoshinobu; Nara, Kiyomitsu; Ito, Hiromi; Matsumoto, Kana; Nagae, Masamichi; Yamaguchi, Yoshiki; Nakajima, Madoka; Miyajima, Masakazu; Arai, Hajime; Kuno, Atsushi; Narimatsu, Hisashi; Shirotani, Keiro; Hashimoto, Yasuhiro

    2013-09-01

    We developed a high-throughput Enzyme-linked immunosorbent assay (ELISA) for measuring α2,6-sialylated transferrin (Tf), based on inhibition of anti-Tf antibody binding to α2,6-sialylated Tf by a lectin, Sambucus sieboldiana Agglutinin (SSA). The inhibition was not observed with other glycoforms, such as periodate-treated, sialidase-treated and sialidase/galactosidase-treated Tf, suggesting that the assay was glycoform specific. This finding was applied to an automated latex-agglutination immunoassay, using SSA lectin as an inhibitor (SSA-ALI). The concentration of α2,6-sialylated Tf measured by SSA-ALI in human cerebrospinal fluid was correlated with that of ELISA (r2 = 0.8554), previously developed for measuring α2,6-sialylated Tf. PMID:23921500

  17. Dr. Lewis' 10-Year Audit.

    PubMed

    Berlin, Joey

    2015-11-01

    Kaufman pediatrician Charles Turner Lewis, MD, battled fraud allegations levied against him by the Office of Inspector General (OIG) from 2005 to 2008 and emerged victorious. To his dismay, he is once again on the receiving end of an OIG letter alleging Medicaid overpayment. The 2015 Texas Legislature responded to TMA's call for improvements in OIG Medicaid fraud investigations of physicians with passage of Senate Bill 207. Organized medicine hopes the law's safeguards will afford due process to doctors under investigation. PMID:26536514

  18. Aberrant sialylation causes dilated cardiomyopathy and stress-induced heart failure.

    PubMed

    Deng, Wei; Ednie, Andrew R; Qi, Jianyong; Bennett, Eric S

    2016-09-01

    Dilated cardiomyopathy (DCM), the third most common cause of heart failure, is often associated with arrhythmias and sudden cardiac death if not controlled. The majority of DCM is of unknown etiology. Protein sialylation is altered in human DCM, with responsible mechanisms not yet described. Here we sought to investigate the impact of clinically relevant changes in sialylation on cardiac function using a novel model for altered glycoprotein sialylation that leads to DCM and to chronic stress-induced heart failure (HF), deletion of the sialyltransferase, ST3Gal4. We previously reported that 12- to 20-week-old ST3Gal4 (-/-) mice showed aberrant cardiac voltage-gated ion channel sialylation and gating that contribute to a pro-arrhythmogenic phenotype. Here, echocardiography supported by histology revealed modest dilated and thinner-walled left ventricles without increased fibrosis in ST3Gal4 (-/-) mice starting at 1 year of age. Cardiac calcineurin expression in younger (16-20 weeks old) ST3Gal4 (-/-) hearts was significantly reduced compared to WT. Transverse aortic constriction (TAC) was used as a chronic stressor on the younger mice to determine whether the ability to compensate against a pathologic insult is compromised in the ST3Gal4 (-/-) heart, as suggested by previous reports describing the functional implications of reduced cardiac calcineurin levels. TAC'd ST3Gal4 (-/-) mice presented with significantly reduced systolic function and ventricular dilation that deteriorated into congestive HF within 6 weeks post-surgery, while constricted WT hearts remained well-adapted throughout (ejection fraction, ST3Gal4 (-/-) = 34 ± 5.2 %; WT = 53.8 ± 7.4 %; p < 0.05). Thus, a novel, sialo-dependent model for DCM/HF is described in which clinically relevant reduced sialylation results in increased arrhythmogenicity and reduced cardiac calcineurin levels that precede cardiomyopathy and TAC-induced HF, suggesting a causal link among aberrant sialylation

  19. Activation of Protein Kinase C-α and Src Kinase Increases Urea Transporter A1 α-2, 6 Sialylation

    PubMed Central

    Li, Xuechen; Yang, Baoxue; Chen, Minguang; Klein, Janet D.; Sands, Jeff M.

    2015-01-01

    The urea transporter A1 (UT-A1) is a glycosylated protein with two glycoforms: 117 and 97 kD. In diabetes, the increased abundance of the heavily glycosylated 117-kD UT-A1 corresponds to an increase of kidney tubule urea permeability. We previously reported that diabetes not only causes an increase of UT-A1 protein abundance but also, results in UT-A1 glycan changes, including an increase of sialic acid content. Because activation of the diacylglycerol (DAG)-protein kinase C (PKC) pathway is elevated in diabetes and PKC-α regulates UT-A1 urea transport activity, we explored the role of PKC in UT-A1 glycan sialylation. We found that activation of PKC specifically promotes UT-A1 glycan sialylation in both UT-A1-MDCK cells and rat kidney inner medullary collecting duct suspensions, and inhibition of PKC activity blocks high glucose-induced UT-A1 sialylation. Overexpression of PKC-α promoted UT-A1 sialylation and membrane surface expression. Conversely, PKC-α–deficient mice had significantly less sialylated UT-A1 compared with wild-type mice. Furthermore, the effect of PKC-α–induced UT-A1 sialylation was mainly mediated by Src kinase but not Raf-1 kinase. Functionally, increased UT-A1 sialylation corresponded with enhanced urea transport activity. Thus, our results reveal a novel mechanism by which PKC regulates UT-A1 function by increasing glycan sialylation through Src kinase pathways, which may have an important role in preventing the osmotic diuresis caused by glucosuria under diabetic conditions. PMID:25300290

  20. Molecular characterization of the interaction between sialylated Neisseria gonorrhoeae and factor H.

    PubMed

    Shaughnessy, Jutamas; Ram, Sanjay; Bhattacharjee, Arnab; Pedrosa, Joana; Tran, Connie; Horvath, Gabor; Monks, Brian; Visintin, Alberto; Jokiranta, T Sakari; Rice, Peter A

    2011-06-24

    Human factor H (HufH), a key inhibitor of the alternative pathway of complement, binds to Neisseria gonorrhoeae and constitutes an important mechanism of human-specific complement evasion. The C-terminal domain 20 of HufH contains the binding site for sialylated gonococci. We exploited differences in amino acid sequences between human and non-binding chimpanzee fH domain 20 to create cross-species mutations to define amino acids important for binding to sialylated gonococci. We used fH/Fc fusion constructs that contained contiguous fH domains 18-20 fused to Fc fragments of murine IgG2a. The Fc region was used both as a tag for detection of each fusion molecule on the bacterial surface and as an indicator for complement-dependent killing. Arg-1203 was critical for binding to both porin (Por) B.1A and PorB.1B strains. Modeling of the R1203N human-to-chimpanzee mutation using the crystal structure of HufH19-20 as a template showed a loss of positive charge that protrudes at the C terminus of domain 20. We tested the functional importance of Arg-1203 by incubating sialylated gonococci with normal human serum, in the presence of wild-type HufH18-20/Fc or its R1203A mutant. Gonococci bound and were killed by wild-type HufH18-20/Fc but not by the R1203A mutant. A recombinant fH/Fc molecule that contained chimpanzee domain 20, humanized only at amino acid 1203 (N1203R) also bound to sialylated gonococci and restored killing. These findings provide further insights into the species specificity of gonococcal infections and proof-of-concept of a novel therapeutic approach against gonorrhea, a disease rapidly becoming resistant to conventional antibiotics. PMID:21531728

  1. Glycosaminoglycans and sialylated glycans sequentially facilitate Merkel cell polyomavirus infectious entry.

    PubMed

    Schowalter, Rachel M; Pastrana, Diana V; Buck, Christopher B

    2011-07-01

    Merkel cell polyomavirus (MCV or MCPyV) appears to be a causal factor in the development of Merkel cell carcinoma, a rare but highly lethal form of skin cancer. Although recent reports indicate that MCV virions are commonly shed from apparently healthy human skin, the precise cellular tropism of the virus in healthy subjects remains unclear. To begin to explore this question, we set out to identify the cellular receptors or co-receptors required for the infectious entry of MCV. Although several previously studied polyomavirus species have been shown to bind to cell surface sialic acid residues associated with glycolipids or glycoproteins, we found that sialylated glycans are not required for initial attachment of MCV virions to cultured human cell lines. Instead, glycosaminoglycans (GAGs), such as heparan sulfate (HS) and chondroitin sulfate (CS), serve as initial attachment receptors during the MCV infectious entry process. Using cell lines deficient in GAG biosynthesis, we found that N-sulfated and/or 6-O-sulfated forms of HS mediate infectious entry of MCV reporter vectors, while CS appears to be dispensable. Intriguingly, although cell lines deficient in sialylated glycans readily bind MCV capsids, the cells are highly resistant to MCV reporter vector-mediated gene transduction. This suggests that sialylated glycans play a post-attachment role in the infectious entry process. Results observed using MCV reporter vectors were confirmed using a novel system for infectious propagation of native MCV virions. Taken together, the findings suggest a model in which MCV infectious entry occurs via initial cell binding mediated primarily by HS, followed by secondary interactions with a sialylated entry co-factor. The study should facilitate the development of inhibitors of MCV infection and help shed light on the infectious entry pathways and cellular tropism of the virus. PMID:21829355

  2. Characterization of Monoclonal Antibody LpMab-3 Recognizing Sialylated Glycopeptide of Podoplanin

    PubMed Central

    Oki, Hiroharu; Ogasawara, Satoshi; Kaneko, Mika Kato; Takagi, Michiaki; Yamauchi, Masanori

    2015-01-01

    Podoplanin (PDPN/Aggrus/T1α/gp36/OTS-8), a type I transmembrane sialoglycoprotein, is involved in platelet aggregation, cell invasion, and cancer metastasis. Podoplanin expression in cancer cells or cancer-associated fibroblasts was reported to be involved in poor prognosis of several cancers. Furthermore, podoplanin is expressed in lymphatic endothelial cells or lung type I alveolar cells. Although many anti-podoplanin monoclonal antibodies (MAbs), such as NZ-1 and D2–40, have been established, almost all anti-podoplanin MAbs are produced against a platelet aggregation-inducing (PLAG) domain. In this study, we produced and characterized a novel anti-podoplanin monoclonal antibody, LpMab-3, the epitope of which is a sialylated glycopeptide of podoplanin. We identified the minimum epitope of LpMab-3 as Thr76–Glu81 of human podoplanin, which is different from PLAG domain, using Western blot analysis and flow cytometry. Immunohistochemical analysis showed that LpMab-3 is useful for detecting lung type I alveolar cells and lymphatic endothelial cells. Because LpMab-3 detects only sialylated podoplanin, it could be useful for uncovering the physiological function of sialylated human podoplanin. PMID:25723283

  3. Galactose supplementation enhance sialylation of recombinant Fc-fusion protein in CHO cell: an insight into the role of galactosylation in sialylation.

    PubMed

    Liu, Jintao; Wang, Jie; Fan, Li; Chen, Xinning; Hu, Dongdong; Deng, Xiancun; Poon, H Fai; Wang, Haibin; Liu, Xuping; Tan, Wen-Song

    2015-07-01

    Sialic acid levels of therapeutic glycoprotein play an important role in plasma half-life. An undesirable decrease of sialic acid content was observed when we increased Fc-fusion protein productivity fourfold in a GS-CHO cell line by bioprocess optimization. We investigated the potential mechanism for the sialic acid content reduction. We found that limited nucleotide sugar precursor and the extracellular sialidase were not responsible for the reduction of the sialic acid content after titer improvement. Oligosaccharide analysis revealed that the lack of protein galactosylation was the potential cause for the reduction of sialic acid content. Thus we validated this notion by evaluated galactose supplementation in 2 L bioreactors. Cell culture performance was not impacted by addition of up to 40 mM galactose except for the glucose consumption rate. Addition of 20 mM galactose to the bioreactor resulted in the increase of 44 % for total sialic acid content and 20.3 % for sialylated glycans. These data were further validated when the process was run on 200 L scaled bioreactor. These data together show that the galactosylation plays an apparent role in sialylation in our current system. PMID:25931375

  4. Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: distributions of sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

    SciTech Connect

    Green, E.D.; Baenziger, J.U.

    1988-01-05

    The asparagine-linked oligosaccharides on the pituitary glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) consist of a heterogeneous array of neutral, sulfated, sialylated, and sulfated/sialylated structures. In this study, the authors determined the relative quantities of the various asparagine-linked oligosaccharides on LH, FSH, and TSH from these three animal species. The proportions of sulfated versus sialylated oligosaccharides varied markedly among the different hormones. Both hormone- and animal species-specific differences in the types and distributions of sulfated, sialylated, and sulfated/sialylated structures were evident. In particular, LH and FSH, which are synthesized in the same pituitary cell and bear ..cap alpha..-subunits with the identical amino acid sequence, contained significantly different distributions of sulfated and sialylated oligosaccharides. For all three animal species, the ratio of sialylated to sulfated oligosaccharides differed by >10-fold for LH and FSH, with sulfated structures dominating on LH and sialylated structures on FSH. Sialylated oligosaccharides were also heterogeneous with respect to sialic acid linkage (..cap alpha..2,3 versus ..cap alpha..2,6). The differences in oligosaccharide structures among the various pituitary glycoprotein hormones as well as among the various glycosylation sites within a single hormone support the hypothesis that glycosylation may serve important functional roles in the expression and/or regulation of hormone bioactivity.

  5. Effect of sialylation and complexity of FSH oligosaccharides on inhibin production by granulosa cells.

    PubMed

    Loreti, Nazareth; Ambao, Verónica; Andreone, Luz; Trigo, Romina; Bussmann, Ursula; Campo, Stella

    2013-02-01

    Granulosa cell (GC) inhibin A and B production is regulated by FSH and gonadal factors. This gonadotrophin is released as a mixture of glycoforms, which induce different biological responses in vivo and in vitro. Our aim was to determine the effect of recombinant human FSH (rhFSH) glycosylation variants on inhibin A and B production by rat GCs. Preparative isoelectro focusing was used to isolate more acidic/sialylated (pH <4.00) and less acidic/sialylated (pH >5.00) rhFSH charge analogues. Concanavalin A was used to isolate unbound and firmly bound rhFSH glycoforms on the basis of their oligosaccharide complexity. GCs, obtained from oestrogen-primed immature rats, were cultured with either native rhFSH or its glycosylation variants. Inhibin A and B were determined using specific ELISAs. Results were expressed as mean±s.e.m. Under basal conditions, inhibin A was the predominant dimer produced (inhibin A: 673±55; inhibin B: 80±4  pg/ml). More acidic/sialylated charge analogues stimulated inhibin B production when compared to inhibin A at all doses studied; by contrast, less acidic/sialylated charge analogues stimulated inhibin A production and elicited no effect on inhibin B. Glycoforms bearing complex oligosaccharides showed a potent stimulatory effect on inhibin B when compared to inhibin A production (i.e. dose 1  ng/ml: 4.9±0.5 vs 0.9±0.1-fold stimulation, P<0.001). Glycoforms bearing hybrid-type oligosaccharides favoured inhibin A production (i.e. dose 4  ng/ml 2.9±0.1 vs 1.6±0.1-fold stimulation, P<0.05). These results show that the sialylation degree as well as the complexity of oligosaccharides present in the rhFSH molecule may be considered additional factors that differentially regulate dimeric inhibin production by rat GCs. PMID:23166369

  6. Anti-rhesus D prophylaxis in pregnant women is based on sialylated IgG antibodies

    PubMed Central

    Ehlers, Marc

    2013-01-01

    Red blood cells (RBCs) from a rhesus D (RhD)-positive fetus that reach the bloodstream of an RhD-negative pregnant woman during birth can induce a pathogenic antibody (Ab) response against the RhD-positive RBCs, leading to fetal hemolytic disease in subsequent pregnancies. To prevent a pathogenic immune reaction, the RhD-negative mother receives serum immunoglobulin G (IgG) containing polyclonal RhD-specific IgG Abs that is purified from healthy RhD-negative men immunized with RhD-positive RBCs. However, the protective mechanism of these polyclonal RhD-specific IgG Abs is unclear. It has become increasingly clear that the effector function of IgG Abs is regulated by the glycan pattern linked to the Fc region of IgG Abs. Non-fucosylated (afucosylated) IgG Abs have a higher affinity for activating Fc gamma receptors, and thus induce a stronger Ab-dependent cellular cytotoxicity (ADCC) reaction than do fucosylated IgG Abs. Agalactosylated and asialylated, autoantigen-specific serum IgG Abs correlate with pro-inflammatory immune responses and disease activity in patients with rheumatoid arthritis. In contrast, galactosylated and sialylated IgG Abs are immunosuppressive and inhibit in form of immune complexes (ICs) dendritic cell (DC) maturation and pro-inflammatory T and B cell immune responses in an antigen-specific manner. However, the galactosylation and sialylation levels of the protective polyclonal RhD-specific IgG Abs are unknown. Here, we purified RhD-specific IgG Abs from the approved commercial product Rhophylac® (CSL Behring) and found that these RhD-specific IgG Abs were even more galactosylated and sialylated than the total Rhophylac® IgG Abs. This result suggests that these galactosylated and sialylated polyclonal RhD-specific IgG Abs are immunosuppressive and induce tolerance against RhD, which would be in strong contrast to a low fucosylated, low galactosylated and low sialylated monoclonal RhD-specific IgG Ab developed to prevent fetal hemolytic

  7. Lactation Stage-Related Expression of Sialylated and Fucosylated Glycotopes of Human Milk α-1-Acid Glycoprotein

    PubMed Central

    Hirnle, Lidia; Berghausen-Mazur, Marta; Kątnik-Prastowska, Iwona M.

    2014-01-01

    Abstract Background: Because terminal sugars of α-1-acid glycoprotein (AGP) are reported to be involved in anti-inflammatory and immunomodulatory processes, their expressions might have an influence on the proper function of immune system of newborns. Here, relative amounts of sialylated and fucosylated glycotopes on human milk AGP over normal lactation were investigated. Materials and Methods: AGP concentration and relative amounts of its sialylated and fucosylated glycovariants were analyzed in early colostrum, colostrum, and transitional and mature milk samples of 127 healthy mothers by lectin–AGP enzyme-linked immunosorbent assay using α2,3- and α2,6-sialic acid and α1,2-, α1,3-, and α1,6-fucose specific biotinylated Maackia amurensis, Sambucus nigra, Ulex europaeus, Tetragonolobus purpureus, and Lens culinaris lectins, respectively. Results: AGP concentration in human milk was about 30 times lower than in plasma of lactating mothers and decreased gradually over lactation. Milk AGP showed significantly higher expression of sialylated and fucosylated glycotopes in comparison with those of plasma AGP. Milk AGP glycovariants containing α2,6-sialylated and α1,6- and α1,2-fucosylated glycotopes showed the highest relative amounts in early colostrums. With progression of lactation, the expressions of glycotopes α1,2-fucosylated decreased starting from Day 4 and those of α2,6-sialylated and α1,6-fucosylated from Day 8 of lactation, whereas the level of α2,3-sialyl-glycotope was almost constant over 45 days of lactation. In contrast, the expression of α1,3-linked fucose on AGP was low in colostrums and significantly higher in transitional and mature milk. Conclusions: The relative amounts of sialylated and fucosylated glycovariants of human hindmilk AGP significantly varied between Days 2 and 45 of normal lactation. PMID:24892765

  8. Fort Lewis Exceptional Family Member Program (EFMP)

    ERIC Educational Resources Information Center

    Hebdon, Heather

    2007-01-01

    Located in the shadow of Mt. Rainier, Fort Lewis is the home of the highest per capita exceptional family member population in the Army. Ideally located on the Northwest coast of Washington State, Fort Lewis is home to the Strykers and First Brigade. Combined with its close proximity to McChord Air Force Base, the installation is ideally suited to…

  9. Controlled tetra-Fc sialylation of IVIg results in a drug candidate with consistent enhanced anti-inflammatory activity

    PubMed Central

    Washburn, Nathaniel; Schwab, Inessa; Ortiz, Daniel; Bhatnagar, Naveen; Lansing, Jonathan C.; Medeiros, Amy; Tyler, Steven; Mekala, Divya; Cochran, Edward; Sarvaiya, Hetal; Garofalo, Kevin; Meccariello, Robin; Meador, James W.; Rutitzky, Laura; Schultes, Birgit C.; Ling, Leona; Avery, William; Nimmerjahn, Falk; Manning, Anthony M.; Kaundinya, Ganesh V.; Bosques, Carlos J.

    2015-01-01

    Despite the beneficial therapeutic effects of intravenous immunoglobulin (IVIg) in inflammatory diseases, consistent therapeutic efficacy and potency remain major limitations for patients and physicians using IVIg. These limitations have stimulated a desire to generate therapeutic alternatives that could leverage the broad mechanisms of action of IVIg while improving therapeutic consistency and potency. The identification of the important anti-inflammatory role of fragment crystallizable domain (Fc) sialylation has presented an opportunity to develop more potent Ig therapies. However, translating this concept to potent anti-inflammatory therapeutics has been hampered by the difficulty of generating suitable sialylated products for clinical use. Therefore, we set out to develop the first, to our knowledge, robust and scalable process for generating a well-qualified sialylated IVIg drug candidate with maximum Fc sialylation devoid of unwanted alterations to the IVIg mixture. Here, we describe a controlled enzymatic, scalable process to produce a tetra-Fc–sialylated (s4-IVIg) IVIg drug candidate and its qualification across a wide panel of analytic assays, including physicochemical, pharmacokinetic, biodistribution, and in vivo animal models of inflammation. Our in vivo characterization of this drug candidate revealed consistent, enhanced anti-inflammatory activity up to 10-fold higher than IVIg across different animal models. To our knowledge, this candidate represents the first s4-IVIg suitable for clinical use; it is also a valuable therapeutic alternative with more consistent and potent anti-inflammatory activity. PMID:25733881

  10. Lectin staining and Western blot data showing differential sialylation of nutrient-deprived cancer cells to sialic acid supplementation

    PubMed Central

    Badr, Haitham A.; AlSadek, Dina M.M.; Mathew, Mohit P.; Li, Chen-Zhong; Djansugurova, Leyla B.; Yarema, Kevin J.; Ahmed, Hafiz

    2015-01-01

    This report provides data that are specifically related to the differential sialylation of nutrient deprived breast cancer cells to sialic acid supplementation in support of the research article entitled, “Nutrient-deprived cancer cells preferentially use sialic acid to maintain cell surface glycosylation" [1]. Particularly, breast cancer cells, when supplemented with sialic acid under nutrient deprivation, display sialylated glycans at the cell surface, but non-malignant mammary cells show sialylated glycans intracellularly. The impact of sialic acid supplementation under nutrient deprivation was demonstrated by measuring levels of expression and sialylation of two markers, EGFR1 and MUC1. This Data in Brief article complements the main manuscript by providing detailed instructions and representative results for cell-level imaging and Western blot analyses of changes in sialylation during nutrient deprivation and sialic acid supplementation. These methods can be readily generalized for the study of many types of glycosylation and various glycoprotein markers through the appropriate selection of fluorescently-labeled lectins. PMID:26629491

  11. Increased sialylation as a phenomenon in accommodation of the parasitic nematode Trichinella spiralis (Owen, 1835) in skeletal muscle fibres.

    PubMed

    Milcheva, Rositsa; Ivanov, Dimitar; Iliev, Ivan; Russev, Russy; Petkova, Svetlozara; Babal, Pavel

    2015-01-01

    The biology of sialic acids has been an object of interest in many models of acquired and inherited skeletal muscle pathology. The present study focuses on the sialylation changes in mouse skeletal muscle after invasion by the parasitic nematode Trichinella spiralis (Owen, 1835). Asynchronous infection with T. spiralis was induced in mice that were sacrificed at different time points of the muscle phase of the disease. The amounts of free sialic acid, sialylated glycoproteins and total sialyltransferase activity were quantified. Histochemistry with lectins specific for sialic acid was performed in order to localise distribution of sialylated glycoconjugates and to clarify the type of linkage of the sialic acid residues on the carbohydrate chains. Elevated intracellular accumulation of α-2,3- and α-2,6-sialylated glycoconjugates was found only within the affected sarcoplasm of muscle fibres invaded by the parasite. The levels of free and protein-bound sialic acid were increased and the total sialyltransferase activity was also elevated in the skeletal muscle tissue of animals with trichinellosis. We suggest that the biological significance of this phenomenon might be associated with securing integrity of the newly formed nurse cell within the surrounding healthy skeletal muscle tissue. The increased sialylation might inhibit the affected muscle cell contractility through decreased membrane ion gating, helping the parasite accommodation process. PMID:26373236

  12. Prodromal dementia with Lewy bodies.

    PubMed

    Fujishiro, Hiroshige; Nakamura, Shinichiro; Sato, Kiyoshi; Iseki, Eizo

    2015-07-01

    Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementing disorder after Alzheimer's disease (AD), but there is limited information regarding the prodromal DLB state compared with that of AD. Parkinson's disease (PD) and DLB share common prodromal symptoms with Lewy body disease (LBD), allowing us to use a common strategy for identifying the individuals with an underlying pathophysiology of LBD. Dysautonomia, olfactory dysfunction, rapid eye movement sleep behavior disorder (RBD) and psychiatric symptoms antedate the onset of dementia by years or even decades in patients with DLB. Although RBD is the most potentially accurate prodromal predictor of DLB, disease progression before the onset of dementia could differ between the prodromal DLB state with and without RBD. Experts who specialize in idiopathic RBD and DLB might need communication in order to clarify the clinical relevance of RBD with the disease progression of DLB. The presence of prodromal LBD symptoms or findings of occipital hypoperfusion/hypometabolism helps us to predict the possible pathophysiological process of LBD in non-demented patients. This approach might provide the opportunity for additional neuroimaging, including cardiac (123) I-metaiodobenzylguanidine scintigraphy and dopamine transporter imaging. Although limited radiological findings in patients with prodromal DLB states have been reported, there is now a need for larger clinical multisite studies with pathological verification. The long prodromal phase of DLB provides a critical opportunity for potential intervention with disease-modifying therapy, but only if we are able to clearly identify the diversity in the clinical courses of DLB. In the present article, we reviewed the limited literature regarding the clinical profiles of prodromal DLB. PMID:25690399

  13. Bioinspired Saccharide-Saccharide Interaction and Smart Polymer for Specific Enrichment of Sialylated Glycopeptides.

    PubMed

    Li, Xiuling; Xiong, Yuting; Qing, Guangyan; Jiang, Ge; Li, Xianqin; Sun, Taolei; Liang, Xinmiao

    2016-06-01

    Abnormal sialylation of proteins is highly associated with many major diseases, such as cancers and neurodegenerative diseases. However, this study is challenging owing to the difficulty in enriching trace sialylated glycopeptides (SGs) from highly complex biosamples. The key to solving this problem relies strongly on the design of novel SG receptors to capture the sialic acid (SA) moieties in a specific and tunable manner. Inspired by the saccharide-saccharide interactions in life systems, here we introduce saccharide-based SG receptors into this study. Allose (a monosaccharide) displays specific and pH-sensitive binding toward SAs. Integrating allose units into a polyacrylamide chain generates a saccharide-responsive smart copolymer (SRSC). Such design significantly improves the selectivity of SA binding; meanwhile, this binding can be intelligently triggered in a large extent by solution polarity and pH. As a result, SRSC exhibits high-performance enrichment capacity toward SGs, even under 500-fold interference of bovine serum albumins digests, which is notably higher than conventional materials. In real biosamples of HeLa cell lysates, 180 sialylated glycosylation sites (SGSs) have been identified using SRSC. This is apparently superior to those obtained by SA-binding lectins including WGA (18 SGSs) and SNA (22 SGSs). Furthermore, lactose displays good chemoselectivity toward diverse disaccharides, which indicated the good potential of lactose-based material in glycan discrimination. Subsequently, the lactose-based SRSC facilitates the stepwise isolation of O-linked or N-linked SGs with the same peptide sequence but varied glycans by CH3CN/H2O gradients. This study opens a new avenue for next generation of glycopeptide enrichment materials. PMID:27172767

  14. Systemic Blockade of Sialylation in Mice with a Global Inhibitor of Sialyltransferases*

    PubMed Central

    Macauley, Matthew S.; Arlian, Britni M.; Rillahan, Cory D.; Pang, Poh-Choo; Bortell, Nikki; Marcondes, Maria Cecilia G.; Haslam, Stuart M.; Dell, Anne; Paulson, James C.

    2014-01-01

    Sialic acid terminates glycans of glycoproteins and glycolipids that play numerous biological roles in health and disease. Although genetic tools are available for interrogating the effects of decreased or abolished sialoside expression in mice, pharmacological inhibition of the sialyltransferase family has, to date, not been possible. We have recently shown that a sialic acid analog, 2,4,7,8,9-pentaacetyl-3Fax-Neu5Ac-CO2Me (3F-NeuAc), added to the media of cultured cells shuts down sialylation by a mechanism involving its intracellular conversion to CMP-3F-NeuAc, a competitive inhibitor of all sialyltransferases. Here we show that administering 3F-NeuAc to mice dramatically decreases sialylated glycans in cells of all tissues tested, including blood, spleen, liver, brain, lung, heart, kidney, and testes. A single dose results in greatly decreased sialoside expression for over 7 weeks in some tissues. Although blockade of sialylation with 3F-NeuAc does not affect viability of cultured cells, its use in vivo has a deleterious “on target” effect on liver and kidney function. After administration of 3F-NeuAc, liver enzymes in the blood are dramatically altered, and mice develop proteinuria concomitant with dramatic loss of sialic acid in the glomeruli within 4 days, leading to irreversible kidney dysfunction and failure to thrive. These results confirm a critical role for sialosides in liver and kidney function and document the feasibility of pharmacological inhibition of sialyltransferases for in vivo modulation of sialoside expression. PMID:25368325

  15. Systemic blockade of sialylation in mice with a global inhibitor of sialyltransferases.

    PubMed

    Macauley, Matthew S; Arlian, Britni M; Rillahan, Cory D; Pang, Poh-Choo; Bortell, Nikki; Marcondes, Maria Cecilia G; Haslam, Stuart M; Dell, Anne; Paulson, James C

    2014-12-19

    Sialic acid terminates glycans of glycoproteins and glycolipids that play numerous biological roles in health and disease. Although genetic tools are available for interrogating the effects of decreased or abolished sialoside expression in mice, pharmacological inhibition of the sialyltransferase family has, to date, not been possible. We have recently shown that a sialic acid analog, 2,4,7,8,9-pentaacetyl-3Fax-Neu5Ac-CO2Me (3F-NeuAc), added to the media of cultured cells shuts down sialylation by a mechanism involving its intracellular conversion to CMP-3F-NeuAc, a competitive inhibitor of all sialyltransferases. Here we show that administering 3F-NeuAc to mice dramatically decreases sialylated glycans in cells of all tissues tested, including blood, spleen, liver, brain, lung, heart, kidney, and testes. A single dose results in greatly decreased sialoside expression for over 7 weeks in some tissues. Although blockade of sialylation with 3F-NeuAc does not affect viability of cultured cells, its use in vivo has a deleterious "on target" effect on liver and kidney function. After administration of 3F-NeuAc, liver enzymes in the blood are dramatically altered, and mice develop proteinuria concomitant with dramatic loss of sialic acid in the glomeruli within 4 days, leading to irreversible kidney dysfunction and failure to thrive. These results confirm a critical role for sialosides in liver and kidney function and document the feasibility of pharmacological inhibition of sialyltransferases for in vivo modulation of sialoside expression. PMID:25368325

  16. Enhanced sialylation of a human chimeric IgG1 variant produced in human and rodent cell lines.

    PubMed

    Mimura, Yusuke; Kelly, Ronan M; Unwin, Louise; Albrecht, Simone; Jefferis, Roy; Goodall, Margaret; Mizukami, Yoichi; Mimura-Kimura, Yuka; Matsumoto, Tsuneo; Ueoka, Hiroshi; Rudd, Pauline M

    2016-01-01

    Glycosylation of the IgG-Fc is essential for optimal binding and activation of Fcγ receptors and the C1q component of complement. However, it has been reported that the effector functions are down-regulated when the Fc glycans terminate in sialic acid residues and that sialylated IgG mediates anti-inflammatory effects of intravenous immunoglobulin (IVIG). Although recombinant IgG is hypo-sialylated, Fc sialylation is shown to be markedly increased when a mouse/human chimeric IgG3 Phe243Ala (F243A) variant is expressed in Chinese hamster ovary (CHO)-K1 cells. Here we investigate whether sialylation is increased in IgG1 F243A when expressed in CHO-K1, mouse myeloma J558L and human embryonic kidney (HEK) 293. Although the sialylation level was 2-5% for IgG1 wild type (WT), it was increased to 31%, 10% and 33% for the variant from CHO-K1, J558L and HEK293 cells, respectively. Interestingly, an increased addition of bisecting GlcNAc and α(1-3)-galactose residues to the Fc glycan was observed for HEK293-derived and J558L-derived IgG1 F243A, respectively. Fucosylation of HEK293-derived IgG1 F243A was maintained despite increased bisecting GlcNAc content. Although sialic acid and bisecting GlcNAc residues are reported to have an opposing effect on antibody-dependent cellular cytotoxicity (ADCC), IgG1 F243A showed 7 times lower ADCC activities than IgG1 WT, irrespective of bisecting GlcNAc residue. Thus, highly sialylated, human cell-derived IgG1 F243A with lowered ADCC activity may be of interest for the development of therapeutic antibodies with anti-inflammatory properties as an alternative to IVIG. PMID:26627984

  17. Dementia with Lewy bodies in Meige Syndrome

    PubMed Central

    Ho, Ho Yin; Yu, Chi Shing

    2012-01-01

    Meige syndrome is a rare form of segmental dystonia characterized by blepharospasm and oromandibular dystonia. A few case reports of Meige syndrome have been associated with Lewy body pathologies, and the syndrome was also proposed for inclusion in the spectrum of Lewy body disease. We report a case of an elderly gentleman with a history of Meige syndrome for more than 10 years who developed dementia with Lewy bodies. Updated clinical and pathological evidence of linkages between these two conditions is also presented. PMID:22984651

  18. The Use of C. S. Lewis's "Poems" for Oral Interpretation.

    ERIC Educational Resources Information Center

    Keefe, Carolyn

    Suggestions are offered in this paper for adapting C. S. Lewis's poems for oral interpretation. A discussion of Lewis's lifelong correspondence with his friend Arthur Greeves provides insights into Lewis's perceptions of his own writing. Eighty poems selected from Lewis's "Poems" as appropriate for oral interpretation are classified according to…

  19. Development of a Lewis Base Catalyzed Selenocyclization Reaction

    ERIC Educational Resources Information Center

    Collins, William

    2009-01-01

    The concept of Lewis base activation of selenium Lewis acids has been effectively reduced to practice in the Lewis base catalyzed selenofunctionalization of unactivated olefins. In this reaction, the weakly acidic species, "N"-phenylselenyl succinimide, is cooperatively activated by the addition of a "soft" Lewis base donor (phosphine sulfides,…

  20. Abegg, Lewis, Langmuir, and the Octet Rule.

    ERIC Educational Resources Information Center

    Jensen, William B.

    1984-01-01

    Discusses major events leading to the development of the octet rule. Three conclusions based on the work of Mendeleev, Abegg, Thompson, Kossel, Lewis, and Langmuir are considered as is the debate over the rule's validity. (JN)

  1. 90 Seconds of Discovery: Frustrated Lewis Pairs

    SciTech Connect

    Kathmann, Shawn; Schenter, Greg; Autrey, Tom

    2014-02-14

    Hydrogen activating catalysts play an important role in producing valuable chemicals, such as biofuels and ammonia. As a part of efforts to develop the next generation of these catalysts, PNNL researchers have found potential in Frustrated Lewis Pairs.

  2. 90 Seconds of Discovery: Frustrated Lewis Pairs

    ScienceCinema

    Kathmann, Shawn; Schenter, Greg; Autrey, Tom

    2014-07-21

    Hydrogen activating catalysts play an important role in producing valuable chemicals, such as biofuels and ammonia. As a part of efforts to develop the next generation of these catalysts, PNNL researchers have found potential in Frustrated Lewis Pairs.

  3. Lewis Research Center: Commercialization Success Stories

    NASA Technical Reports Server (NTRS)

    Heyward, Ann O.

    1996-01-01

    The NASA Lewis Research Center, located in Cleveland, Ohio, has a portfolio of research and technology capabilities and facilities that afford opportunities for productive partnerships with industry in a broad range of industry sectors. In response to the President's agenda in the area of technology for economic growth (Clinton/Gore 1993), the National Performance Review (1993), NASA's Agenda for Change (1994), and the needs of its customers, NASA Lewis Research Center has sought and achieved significant successes in technology transfer and commercialization. This paper discusses a sampling of Lewis Research Center's successes in this area, and lessons learned that Lewis Research Center is applying in pursuit of continuous improvement and excellence in technology transfer and commercialization.

  4. G. N. Lewis and the Chemical Bond.

    ERIC Educational Resources Information Center

    Pauling, Linus

    1984-01-01

    Discusses the contributions of G. N. Lewis to chemistry, focusing on his formulation of the basic principle of the chemical bond--the idea that the chemical bond consists of a pair of electrons held jointly by two atoms. (JN)

  5. SSTI- Lewis Spacecraft Nickel-Hydrogen Battery

    NASA Technical Reports Server (NTRS)

    Tobias, R. F.

    1997-01-01

    Topics considered include: NASA-Small Spacecraft Technology Initiative (SSTI) objectives, SSTI-Lewis overview, battery requirement, two cells Common Pressure Vessel (CPV) design summary, CPV electric performance, battery design summary, battery functional description, battery performance.

  6. Pueblo Pottery: Continuity and Change. Lucy Lewis.

    ERIC Educational Resources Information Center

    Herzog, Melanie

    1991-01-01

    Describes Lucy Lewis' ceramic work which is inspired by the ancient pottery of her Acoma Pueblo artistic heritage. Discusses concepts of tradition, artistic heritage, and change over time. Outlines related ceramic and discussion activities for elementary and secondary students. (KM)

  7. Excerpts from the Books of Bernard Lewis.

    ERIC Educational Resources Information Center

    Lewis, Bernard

    1990-01-01

    Presents excerpts from the books of Bernard Lewis on Arab culture and history; Islamic religion, history, and politics; Orientalism; and slavery in the Middle East. Includes an excerpt on historiography and the problems of historical scholarship. (RW)

  8. Sialylation of Thomsen-Friedenreich antigen is a noninvasive blood-based biomarker for GNE myopathy

    PubMed Central

    Leoyklang, Petcharat; Malicdan, May Christine; Yardeni, Tal; Celeste, Frank; Ciccone, Carla; Li, Xueli; Jiang, Rong; Gahl, William A.; Carrillo-Carrasco, Nuria; He, Miao; Huizing, Marjan

    2014-01-01

    GNE myopathy is an adult-onset progressive myopathy, resulting from mutations in GNE, the key enzyme of sialic acid synthesis. The pathomechanism of GNE myopathy likely involves aberrant sialylation, since administration of sialic acid itself, or its precursor, N-acetylmannosamine (ManNAc), rescued hyposialylation of GNE myopathy mice. Recently, clinical trials for GNE myopathy patients were initiated. A robust, noninvasive biomarker is highly desirable for diagnosis of GNE myopathy and for evaluating response to therapy. Since muscle biopsies of patients with GNE myopathy demonstrated hyposialylation of predominantly O-linked glycans, we analyzed the O-linked glycome of patients’ plasma proteins using mass spectrometry. Most patients showed increased plasma levels of the core 1 O-linked glycan, Thomsen-Friedenreich (T)-antigen and/or decreased amounts of its sialylated form, ST-antigen. In addition, compared to unaffected individuals, all analyzed patients had a consistently increased ratio of T-antigen to ST-antigen. Importantly, the T/ST ratios were in the normal range in a GNE myopathy patient treated with intravenous immunoglobulins as a source of sialic acid, indicating response to therapy. Natural history and clinical trial data will reveal whether T/ST ratios can be correlated to muscle function. These findings not only highlight plasma T/ST ratios as a robust blood-based biomarker for GNE myopathy, but may also help explain the pathology and course of the disease. PMID:25123033

  9. Sialylation of the prion protein glycans controls prion replication rate and glycoform ratio

    PubMed Central

    Katorcha, Elizaveta; Makarava, Natallia; Savtchenko, Regina; Baskakov, Ilia V.

    2015-01-01

    Prion or PrPSc is a proteinaceous infectious agent that consists of a misfolded and aggregated form of a sialoglycoprotein called prion protein or PrPC. PrPC has two sialylated N-linked carbohydrates. In PrPSc, the glycans are directed outward, with the terminal sialic acid residues creating a negative charge on the surface of prion particles. The current study proposes a new hypothesis that electrostatic repulsion between sialic residues creates structural constraints that control prion replication and PrPSc glycoform ratio. In support of this hypothesis, here we show that diglycosylated PrPC molecules that have more sialic groups per molecule than monoglycosylated PrPC were preferentially excluded from conversion. However, when partially desialylated PrPC was used as a substrate, recruitment of three glycoforms into PrPSc was found to be proportional to their respective populations in the substrate. In addition, hypersialylated molecules were also excluded from conversion in the strains with the strongest structural constraints, a strategy that helped reduce electrostatic repulsion. Moreover, as predicted by the hypothesis, partial desialylation of PrPC significantly increased the replication rate. This study illustrates that sialylation of N-linked glycans creates a prion replication barrier that controls replication rate and glycoform ratios and has broad implications. PMID:26576925

  10. Cationic amphipathic peptides accumulate sialylated proteins and lipids in the plasma membrane of eukaryotic host cells

    PubMed Central

    Weghuber, Julian; Aichinger, Michael C.; Brameshuber, Mario; Wieser, Stefan; Ruprecht, Verena; Plochberger, Birgit; Madl, Josef; Horner, Andreas; Reipert, Siegfried; Lohner, Karl; Henics, Tamás; Schütz, Gerhard J.

    2011-01-01

    Cationic antimicrobial peptides (CAMPs) selectively target bacterial membranes by electrostatic interactions with negatively charged lipids. It turned out that for inhibition of microbial growth a high CAMP membrane concentration is required, which can be realized by the incorporation of hydrophobic groups within the peptide. Increasing hydrophobicity, however, reduces the CAMP selectivity for bacterial over eukaryotic host membranes, thereby causing the risk of detrimental side-effects. In this study we addressed how cationic amphipathic peptides—in particular a CAMP with Lysine–Leucine–Lysine repeats (termed KLK)—affect the localization and dynamics of molecules in eukaryotic membranes. We found KLK to selectively inhibit the endocytosis of a subgroup of membrane proteins and lipids by electrostatically interacting with negatively charged sialic acid moieties. Ultrastructural characterization revealed the formation of membrane invaginations representing fission or fusion intermediates, in which the sialylated proteins and lipids were immobilized. Experiments on structurally different cationic amphipathic peptides (KLK, 6-MO-LF11-322 and NK14-2) indicated a cooperation of electrostatic and hydrophobic forces that selectively arrest sialylated membrane constituents. PMID:21718688

  11. Sialylated Milk Oligosaccharides Promote Microbiota-Dependent Growth in Models of Infant Undernutrition.

    PubMed

    Charbonneau, Mark R; O'Donnell, David; Blanton, Laura V; Totten, Sarah M; Davis, Jasmine C C; Barratt, Michael J; Cheng, Jiye; Guruge, Janaki; Talcott, Michael; Bain, James R; Muehlbauer, Michael J; Ilkayeva, Olga; Wu, Chao; Struckmeyer, Tedd; Barile, Daniela; Mangani, Charles; Jorgensen, Josh; Fan, Yue-mei; Maleta, Kenneth; Dewey, Kathryn G; Ashorn, Per; Newgard, Christopher B; Lebrilla, Carlito; Mills, David A; Gordon, Jeffrey I

    2016-02-25

    Identifying interventions that more effectively promote healthy growth of children with undernutrition is a pressing global health goal. Analysis of human milk oligosaccharides (HMOs) from 6-month-postpartum mothers in two Malawian birth cohorts revealed that sialylated HMOs are significantly less abundant in those with severely stunted infants. To explore this association, we colonized young germ-free mice with a consortium of bacterial strains cultured from the fecal microbiota of a 6-month-old stunted Malawian infant and fed recipient animals a prototypic Malawian diet with or without purified sialylated bovine milk oligosaccharides (S-BMO). S-BMO produced a microbiota-dependent augmentation of lean body mass gain, changed bone morphology, and altered liver, muscle, and brain metabolism in ways indicative of a greater ability to utilize nutrients for anabolism. These effects were also documented in gnotobiotic piglets using the same consortium and Malawian diet. These preclinical models indicate a causal, microbiota-dependent relationship between S-BMO and growth promotion. PMID:26898329

  12. Research and technology, Lewis Research Center

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The NASA Lewis Research Center's research and technology accomplishments for fiscal year 1985 are summarized. The report is organized into five major sections covering aeronautics, aerospace technology, spaceflight systems, space station systems, and computational technology support. This organization of the report roughly parallels the organization of the Center into directorates. Where appropriate, subheadings are used to identify special topics under the major headings. Results of all research and technology work performed during the fiscal year are contained in Lewis-published technical reports and presentations prepared either by Lewis scientists and engineers or by contractor personnel. In addition, significant results are presented by university faculty or graduate students in technical sessions and in journals of the technical societies. For the reader who desires more information about a particular subject, the Lewis contact will provide that information or references. In 1985, five Lewis products were selected by Research and Development Magazine for IR-100 awards. All are described and identified. In addition, the Lewis Distinguished Paper for 1984 to 1985, which was selected by the Chief Scientist and a research advisory board, is included and so identified.

  13. Core 2 branching beta1,6-N-acetylglucosaminyltransferase and high endothelial venule-restricted sulfotransferase collaboratively control lymphocyte homing.

    PubMed

    Hiraoka, Nobuyoshi; Kawashima, Hiroto; Petryniak, Bronislawa; Nakayama, Jun; Mitoma, Junya; Marth, Jamey D; Lowe, John B; Fukuda, Minoru

    2004-01-23

    L-selectin mediates lymphocyte homing by facilitating lymphocyte adhesion to carbohydrate ligands expressed on high endothelial venules (HEV) of the secondary lymphoid organs. Previous studies demonstrated that L-selectin ligand sulfotransferase (LSST) forms 6-sulfo sialyl Lewis x (sLe(x)) on both core 2 branch and MECA-79-positive extended core 1 O-glycans, but the chemical nature and roles of HEV ligands elaborated by LSST and core 2 beta1,6-N-acetylglucosaminyltransferase-1 (Core2GlcNAcT) have been undefined. In the present study, we have generated mutant mice with deficient LSST and show that inactivation of LSST gene alone leads to only partial impairment of lymphocyte homing to peripheral lymph nodes and moderate reduction in lymphocyte counts in the peripheral lymph nodes, despite the fact that L-selectin ligands that contain 6-sulfo sLe(x) are reduced at HEV. By contrast, LSST/Core2GlcNAcT double null mice exhibited a markedly reduced lymphocyte homing and reduced lymphocyte counts as a result of significantly decreased 6-sulfo sLe(x) on HEV L-selectin counterreceptors, relative to LSST- or Core2GlcNAcT-single null mice. Moreover, induction of LSST and Core2GlcNAcT transcripts was observed in HEV-like structure formed in the salivary gland of the non-obese diabetic mouse, which displays chronic inflammation. These results indicate that LSST and Core2GlcNAcT cooperatively synthesize HEV-specific L-selectin ligands required for lymphocyte homing and suggest that LSST and Core2GlcNAcT play a critical role in lymphocyte trafficking during chronic inflammation. PMID:14593101

  14. Positive regulation of the enzymatic activity of gastric H(+),K(+)-ATPase by sialylation of its β-subunit.

    PubMed

    Fujii, Takuto; Watanabe, Midori; Shimizu, Takahiro; Takeshima, Hiroshi; Kushiro, Keiichiro; Takai, Madoka; Sakai, Hideki

    2016-06-01

    The gastric proton pump (H(+),K(+)-ATPase) consists of a catalytic α-subunit (αHK) and a glycosylated β-subunit (βHK). βHK glycosylation is essential for the apical trafficking and stability of αHK in gastric parietal cells. Here, we report the properties of sialic acids at the termini of the oligosaccharide chains of βHK. Sialylation of βHK was found in LLC-PK1 cells stably expressing αHK and βHK by staining of the cells with lectin-tagged fluorescent polymeric nanoparticles. This sialylation was also confirmed by biochemical studies using sialic acid-binding lectin beads and an anti-βHK antibody. The sialic acids of βHK are cleaved enzymatically by neuraminidase (sialidase) and nonenzymatically by an acidic solution (pH5). Interestingly, the enzymatic activity of H(+),K(+)-ATPase was significantly decreased by cleavage of the sialic acids of βHK. In contrast, βHK was not sialylated in the gastric tubulovesicles prepared from the stomach of fed hogs. The H(+),K(+)-ATPase activity in these tubulovesicles was not significantly altered by neuraminidase. Importantly, the sialylation of βHK was observed in the gastric samples prepared from the stomach of famotidine (a histamine H2 receptor antagonist)-treated rats, but not histamine (an acid secretagogue)-treated rats. The enzymatic activity of H(+),K(+)-ATPase in the samples of the famotidine-treated rats was significantly higher than in the histamine-treated rats. The effects of famotidine were weakened by neuraminidase. These results indicate that βHK is sialylated at neutral or weakly acidic pH, but not at acidic pH, suggesting that the sialic acids of βHK positively regulate the enzymatic activity of αHK. PMID:26922883

  15. The expression of sialylated high-antennary N-glycans in edible bird's nest.

    PubMed

    Yagi, Hirokazu; Yasukawa, Naoko; Yu, Shin-Yi; Guo, Chao-Tan; Takahashi, Noriko; Takahashi, Tadanobu; Bukawa, Wakoto; Suzuki, Takashi; Khoo, Kay-Hooi; Suzuki, Yasuo; Kato, Koichi

    2008-06-01

    Edible bird's nest (EBN) is the nest made from the saliva of Collocalia swift. Recently, we have found that EBN extract could strongly inhibit infection of influenza viruses in a host-range-independent manner [Guo, C. T.; Takahashi, T.; Bukawa, W.; Takahashi, N.; Yagi, H.; Kato, K.; Hidari, K. I.; Miyamoto, D.; Suzuki, T.; Suzuki, Y. Antiviral Res.2006, 70, 140-146]. Although this antiviral activity might be attributed to O- or N-glycoconjugates, no N-glycan structures have so far been described for EBN. Here, we report the N-glycosylation profile of EBN, in which a tri-antennary N-glycan bearing the alpha2,3-N-acetylneuraminic acid residues is displayed as a major component. We suggest that the sialylated high-antennary N-glycans of EBN contribute to the inhibition of influenza viral infection. PMID:18439991

  16. Sialylated galacto-oligosaccharides and 2'-fucosyllactose reduce necrotising enterocolitis in neonatal rats.

    PubMed

    Autran, Chloe A; Schoterman, Margriet H C; Jantscher-Krenn, Evelyn; Kamerling, Johannis P; Bode, Lars

    2016-07-01

    Necrotising enterocolitis (NEC) is one of the most frequent and fatal intestinal disorders in preterm infants and has very limited treatment options. Breast-fed infants are at a 6-10-fold lower NEC risk than formula-fed infants, and we have previously shown that human milk oligosaccharides (HMO) improved survival and reduced pathology in a rat NEC model. The HMO disialyllacto-N-tetraose (DSLNT) was most effective, and sialylation was shown to be essential for its protective effect. Galacto-oligosaccharides (GOS), currently added to some infant formula, but not containing sialic acid, had no effect. In addition to DSLNT, our previous work also showed that the neutral HMO fraction, which contains high concentrations of 2'-fucosyllactose (2'FL), slightly improved pathology scores. Here, we assessed the in vivo efficacy of 2'FL, as well as of GOS that we enzymatically sialylated (Sia-GOS). Neonatal rats were randomised into the following study groups - dam-fed (DF), formula-fed (FF), FF containing pooled HMO (10 mg/ml), GOS (8 mg/ml), Sia-GOS (500 µm) or 2'FL (2 mg/ml) - and subjected to the established NEC protocol. The DF and HMO groups had the lowest pathology scores with mean values of 0·67 (sd 0·34) and 0·90 (sd 0·47), respectively. The FF group had significantly elevated pathology scores of 2·02 (sd 0·63). Although the addition of GOS to the formula had no protective effect and generated scores of 2·00 (sd 0·63), the addition of Sia-GOS or 2'FL significantly lowered pathology scores to 1·32 (sd 0·56) (P<0·0034) and 1·43 (sd 0·51) (P<0·0040), respectively. The results warrant further studies to investigate the underlying mechanisms and to assess safety and efficacy in human neonates. PMID:27212112

  17. Sialylated intravenous immunoglobulin suppress anti-ganglioside antibody mediated nerve injury.

    PubMed

    Zhang, Gang; Massaad, Cynthia A; Gao, Tong; Pillai, Laila; Bogdanova, Nataliia; Ghauri, Sameera; Sheikh, Kazim A

    2016-08-01

    The precise mechanisms underlying the efficacy of intravenous immunoglobulin (IVIg) in autoimmune neurological disorders including Guillain-Barré syndrome (GBS) are not known. Anti-ganglioside antibodies have been reported to be pathogenic in some variants of GBS, and we have developed passive transfer animal models to study anti-ganglioside antibody mediated-endoneurial inflammation and associated neuropathological effects and to evaluate the efficacy of new therapeutic approaches. Some studies indicate that IVIg's anti-inflammatory activity resides in a minor sialylated IVIg (sIVIg) fractions and is dependent on an innate Th2 response via binding to a specific ICAM3-grabbing nonintegrin related 1 receptor (SIGN-R1). Therefore the efficacy of IVIg, IVIg fractions with various IgG Fc sialylation status, and the involvement of Th2 pathway were examined in one of our animal model of antibody-mediated inhibition of axonal regeneration. We demonstrate that both IVIg and sIVIg ameliorated anti-glycan antibody mediated-pathological effect, whereas, the unsialylated fractions of IVIg were not beneficial in our model. Tenfold lower doses of sIVIg compared to whole IVIg provided equivalent efficacy in our studies. Moreover, we found that whole IVIg and sIVIg significantly upregulates the gene expression of IL-33, which itself can provide protection from antibody-mediated nerve injury in our model. Our results support that the SIGN-R1-Th2 pathway is involved in the anti-inflammatory effects of IVIg on endoneurium in our model and elements of this pathway including IL-33 can provide novel therapeutics in inflammatory neuropathies. PMID:27208700

  18. NASA Lewis Wind Tunnel Model Systems Criteria

    NASA Technical Reports Server (NTRS)

    Soeder, Ronald H.; Haller, Henry C.

    1994-01-01

    This report describes criteria for the design, analysis, quality assurance, and documentation of models or test articles that are to be tested in the aeropropulsion facilities at the NASA Lewis Research Center. The report presents three methods for computing model allowable stresses on the basis of the yield stress or ultimate stress, and it gives quality assurance criteria for models tested in Lewis' aeropropulsion facilities. Both customer-furnished model systems and in-house model systems are discussed. The functions of the facility manager, project engineer, operations engineer, research engineer, and facility electrical engineer are defined. The format for pretest meetings, prerun safety meetings, and the model criteria review are outlined Then, the format for the model systems report (a requirement for each model that is to be tested at NASA Lewis) is described, the engineers that are responsible for developing the model systems report are listed, and the time table for its delivery to the facility manager is given.

  19. UPDATE ON DEMENTIA WITH LEWY BODIES

    PubMed Central

    Karantzoulis, Stella; Galvin, James E.

    2014-01-01

    Dementia with Lewy bodies (DLB) is the second most common form of dementia after Alzheimer disease (AD). DLB is characterized pathologically by Lewy body and Lewy neuritic pathology, often with variable levels of Alzheimer-type pathology. Core clinical features include fluctuating cognition, visual hallucinations, and parkinsonism resulting in greater impairments of quality of life, more caregiver burden, and higher health-related costs compared with AD. These issues, together with a high sensitivity to adverse events with treatment with antipsychotic agents, make the need for an early and accurate diagnosis of DLB essential. Unfortunately, current consensus criteria are highly specific but lack sufficient sensitivity. Use of composite risk scores may improve accuracy of clinical diagnosis. Imaging findings, particularly targeting dopaminergic systems have shown promise as potential markers to differentiate DLB from AD. A combination of non-pharmacologic treatments and pharmacotherapy interventions may maximize cognitive function and overall quality of life in DLB patients. PMID:25379359

  20. Rocket Propulsion Research at Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Dawson, Virginia P.

    1992-01-01

    A small contingent of engineers at NASA Lewis Research Center pioneered in basic research on liquid propellants for rockets shortly after World War II. Carried on through the 1950s, this work influenced the important early decisions made by Abe Silverstein when he took charge of the Office of Space Flight Programs for NASA. He strongly supported the development of liquid hydrogen as a propulsion fuel in the face of resistance from Wernher von Braun. Members of the Lewis staff played an important role in bringing liquid hydrogen technology to the point of reliability through their management of the Centaur Program. This paper demonstrates how the personality and engineering intuition of Abe Silverstein shaped the Centaur program and left a lasting imprint on the laboratory research tradition. Many of the current leaders of Lewis Research Center received their first hands-on engineering experience when they worked on the Centaur program in the 1960s.

  1. Intramolecular cooperativity in frustrated Lewis pairs.

    PubMed

    Körte, Leif A; Blomeyer, Sebastian; Heidemeyer, Shari; Mix, Andreas; Neumann, Beate; Mitzel, Norbert W

    2016-08-01

    The doubly Lewis-acid functionalised aniline PhN[(CH2)3B(C6F5)2]2 features two competing boron functions in fast exchange for binding to the central Lewis base. It shows catalytic activity typical for FLPs in H/D-scrambling and catalytic hydrogenation experiments. By contrast, the singly acid-functionalised PhMeN(CH2)3B(C6F5)2 reveals a dramatically smaller catalytic activity in analogous experiments. PMID:27440500

  2. Lewis hybrid computing system, users manual

    NASA Technical Reports Server (NTRS)

    Bruton, W. M.; Cwynar, D. S.

    1979-01-01

    The Lewis Research Center's Hybrid Simulation Lab contains a collection of analog, digital, and hybrid (combined analog and digital) computing equipment suitable for the dynamic simulation and analysis of complex systems. This report is intended as a guide to users of these computing systems. The report describes the available equipment' and outlines procedures for its use. Particular is given to the operation of the PACER 100 digital processor. System software to accomplish the usual digital tasks such as compiling, editing, etc. and Lewis-developed special purpose software are described.

  3. In dementia with Lewy bodies, Braak stage determines phenotype, not Lewy body distribution.

    PubMed

    Weisman, D; Cho, M; Taylor, C; Adame, A; Thal, L J; Hansen, L A

    2007-07-24

    We used an autopsy series to determine whether the newest dementia with Lewy bodies (DLB) consensus pathologic classification correlates with premortem diagnosis of DLB. Neocortical sections from a total of 95 cases with Lewy bodies were stained with alpha-synuclein antibodies. We assigned cases according to the DLB consensus' categories and found a significant association with the premortem clinical diagnosis of DLB. Clinical diagnosis of DLB, however, depended on the presence of low Alzheimer disease pathology (by Braak staging) rather than on Lewy body distribution. PMID:17646627

  4. α-2,3-Sialyltransferase Expression Level Impacts the Kinetics of Lipooligosaccharide Sialylation, Complement Resistance, and the Ability of Neisseria gonorrhoeae to Colonize the Murine Genital Tract

    PubMed Central

    Gulati, Sunita; Burrowes, Elizabeth; Zheng, Bo; Ram, Sanjay; Rice, Peter A.

    2015-01-01

    ABSTRACT  Neisseria meningitidis and Neisseria gonorrhoeae modify the terminal lacto-N-neotetraose moiety of their lipooligosaccharide (LOS) with sialic acid. N. gonorrhoeae LOS sialylation blocks killing by complement, which is mediated at least in part by enhanced binding of the complement inhibitor factor H (FH). The role of LOS sialylation in resistance of N. meningitidis to serum killing is less well defined. Sialylation in each species is catalyzed by the enzyme LOS α-2,3-sialyltransferase (Lst). Previous studies have shown increased Lst activity in N. gonorrhoeae compared to N. meningitidis due to an ~5-fold increase in lst transcription. Using isogenic N. gonorrhoeae strains engineered to express gonococcal lst from either the N. gonorrhoeae or N. meningitidis lst promoter, we show that decreased expression of lst (driven by the N. meningitidis promoter) reduced LOS sialylation as determined by less incorporation of tritium-labeled cytidine monophospho-N-acetylneuraminic acid (CMP-NANA; the donor molecule for sialic acid). Diminished LOS sialylation resulted in reduced rates of FH binding and increased pathway activation compared to N. gonorrhoeae promoter-driven lst expression. The N. meningitidis lst promoter generated sufficient Lst to sialylate N. gonorrhoeae LOS in vivo, and the level of sialylation after 24 h in the mouse genital tract was sufficient to mediate resistance to human serum ex vivo. Despite demonstrable LOS sialylation in vivo, gonococci harboring the N. meningitidis lst promoter were outcompeted by those with the N. gonorrhoeae lst promoter during coinfection of the vaginal tract of estradiol-treated mice. These data highlight the importance of high lst expression levels for gonococcal pathogenesis. PMID:25650401

  5. Lewy Body Dementia: Information for Patients, Families, and Professionals

    MedlinePlus

    ... About ADEAR Lewy Body Dementia: Information for Patients, Families, and Professionals Introduction Lewy body dementia mostly affects ... find a cure—people with LBD and their families struggle day to day to get an accurate ...

  6. Lewis Carroll's Formula for Calendar Calculating.

    ERIC Educational Resources Information Center

    Spitz, Herman H.

    1993-01-01

    This paper presents Lewis Carroll's formula for mentally calculating the day of the week of a given date. The paper concludes that such formulas are too complex for individuals of low intelligence to learn by themselves, and thus "idiots savants" who perform such calendar calculations must be using other systems. (JDD)

  7. Reply to Tone Kvernbekk and Ann Lewis

    ERIC Educational Resources Information Center

    Tangen, Reidun

    2008-01-01

    The purpose of this reply to Kvernbekk and Lewis's comments regarding the discussion on epistemological and ethical problems of listening to children's voices, is not to propose a coherent foundation free from any epistemological tensions. Rather, Tangen's intent is primarily to explore different perspectives in order to disclose some of their…

  8. Teaching a Model for Writing Lewis Structures.

    ERIC Educational Resources Information Center

    Pardo, Juan Quilez

    1989-01-01

    Presents a didactic model to improve the teaching/learning process in the representation of Lewis structures. Places special emphasis on the calculation and reduction of formal charges, and in the representation of molecules in which the central atom has expanded its valence shell. (MVL)

  9. Lewis and Clark--Indiana Connections.

    ERIC Educational Resources Information Center

    Bennett, Pamela J., Ed.

    2003-01-01

    The state of Indiana has an important, recognized connection to the Lewis and Clark Expedition. That connection is reinforced with a National Signature Event in Clarksville (Indiana) during October 2003. Until the expedition party left its winter camp in May 1804, it remained in Indiana Territory, governed from Vincennes (Indiana) by William Henry…

  10. Celebrating the Bicentennial of Lewis and Clark

    ERIC Educational Resources Information Center

    Morris, Ronald V.; McNeely, Jean

    2005-01-01

    Lewis, Clark, and the Corps of Discovery traveled westward from 1803 to 1806; therefore, the bicentennial of the expedition is being celebrated from 2003 until 2006. Students and teachers celebrating the bicentennial and Jefferson's Louisiana Purchase in 1803 can use social studies classes to help them connect with their community and to reach a…

  11. Composites research at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Levine, Stanley R.; Duffy, Stephen; Vary, Alex; Nathal, Michael V.; Miner, Robert V.; Arnold, Steven M.; Castelli, Michael G.; Hopkins, Dale A.; Meador, Michael A.

    1994-01-01

    Composites research at NASA Lewis is focused on their applications in aircraft propulsion, space propulsion, and space power, with the first being predominant. Research on polymer-, metal-, and ceramic-matrix composites is being carried out from an integrated materials and structures viewpoint. This paper outlines some of the topics being pursued from the standpoint of key technical issues, current status, and future directions.

  12. Teaching Beginning Chemistry Students Simple Lewis Dot Structures

    ERIC Educational Resources Information Center

    Nassiff, Peter; Czerwinski, Wendy A.

    2015-01-01

    Students beginning their initial study of chemistry often have a difficult time mastering simple Lewis dot structures. Textbooks show students how to manipulate Lewis structures by moving valence electron dots around the chemical structure so each atom has an octet or duet. However, an easier method of teaching Lewis structures for simple…

  13. An Overview of Lewis Basicity and Affinity Scales

    ERIC Educational Resources Information Center

    Laurence, Christian; Graton, Jerome; Gal, Jean-Francois

    2011-01-01

    The impossibility of establishing a universal scale of Lewis basicity does not prevent the determination of the quantitative behavior of Lewis bases, thanks to scales constructed against particular Lewis acids: BF[subscript 3], 4-FC[subscript 6]H[subscript 4]OH, I[subscript 2], Li[superscript +], Na[superscript +], K[superscript +], Al[superscript…

  14. Getting the Weights of Lewis Structures out of Huckel Theory: Huckel-Lewis Configuration Interaction (HL-CI)

    ERIC Educational Resources Information Center

    Humbel, Stephane

    2007-01-01

    A simple method is proposed based on energies obtained with the Huckel theory to compute the weights of the structures. The Huckel-Lewis CI technique extends to the Huckel theory the field of the resonance between Lewis structures.

  15. A rationally engineered yeast pyruvyltransferase Pvg1p introduces sialylation-like properties in neo-human-type complex oligosaccharide.

    PubMed

    Higuchi, Yujiro; Yoshinaga, Sho; Yoritsune, Ken-Ichi; Tateno, Hiroaki; Hirabayashi, Jun; Nakakita, Shin-Ichi; Kanekiyo, Miho; Kakuta, Yoshimitsu; Takegawa, Kaoru

    2016-01-01

    Pyruvylation onto the terminus of oligosaccharide, widely seen from prokaryote to eukaryote, confers negative charges on the cell surface and seems to be functionally similar to sialylation, which is found at the end of human-type complex oligosaccharide. However, detailed molecular mechanisms underlying pyruvylation have not been clarified well. Here, we first determined the crystal structure of fission yeast pyruvyltransferase Pvg1p at a resolution of 2.46 Å. Subsequently, by combining molecular modeling with mutational analysis of active site residues, we obtained a Pvg1p mutant (Pvg1p(H168C)) that efficiently transferred pyruvyl moiety onto a human-type complex glycopeptide. The resultant pyruvylated human-type complex glycopeptide recognized similar lectins on lectin arrays as the α2,6-sialyl glycopeptides. This newly-generated pyruvylation of human-type complex oligosaccharides would provide a novel method for glyco-bioengineering. PMID:27194449

  16. A rationally engineered yeast pyruvyltransferase Pvg1p introduces sialylation-like properties in neo-human-type complex oligosaccharide

    PubMed Central

    Higuchi, Yujiro; Yoshinaga, Sho; Yoritsune, Ken-ichi; Tateno, Hiroaki; Hirabayashi, Jun; Nakakita, Shin-ichi; Kanekiyo, Miho; Kakuta, Yoshimitsu; Takegawa, Kaoru

    2016-01-01

    Pyruvylation onto the terminus of oligosaccharide, widely seen from prokaryote to eukaryote, confers negative charges on the cell surface and seems to be functionally similar to sialylation, which is found at the end of human-type complex oligosaccharide. However, detailed molecular mechanisms underlying pyruvylation have not been clarified well. Here, we first determined the crystal structure of fission yeast pyruvyltransferase Pvg1p at a resolution of 2.46 Å. Subsequently, by combining molecular modeling with mutational analysis of active site residues, we obtained a Pvg1p mutant (Pvg1pH168C) that efficiently transferred pyruvyl moiety onto a human-type complex glycopeptide. The resultant pyruvylated human-type complex glycopeptide recognized similar lectins on lectin arrays as the α2,6-sialyl glycopeptides. This newly-generated pyruvylation of human-type complex oligosaccharides would provide a novel method for glyco-bioengineering. PMID:27194449

  17. CSF N-glycan profile reveals sialylation deficiency in a patient with GM2 gangliosidosis presenting as childhood disintegrative disorder.

    PubMed

    Barone, Rita; Sturiale, Luisella; Fiumara, Agata; Palmigiano, Angelo; Bua, Rosaria O; Rizzo, Renata; Zappia, Mario; Garozzo, Domenico

    2016-04-01

    Protein N-glycosylation consists in the synthesis and processing of the oligosaccharide moiety (N-glycan) linked to a protein and it serves several functions for the proper central nervous system (CNS) development and function. Previous experimental and clinical studies have shown the importance of proper glycoprotein sialylation for the synaptic function and the occurrence of autism spectrum disorders (ASD) in the presence of sialylation deficiency in the CNS. Late-onset Tay Sachs disease (LOTSD) is a lysosomal disorder caused by mutations in the HEXA gene resulting in GM2-ganglioside storage in the CNS. It is characterized by progressive neurological impairment and high co-occurrence of psychiatric disturbances. We studied the N-glycome profile of the cerebrospinal fluid (CSF) in a 14 year-old patient with GM2-gangliosidosis (LOTSD). At the age of 4, the patient presented regressive autism fulfilling criteria for childhood disintegrative disorder (CDD). A CSF sample was obtained in the course of diagnostic work-up for the suspicion of an underlying neurodegenerative disorder. We found definite changes of CSF N-glycans due to a dramatic decrease of sialylated biantennary and triantennary structures and an increase of asialo-core fucosylated bisected N-glycans. No changes of total plasma N-glycans were found. Herein findings highlight possible relationships between the early onset psychiatric disturbance featuring CDD in the patient and defective protein sialylation in the CNS. In conclusion, the study first shows aberrant N-glycan structures of CSF proteins in LOTSD; unveils possible pathomechanisms of GM2-gangliosidosis; supports existing relationships between neuropsychiatric disorders and unproper protein glycosylation in the CNS. PMID:26286102

  18. Sialylation of Glycosylphosphatidylinositol (GPI) Anchors of Mammalian Prions Is Regulated in a Host-, Tissue-, and Cell-specific Manner.

    PubMed

    Katorcha, Elizaveta; Srivastava, Saurabh; Klimova, Nina; Baskakov, Ilia V

    2016-08-12

    Prions or PrP(Sc) are proteinaceous infectious agents that consist of misfolded, self-replicating states of the prion protein or PrP(C) PrP(C) is posttranslationally modified with N-linked glycans and a sialylated glycosylphosphatidylinositol (GPI) anchor. Conformational conversion of PrP(C) gives rise to glycosylated and GPI-anchored PrP(Sc) The question of the sialylation status of GPIs within PrP(Sc) has been controversial. Previous studies that examined scrapie brains reported that both sialo- and asialo-GPIs were present in PrP(Sc), with the majority being asialo-GPIs. In contrast, recent work that employed cultured cells claimed that only PrP(C) with sialylo-GPIs could be recruited into PrP(Sc), whereas PrP(C) with asialo-GPIs inhibited conversion. To resolve this controversy, we analyzed the sialylation status of GPIs within PrP(Sc) generated in the brain, spleen, or cultured N2a or C2C12 myotube cells. We found that recruiting PrP(C) with both sialo- and asialo-GPIs is a common feature of PrP(Sc) The mixtures of sialo- and asialo-GPIs were observed in PrP(Sc) universally regardless of prion strain as well as host, tissue, or type of cells that produced PrP(Sc) Remarkably, the proportion of sialo- versus asialo-GPIs was found to be controlled by host, tissue, and cell type but not prion strain. In summary, this study found no strain-specific preferences for selecting PrP(C) with sialo- versus asialo-GPIs. Instead, this work suggests that the sialylation status of GPIs within PrP(Sc) is regulated in a cell-, tissue-, or host-specific manner and is likely to be determined by the specifics of GPI biosynthesis. PMID:27317661

  19. Increase in Sialylation and Branching in the Mouse Serum N-glycome Correlates with Inflammation and Ovarian Tumour Progression

    PubMed Central

    Saldova, Radka; Piccard, Helene; Pérez-Garay, Marta; Harvey, David J.; Struwe, Weston B.; Galligan, Marie C.; Berghmans, Nele; Madden, Stephen F.; Peracaula, Rosa; Opdenakker, Ghislain; Rudd, Pauline M.

    2013-01-01

    Ovarian cancer is the most lethal gynaecological cancer and is often diagnosed in late stage, often as the result of the unavailability of sufficiently sensitive biomarkers for early detection, tumour progression and tumour-associated inflammation. Glycosylation is the most common posttranslational modification of proteins; it is altered in cancer and therefore is a potential source of biomarkers. We investigated the quantitative and qualitative effects of anti-inflammatory (acetylsalicylic acid) and pro-inflammatory (thioglycolate and chlorite-oxidized oxyamylose) drugs on glycosylation in mouse cancer serum. A significant increase in sialylation and branching of glycans in mice treated with an inflammation-inducing compound was observed. Moreover, the increases in sialylation correlated with increased tumour sizes. Increases in sialylation and branching were consistent with increased expression of sialyltransferases and the branching enzyme MGAT5. Because the sialyltransferases are highly conserved among species, the described changes in the ovarian cancer mouse model are relevant to humans and serum N-glycome analysis for monitoring disease treatment and progression might be a useful biomarker. PMID:24023608

  20. The Association of Human Apolipoprotein C-III Sialylation Proteoforms with Plasma Triglycerides

    PubMed Central

    Yassine, Hussein N.; Trenchevska, Olgica; Ramrakhiani, Ambika; Parekh, Aarushi; Koska, Juraj; Walker, Ryan W.; Billheimer, Dean; Reaven, Peter D.; Yen, Frances T.; Nelson, Randall W.; Goran, Michael I.; Nedelkov, Dobrin

    2015-01-01

    Introduction Apolipoprotein C-III (apoC-III) regulates triglyceride (TG) metabolism. In plasma, apoC-III exists in non-sialylated (apoC-III0a without glycosylation and apoC-III0b with glycosylation), monosialylated (apoC-III1) or disialylated (apoC-III2) proteoforms. Our aim was to clarify the relationship between apoC-III sialylation proteoforms with fasting plasma TG concentrations. Methods In 204 non-diabetic adolescent participants, the relative abundance of apoC-III plasma proteoforms was measured using mass spectrometric immunoassay. Results Compared with the healthy weight subgroup (n = 16), the ratios of apoC-III0a, apoC-III0b, and apoC-III1 to apoC-III2 were significantly greater in overweight (n = 33) and obese participants (n = 155). These ratios were positively correlated with BMI z-scores and negatively correlated with measures of insulin sensitivity (Si). The relationship of apoC-III1 / apoC-III2 with Si persisted after adjusting for BMI (p = 0.02). Fasting TG was correlated with the ratio of apoC-III0a / apoC-III2 (r = 0.47, p<0.001), apoC-III0b / apoC-III2 (r = 0.41, p<0.001), apoC-III1 / apoC-III2 (r = 0.43, p<0.001). By examining apoC-III concentrations, the association of apoC-III proteoforms with TG was driven by apoC-III0a (r = 0.57, p<0.001), apoC-III0b (r = 0.56. p<0.001) and apoC-III1 (r = 0.67, p<0.001), but not apoC-III2 (r = 0.006, p = 0.9) concentrations, indicating that apoC-III relationship with plasma TG differed in apoC-III2 compared with the other proteoforms. Conclusion We conclude that apoC-III0a, apoC-III0b, and apoC-III1, but not apoC- III2 appear to be under metabolic control and associate with fasting plasma TG. Measurement of apoC-III proteoforms can offer insights into the biology of TG metabolism in obesity. PMID:26633899

  1. Modern Exploration of the Lewis and Clark Expedition

    NASA Technical Reports Server (NTRS)

    2006-01-01

    The Lewis and Clark Geosystem is an online collection of private, state, local, and Federal data resources associated with the geography of the Lewis and Clark Expedition. Data were compiled from key partners including NASA s Stennis Space Center, the U.S. Army Corps of Engineers, the U.S. Fish and Wildlife Service, the U.S. Geological Survey (USGS), the University of Montana, the U.S. Department of Agriculture Forest Service, and from a collection of Lewis and Clark scholars. It combines modern views of the landscape with historical aerial photography, cartography, and other geographical data resources and historical sources, including: The Journals of the Lewis and Clark Expedition, the Academy of Natural Science's Lewis and Clark Herbarium, high-resolution copies of the American Philosophical Society s primary-source Lewis and Clark Journals, The Library of Congress Lewis and Clark cartography collection, as well as artifacts from the Smithsonian Institution and other sources.

  2. A Biography of Distinguished Scientist Gilbert Newton Lewis (by Edward S. Lewis)

    NASA Astrophysics Data System (ADS)

    Harris, Reviewed By Harold H.

    1999-11-01

    The Edward Mellen Press: Lewiston, NY, 1998. 114 pp + index. ISBN 0-7734-8284-9. $69.95. There may not be a surname better known to students of chemistry than Lewis, from the Lewis electron-dot diagrams and the Lewis theory of acids and bases. More advanced students may know of the groundbreaking textbook Thermodynamics, by Lewis and Randall. Yet few Americans know much about this remarkable U.S.-born scholar, whose contributions equal those of the greatest scientists. He is a chemist-educator of whom we should be as proud and as well informed as we are of Linus Pauling, who was part of the westward movement of science in this country that G. N. Lewis began, or of the recently deceased Glenn Seaborg, who was one of the many students of Lewis who achieved renown. Gilbert N. Lewis was born in Weymouth, Massachusetts, in 1875, but his family moved to near Lincoln, Nebraska, in 1884. He spent two years at the University of Nebraska, but then moved to Harvard when his father became an executive at Merchants Trust Company in Boston. Young Lewis (then only 17) was also said to have been disappointed with the quality of education in Nebraska, and this may have been part of the impetus for the family's move east. After earning his baccalaureate at Harvard, he taught for a year at Phillips Andover Academy before returning to Harvard to study for his doctorate, which he completed 100 years ago, in 1899, under T. W. Richards. Lewis's doctoral work was on the thermodynamics of zinc and cadmium amalgams. At that time, physical chemistry was only beginning to achieve recognition as a branch of science, and its boundaries were ill defined. Edward Lewis quotes his father as often saying, "Physical chemistry is anything interesting." Like many chemists of his time, Lewis went to Europe to complete his preparation for a career; he was in the laboratories of Ostwald in Leipzig and Nernst in Göttingen in 1900-1901. On his return to the United States, he was an instructor at Harvard

  3. Enhanced sialylation and in vivo efficacy of recombinant human α-galactosidase through in vitro glycosylation

    PubMed Central

    Sohn, Youngsoo; Lee, Jung Mi; Park, Heung-Rok; Jung, Sung-Chul; Park, Tai Hyun; Oh, Doo-Byoung

    2013-01-01

    Human α-galactosidase A (GLA) has been used in enzyme replacement therapy for patients with Fabry disease. We expressed recombinant GLA from Chinese hamster ovary cells with very high productivity. When compared to an approved GLA (agalsidase beta), its size and charge were found to be smaller and more neutral. These differences resulted from the lack of terminal sialic acids playing essential roles in the serum half-life and proper tissue targeting. Because a simple sialylation reaction was not enough to increase the sialic acid content, a combined reaction using galactosyltransferase, sialyltransferase, and their sugar substrates at the same time was developed and optimized to reduce the incubation time. The product generated by this reaction had nearly the same size, isoelectric points, and sialic acid content as agalsidase beta. Furthermore, it had better in vivo efficacy to degrade the accumulated globotriaosylceramide in target organs of Fabry mice compared to an unmodified version. [BMB Reports 2013; 46(3): 157-162] PMID:23527859

  4. Sialylated oligosaccharides O-glycosidically linked to glycoprotein C from herpes simplex virus type 1.

    PubMed

    Dall'Olio, F; Malagolini, N; Speziali, V; Campadelli-Fiume, G; Serafini-Cessi, F

    1985-10-01

    Glycoprotein C (gC) was purified by immunoabsorbent from herpes simplex virus type-1-infected BHK cells labeled with [14C]glucosamine for 11 h and chased for 3 h. Glycopeptides obtained by pronase digestion of gC were fractionated by Bio-Gel filtration and concanavalin A-Sepharose chromatography. Each glycopeptide fraction was analyzed for amino sugar composition by thin-layer chromatography. The majority of radioactivity was recovered as N-acetylglucosamine, but a significant amount of labeled N-acetylgalactosamine was detected and recovered preferentially in some glycopeptide species. Mild alkaline borohydride treatment of the glycopeptides resulted in the release of small degradation products which contained N-acetylgalactosaminitol as the major labeled component and a drastic reduction of N-acetylgalactosamine in the residual glycopeptides. These results demonstrated that gC carries O-glycosidically linked oligosaccharides in addition to the N-linked di- and triantennary glycans previously described (F. Serafini-Cessi, F. Dall'Olio, L. Pereira, and G. Campadelli-Fiume, J. Virol. 51:838-844, 1984). Chromatographic behavior on DEAE-Sephacel chromatography and neuraminidase digestion of O-linked oligosaccharides indicated the presence of two major sialylated species carrying one and two sialic acid residues, respectively. The characterization of a peculiar glycopeptide species supported the notion that some of the O-linked oligosaccharides are bound to a cluster of hydroxyamino acids located near an N-glycosylation site which carries one N-linked diantennary oligosaccharide. PMID:2993643

  5. Changes in the sialylation and sulfation of secreted thyrotropin in congenital hypothyroidism

    SciTech Connect

    Gyves, P.W.; Gesundheit, N.; Thotakura, N.R.; Stannard, B.S.; DeCherney, G.S.; Weintraub, B.D. )

    1990-05-01

    The authors have examined the oligosaccharide structure of secreted thyrotropin (TSH) in perinatal and mature rats with congenital primary hypothyroidism. Rat pituitaries from euthyroid control animals and those rendered hypothyroid by methimazole treatment were incubated with ({sup 3}H)glucosamine in vitro. Secreted TSH was purified, and oligosaccharides were enzymatically released and characterized by anion-exchange HPLC. In perinatal hypothyroid animals compared with control animals, oligosaccharides from TSH {alpha} and {beta} subunits contained more species with three or more negative charges. Moreover, perinatal hypothyroid animals demonstrated a dramatic increase in the ratio of sialylated to sulfated species within oligosaccharides of the same negative charge. In mature hypothyroid 9-week-old animals compared with control animals, changes were less pronounced, suggesting that endocrine regulation of oligosaccharide structure is dependent upon the maturational state of the animal. Together, these data provide direct evidence and characterization of specific changes in the structure of a secreted pituitary glycoprotein hormone occurring as a result of in vivo endocrine alterations during early development. Moreover, they provide a potential structural basis to explain the delayed clearance of both TSH and the gonadotropins with end-organ deficiency, which may have important implications for the in vivo biological activities of these hormones.

  6. Sialyl-Tn in Cancer: (How) Did We Miss the Target?

    PubMed Central

    Julien, Sylvain; Videira, Paula A.; Delannoy, Philippe

    2012-01-01

    Sialyl-Tn antigen (STn) is a short O-glycan containing a sialic acid residue α2,6-linked to GalNAcα-O-Ser/Thr. The biosynthesis of STn is mediated by a specific sialyltransferase termed ST6GalNAc I, which competes with O-glycans elongating glycosyltransferases and prevents cancer cells from exhibiting longer O-glycans. While weakly expressed by fetal and normal adult tissues, STn is expressed by more than 80% of human carcinomas and in all cases, STn detection is associated with adverse outcome and decreased overall survival for the patients. Because of its pan-carcinoma expression associated with an adverse outcome, an anti-cancer vaccine, named Theratope, has been designed towards the STn epitope. In spite of the great enthusiasm around this immunotherapy, Theratope failed on Phase III clinical trial. However, in lieu of missing this target, one should consider to revise the Theratope design and the actual facts. In this review, we highlight the many lessons that can be learned from this failure from the immunological standpoint, as well as from the drug design and formulation and patient selection. Moreover, an irrefutable knowledge is arising from novel immunotherapies targeting other carbohydrate antigens and STn carrier proteins, such as MUC1, that will warrantee the future development of more successful anti-STn immunotherapy strategies. PMID:24970145

  7. Serum amyloid P is a sialylated glycoprotein inhibitor of influenza A viruses.

    PubMed

    Job, Emma R; Bottazzi, Barbara; Gilbertson, Brad; Edenborough, Kathryn M; Brown, Lorena E; Mantovani, Alberto; Brooks, Andrew G; Reading, Patrick C

    2013-01-01

    Members of the pentraxin family, including PTX3 and serum amyloid P component (SAP), have been reported to play a role in innate host defence against a range of microbial pathogens, yet little is known regarding their antiviral activities. In this study, we demonstrate that human SAP binds to human influenza A virus (IAV) strains and mediates a range of antiviral activities, including inhibition of IAV-induced hemagglutination (HA), neutralization of virus infectivity and inhibition of the enzymatic activity of the viral neuraminidase (NA). Characterization of the anti-IAV activity of SAP after periodate or bacterial sialidase treatment demonstrated that α(2,6)-linked sialic acid residues on the glycosidic moiety of SAP are critical for recognition by the HA of susceptible IAV strains. Other proteins of the innate immune system, namely human surfactant protein A and porcine surfactant protein D, have been reported to express sialylated glycans which facilitate inhibition of particular IAV strains, yet the specific viral determinants for recognition of these inhibitors have not been defined. Herein, we have selected virus mutants in the presence of human SAP and identified specific residues in the receptor-binding pocket of the viral HA which are critical for recognition and therefore susceptibility to the antiviral activities of SAP. Given the widespread expression of α(2,6)-linked sialic acid in the human respiratory tract, we propose that SAP may act as an effective receptor mimic to limit IAV infection of airway epithelial cells. PMID:23544079

  8. Fuels research studies at NASA Lewis

    NASA Technical Reports Server (NTRS)

    Antoine, A. C.

    1982-01-01

    Fuels research studies carried out in a variety of areas related to aviation propulsion, ground transportation, and stationary power generation systems are discussed. The major efforts are directed to studies on fuels for jet aircraft. These studies involve fuels preparation, fuels analysis, and fuel quality evaluations. The scope and direction of research activities in these areas is discussed, descriptions of Lewis capabilities and facilities given, and results of recent research efforts reported.

  9. The NASA-Lewis terrestrial photovoltaics program

    NASA Technical Reports Server (NTRS)

    Bernatowicz, D. T.

    1974-01-01

    Those parts of the present NASA-Lewis research and technology effort on solar cells and arrays having relevance to terrestrial uses are outlined. These include raising cell efficiency, developing the FEP-covered module concept, and exploring low-cost cell concepts. Solar cell-battery power systems for remote weather stations have been built to demonstrate the capabilities of solar cells for terrestrial applications.

  10. Lewis Research Center earth resources program

    NASA Technical Reports Server (NTRS)

    Mark, H.

    1972-01-01

    The Lewis Research Center earth resources program efforts are in the areas of: (1) monitoring and rapid evaluation of water quality; (2) determining ice-type and ice coverage distribution to aid operations in a possible extension of the Great Lakes ice navigation and shipping season; (3) monitoring spread of crop viruses; and (4) extent of damage to strip mined areas as well as success of efforts to rehabilitate such areas for agriculture.

  11. Dual Lewis Acid/Lewis Base Catalyzed Acylcyanation of Aldehydes: A Mechanistic Study.

    PubMed

    Laurell Nash, Anna; Hertzberg, Robin; Wen, Ye-Qian; Dahlgren, Björn; Brinck, Tore; Moberg, Christina

    2016-03-01

    A mechanistic investigation, which included a Hammett correlation analysis, evaluation of the effect of variation of catalyst composition, and low-temperature NMR spectroscopy studies, of the Lewis acid-Lewis base catalyzed addition of acetyl cyanide to prochiral aldehydes provides support for a reaction route that involves Lewis base activation of the acyl cyanide with formation of a potent acylating agent and cyanide ion. The cyanide ion adds to the carbonyl group of the Lewis acid activated aldehyde. O-Acylation by the acylated Lewis base to form the final cyanohydrin ester occurs prior to decomplexation from titanium. For less reactive aldehydes, the addition of cyanide is the rate-determining step, whereas, for more reactive, electron-deficient aldehydes, cyanide addition is rapid and reversible and is followed by rate-limiting acylation. The resting state of the catalyst lies outside the catalytic cycle and is believed to be a monomeric titanium complex with two alcoholate ligands, which only slowly converts into the product. PMID:26592522

  12. Lewis' Educational and Research Collaborative Internship Program

    NASA Technical Reports Server (NTRS)

    Heyward, Ann; Gott, Susan (Technical Monitor)

    2004-01-01

    The Lewis Educational and Research Collaborative Internship Program (LERCIP) is a collaborative undertaking by the Office of Educational Programs at NASA Glenn Research Center at Lewis Field (formerly NASA Lewis Research Center) and the Ohio Aerospace Institute. This program provides 10-week internships in addition to summer and winter extensions if funding is available and/or is requested by mentor (no less than 1 week no more than 4 weeks) for undergraduate/graduate students and secondary school teachers. Students who meet the travel reimbursement criteria receive up to $500 for travel expenses. Approximately 178 interns are selected to participate in this program each year and begin arriving the fourth week in May. The internships provide students with introductory professional experiences to complement their academic programs. The interns are given assignments on research and development projects under the personal guidance of NASA professional staff members. Each intern is assigned a NASA mentor who facilitates a research assignment. In addition to the research assignment, the summer program includes a strong educational component that enhances the professional stature of the participants. The educational activities include a research symposium and a variety of workshops, and lectures. An important aspect of the program is that it includes students with diverse social, cultural and economic backgrounds. The purpose of this report is to document the program accomplishments for 2004.

  13. A Biographical Sketch of Lewis Dexter

    PubMed Central

    Mukhopadhyay, Madhuri

    2001-01-01

    Dr. Lewis Dexter was an outstanding cardiovascular physiologist and clinician, a respected teacher and scientist, and, most importantly, a fine human being. During his life, he brought the cardiac catheter from the laboratory to the patient and trained several generations of cardiologists. Dexter's laboratory was the first to elucidate the pathophysiologic alterations present in many forms of congenital heart disease, including atrial septal defects, patent ductus arteriosus, tetralogy of Fallot, ventricular septal defects, and pulmonic stenosis. Subsequent work in Dexter's laboratory led to the 1st measurements of pulmonary capillary wedge pressure and to the precise calculation of stenotic valve areas from hemodynamic parameters measured during cardiac catheterization. During a teaching exercise, Dexter demonstrated that exercise with a cardiac catheter in the heart was safe and produced clinically important data, by having a cardiac catheter inserted in himself. Over the years, many significant pathophysiologic studies that explored pulmonary embolism, valvular heart disease, right and left ventricular function, and pulmonary hypertension were published from Dexter's laboratory. But Lewis Dexter was more than a brilliant researcher. “Lew” was very close to his fellows and students, whom he considered extensions of his family. Dexter was a remarkable teacher, a compassionate physician, and a scrupulously honest investigator. Dr. Lewis Dexter had a major impact on modern medicine and was one of the great cardiologists of the 20th century. PMID:11453126

  14. Lewis Information Network (LINK): Background and overview

    NASA Technical Reports Server (NTRS)

    Schulte, Roger R.

    1987-01-01

    The NASA Lewis Research Center supports many research facilities with many isolated buildings, including wind tunnels, test cells, and research laboratories. These facilities are all located on a 350 acre campus adjacent to the Cleveland Hopkins Airport. The function of NASA-Lewis is to do basic and applied research in all areas of aeronautics, fluid mechanics, materials and structures, space propulsion, and energy systems. These functions require a great variety of remote high speed, high volume data communications for computing and interactive graphic capabilities. In addition, new requirements for local distribution of intercenter video teleconferencing and data communications via satellite have developed. To address these and future communications requirements for the next 15 yrs, a project team was organized to design and implement a new high speed communication system that would handle both data and video information in a common lab-wide Local Area Network. The project team selected cable television broadband coaxial cable technology as the communications medium and first installation of in-ground cable began in the summer of 1980. The Lewis Information Network (LINK) became operational in August 1982 and has become the backbone of all data communications and video.

  15. Frustrated Lewis pairs: from concept to catalysis.

    PubMed

    Stephan, Douglas W

    2015-02-17

    CONSPECTUS: Frustrated Lewis pair (FLP) chemistry has emerged in the past decade as a strategy that enables main-group compounds to activate small molecules. This concept is based on the notion that combinations of Lewis acids and bases that are sterically prevented from forming classical Lewis acid-base adducts have Lewis acidity and basicity available for interaction with a third molecule. This concept has been applied to stoichiometric reactivity and then extended to catalysis. This Account describes three examples of such developments: hydrogenation, hydroamination, and CO2 reduction. The most dramatic finding from FLP chemistry was the discovery that FLPs can activate H2, thus countering the long-existing dogma that metals are required for such activation. This finding of stoichiometric reactivity was subsequently evolved to employ simple main-group species as catalysts in hydrogenations. While the initial studies focused on imines, subsequent studies uncovered FLP catalysts for a variety of organic substrates, including enamines, silyl enol ethers, olefins, and alkynes. Moreover, FLP reductions of aromatic anilines and N-heterocycles have been developed, while very recent extensions have uncovered the utility of FLP catalysts for ketone reductions. FLPs have also been shown to undergo stoichiometric reactivity with terminal alkynes. Typically, either deprotonation or FLP addition reaction products are observed, depending largely on the basicity of the Lewis base. While a variety of acid/base combinations have been exploited to afford a variety of zwitterionic products, this reactivity can also be extended to catalysis. When secondary aryl amines are employed, hydroamination of alkynes can be performed catalytically, providing a facile, metal-free route to enamines. In a similar fashion, initial studies of FLPs with CO2 demonstrated their ability to capture this greenhouse gas. Again, modification of the constituents of the FLP led to the discovery of reaction

  16. The α-Glycosidation of Partially Unprotected N-Acetyl and N-Glycolyl Sialyl Donors in the Absence of a Nitrile Solvent Effect.

    PubMed

    Aoyagi, Taku; Ohira, Shuichi; Fuse, Shinichiro; Uzawa, Jun; Yamaguchi, Yoshiki; Tanaka, Hiroshi

    2016-05-10

    The synthesis of α-sialosides is one of the most difficult reactions in carbohydrate chemistry and is considered to be both a thermodynamically and kinetically disfavored process. The use of acetonitrile as a solvent is an effective solution for the α-selective glycosidation of N-acetyl sialic acids. In this report, we report on the α-glycosidation of partially unprotected N-acetyl and N-glycolyl donors in the absence of a nitrile solvent effect. The 9-O-benzyl-N-acetylthiosialoside underwent glycosidation in CH2 Cl2 with a good α-selectivity. On the other hand, the 4,7,8-O-triacetyl-9-O-benzyl-N-acetylthiosialoside was converted to β-sialoside as a major product under the same reaction conditions. The results indicate that the O-acetyl protection of the sialyl donor was a major factor in reducing the α-selectivity of sialylation. After tuning of the protecting groups of the hydroxy groups at the 4,7,8 position on the sialyl donor, we found that the 9-O-benzyl-4-O-chloroacetyl-N-acetylthiosialoside underwent sialylation with excellent α-selectivity in CH2 Cl2 . To demonstrate the utility of the method, straightforward synthesis of α(2,9) disialosides containing N-acetyl and/or N-glycolyl groups was achieved by using the two N-acetyl and N-glycolyl sialyl donors. PMID:27060996

  17. Ultrasensitive electrochemical biosensor based on reduced graphene oxide-tetraethylene pentamine-BMIMPF6 hybrids for the detection of α2,6-sialylated glycans in human serum.

    PubMed

    Li, Yuliang; He, Junlin; Niu, Yazhen; Yu, Chao

    2015-12-15

    In this paper, a simple, ultrasensitive and label-free electrochemical α2,6-sialylated glycans biosensor based on reduced graphene oxide-tetraethylene pentamine-1-butyl-3-methylimidazolium hexafluorophosphate (BMIMPF6) hybrids was developed. Due to the abundance of amino groups from reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) and the electrostatic interaction of BMIMPF6, bimetallic gold platinum alloy nanoparticles (AuPtNPs) were densely adsorbed onto the surface of the nanocomposite, providing a large surface area available for the immobilization of Sambucus nigra agglutinin (SNA). AuPtNPs have excellent conductivity and catalytic activity, which can promote electron transfer between the electrolyte solution and the surface of electrode and can enhance the sensitivity of biosensor. SNA, which specifically binds α2,6-sialylated glycans, was covalently immobilized on AuPtNPs for specific detection of α2,6-sialylated glycans in human serum. Under optimal experimental conditions, amperometric response changes were used to detect α2,6-sialylated glycans with a broad linear range of 10 fg mL(-1) -1 μg mL(-1) and a low detection limit of 3 fg mL(-1) (S/N=3). When applied to spiked serum samples, the recovery of the developed biosensor ranged from 100.8% to 101.4%, suggesting that the electrochemical biosensor would be suitable for the practical detection of α2,6-sialylated glycans. PMID:26257188

  18. Transition-Metal Oxos as the Lewis Basic Component of Frustrated Lewis Pairs.

    PubMed

    Lambic, Nikola S; Sommer, Roger D; Ison, Elon A

    2016-04-13

    The reaction of oxorhenium complexes that incorporate diamidopyridine (DAP) ligands with B(C6F5)3 results in the formation of classical Lewis acid-base adducts. The adducts effectively catalyze the hydrogenation of a variety of unactivated olefins at 100 °C. Control reactions with these complexes or B(C6F5)3 alone did not yield any hydrogenated products under these conditions. Mechanistic studies suggest a frustrated Lewis pair is generated between the oxorhenium DAP complexes and B(C6F5)3, which is effective at olefin hydrogenation. Thus, we demonstrate for the first time that the incorporation of a transition-metal oxo in a frustrated Lewis pair can have a synergistic effect and results in enhanced catalytic activity. PMID:27002927

  19. UDP-GlcNAc2-epimerase regulates cell surface sialylation and ceramide-induced cell death in human malignant lymphoma.

    PubMed

    Suzuki, Osamu; Tasaki, Kazuhiro; Kusakabe, Takashi; Abe, Masafumi

    2008-09-01

    Stress signals induce ceramide (cer) through sphingomyelinase activation, and metabolites of cer such as sphingosine (Sph) and sphingosine-1-phoshate (S-1-P) play a significant role in many biological processes. This study aimed to elucidate the association between the alteration in cell surface sialylation and ceramide-induced cell death in the human Burkitt's lymphoma cell line, HBL-8. The highly sialylated 3G3 clone was less sensitive to C6-ceramide-induced cell death. On the other hand, the hyposialylated 3D2 clone was more sensitive to C6-ceramide-induced cell death. Neuraminidase treatment or knockdown by siRNA of uridine diphosphate-N-acetylglucosamine 2-epimerase (UDP-GlcNAc2-epimerase), which is a key enzyme of sialic acid biosynthesis, enhanced the amount of cell death induced by C6-ceramide in the highly sialylated 3G3 clone. Sialic acid metabolic complementation assays using several precursors of sialic acid showed that cell surface resialylation by N-acetyl-D-mannosamine (ManNAc) inhibited C6-ceramide-induced cell death. The amount of cell death by C6-ceramide was enhanced after pretreatment with phosphatidylinositol 3-kinase (PI3K) inhibitor, LY294002 in both clones. In addition, clone 3G3 was less sensitive to Sph than the 3D2 clone. In conclusion, in human malignant lymphoma, ceramide and its metabolite-induced cell death is regulated by the amount of sialic acid on the cell surface which in turn is regulated by mRNA expression of UDP-GlcNAc2-epimerase. PMID:18698493

  20. Trypanosoma cruzi Subverts Host Cell Sialylation and May Compromise Antigen-specific CD8+ T Cell Responses*

    PubMed Central

    Freire-de-Lima, Leonardo; Alisson-Silva, Frederico; Carvalho, Sebastião T.; Takiya, Christina M.; Rodrigues, Maurício M.; DosReis, George A.; Mendonça-Previato, Lucia; Previato, José O.; Todeschini, Adriane R.

    2010-01-01

    Upon activation, cytotoxic CD8+ T lymphocytes are desialylated exposing β-galactose residues in a physiological change that enhances their effector activity and that can be monitored on the basis of increased binding of the lectin peanut agglutinin. Herein, we investigated the impact of sialylation mediated by trans-sialidase, a specific and unique Trypanosoma transglycosylase for sialic acid, on CD8+ T cell response of mice infected with T. cruzi. Our data demonstrate that T. cruzi uses its trans-sialidase enzyme to resialylate the CD8+ T cell surface, thereby dampening antigen-specific CD8+ T cell response that might favor its own persistence in the mammalian host. Binding of the monoclonal antibody S7, which recognizes sialic acid-containing epitopes on the 115-kDa isoform of CD43, was augmented on CD8+ T cells from ST3Gal-I-deficient infected mice, indicating that CD43 is one sialic acid acceptor for trans-sialidase activity on the CD8+ T cell surface. The cytotoxic activity of antigen-experienced CD8+ T cells against the immunodominant trans-sialidase synthetic peptide IYNVGQVSI was decreased following active trans-sialidase- mediated resialylation in vitro and in vivo. Inhibition of the parasite's native trans-sialidase activity during infection strongly decreased CD8+ T cell sialylation, reverting it to the glycosylation status expected in the absence of parasite manipulation increasing mouse survival. Taken together, these results demonstrate, for the first time, that T. cruzi subverts sialylation to attenuate CD8+ T cell interactions with peptide-major histocompatibility complex class I complexes. CD8+ T cell resialylation may represent a sophisticated strategy to ensure lifetime host parasitism. PMID:20106975

  1. Dementia with Lewy bodies: early diagnostic challenges.

    PubMed

    Fujishiro, Hiroshige; Iseki, Eizo; Nakamura, Shinichiro; Kasanuki, Koji; Chiba, Yuhei; Ota, Kazumi; Murayama, Norio; Sato, Kiyoshi

    2013-06-01

    Dementia with Lewy bodies (DLB) is defined pathologically as neurodegeneration associated with Lewy bodies (LB). LB-related symptoms, including olfactory dysfunction, dysautonomia, and mood and sleep disorders, are increasingly recognized as clinical signs that enable the early detection of DLB, because these symptoms often antedate dementia by years or even decades. It remains unknown if the clinical history of LB-related symptoms is sufficient for the prodromal state of DLB to be suspected in memory clinics. We retrospectively investigated the clinical courses, including olfactory dysfunction, dysautonomia, depression, and rapid eye movement sleep behaviour disorder, of 90 patients with probable DLB. The timing of LB-related symptoms that preceded or followed relative to the onset of memory loss was calculated. LB-related symptoms were present in 79 of 90 patients (87.8%) with probable DLB before or at the time of memory loss onset. These symptoms preceded the onset of memory loss between 1.2 and 9.3 years. We also report on four non-demented patients with a clinical history of LB-related symptoms in our memory clinic. All four patients showed reduced cardiac [(123) I]-metaiodobenzylguanidine levels. Moreover, [(18) F]fluoro-D-glucose positron emission tomography scans revealed glucose hypometabolism in the occipital cortex in two patients. One patient converted to probable DLB with the development of parkinsonism 2 years after major depression was diagnosed. Based on a clinical history of LB-related symptoms, we propose a conceptual framework to identify these symptomatic but non-demented individuals that led us to suspect the underlying pathophysiology of Lewy body disease. Further prospective study is warranted to determine the clinical significance of LB-related symptoms in non-demented patients. PMID:23909972

  2. Loss of Cellular Sialidases Does Not Affect the Sialylation Status of the Prion Protein but Increases the Amounts of Its Proteolytic Fragment C1

    PubMed Central

    Katorcha, Elizaveta; Klimova, Nina; Makarava, Natallia; Savtchenko, Regina; Pan, Xuefang; Annunziata, Ida; Takahashi, Kohta; Miyagi, Taeko; Pshezhetsky, Alexey V.; d’Azzo, Alessandra; Baskakov, Ilia V.

    2015-01-01

    The central molecular event underlying prion diseases involves conformational change of the cellular form of the prion protein (PrPC), which is a sialoglycoprotein, into the disease-associated, transmissible form denoted PrPSc. Recent studies revealed a correlation between the sialylation status of PrPSc and incubation time to disease and introduced a new hypothesis that progression of prion diseases could be controlled or reversed by altering the sialylation level of PrPC. Of the four known mammalian sialidases, the enzymes that cleave off sialic acid residues, only NEU1, NEU3 and NEU4 are expressed in the brain. To test whether cellular sialidases control the steady-state sialylation level of PrPC and to identify the putative sialidase responsible for desialylating PrPC, we analyzed brain-derived PrPC from knockout mice deficient in Neu1, Neu3, Neu4, or from Neu3/Neu4 double knockouts. Surprisingly, no differences in the sialylation of PrPC or its proteolytic product C1 were noticed in any of the knockout mice tested as compared to the age-matched controls. However, significantly higher amounts of the C1 fragment relative to full-length PrPC were detected in the brains of Neu1 knockout mice as compared to WT mice or to the other knockout mice. Additional experiments revealed that in neuroblastoma cell line the sialylation pattern of C1 could be changed by an inhibitor of sialylatransferases. In summary, this study suggests that targeting cellular sialidases is apparently not the correct strategy for altering the sialylation levels of PrPC, whereas modulating the activity of sialylatransferases might offer a more promising approach. Our findings also suggest that catabolism of PrPC involves its α-cleavage followed by desialylation of the resulting C1 fragments by NEU1 and consequent fast degradation of the desialylated products. PMID:26569607

  3. Lewis Carroll's formula for calendar calculating.

    PubMed

    Spitz, H H

    1994-03-01

    One of the extraordinary skills occasionally displayed by individuals of low intelligence (so-called idiots savants) is the ability to name, within seconds, the day of the week for any given date, sometimes over a range of centuries. A number of scholarly papers contain references to formulas that can be used in making this calculation, but none cites one of the earliest published methods, that of Lewis Carroll. However, formulas such as Carroll's are too complex to be self-taught by idiots savants and, consequently, cannot account for their remarkable performance. Alternative explanatory hypotheses were briefly discussed. PMID:8192906

  4. Microglia in dementia with Lewy bodies.

    PubMed

    Streit, Wolfgang J; Xue, Qing-Shan

    2016-07-01

    Microglial activation (neuroinflammation) is often cited as a pathogenic factor in the development of neurodegenerative diseases. However, there are significant caveats associated with the idea that inflammation directly causes either α-synuclein pathology or neurofibrillary degeneration (NFD). We have performed immunohistochemical studies on microglial cells in five cases of dementia with Lewy bodies (DLB), median age 87, and nine cases of non-demented (ND) controls, median age 74, using tissue samples from the temporal lobe and the superior frontal gyrus. Three different antibodies known to label microglia and macrophages were employed: iba1, anti-CD68, and anti-ferritin. All DLB cases showed both α-synuclein pathology (Lewy bodies and neurites) and NFD ranging from Braak stage II to IV. In contrast, all controls were devoid of α-synuclein pathology but did show NFD ranging from Braak stage I to III. Using iba1 labeling, our current results show a notable absence of activated microglia in all cases with the exception of two controls that showed small focal areas of microglial activation and macrophage formation. Both iba1 and ferritin antibodies revealed a mixture of ramified and dystrophic microglial cells throughout the regions examined, and there were no measurable differences in the prevalence of dystrophic microglial cells between DLB and controls. Double-labeling for α-synuclein and iba1-positive microglia showed that cortical Lewy bodies were surrounded by both ramified and dystrophic microglial cells. We found an increase in CD68 expression in DLB cases relative to controls. Since microglial dystrophy has been linked to NFD and since it did not appear to be worse in DLB cases over controls, our findings support the idea that the additional Lewy body pathology in DLB is not the result of intensified microglial dystrophy. CD68 is likely associated with lipofuscin deposits in microglial cells which may be increased in DLB cases because of impaired

  5. NASA Lewis Research Center Futuring Workshop

    NASA Technical Reports Server (NTRS)

    Boroush, Mark; Stover, John; Thomas, Charles

    1987-01-01

    On October 21 and 22, 1986, the Futures Group ran a two-day Futuring Workshop on the premises of NASA Lewis Research Center. The workshop had four main goals: to acquaint participants with the general history of technology forecasting; to familiarize participants with the range of forecasting methodologies; to acquaint participants with the range of applicability, strengths, and limitations of each method; and to offer participants some hands-on experience by working through both judgmental and quantitative case studies. Among the topics addressed during this workshop were: information sources; judgmental techniques; quantitative techniques; merger of judgment with quantitative measurement; data collection methods; and dealing with uncertainty.

  6. NASA Lewis Research Center photovoltaic application experiments

    NASA Technical Reports Server (NTRS)

    Ratajczak, A.; Bifano, W.; Martz, J.; Odonnell, P.

    1978-01-01

    The NASA Lewis Research Center has installed 16 geographically dispersed terrestrial photovoltaic systems as part of the DOE National Photovoltaic Program. Four additional experiments are in progress. Currently, operating systems are powering refrigerators, a highway warning sign, forest lookout towers, remote weather stations, a water chiller and insect survey traps. Experiments in progress include the world's first village power system, an air pollution monitor and seismic sensors. Under a separate activity, funded by the U.S. Agency for International Development, a PV-powered water pump and grain grinder is being prepared for an African village. System descriptions and status are included in this report.

  7. Ultrafast hydrolysis of a Lewis photoacid.

    PubMed

    Henrich, Joseph D; Suchyta, Scott; Kohler, Bern

    2015-02-12

    This study explores the concept that electronic excitation can dramatically enhance Lewis acidity. Specifically, it is shown that photoexcitation transforms an electron-deficient organic compound of negligible Lewis acidity in its electronic ground state into a potent excited-state Lewis acid that releases a proton from a nearby water molecule in 3.1 ps. It was shown previously (Peon et al. J. Phys. Chem. A 2001, 105, 5768) that the excited state of methyl viologen (MV(2+)) is quenched rapidly in aqueous solution with the formation of an unidentified photoproduct. In this study, the quenching mechanism and the identity of the photoproduct were investigated by the femtosecond transient absorption and fluorescence upconversion techniques. Transient absorption signals at UV probe wavelengths reveal a long-lived species with a pH-dependent lifetime due to reaction with hydronium ions at a bimolecular rate of 3.1 × 10(9) M(-1) s(-1). This species is revealed to be a charge-transfer complex consisting of a ground-state MV(2+) ion and a hydroxide ion formed when a water molecule transfers a proton to the bulk solvent. Formation of a contact ion pair between MV(2+) and hydroxide shifts the absorption spectrum of the former ion by a few nm to longer wavelengths, yielding a transient absorption spectrum with a distinctive triangle wave appearance. The slight shift of this spectrum, which is in excellent agreement with steady-state difference spectra recorded for MV(2+) at high pH, is consistent with an ion pair but not with a covalent adduct (pseudobase). The long lifetime of the ion pair at neutral pH indicates that dissociation occurs many orders of magnitude more slowly than predicted by the Smoluchowski-Debye equation. Remarkably, there is no evidence of geminate recombination, suggesting that the proton that is transferred to the solvent is conducted at least several water shells away. Although the hydrolysis mechanism has yet to be fully established, evidence suggests

  8. A Biography of Distinguished Scientist Gilbert Newton Lewis (by Edward S. Lewis)

    NASA Astrophysics Data System (ADS)

    Harris, Reviewed By Harold H.

    1999-11-01

    The Edward Mellen Press: Lewiston, NY, 1998. 114 pp + index. ISBN 0-7734-8284-9. $69.95. There may not be a surname better known to students of chemistry than Lewis, from the Lewis electron-dot diagrams and the Lewis theory of acids and bases. More advanced students may know of the groundbreaking textbook Thermodynamics, by Lewis and Randall. Yet few Americans know much about this remarkable U.S.-born scholar, whose contributions equal those of the greatest scientists. He is a chemist-educator of whom we should be as proud and as well informed as we are of Linus Pauling, who was part of the westward movement of science in this country that G. N. Lewis began, or of the recently deceased Glenn Seaborg, who was one of the many students of Lewis who achieved renown. Gilbert N. Lewis was born in Weymouth, Massachusetts, in 1875, but his family moved to near Lincoln, Nebraska, in 1884. He spent two years at the University of Nebraska, but then moved to Harvard when his father became an executive at Merchants Trust Company in Boston. Young Lewis (then only 17) was also said to have been disappointed with the quality of education in Nebraska, and this may have been part of the impetus for the family's move east. After earning his baccalaureate at Harvard, he taught for a year at Phillips Andover Academy before returning to Harvard to study for his doctorate, which he completed 100 years ago, in 1899, under T. W. Richards. Lewis's doctoral work was on the thermodynamics of zinc and cadmium amalgams. At that time, physical chemistry was only beginning to achieve recognition as a branch of science, and its boundaries were ill defined. Edward Lewis quotes his father as often saying, "Physical chemistry is anything interesting." Like many chemists of his time, Lewis went to Europe to complete his preparation for a career; he was in the laboratories of Ostwald in Leipzig and Nernst in Göttingen in 1900-1901. On his return to the United States, he was an instructor at Harvard

  9. Neurophysiological biomarkers for Lewy body dementias

    PubMed Central

    Cromarty, Ruth A.; Elder, Greg J.; Graziadio, Sara; Baker, Mark; Bonanni, Laura; Onofrj, Marco; O’Brien, John T.; Taylor, John-Paul

    2016-01-01

    Objective Lewy body dementias (LBD) include both dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD), and the differentiation of LBD from other neurodegenerative dementias can be difficult. Currently, there are few biomarkers which might assist early diagnosis, map onto LBD symptom severity, and provide metrics of treatment response. Traditionally, biomarkers in LBD have focussed on neuroimaging modalities; however, as biomarkers need to be simple, inexpensive and non-invasive, neurophysiological approaches might also be useful as LBD biomarkers. Methods In this review, we searched PubMED and PsycINFO databases in a semi-systematic manner in order to identify potential neurophysiological biomarkers in the LBDs. Results We identified 1491 studies; of these, 37 studies specifically examined neurophysiological biomarkers in LBD patients. We found that there was substantial heterogeneity with respect to methodologies and patient cohorts. Conclusion Generally, many of the findings have yet to be replicated, although preliminary findings reinforce the potential utility of approaches such as quantitative electroencephalography and motor cortical stimulation paradigms. Significance Various neurophysiological techniques have the potential to be useful biomarkers in the LBDs. We recommend that future studies focus on maximising the diagnostic specificity and sensitivity of the most promising neurophysiological biomarkers. PMID:26183755

  10. Lewy Body Pathology in Familial Alzheimer Disease

    PubMed Central

    Leverenz, James B.; Fishel, Mark A.; Peskind, Elaine R.; Montine, Thomas J.; Nochlin, David; Steinbart, Ellen; Raskind, Murray A.; Schellenberg, Gerard D.; Bird, Thomas D.; Tsuang, Debby

    2006-01-01

    Background The origin and significance of Lewy bodies and neurites (Lewy body pathology [LBP]) in Alzheimer disease (AD) are poorly understood. Objective To examine LBP in the brainstem, limbic cortex, and neocortex of a large number of familial AD cases with mutations in 2 presenilin (PSEN) genes. Methods Twenty-five familial AD cases with 9 known PSEN 1 mutations and 14 familial AD cases with a single PSEN 2 mutation (N141I) were examined for LBP using α-synuclein immunohistochemistry and sampling of multiple brainstem and cortical regions. Results The amygdala was the most vulnerable site for LBP. In fact, virtually all (24 [96%] of 25 cases) of the PSEN 1 mutation cases had LBP in the amygdala. The PSEN 1 mutation cases also had more frequent LBP in the amygdala and neocortex than those with the PSEN 2 mutation. However, within families with a single mutation of either PSEN 1 or PSEN 2, there was frequent variability of the LBP. Conclusion These findings suggest that there are genetic influences on the presence of LBP in familial AD as demonstrated by the differences between PSEN 1 and PSEN 2 mutation cases. PMID:16533963

  11. Sialylation potentials of the silkworm, Bombyx mori; B. mori possesses an active α2,6-sialyltransferase.

    PubMed

    Kajiura, Hiroyuki; Hamaguchi, Yuichi; Mizushima, Hiroki; Misaki, Ryo; Fujiyama, Kazuhito

    2015-12-01

    N-Glycosylation is an important post-translational modification in most secreted and membrane-bound proteins in eukaryotic cells. However, the insect N-glycosylation pathway and the potentials contributing to the N-glycan synthesis are still unclear because most of the studies on these subjects have focused on mammals and plants. Here, we identified Bombyx mori sialyltransferase (BmST), which is a Golgi-localized glycosyltransferase and which can modify N-glycans. BmST was ubiquitously expressed in different organs and in various stages of development and localized at the Golgi. Biochemical analysis using Sf9-expressed BmST revealed that BmST encoded α2,6-sialyltransferase and transferred N-acetylneuraminic acid (NeuAc) to the nonreducing terminus of Galβ1-R, but exhibited the highest activity toward GalNAcβ1,4-GlcNAc-R. Unlike human α2,6-sialyltransferase, BmST required the post-translational modification, especially N-glycosylation, for its full activity. N-Glycoprotein analysis of B. mori fifth instar larvae revealed that high-mannose-type structure was predominant and GlcNAc-linked and fucosylated structures were observed but endogenous galactosyl-, N-acetylgalactosaminyl- and sialyl-N-glycoproteins were undetectable under the standard analytical approach. These results indicate that B. mori genome encodes an α2,6-sialyltransferase, but further investigations of the sialylation potentials are necessary. PMID:26306633

  12. Intrinsic hepatocyte dedifferentiation is accompanied by upregulation of mesenchymal markers, protein sialylation and core alpha 1,6 linked fucosylation.

    PubMed

    Mehta, Anand; Comunale, Mary Ann; Rawat, Siddhartha; Casciano, Jessica C; Lamontagne, Jason; Herrera, Harmin; Ramanathan, Aarti; Betesh, Lucy; Wang, Mengjun; Norton, Pamela; Steel, Laura F; Bouchard, Michael J

    2016-01-01

    Alterations in N-linked glycosylation have long been associated with cancer but for the most part, the reasons why have remained poorly understood. Here we show that increased core fucosylation is associated with de-differentiation of primary hepatocytes and with the appearance of markers indicative of a transition of cells from an epithelial to a mesenchymal state. This increase in core fucosylation was associated with increased levels of two enzymes involved in α-1,6 linked fucosylation, GDP-mannose 4, 6-dehydratase (Gmds) and to a lesser extent fucosyltransferase 8 (Fut8). In addition, the activation of cancer-associated cellular signaling pathways in primary rat hepatocytes can increase core fucosylation and induce additional glycoform alterations on hepatocyte proteins. Specifically, we show that increased levels of protein sialylation and α-1,6-linked core fucosylation are observed following activation of the β-catenin pathway. Activation of the Akt signaling pathway or induction of hypoxia also results in increased levels of fucosylation and sialylation. We believe that this knowledge will help in the better understanding of the genetic factors associated with altered glycosylation and may allow for the development of more clinically relevant biomarkers. PMID:27328854

  13. Intrinsic hepatocyte dedifferentiation is accompanied by upregulation of mesenchymal markers, protein sialylation and core alpha 1,6 linked fucosylation

    PubMed Central

    Mehta, Anand; Comunale, Mary Ann; Rawat, Siddhartha; Casciano, Jessica C.; Lamontagne, Jason; Herrera, Harmin; Ramanathan, Aarti; Betesh, Lucy; Wang, Mengjun; Norton, Pamela; Steel, Laura F.; Bouchard, Michael J.

    2016-01-01

    Alterations in N-linked glycosylation have long been associated with cancer but for the most part, the reasons why have remained poorly understood. Here we show that increased core fucosylation is associated with de-differentiation of primary hepatocytes and with the appearance of markers indicative of a transition of cells from an epithelial to a mesenchymal state. This increase in core fucosylation was associated with increased levels of two enzymes involved in α-1,6 linked fucosylation, GDP-mannose 4, 6-dehydratase (Gmds) and to a lesser extent fucosyltransferase 8 (Fut8). In addition, the activation of cancer-associated cellular signaling pathways in primary rat hepatocytes can increase core fucosylation and induce additional glycoform alterations on hepatocyte proteins. Specifically, we show that increased levels of protein sialylation and α-1,6-linked core fucosylation are observed following activation of the β-catenin pathway. Activation of the Akt signaling pathway or induction of hypoxia also results in increased levels of fucosylation and sialylation. We believe that this knowledge will help in the better understanding of the genetic factors associated with altered glycosylation and may allow for the development of more clinically relevant biomarkers. PMID:27328854

  14. Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells

    PubMed Central

    Perdicchio, Maurizio; Cornelissen, Lenneke A. M.; Streng-Ouwehand, Ingeborg; Engels, Steef; Verstege, Marleen I.; Boon, Louis; Geerts, Dirk

    2016-01-01

    The increased presence of sialylated glycans on the tumor surface has been linked to poor prognosis, yet the effects on tumor-specific T cell immunity are hardly studied. We here show that hypersialylation of B16 melanoma substantially influences tumor growth by preventing the formation of effector T cells and facilitating the presence of high regulatory T cell (Treg) frequencies. Knock-down of the sialic acid transporter created “sialic acid low” tumors, that grew slower in-vivo than hypersialylated tumors, altered the Treg/Teffector balance, favoring immunological tumor control. The enhanced effector T cell response in developing “sialic acid low” tumors was preceded by and dependent on an increased influx and activity of Natural Killer (NK) cells. Thus, tumor hypersialylation orchestrates immune escape at the level of NK and Teff/Treg balance within the tumor microenvironment, herewith dampening tumor-specific T cell control. Reducing sialylation provides a therapeutic option to render tumors permissive to immune attack. PMID:26741508

  15. Sialylation of N-linked glycans influences the immunomodulatory effects of IgM on T cells.

    PubMed

    Colucci, Manuela; Stöckmann, Henning; Butera, Alessia; Masotti, Andrea; Baldassarre, Antonella; Giorda, Ezio; Petrini, Stefania; Rudd, Pauline M; Sitia, Roberto; Emma, Francesco; Vivarelli, Marina

    2015-01-01

    Human serum IgM Abs are composed of heavily glycosylated polymers with five glycosylation sites on the μ (heavy) chain and one glycosylation site on the J chain. In contrast to IgG glycans, which are vital for a number of biological functions, virtually nothing is known about structure-function relationships of IgM glycans. Natural IgM is the earliest Ig produced and recognizes multiple Ags with low affinity, whereas immune IgM is induced by Ag exposure and is characterized by a higher Ag specificity. Natural anti-lymphocyte IgM is present in the serum of healthy individuals and increases in inflammatory conditions. It is able to inhibit T cell activation, but the underlying molecular mechanism is not understood. In this study, to our knowledge, we show for the first time that sialylated N-linked glycans induce the internalization of IgM by T cells, which in turn causes severe inhibition of T cell responses. The absence of sialic acid residues abolishes these inhibitory activities, showing a key role of sialylated N-glycans in inducing the IgM-mediated immune suppression. PMID:25422509

  16. Tumor sialylation impedes T cell mediated anti-tumor responses while promoting tumor associated-regulatory T cells.

    PubMed

    Perdicchio, Maurizio; Cornelissen, Lenneke A M; Streng-Ouwehand, Ingeborg; Engels, Steef; Verstege, Marleen I; Boon, Louis; Geerts, Dirk; van Kooyk, Yvette; Unger, Wendy W J

    2016-02-23

    The increased presence of sialylated glycans on the tumor surface has been linked to poor prognosis, yet the effects on tumor-specific T cell immunity are hardly studied. We here show that hypersialylation of B16 melanoma substantially influences tumor growth by preventing the formation of effector T cells and facilitating the presence of high regulatory T cell (Treg) frequencies. Knock-down of the sialic acid transporter created "sialic acid low" tumors, that grew slower in-vivo than hypersialylated tumors, altered the Treg/Teffector balance, favoring immunological tumor control. The enhanced effector T cell response in developing "sialic acid low" tumors was preceded by and dependent on an increased influx and activity of Natural Killer (NK) cells. Thus, tumor hypersialylation orchestrates immune escape at the level of NK and Teff/Treg balance within the tumor microenvironment, herewith dampening tumor-specific T cell control. Reducing sialylation provides a therapeutic option to render tumors permissive to immune attack. PMID:26741508

  17. Interview with Smithsonian NASM Spacesuit Curator Dr. Cathleen Lewis

    NASA Technical Reports Server (NTRS)

    Lewis, Cathleen; Wright, Rebecca

    2012-01-01

    Dr. Cathleen Lewis was interviewed by Rebecca Wright during the presentation of an "Interview with Smithsonian NASM Spacesuit Curator Dr. Cathleen Lewis" on May 14, 2012. Topics included the care, size, and history of the spacesuit collection at the Smithsonian and the recent move to the state-of-the-art permanent storage facility at the Udvar-Hazy facility in Virginia.

  18. Difficulty Processing Temporary Syntactic Ambiguities in Lewy Body Spectrum Disorder

    ERIC Educational Resources Information Center

    Grossman, Murray; Gross, Rachel G.; Moore, Peachie; Dreyfuss, Michael; McMillan, Corey T.; Cook, Philip A.; Ash, Sherry; Siderowf, Andrew

    2012-01-01

    While grammatical aspects of language are preserved, executive deficits are prominent in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's dementia (PDD) and dementia with Lewy bodies (DLB). We examined executive control during sentence processing in LBSD by assessing temporary structural ambiguities. Using an…

  19. Impairments of Speech Fluency in Lewy Body Spectrum Disorder

    ERIC Educational Resources Information Center

    Ash, Sharon; McMillan, Corey; Gross, Rachel G.; Cook, Philip; Gunawardena, Delani; Morgan, Brianna; Boller, Ashley; Siderowf, Andrew; Grossman, Murray

    2012-01-01

    Few studies have examined connected speech in demented and non-demented patients with Parkinson's disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured…

  20. The Organization of Narrative Discourse in Lewy Body Spectrum Disorder

    ERIC Educational Resources Information Center

    Ash, Sharon; McMillan, Corey; Gross, Rachel G.; Cook, Philip; Morgan, Brianna; Boller, Ashley; Dreyfuss, Michael; Siderowf, Andrew; Grossman, Murray

    2011-01-01

    Narrative discourse is an essential component of day-to-day communication, but little is known about narrative in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB). We performed a detailed analysis of a semi-structured speech sample in 32 non-aphasic…

  1. Thoughts on Teaching: John L. Lewis, Jesus, and President Bush.

    ERIC Educational Resources Information Center

    Starnes, Bobby Ann

    2004-01-01

    Bobby Ann Starnes, the author of this article, grew up with portraits of two important people displayed prominently in her home, Jesus, and John L. Lewis. Lewis, a giant among American leaders in the first half of the twentieth century, sent hundreds of organizers to help create some of the nation's leading labor unions, including the United…

  2. Structural basis for sulfation-dependent self-glycan recognition by the human immune-inhibitory receptor Siglec-8.

    PubMed

    Pröpster, Johannes M; Yang, Fan; Rabbani, Said; Ernst, Beat; Allain, Frédéric H-T; Schubert, Mario

    2016-07-19

    Siglec-8 is a human immune-inhibitory receptor that, when engaged by specific self-glycans, triggers eosinophil apoptosis and inhibits mast cell degranulation, providing an endogenous mechanism to down-regulate immune responses of these central inflammatory effector cells. Here we used solution NMR spectroscopy to dissect the fine specificity of Siglec-8 toward different sialylated and sulfated carbohydrate ligands and determined the structure of the Siglec-8 lectin domain in complex with its prime glycan target 6'-sulfo sialyl Lewis(x) A canonical motif for sialic acid recognition, extended by a secondary motif formed by unique loop regions, recognizing 6-O-sulfated galactose dictates tight specificity distinct from other Siglec family members and any other endogenous glycan recognition receptors. Structure-guided mutagenesis revealed key contacts of both interfaces to be equally essential for binding. Our work provides critical structural and mechanistic insights into how Siglec-8 selectively recognizes its glycan target, rationalizes the functional impact of site-specific glycan sulfation in modulating this lectin-glycan interaction, and will enable the rational design of Siglec-8-targeted agonists to treat eosinophil- and mast cell-related allergic and inflammatory diseases, such as asthma. PMID:27357658

  3. Asparagine-linked oligosaccharides on lutropin, follitropin, and thyrotropin: structural elucidation of the sulfated and sialylated oligosaccharides on bovine, ovine, and human pituitary glycoprotein hormones

    SciTech Connect

    Green, E.D.; Baenziger, J.U.

    1988-01-05

    The authors have elucidated the structures of the anionic asparagine-linked oligosaccharides present on the glycoprotein hormones lutropin (luteinizing hormone), follitropin (follicle-stimulating hormone), and thyrotropin (thyroid-stimulating hormone). Purified hormones, isolated from bovine, ovine, and human pituitaries, were digested with N-glycanase, and the released oligosaccharides were reduced with NaB(/sup 3/H)/sub 4/. The /sup 3/H-labeled oligosaccharides from each hormone were then fractionated by anion-exchange high performance liquid chromatography (HPLC) into populations differing in the number of sulfate and/or sialic acid moieties. The sulfated, sialylated, and sulfated/sialylated structures, which together comprised 67-90% of the asparagine-linked oligosaccharides on the pituitary glycoprotein hormones, were highly heterogeneous and displayed hormone- as well as animal species-specific features. A previously uncharacterized dibranched oligosaccharide, bearing one residue each of sulfate and sialic acid, was found on all of the hormones except bovine lutropin. In this study, they describe the purification and detailed structural characterizations of the sulfated, sialylated, and sulfated/sialylated oligosaccharides found on lutropin, follitropin, and thyrotropin from several animal species.

  4. Aluminium Diphosphamethanides: Hidden Frustrated Lewis Pairs.

    PubMed

    Styra, Steffen; Radius, Michael; Moos, Eric; Bihlmeier, Angela; Breher, Frank

    2016-07-01

    The synthesis and characterisation of two aluminium diphosphamethanide complexes, [Al(tBu)2 {κ(2) P,P'-Mes*PCHPMes*}] (3) and [Al(C6 F5 )2 {κ(2) P,P'-Mes*PCHPMes*}] (4), and the silylated analogue, Mes*PCHP(SiMe3 )Mes* (5), are reported. The aluminium complexes feature four-membered PCPAl core structures consisting of diphosphaallyl ligands. The silylated phosphine 5 was found to be a valuable precursor for the synthesis of 4 as it cleanly reacts with the diaryl aluminium chloride [(C6 F5 )2 AlCl]2 . The aluminium complex 3 reacts with molecular dihydrogen at room temperature under formation of the acyclic σ(2) λ(3) ,σ(3) λ(3) -diphosphine Mes*PCHP(H)Mes* and the corresponding dialkyl aluminium hydride [tBu2 AlH]3 . Thus, 3 belongs to the family of so-called hidden frustrated Lewis pairs. PMID:27271936

  5. NASA Lewis Meshed VSAT Workshop meeting summary

    NASA Technical Reports Server (NTRS)

    Ivancic, William

    1993-01-01

    NASA Lewis Research Center's Space Electronics Division (SED) hosted a workshop to address specific topics related to future meshed very small-aperture terminal (VSAT) satellite communications networks. The ideas generated by this workshop will help to identify potential markets and focus technology development within the commercial satellite communications industry and NASA. The workshop resulted in recommendations concerning these principal points of interest: the window of opportunity for a meshed VSAT system; system availability; ground terminal antenna sizes; recommended multifrequency for time division multiple access (TDMA) uplink; a packet switch design concept for narrowband; and fault tolerance design concepts. This report presents a summary of group presentations and discussion associated with the technological, economic, and operational issues of meshed VSAT architectures that utilize processing satellites.

  6. [Differential diagnosis of dementia with lewy bodies].

    PubMed

    Orimo, Satoshi

    2015-04-01

    Kosaka and colleagues first reported dementia with Lewy bodies (DLB) in 1976. They have also established the concept of DLB. It is important to differentiate DLB from other dementia, especially Alzheimer disease (AD), because the medical treatment, management, and prognosis of DLB and AD are different. We have used several clinical features and imaging tools to differentiate between DLB and AD. With regard to clinical features, patients with DLB have relatively mild memory disturbances and fluctuating cognition. However, compared to patients with AD they have more severe disturbances of attention and executive, visuospatial functions, visual hallucination, depression, autonomic symptoms. In addition, they show the presence of REM sleep behavior disorder and idiopathic parkinsonism. On performing imaging analysis, patients with DLB showed milder atrophy in the medial temporal lobe on brain MRI, reduced occipital activity on SPECT or PET, reduced MIBG uptake on MIBG cardiac scintigraphy, and low dopamine transporter activity in the basal ganglia on SPECT or PET. PMID:25846590

  7. Formylborane formation with frustrated Lewis pair templates.

    PubMed

    Sajid, Muhammad; Kehr, Gerald; Daniliuc, Constantin G; Erker, Gerhard

    2014-01-20

    Boranes R2 BH react with carbon monoxide by forming the respective borane carbonyl compounds R2 BH(CO). The formation of (C6 F5 )2 BH(CO) derived from the Piers borane, HB(C6 F5 )2 , is a typical example. Subsequent CO-hydroboration does not take place, since the formation of the formylborane is usually endothermic. However, an "η(2) -formylborane" was formed by CO-hydroboration with the Piers borane at vicinal phosphane/borane frustrated Lewis pair (FLP) templates. Subsequent treatment with pyridine liberated the intact formylborane from the FLP framework, and (pyridine)(C6 F5 )2 BCHO was then isolated as a stable compound. This product underwent typical reactions of carbonyl compounds, such as Wittig olefination. PMID:24338931

  8. Superconducting Microwave Electronics at Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Warner, Joseph D.; Bhasin, Kul B.; Leonard, Regis F.

    1991-01-01

    Over the last three years, NASA Lewis Research Center has investigated the application of newly discovered high temperature superconductors to microwave electronics. Using thin films of YBa2Cu3O7-delta and Tl2Ca2Ba2Cu3Ox deposited on a variety of substrates, including strontium titanate, lanthanum gallate, lanthanum aluminate and magnesium oxide, a number of microwave circuits have been fabricated and evaluated. These include a cavity resonator at 60 GHz, microstrip resonators at 35 GHz, a superconducting antenna array at 35 GHz, a dielectric resonator at 9 GHz, and a microstrip filter at 5 GHz. Performance of some of these circuits as well as suggestions for other applications are reported.

  9. LpMab-12 Established by CasMab Technology Specifically Detects Sialylated O-Glycan on Thr52 of Platelet Aggregation-Stimulating Domain of Human Podoplanin

    PubMed Central

    Kato, Yukinari; Ogasawara, Satoshi; Oki, Hiroharu; Goichberg, Polina; Honma, Ryusuke; Fujii, Yuki; Kaneko, Mika K.

    2016-01-01

    Podoplanin (PDPN), also known as Aggrus, possesses three tandem repeat of platelet aggregation-stimulating (PLAG) domains in its N-terminus. Among the PLAG domains, sialylated O-glycan on Thr52 of PLAG3 is essential for the binding to C-type lectin-like receptor-2 (CLEC-2) and the platelet-aggregating activity of human PDPN (hPDPN). Although various anti-hPDPN monoclonal antibodies (mAbs) have been generated, no specific mAb has been reported to target the epitope containing glycosylated Thr52. We recently established CasMab technology to develop mAbs against glycosylated membrane proteins. Herein, we report the development of a novel anti-glycopeptide mAb (GpMab), LpMab-12. LpMab-12 detected endogenous hPDPN by flow cytometry. Immunohistochemical analyses also showed that hPDPN-expressing lymphatic endothelial and cancer cells were clearly labeled by LpMab-12. The minimal epitope of LpMab-12 was identified as Asp49–Pro53 of hPDPN. Furthermore, LpMab-12 reacted with the synthetic glycopeptide of hPDPN, corresponding to 38–54 amino acids (hpp3854: 38-EGGVAMPGAEDDVVTPG-54), which carries α2–6 sialylated N-acetyl-D-galactosamine (GalNAc) on Thr52. LpMab-12 did not recognize non-sialylated GalNAc-attached glycopeptide, indicating that sialylated GalNAc on Thr52 is necessary for the binding of LpMab-12 to hPDPN. Thus, LpMab-12 could serve as a new diagnostic tool for determining whether hPDPN possesses the sialylation on Thr52, a site-specific post-translational modification critical for the hPDPN association with CLEC-2. PMID:27031228

  10. Expression of blood group antigens H-2, Le(y), and sialylated-Le(a) in human colorectal carcinoma. An immunohistochemical study using double-labeling techniques.

    PubMed Central

    Cooper, H. S.; Malecha, M. J.; Bass, C.; Fagel, P. L.; Steplewski, Z.

    1991-01-01

    In this study, double-labeling immunohistochemistry was used to gain insight into the coexpression or interrelationship between blood group antigens (BGA) that are differentiation antigens in the normal colon, and BGA that are sequential moieties in the same synthetic pathway. Paired-wise Sialylated-Le(a)/Le(y) and H-2/Le(y) was studied. The Sialylated-Le(a) and Le(y) are synthesized from type 1 and type 2 backbones, respectively. In the normal colon, the Le(y) and Sialylated-Le(a) are expressed by cells at the base and surface of the crypt, respectively, representing undifferentiated and differentiated enterocytes. The H-2 is considered oncofetal in nature, and is considered to be the immediate precursor in the synthesis of Le(y). In individual cancers. Sialylated-Lea and Le(y) were detected in different cancer cells within the same malignant glands, separately in different glands, and in different subcellular compartments of the same cell. Both H-2 and Le(y) were coexpressed in the same individual cells in 92% of cancers expressing both these BGA. In 50% of the cancers, the H-2 and Le(y) also were expressed separately in different malignant glands within individual tumors. These findings indicate that, in colorectal cancers, differentiation antigens (Sialylated Le(a) and Le(y)) are expressed by different individual cells within the same malignant gland somewhat, recapitulating the normal colon crypt. Antigens of different backbones occasionally may be expressed in the same cells but within different subcellular compartments. Precursor accumulation is common in cancers, and antigens in the same synthetic pathway are coexpressed in the same cell. The expression of H-2 and Le(y) in different glands (lack of coexpression) may be explained possibly by aberrant synthesis of Le(y) by an alternate pathway. Images Figure 1 PMID:1987759

  11. Treatment Response in Kawasaki Disease Is Associated with Sialylation Levels of Endogenous but Not Therapeutic Intravenous Immunoglobulin G

    PubMed Central

    Ogata, Shohei; Shimizu, Chisato; Franco, Alessandra; Touma, Ranim; Kanegaye, John T.; Choudhury, Biswa P.; Naidu, Natasha N.; Kanda, Yutaka; Hoang, Long T.; Hibberd, Martin L.; Tremoulet, Adriana H.; Varki, Ajit; Burns, Jane C.

    2013-01-01

    Objectives Although intravenous immunoglobulin (IVIG) is highly effective in Kawasaki disease (KD), mechanisms are not understood and 10-20% of patients are treatment-resistant, manifesting a higher rate of coronary artery aneurysms. Murine models suggest that α2-6-linked sialic acid (α2-6Sia) content of IVIG is critical for suppressing inflammation. However, pro-inflammatory states also up-regulate endogenous levels of β-galactoside:α2-6 sialyltransferase-I (ST6Gal-I), the enzyme that catalyzes addition of α2-6Sias to N-glycans. We asked whether IVIG failures correlated with levels of α2-6Sia on infused IVIG or on the patient’s own endogenous IgG. Methods We quantified levels of α2-6Sia in infused IVIG and endogenous IgG from 10 IVIG-responsive and 10 resistant KD subjects using multiple approaches. Transcript levels of ST6GAL1, in patient whole blood and B cell lines were evaluated by RT-PCR. Plasma soluble (s)ST6Gal-I levels were measured by ELISA. Results There was no consistent difference in median sialylation levels of infused IVIG between groups. However, α2-6Sia levels in endogenous IgG, ST6GAL1 transcript levels, and ST6Gal-I protein in serum from IVIG-resistant KD subjects were lower than in responsive subjects at both pre-treatment and one-year time points (p <0.001, respectively). Conclusions Our data indicate sialylation levels of therapeutic IVIG are unrelated to treatment response in KD. Rather, lower sialylation of endogenous IgG and lower blood levels of ST6GALI mRNA and ST6Gal-I enzyme predict therapy resistance. These differences were stable over time, suggesting a genetic basis. Because IVIG-resistance increases risk of coronary artery aneurysms, our findings have important implications for the identification and treatment of such individuals. PMID:24324693

  12. Fragmentation of Lewis-type trisaccharides in the gas phase

    NASA Astrophysics Data System (ADS)

    Suzuki, Hiroaki; Yamagaki, Tohru; Tachibana, Kazuo; Fukui, Kazuhiko

    2008-11-01

    The mechanisms of fragmentation of the chlorinated Lewis-type trisaccharides Lewis a and Lewis X were studied by using experimental and theoretical methods. In the fragment ion spectra obtained by ESI-CID-MS, C- and Z-type fragmentations corresponding to 4- and 3-linked glycosyl bond cleavages of the N-acetylglucosamine moiety were observed. The relationships of the relative ion intensities of C- and Z-type fragmentations were Z > C in Lewis a and C > Z in Lewis X, suggesting that the relationships of the activation energies were C > Z in Lewis a and Z > C in Lewis X. Anomeric and acetoamide groups were assumed to be included in the mechanisms of C- and Z-type fragmentation; we therefore analyzed 3-fucosyllactose and methylated Lewis-type trisaccharides, which are the derivatives of Lewis-type trisaccharides. These analyses revealed that C-type fragmentation was little influenced by anomeric group and that Z-type fragmentation was influenced by both the anomeric and the acetoamide groups. Fragmentation mechanisms were proposed on the basis of the experimental results and were calculated at the HF/3-21G(d), HF/6-31G(d) levels. From the calculations, C-type fragmentation of the 4-linkage was considered to take place by electron transfer from the acetoamide group, and Z-type fragmentation at the 3-linkage was considered to take place in two steps: (i) elimination of the 3-linked saccharide moiety, and (ii) deprotonation of an anomeric proton by a chloride anion. The activation energies for C- and Z-type fragmentations, as determined by HF calculations, were consistent with the experimentally assumed trends.

  13. Influenza promotes pneumococcal growth during co-infection by providing host sialylated substrates as a nutrient source

    PubMed Central

    Siegel, Steven J.; Roche, Aoife M.; Weiser, Jeffrey N.

    2014-01-01

    Summary Much of the mortality attributed to influenza virus is due to secondary bacterial pneumonia, particularly from Streptococcus pneumoniae. However, mechanisms underlying this co-infection are incompletely understood. We find that prior influenza infection enhances pneumococcal colonization of the murine nasopharynx, which in-turn promotes bacterial spread to the lungs. Influenza accelerates bacterial replication in vivo, and sialic acid, a major component of airway glycoconjugates, is identified as the host-derived metabolite that stimulates pneumococcal proliferation. Influenza infection increases sialic acid and sialylated mucin availability, and enhances desialylation of host glycoconjugates. Pneumococcal genes for sialic acid catabolism are required for influenza to promote bacterial growth. Decreasing sialic acid availability in vivo by genetic deletion of the major airway mucin Muc5ac or mucolytic treatment limits influenza-induced pneumococcal replication. Our findings suggest that higher rates of disease during co-infection could stem from influenza-provided sialic acid, which increases pneumococcal proliferation, colonization and aspiration. PMID:25011108

  14. Increasing the α 2, 6 Sialylation of Glycoproteins May Contribute to Metastatic Spread and Therapeutic Resistance in Colorectal Cancer

    PubMed Central

    Park, Jung-Jin

    2013-01-01

    Abnormal glycosylation due to dysregulated glycosyltransferases and glycosidases is a key phenomenon of many malignancies, including colorectal cancer (CRC). In particular, increased ST6 Gal I (β-galactoside α 2, 6 sialyltransferase) and subsequently elevated levels of cell-surface α 2, 6-linked sialic acids have been associated with metastasis and therapeutic failure in CRC. As many CRC patients experience metastasis to the liver or lung and fail to respond to curative therapies, intensive research efforts have sought to identify the molecular changes underlying CRC metastasis. ST6 Gal I has been shown to facilitate CRC metastasis, and we believe that additional investigations into the involvement of ST6 Gal I in CRC could facilitate the development of new diagnostic and therapeutic targets. This review summarizes how ST6 Gal I has been implicated in the altered expression of sialylated glycoproteins, which have been linked to CRC metastasis, radioresistance, and chemoresistance. PMID:24312702

  15. Sialyl-Tn antigen expression occurs early during human mammary carcinogenesis and is associated with high nuclear grade and aneuploidy.

    PubMed

    Cho, S H; Sahin, A; Hortobagyi, G N; Hittelman, W N; Dhingra, K

    1994-12-15

    Sialyl-Tn (STn) antigen represents an aberrant glycosylation product of cell surface mucin in adenocarcinomas. We studied its expression in 40 breast carcinomas (35 of which included in situ carcinomas) by performing immunostaining with B72.3 monoclonal antibody. STn expression was observed in 50% of cases and was equally frequent in in situ and in invasive carcinomas. Positive STn staining significantly correlated with high nuclear grade (P = 0.001), aneuploidy (P < 0.001) and high S-phase fraction (P = 0.02). No correlation was observed between STn staining and age, menopausal status, presence of invasive component, or hormone receptor positivity. STn staining may provide an objective marker of dedifferentiation of breast tumors and should be investigated further for its prognostic value in breast cancers and as a biomarker of malignant transformation of breast epithelium. PMID:7987817

  16. The biosynthesis of brain gangliosides. Separation of membranes with different ratios of ganglioside sialylating activity to gangliosides.

    PubMed Central

    Landa, C A; Maccioni, H J; Arce, A; Caputto, R

    1977-01-01

    Brain subcellular fractions were analysed for ganglioside-sialylating activity by measuring the incorporation of N-[3H]acetylneuraminic acid from CMP-N-[3H]acetylneuraminic acid into endogenous ganglioside acceptors (endogenous incorporation) and into exogenous lactosyceramide (haematoside synthetase activity). The ratios of endogenous incorporation to gangliosides and of haematoside synthetase to gangliosides for the synaptosomal and mitochondrial fractions from a washed crude mitochondrial fraction were lower than those obtained for other membrane fractions. The differences appear to reflect intrinsic characteristics of each membrane fraction. The results of labelling in vitro and the time course of labelling of gangliosides of the different subcellular fractions in vivo after injection of N-[3H]acetylmannosamine are consistent with the possibility of a subcellular site for synthesis of gangliosides different from that of ganglioside deposition. PMID:606237

  17. Human Surfactant Protein A2 Gene Mutations Impair Dimmer/Trimer Assembly Leading to Deficiency in Protein Sialylation and Secretion

    PubMed Central

    Shen, Haitao; Li, Hui; Yang, Wenbing; Pan, Bing; Huang, Guowei; Lin, Guangyu; Ma, Lian; Willard, Belinda; Gu, Jiang; Zheng, Lemin; Wang, Yongyu

    2012-01-01

    Surfactant protein A2 (SP-A2) plays an essential role in surfactant metabolism and lung host defense. SP-A2 mutations in the carbohydrate recognition domain have been related to familial pulmonary fibrosis and can lead to a recombinant protein secretion deficiency in vitro. In this study, we explored the molecular mechanism of protein secretion deficiency and the subsequent biological effects in CHO-K1 cells expressing both wild-type and several different mutant forms of SP-A2. We demonstrate that the SP-A2 G231V and F198S mutants impair the formation of dimmer/trimer SP-A2 which contributes to the protein secretion defect. A deficiency in sialylation, but not N-linked glycosylation, is critical to the observed dimmer/trimer impairment-induced secretion defect. Furthermore, both mutant forms accumulate in the ER and form NP-40-insoluble aggregates. In addition, the soluble mutant SP-A2 could be partially degraded through the proteasome pathway but not the lysosome or autophagy pathway. Intriguingly, 4-phenylbutyrate acid (4-PBA), a chemical chaperone, alleviates aggregate formation and partially rescued the protein secretion of SP-A2 mutants. In conclusion, SP-A2 G231V and F198S mutants impair the dimmer/trimer assembly, which contributes to the protein sialylation and secretion deficiency. The intracellular protein mutants could be partially degraded through the proteasome pathway and also formed aggregates. The treatment of the cells with 4-PBA resulted in reduced aggregation and rescued the secretion of mutant SP-A2. PMID:23056344

  18. Evolutionarily conserved paired immunoglobulin-like receptor α (PILRα) domain mediates its interaction with diverse sialylated ligands.

    PubMed

    Sun, Yonglian; Senger, Kate; Baginski, Tomasz K; Mazloom, Anita; Chinn, Yvonne; Pantua, Homer; Hamidzadeh, Kajal; Ramani, Sree Ranjani; Luis, Elizabeth; Tom, Irene; Sebrell, Andrew; Quinones, Gabriel; Ma, Yan; Mukhyala, Kiran; Sai, Tao; Ding, Jiabing; Haley, Benjamin; Shadnia, Hooman; Kapadia, Sharookh B; Gonzalez, Lino C; Hass, Philip E; Zarrin, Ali A

    2012-05-01

    Paired immunoglobulin-like receptor (PILR) α is an inhibitory receptor that recognizes several ligands, including mouse CD99, PILR-associating neural protein, and Herpes simplex virus-1 glycoprotein B. The physiological function(s) of interactions between PILRα and its cellular ligands are not well understood, as are the molecular determinants of PILRα/ligand interactions. To address these uncertainties, we sought to identify additional PILRα ligands and further define the molecular basis for PILRα/ligand interactions. Here, we identify two novel PILRα binding partners, neuronal differentiation and proliferation factor-1 (NPDC1), and collectin-12 (COLEC12). We find that sialylated O-glycans on these novel PILRα ligands, and on known PILRα ligands, are compulsory for PILRα binding. Sialylation-dependent ligand recognition is also a property of SIGLEC1, a member of the sialic acid-binding Ig-like lectins. SIGLEC1 Ig domain shares ∼22% sequence identity with PILRα, an identity that includes a conserved arginine localized to position 97 in mouse and human SIGLEC1, position 133 in mouse PILRα and position 126 in human PILRα. We observe that PILRα/ligand interactions require conserved PILRα Arg-133 (mouse) and Arg-126 (human), in correspondence with a previously reported requirement for SIGLEC1 Arg-197 in SIGLEC1/ligand interactions. Homology modeling identifies striking similarities between PILRα and SIGLEC1 ligand binding pockets as well as at least one set of distinctive interactions in the galactoxyl-binding site. Binding studies suggest that PILRα recognizes a complex ligand domain involving both sialic acid and protein motif(s). Thus, PILRα is evolved to engage multiple ligands with common molecular determinants to modulate myeloid cell functions in anatomical settings where PILRα ligands are expressed. PMID:22396535

  19. Evolutionarily Conserved Paired Immunoglobulin-like Receptor α (PILRα) Domain Mediates Its Interaction with Diverse Sialylated Ligands

    PubMed Central

    Sun, Yonglian; Senger, Kate; Baginski, Tomasz K.; Mazloom, Anita; Chinn, Yvonne; Pantua, Homer; Hamidzadeh, Kajal; Ramani, Sree Ranjani; Luis, Elizabeth; Tom, Irene; Sebrell, Andrew; Quinones, Gabriel; Ma, Yan; Mukhyala, Kiran; Sai, Tao; Ding, Jiabing; Haley, Benjamin; Shadnia, Hooman; Kapadia, Sharookh B.; Gonzalez, Lino C.; Hass, Philip E.; Zarrin, Ali A.

    2012-01-01

    Paired immunoglobulin-like receptor (PILR) α is an inhibitory receptor that recognizes several ligands, including mouse CD99, PILR-associating neural protein, and Herpes simplex virus-1 glycoprotein B. The physiological function(s) of interactions between PILRα and its cellular ligands are not well understood, as are the molecular determinants of PILRα/ligand interactions. To address these uncertainties, we sought to identify additional PILRα ligands and further define the molecular basis for PILRα/ligand interactions. Here, we identify two novel PILRα binding partners, neuronal differentiation and proliferation factor-1 (NPDC1), and collectin-12 (COLEC12). We find that sialylated O-glycans on these novel PILRα ligands, and on known PILRα ligands, are compulsory for PILRα binding. Sialylation-dependent ligand recognition is also a property of SIGLEC1, a member of the sialic acid-binding Ig-like lectins. SIGLEC1 Ig domain shares ∼22% sequence identity with PILRα, an identity that includes a conserved arginine localized to position 97 in mouse and human SIGLEC1, position 133 in mouse PILRα and position 126 in human PILRα. We observe that PILRα/ligand interactions require conserved PILRα Arg-133 (mouse) and Arg-126 (human), in correspondence with a previously reported requirement for SIGLEC1 Arg-197 in SIGLEC1/ligand interactions. Homology modeling identifies striking similarities between PILRα and SIGLEC1 ligand binding pockets as well as at least one set of distinctive interactions in the galactoxyl-binding site. Binding studies suggest that PILRα recognizes a complex ligand domain involving both sialic acid and protein motif(s). Thus, PILRα is evolved to engage multiple ligands with common molecular determinants to modulate myeloid cell functions in anatomical settings where PILRα ligands are expressed. PMID:22396535

  20. Hepatocellular expression of a novel glycoprotein with sialylated difucosyl Lex activity in the active inflammatory lesions of chronic liver disease.

    PubMed Central

    Okada, Y.; Shimoe, T.; Muguruma, M.; Usumoto, R.; Tsuji, T.; Jinno, K.; Moriwaki, S.; Shin, S.; Hakomori, S.

    1988-01-01

    Hepatic expression of sialylated difucosyl Lex antigen (SDLex, NeuAc alpha 2-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-3Gal beta 1-4(Fuc alpha 1-3)GlcNAc beta 1-) was studied with monoclonal antibody FH6, which defines this structure. Hepatocytes in the severe form of chronic active hepatitis and liver cirrhosis strongly expressed SDLex. The antigen was only weakly and focally detected in chronic persistent hepatitis. The mild form of chronic active hepatitis showed intermediate expression. SDLex expressed along the liver cell membranes displayed a honeycomb pattern when extensively expressed in the severe form of chronic active hepatitis or in liver cirrhosis. Cytoplasmic expression was faint and focal. Preferential tissue distribution was at the periphery of the hepatic lobules where the distruction of the limiting plate was present. The antigen was also expressed in sinusoidal lining cells and polymorphonuclear cells but not in the biliary epithelia. Hepatocytes expressing SDLex did not express related carbohydrate antigens, ie, Type 2 chain N-acetyllactosamine, Lex, and sialylated Lea. On subcellular fractionation, the microsome fraction contained the majority of the antigen activity. SDS-PAGE and Western blot analysis revealed one major SDLex-active glycoprotein with an apparent molecular weight of 110 kilodaltons. This glycoprotein was different from SDLex-active glycoproteins found in the sera of cancer patients. No ganglioside showed FH6 reactivity. These results indicate that liver cells in active inflammatory lesion expressed a novel glycoprotein carrying SDLex antigen in honeycomblike membrane-associated pattern. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:3341453

  1. Lewis Acid-Base, Molecular Modeling, and Isotopic Labeling in a Sophomore Inorganic Chemistry Laboratory

    ERIC Educational Resources Information Center

    Nataro, Chip; Ferguson, Michelle A.; Bocage, Katherine M.; Hess, Brian J.; Ross, Vincent J.; Swarr, Daniel T.

    2004-01-01

    An experiment to prepare a deuterium labeled adduct of a Lewis acid and Lewis base, to use computational methods allowing students to visualize the LUMO of Lewis acids, the HOMO of Lewis bases and the molecular orbitals of the adduct that is formed is developed. This allows students to see the interplay between calculated and experimental results.

  2. Polysomnographic Findings in Dementia With Lewy Bodies

    PubMed Central

    Pao, Winnie C.; Boeve, Bradley F.; Ferman, Tanis J.; Lin, Sioung-Chi; Smith, Glenn E.; Knopman, David S.; Graff-Radford, Neill R.; Petersen, Ronald C.; Parisi, Joseph E.; Dickson, Dennis W.; Silber, Michael H.

    2013-01-01

    Introduction The clinical features of dementia with Lewy bodies (DLB) during wakefulness are well known. Other than REM sleep behavior disorder (RBD), only limited data exists on other sleep disturbances and disorders in DLB. We sought to characterize the polysomnographic (PSG) findings in a series of DLB patients with sleep-related complaints. Methods Retrospective study of patients with DLB who underwent clinical PSG at Mayo Clinic Rochester or Mayo Clinic Jacksonville over an almost 11 year span for evaluation of dream enactment behavior, excessive nocturnal movements, sleep apnea, hypersomnolence, or insomnia. The following variables were analyzed: respiratory disturbance index (RDI) in disordered breathing events/hour, periodic limb movement arousal index (PLMAI), arousals for no apparent reason (AFNAR), total arousal index (TAI), presence of REM sleep without atonia (RSWA), and percent sleep efficiency (SE). Results Data on 78 patients (71M, 7F) were analyzed. The mean age was 71 ± 8 years. Seventy-five (96%) patients had histories of recurrent dream enactment during sleep with 83% showing confirmation of RSWA +/- dream enactment during PSG. Mean RDI = 11.9 ± 5.8, PLMAI = 5.9 ± 8.5, AFNARI = 10.7 ± 12.0, and TAI = 26.6 ± 17.4. SE was <80% in 72% of the sample, <70% in 49%, and <60% in 24%. In patients who did not show evidence of significant disordered breathing (23 with RDI<5), 62% of arousals were AFNARs. In those patients who had significant disordered breathing (55 with RDI ≥ 5), 36% of arousals were AFNARs. Six patients underwent evaluations with PSG plus MSLT. Two patients had mean initial sleep latencies less than five minutes, and both had RDI<5. No patient had any sleep onset rapid eye movement periods. Nineteen patients have undergone neuropathologic examination, and 18 have had limbic- or neocortical-predominant Lewy body pathology. One had progressive supranuclear palsy, but no REM sleep was recorded in prior PSG. Conclusions In patients

  3. Clinical Features of Alzheimer Disease With and Without Lewy Bodies

    PubMed Central

    Chung, Eun Joo; Babulal, Ganesh M.; Monsell, Sarah E.; Cairns, Nigel J.; Roe, Catherine M.; Morris, John C.

    2015-01-01

    IMPORTANCE Lewy bodies are a frequent coexisting pathology in late-onset Alzheimer disease (AD). Previous studies have examined the contribution of Lewy bodies to the clinical phenotype of late-onset AD with variable findings. OBJECTIVE To determine whether the presence of Lewy body pathology influences the clinical phenotype and progression of symptoms in longitudinally assessed participants with AD. DESIGN, SETTING, AND PARTICIPANTS Retrospective clinical and pathological cohort study of 531 deceased participants who met the neuropathologic criteria for intermediate or high likelihood of AD according to the National Institute on Aging–Ronald Reagan Institute guidelines for the neuropathologic diagnosis of AD. All participants had a clinical assessment within 2 years of death. The data were obtained from 34 AD centers maintained by the National Alzheimer Coordinating Center and spanned from September 12, 2005, to April 30, 2013. EXPOSURES Standardized neuropathologic assessment and then brain autopsy after death. MAIN OUTCOMES AND MEASURES Clinical and neuropsychiatric test scores. RESULTS The mean (SD) age at death was statistically significantly younger for participants who had AD with Lewy bodies (77.9 [9.5] years) than for participants who had AD without Lewy bodies (80.2 [11.1] years) (P = .01). The mean (SD) age at onset of dementia symptoms was also younger for participants who had AD with Lewy bodies (70.0 [9.9] years) than for participants who had AD without Lewy bodies (72.2 [12.3] years) (P = .03). More men than women had AD with Lewy bodies (P = .01). The frequency of having at least 1 APOE ε4 allele was higher for participants who had AD with Lewy bodies than for participants who had AD without Lewy bodies (P = .03). After adjusting for age, sex, education, frequency of plaques (neuritic and diffuse), and tangle stage, we found that participants who had AD with Lewy bodies had a statistically significantly higher mean (SD) Neuropsychiatric

  4. Distance Learning With NASA Lewis Research Center's Learning Technologies Project

    NASA Technical Reports Server (NTRS)

    Petersen, Ruth

    1998-01-01

    The NASA Lewis Research Center's Learning Technologies Project (LTP) has responded to requests from local school district technology coordinators to provide content for videoconferencing workshops. Over the past year we have offered three teacher professional development workshops that showcase NASA Lewis-developed educational products and NASA educational Internet sites. In order to determine the direction of our involvement with distance learning, the LTP staff conducted a survey of 500 U.S. schools. We received responses from 72 schools that either currently use distance learning or will be using distance learning in 98-99 school year. The results of the survey are summarized in the article. In addition, the article provides information on distance learners, distance learning technologies, and the NASA Lewis LTP videoconferencing workshops. The LTP staff will continue to offer teacher development workshops through videoconferencing during the 98-99 school year. We hope to add workshops on new educational products as they are developed at NASA Lewis.

  5. FEATURE B. MACHINE GUN POSITION WITH LEWIS MOUNT, VIEW FACING ...

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

    FEATURE B. MACHINE GUN POSITION WITH LEWIS MOUNT, VIEW FACING NORTHWEST. - Naval Air Station Barbers Point, Battery-Machine Gun Positions, South of Point Cruz Road & west of Coral Sea Road, Ewa, Honolulu County, HI

  6. FEATURE B. MACHINE GUN POSITION WITH LEWIS MOUNT, VIEW FACING ...

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

    FEATURE B. MACHINE GUN POSITION WITH LEWIS MOUNT, VIEW FACING NORTHWEST (with scale stick). - Naval Air Station Barbers Point, Battery-Machine Gun Positions, South of Point Cruz Road & west of Coral Sea Road, Ewa, Honolulu County, HI

  7. 123I-Metaiodobenzylguanidine Myocardial Scintigraphy in Lewy Body-Related Disorders: A Literature Review

    PubMed Central

    Chung, Eun Joo; Kim, Sang Jin

    2015-01-01

    Lewy body-related disorders are characterized by the presence of Lewy bodies and Lewy neurites, which have abnormal aggregations of α-synuclein in the nigral and extranigral areas, including in the heart. 123I-metaiodobenzylguanidine (MIBG) scintigraphy is a well-known tool to evaluate cardiac sympathetic denervation in the Lewy body-related disorders. MIBG scintigraphy showed low uptake of MIBG in the Lewy body-related disorders, including Parkinson’s disease, dementia with Lewy bodies, pure autonomic failure and rapid eye movement sleep behavior disorder. This review summarizes previous results on the diagnostic applications of MIBG scintigraphy in Lewy body-related disorders. PMID:26090077

  8. Phylogenetic-Derived Insights into the Evolution of Sialylation in Eukaryotes: Comprehensive Analysis of Vertebrate β-Galactoside α2,3/6-Sialyltransferases (ST3Gal and ST6Gal).

    PubMed

    Teppa, Roxana E; Petit, Daniel; Plechakova, Olga; Cogez, Virginie; Harduin-Lepers, Anne

    2016-01-01

    Cell surface of eukaryotic cells is covered with a wide variety of sialylated molecules involved in diverse biological processes and taking part in cell-cell interactions. Although the physiological relevance of these sialylated glycoconjugates in vertebrates begins to be deciphered, the origin and evolution of the genetic machinery implicated in their biosynthetic pathway are poorly understood. Among the variety of actors involved in the sialylation machinery, sialyltransferases are key enzymes for the biosynthesis of sialylated molecules. This review focus on β-galactoside α2,3/6-sialyltransferases belonging to the ST3Gal and ST6Gal families. We propose here an outline of the evolutionary history of these two major ST families. Comparative genomics, molecular phylogeny and structural bioinformatics provided insights into the functional innovations in sialic acid metabolism and enabled to explore how ST-gene function evolved in vertebrates. PMID:27517905

  9. Phylogenetic-Derived Insights into the Evolution of Sialylation in Eukaryotes: Comprehensive Analysis of Vertebrate β-Galactoside α2,3/6-Sialyltransferases (ST3Gal and ST6Gal)

    PubMed Central

    Teppa, Roxana E.; Petit, Daniel; Plechakova, Olga; Cogez, Virginie; Harduin-Lepers, Anne

    2016-01-01

    Cell surface of eukaryotic cells is covered with a wide variety of sialylated molecules involved in diverse biological processes and taking part in cell–cell interactions. Although the physiological relevance of these sialylated glycoconjugates in vertebrates begins to be deciphered, the origin and evolution of the genetic machinery implicated in their biosynthetic pathway are poorly understood. Among the variety of actors involved in the sialylation machinery, sialyltransferases are key enzymes for the biosynthesis of sialylated molecules. This review focus on β-galactoside α2,3/6-sialyltransferases belonging to the ST3Gal and ST6Gal families. We propose here an outline of the evolutionary history of these two major ST families. Comparative genomics, molecular phylogeny and structural bioinformatics provided insights into the functional innovations in sialic acid metabolism and enabled to explore how ST-gene function evolved in vertebrates. PMID:27517905

  10. 1. 1943 Plan View of 'Fort Lewis Station Hospital, Section ...

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

    1. 1943 Plan View of 'Fort Lewis Station Hospital, Section No. 5.' Drawn by V. Steinbrueck for J.C. Boespflug Construction Co. July 23, 1943. HABS 8x10' negative was made from an 8.5 x 11' copy on card stock in the collection of the Community Library, Madigan Army Medical Center, Fort Lewis, WA. - Madigan Hospital, Bounded by Wilson & McKinley Avenues & Garfield & Lincoln Streets, DuPont, Pierce County, WA

  11. Lewis Research Center space station electric power system test facilities

    NASA Technical Reports Server (NTRS)

    Birchenough, Arthur G.; Martin, Donald F.

    1988-01-01

    NASA Lewis Research Center facilities were developed to support testing of the Space Station Electric Power System. The capabilities and plans for these facilities are described. The three facilities which are required in the Phase C/D testing, the Power Systems Facility, the Space Power Facility, and the EPS Simulation Lab, are described in detail. The responsibilities of NASA Lewis and outside groups in conducting tests are also discussed.

  12. ISDN at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Bakes, Catherine Murphy; Goldberg, Fredric; Eubanks, Steven W.

    1992-01-01

    An expository investigation of the potential impact of the Integrated Services Digital Network (ISDN) at NASA Lewis Research Center is described. To properly frame the subject, the paper contains a detailed survey of the components of Narrowband ISDN. The principles and objectives are presented as decreed by the Consultative Committee for International Telephone and Telegraph (CCITT). The various channel types are delineated and their associated service combinations are described. The subscriber-access network functions are explained pictorially via the ISDN reference configuration. A section on switching techniques is presented to enable the reader to understand the emergence of the concept of fast packet switching. This new technology is designed to operate over the high bandwidth, low error rate transmission media that characterizes the LeRC environment. A brief introduction to the next generation of networks is covered with sections on Broadband ISDM (B-ISDN), Asynchronous Transfer Mode (ATM), and Synchronous Optical Networks (SONET). Applications at LeRC are presented, first in terms of targets of opportunity, then in light of compatibility constraints. In-place pilot projects and testing are described that demonstrate actual usage at LeRC.

  13. Lewy body pathology in fetal grafts.

    PubMed

    Chu, Yaping; Kordower, Jeffrey H

    2010-01-01

    Although fetal nigral transplants have been shown to survive grafting into the striatum, increased [(18)F]6-fluroro-L-3,4-dihydroxyphenylalanine ((18)F-DOPA) uptake and improved motor function in open-label assessments have failed to establish any clinical benefits in double-blind, sham-controlled studies. To understand morphological and neurochemical alterations of grafted neurons, we performed postmortem analyses on six Parkinson's disease (PD) patients who had received fetal tissue transplantation 18-19 months, 4 years, and 14 years previously. These studies revealed robust neuronal survival with normal dopaminergic phenotypes in 18-month-old grafts and decreased dopamine transporter and increased cytoplasmic alpha-synuclein in 4-year-old grafts. We also found a decline of both dopamine transporter and tyrosine hydroxylase and the formation of Lewy body-like inclusions in 14-year-old grafts, which stained positive for alpha-synuclein and ubiquitin proteins. These pathological changes suggest that PD is an ongoing process that affects grafted cells in the striatum in a manner similar to how resident dopamine neurons are affected in the substantia nigra. PMID:20146690

  14. False memories in Lewy-body disease.

    PubMed

    Algarabel, Salvador; Pitarque, Alfonso; Sales, Alicia; Meléndez, Juan Carlos; Escudero, Joaquín

    2015-12-01

    Recently, de Boysson, Belleville, Phillips et al. (2011) found that patients with Lewy-body disease (LBD) showed significantly lower rates of false memories than healthy controls, using the Deese-Roediger-McDermott (DRM) experimental procedure. Given that this result could be explained by the practically null rate of true recognition in the LBD group (0.09), we decided to replicate the study by de Boysson et al. (2011), but including a new condition that would maximize the true recognition rate (and analyze its effect on the rate of false memories). Specifically, in a DRM experiment, we manipulated (within subjects) two study and recognition conditions: in the "immediate" condition, both the LBD patients and the control group of healthy older people received a different recognition test after each study list (containing twelve words associated with a non-presented critical word), while in the "delayed" condition (similar to the one in de Boysson et al., 2011), the participants received the entire series of study lists and then took only one recognition test. The results showed that, in both samples, the "immediate" condition produced higher corrected rates of both true and false recognition than the "delayed" condition, although they were both lower in the LBD patients, which shows that these patients are capable of encoding and recognizing the general similitude underlying information (gist memory) in the right conditions. PMID:26355527

  15. Exome sequencing in dementia with Lewy bodies.

    PubMed

    Keogh, M J; Kurzawa-Akanbi, M; Griffin, H; Douroudis, K; Ayers, K L; Hussein, R I; Hudson, G; Pyle, A; Cordell, H J; Attems, J; McKeith, I G; O'Brien, J T; Burn, D J; Morris, C M; Thomas, A J; Chinnery, P F

    2016-01-01

    Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia. Siblings of affected individuals are at greater risk of developing DLB, but little is known about the underlying genetic basis of the disease. We set out to determine whether mutations in known highly penetrant neurodegenerative disease genes are found in patients with DLB. Whole-exome sequencing was performed on 91 neuropathologically confirmed cases of DLB, supplemented by independent APOE genotyping. Genetic variants were classified using established criteria, and additional neuropathological examination was performed for putative mutation carriers. Likely pathogenic variants previously described as causing monogenic forms of neurodegenerative disease were found in 4.4% of patients with DLB. The APOE ɛ4 allele increased the risk of disease (P=0.0001), conferred a shorter disease duration (P=0.043) and earlier age of death (P=0.0015). In conclusion, although known pathogenic mutations in neurodegenerative disease genes are uncommon in DLB, known genetic risk factors are present in >60% of cases. APOE ɛ4 not only modifies disease risk, but also modulates the rate of disease progression. The reduced penetrance of reported pathogenic alleles explains the lack of a family history in most patients, and the presence of variants previously described as causing frontotemporal dementia suggests a mechanistic overlap between DLB and other neurodegenerative diseases. PMID:26836416

  16. Exome sequencing in dementia with Lewy bodies

    PubMed Central

    Keogh, M J; Kurzawa-Akanbi, M; Griffin, H; Douroudis, K; Ayers, K L; Hussein, R I; Hudson, G; Pyle, A; Cordell, H J; Attems, J; McKeith, I G; O'Brien, J T; Burn, D J; Morris, C M; Thomas, A J; Chinnery, P F

    2016-01-01

    Dementia with Lewy bodies (DLB) is the second most common form of degenerative dementia. Siblings of affected individuals are at greater risk of developing DLB, but little is known about the underlying genetic basis of the disease. We set out to determine whether mutations in known highly penetrant neurodegenerative disease genes are found in patients with DLB. Whole-exome sequencing was performed on 91 neuropathologically confirmed cases of DLB, supplemented by independent APOE genotyping. Genetic variants were classified using established criteria, and additional neuropathological examination was performed for putative mutation carriers. Likely pathogenic variants previously described as causing monogenic forms of neurodegenerative disease were found in 4.4% of patients with DLB. The APOE ɛ4 allele increased the risk of disease (P=0.0001), conferred a shorter disease duration (P=0.043) and earlier age of death (P=0.0015). In conclusion, although known pathogenic mutations in neurodegenerative disease genes are uncommon in DLB, known genetic risk factors are present in >60% of cases. APOE ɛ4 not only modifies disease risk, but also modulates the rate of disease progression. The reduced penetrance of reported pathogenic alleles explains the lack of a family history in most patients, and the presence of variants previously described as causing frontotemporal dementia suggests a mechanistic overlap between DLB and other neurodegenerative diseases. PMID:26836416

  17. Lewis Research Center R and D Facilities

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The NASA Lewis Research Center (LeRC) defines and develops advanced technology for high priority national needs. The work of the Center is directed toward new propulsion, power, and communications technologies for application to aeronautics and space, so that U.S. leadership in these areas is ensured. The end product is knowledge, usually in a report, that is made fully available to potential users--the aircraft engine industry, the energy industry, the automotive industry, the space industry, and other NASA centers. In addition to offices and laboratories for almost every kind of physical research in such fields as fluid mechanics, physics, materials, fuels, combustion, thermodynamics, lubrication, heat transfer, and electronics, LeRC has a variety of engineering test cells for experiments with components such as compressors, pumps, conductors, turbines, nozzles, and controls. A number of large facilities can simulate the operating environment for a complete system: altitude chambers for aircraft engines; large supersonic wind tunnels for advanced airframes and propulsion systems; space simulation chambers for electric rockets or spacecraft; and a 420-foot-deep zero-gravity facility for microgravity experiments. Some problems are amenable to detection and solution only in the complete system and at essentially full scale. By combining basic research in pertinent disciplines and generic technologies with applied research on components and complete systems, LeRC has become one of the most productive centers in its field in the world. This brochure describes a number of the facilities that provide LeRC with its exceptional capabilities.

  18. NASA Lewis Stirling engine computer code evaluation

    SciTech Connect

    Sullivan, T.J.

    1989-01-01

    In support of the US Department of Energy's Stirling Engine Highway Vehicle Systems program, the NASA Lewis Stirling engine performance code was evaluated by comparing code predictions without engine-specific calibration factors to GPU-3, P-40, and RE-1000 Stirling engine test data. The error in predicting power output was /minus/11 percent for the P-40 and 12 percent for the RE-1000 at design conditions and 16 percent for the GPU-3 at near-design conditions (2000 rpm engine speed versus 3000 rpm at design). The efficiency and heat input predictions showed better agreement with engine test data than did the power predictions. Concerning all data points, the error in predicting the GPU-3 brake power was significantly larger than for the other engines and was mainly a result of inaccuracy in predicting the pressure phase angle. Analysis into this pressure phase angle prediction error suggested that improvement to the cylinder hysteresis loss model could have a significant effect on overall Stirling engine performance predictions. 13 refs., 26 figs., 3 tabs.

  19. NASA Lewis Stirling engine computer code evaluation

    NASA Technical Reports Server (NTRS)

    Sullivan, Timothy J.

    1989-01-01

    In support of the U.S. Department of Energy's Stirling Engine Highway Vehicle Systems program, the NASA Lewis Stirling engine performance code was evaluated by comparing code predictions without engine-specific calibration factors to GPU-3, P-40, and RE-1000 Stirling engine test data. The error in predicting power output was -11 percent for the P-40 and 12 percent for the Re-1000 at design conditions and 16 percent for the GPU-3 at near-design conditions (2000 rpm engine speed versus 3000 rpm at design). The efficiency and heat input predictions showed better agreement with engine test data than did the power predictions. Concerning all data points, the error in predicting the GPU-3 brake power was significantly larger than for the other engines and was mainly a result of inaccuracy in predicting the pressure phase angle. Analysis into this pressure phase angle prediction error suggested that improvements to the cylinder hysteresis loss model could have a significant effect on overall Stirling engine performance predictions.

  20. Intramolecular Tetrylene Lewis Adducts: Synthesis and Reactivity.

    PubMed

    Schneider, Julia; Krebs, Kilian M; Freitag, Sarah; Eichele, Klaus; Schubert, Hartmut; Wesemann, Lars

    2016-07-01

    A series of benzyl(diphenylphosphino) and o-phenyl(diphenlyphosphino) substituted germylenes and plumbylenes were synthesized by nucleophilic substitution between the respective lithium reagent and tetrylene halide. The Lewis pairs were characterized by X-ray crystallography and NMR spectroscopy. The reactivity of the tetrylenes was investigated with respect to azide addition. In the germylene case, the germaniumimide was formed as the kinetically controlled product, which rearranges upon heating to give the phosphinimide. The stannylene and plumbylene derivatives react with adamantylazide to give the azide adducts. 1-Pentene reacts diastereoselectively with the phosphagermirane to give a cyclic addition product. Trimethysilylacetylene shows an addition with the benzylphosphino-substituted germylene and plumbylene to give the cycloheteropentene molecules. The addition product between phenylacetylene and the four membered Ge-P adduct shows after addition at room temperature a 1,4-phenylmigration to give a cyclic phosphine. Alkylnitrene insertion into a Ge-C bond of the alkyne addition product of the phosphagermirane was found in reaction with adamantylazide. PMID:27273819

  1. Overexpression of α2,3sialyl T-antigen in breast cancer determined by miniaturized glycosyltransferase assays and confirmed using tissue microarray immunohistochemical analysis

    PubMed Central

    Patil, Shilpa A.; Bshara, Wiam; Morrison, Carl; Chandrasekaran, E. V.; Matta, Khushi L.; Neelamegham, Sriram

    2014-01-01

    Glycan structure alterations during cancer regulate disease progression and represent clinical biomarkers. The study determined the degree to which changes in glycosyl transferase activities during cancer can be related to aberrant cell-surface tumor associated carbohydrate structures (TACA). To this end, changes in sialyltransferase (sialylT), fucosyltransferase (fucT) and galactosyltransferase (galT) activity were measured in normal and tumor tissue using a miniaturized enzyme activity assay and synthetic glycoconjugates bearing terminal LacNAc Type-I (Galβ1,3GlcNAc), LacNAc Type-II (Galβ1,4GlcNAc), and mucin core-1/Type-III (Galβ1,3GalNAc) structures. These data were related to TACA using tissue microarrays containing 115 breast and 26 colon cancer specimen. The results show that primary human breast and colon tumors, but not adjacent normal tissue, express elevated β1,3 galT and α2,3sialylT activity that can form α2,3sialylated Type-III glycans (Siaα2,3Galβ1,3GalNAc). Prostate tumors did not exhibit such elevated enzymatic activities. α1,3/4fucT activity was higher in breast, but not colon tissue. The enzymology based prediction of enhanced α2,3sialylated Type-III structures in breast tumors was verified using histochemical analysis of tissue sections and tissue microarrays. Here, the binding of two markers that recognize Galβ1,3GalNAc (peanut lectin and mAb A78-G/A7) was elevated in breast tumor, but not normal control, only upon sialidase treatment. These antigens were also upregulated in colon tumors though to a lesser extent. α2,3sialylated Type-III expression correlated inversely with patient HER2 expression and breast metastatic potential. Overall, enzymology measurements of glycoT activity predict glycan structure changes during cancer. High expression of the α2,3sialylated T-antigen O-glycans occur in breast tumors. A transformation from linear core-1 glycan to other epitopes may accompany metastasis. PMID:25142811

  2. Neu1 desialylation of sialyl alpha-2,3-linked beta-galactosyl residues of TOLL-like receptor 4 is essential for receptor activation and cellular signaling.

    PubMed

    Amith, Schammim Ray; Jayanth, Preethi; Franchuk, Susan; Finlay, Trisha; Seyrantepe, Volkan; Beyaert, Rudi; Pshezhetsky, Alexey V; Szewczuk, Myron R

    2010-02-01

    The ectodomain of TOLL-like receptors (TLR) is highly glycosylated with several N-linked gylcosylation sites located in the inner concave surface. The precise role of these sugar N-glycans in TLR receptor activation is unknown. Recently, we have shown that Neu1 sialidase and not Neu2, -3 and -4 forms a complex with TLR-2, -3 and -4 receptors on the cell-surface membrane of naïve and activated macrophage cells (Glycoconj J DOI 10.1007/s10719-009-9239-8). Activation of Neu1 is induced by TLR ligands binding to their respective receptors. Here, we show that endotoxin lipopolysaccharide (LPS)-induced MyD88/TLR4 complex formation and subsequent NFkappaB activation is dependent on the removal of alpha-2,3-sialyl residue linked to beta-galactoside of TLR4 by the Neu1 activity associated with LPS-stimulated live primary macrophage cells, macrophage and dendritic cell lines but not with primary Neu1-deficient macrophage cells. Exogenous alpha-2,3 sialyl specific neuraminidase (Streptoccocus pneumoniae) and wild-type T. cruzi trans-sialidase (TS) but not the catalytically inactive mutant TSAsp98-Glu mediate TLR4 dimerization to facilitate MyD88/TLR4 complex formation and NFkappaB activation similar to those responses seen with LPS. These same TLR ligand-induced NFkappaB responses are not observed in TLR deficient HEK293 cells, but are re-established in HEK293 cells stably transfected with TLR4/MD2, and are significantly inhibited by alpha-2,3-sialyl specific Maackia amurensis (MAL-2) lectin, alpha-2,3-sialyl specific galectin-1 and neuraminidase inhibitor Tamiflu but not by alpha-2,6-sialyl specific Sambucus nigra lectin (SNA). Taken together, the findings suggest that Neu1 desialylation of alpha-2,3-sialyl residues of TLR receptors enables in removing a steric hinderance to receptor association for TLR activation and cellular signaling. PMID:19796680

  3. Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions.

    PubMed

    Denmark, Scott E; Heemstra, John R

    2007-07-20

    The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated. PMID:17583959

  4. Neuroimaging characteristics of dementia with Lewy bodies.

    PubMed

    Mak, Elijah; Su, Li; Williams, Guy B; O'Brien, John T

    2014-01-01

    This review summarises the findings and applications from neuroimaging studies in dementia with Lewy bodies (DLB), highlighting key differences between DLB and other subtypes of dementia. We also discuss the increasingly important role of imaging biomarkers in differential diagnosis and outline promising areas for future research in DLB. DLB shares common clinical, neuropsychological and pathological features with Parkinson's disease dementia and other dementia subtypes, such as Alzheimer's disease. Despite the development of consensus diagnostic criteria, the sensitivity for differential diagnosis of DLB in clinical practice remains low and many DLB patients will be misdiagnosed. The importance of developing accurate imaging markers in dementia is highlighted by the potential for treatments targeting specific molecular abnormalities as well as the responsiveness to cholinesterase inhibitors and marked neuroleptic sensitivity of DLB. We review various brain imaging techniques that have been applied to investigate DLB, including the characteristic nigrostriatal degeneration in DLB using positron emission tomography (PET) and single-photon emission computed tomography (SPECT) tracers. Dopamine transporter loss has proven to reliably differentiate DLB from other dementias and has been incorporated into the revised clinical diagnostic criteria for DLB. To date, this remains the 'gold standard' for diagnostic imaging of DLB. Regional cerebral blood flow, 18 F-fluorodeoxygluclose-PET and SPECT have also identified marked deficits in the occipital regions with relative sparing of the medial temporal lobe when compared to Alzheimer's disease. In addition, structural, diffusion, and functional magnetic resonance imaging techniques have shown alterations in structure, white matter integrity, and functional activity in DLB. We argue that the multimodal identification of DLB-specific biomarkers has the potential to improve ante-mortem diagnosis and contribute to our

  5. Immunoglobulin A multiple myeloma presenting with Henoch-Schönlein purpura associated with reduced sialylation of IgA1.

    PubMed

    Van Der Helm-Van Mil, Annette H M; Smith, Alice C; Pouria, Shideh; Tarelli, Edward; Brunskill, Nigel J; Eikenboom, Heroen C J

    2003-09-01

    Henoch-Schönlein purpura is characterized by immunoglobulin A1 (IgA1) depositions in blood vessels of the skin or in glomeruli, resulting from altered hinge region O-glycosylation. Henoch-Schönlein purpura is seldom reported as a complication of IgA1 myeloma, even when the circulating IgA concentration is very high. We report two patients with IgA1 myeloma presenting with Henoch-Schönlein purpura. The O-glycosylation of these patients' IgA1 was studied. Both patients showed increased binding to peanut agglutinin lectin, suggesting a low degree of sialylation of the hinge region of IgA1 that was confirmed by mass spectrometry. IgA multiple myeloma, secreting IgA1 molecules with decreased sialylation, presenting with a Henoch-Schönlein purpura-like syndrome was diagnosed. PMID:12956761

  6. Pareidolias: complex visual illusions in dementia with Lewy bodies.

    PubMed

    Uchiyama, Makoto; Nishio, Yoshiyuki; Yokoi, Kayoko; Hirayama, Kazumi; Imamura, Toru; Shimomura, Tatsuo; Mori, Etsuro

    2012-08-01

    Patients rarely experience visual hallucinations while being observed by clinicians. Therefore, instruments to detect visual hallucinations directly from patients are needed. Pareidolias, which are complex visual illusions involving ambiguous forms that are perceived as meaningful objects, are analogous to visual hallucinations and have the potential to be a surrogate indicator of visual hallucinations. In this study, we explored the clinical utility of a newly developed instrument for evoking pareidolic illusions, the Pareidolia test, in patients with dementia with Lewy bodies-one of the most common causes of visual hallucinations in the elderly. Thirty-four patients with dementia with Lewy bodies, 34 patients with Alzheimer's disease and 26 healthy controls were given the Pareidolia test. Patients with dementia with Lewy bodies produced a much greater number of pareidolic illusions compared with those with Alzheimer's disease or controls. A receiver operating characteristic analysis demonstrated that the number of pareidolias differentiated dementia with Lewy bodies from Alzheimer's disease with a sensitivity of 100% and a specificity of 88%. Full-length figures and faces of people and animals accounted for >80% of the contents of pareidolias. Pareidolias were observed in patients with dementia with Lewy bodies who had visual hallucinations as well as those who did not have visual hallucinations, suggesting that pareidolias do not reflect visual hallucinations themselves but may reflect susceptibility to visual hallucinations. A sub-analysis of patients with dementia with Lewy bodies who were or were not treated with donepzil demonstrated that the numbers of pareidolias were correlated with visuoperceptual abilities in the former and with indices of hallucinations and delusional misidentifications in the latter. Arousal and attentional deficits mediated by abnormal cholinergic mechanisms and visuoperceptual dysfunctions are likely to contribute to the development

  7. Increased Sialylation of Anti-Thomsen-Friedenreich Antigen (CD176) Antibodies in Patients with Gastric Cancer: A Diagnostic and Prognostic Potential

    PubMed Central

    Kurtenkov, Oleg; Izotova, Jelena; Sergeyev, Boris

    2014-01-01

    Aim. To study whether alterations in the sialylation of antibodies (Ab) specific to the Thomsen-Friedenreich (TF) glycotope have a diagnostic and prognostic potential in gastric cancer. Methods. Serum samples were taken from patients with gastric carcinoma (n = 142) and controls (n = 61). The level of TF-specific antibodies and their sialylation was detected using ELISA with synthetic TF-polyacrylamide conjugate as antigen and sialic acid-specific Sambucus nigra agglutinin (SNA). Results. The level of TF-specific IgM was significantly decreased in cancer compared with controls (P ≤ 0.001). Cancer patients showed a higher level of SNA binding to anti-TF IgM and IgA (P ≤ 0.001) irrespective of disease stage, tumor morphology, and gender. Changes in the SNA/Ab index demonstrated moderate sensitivity (66–71%) and specificity (60–73%) for stomach cancer. The best diagnostic accuracy (100%) was achieved in 29% patients with high SNA binding and low anti-TF IgM level. This subset of patients demonstrated the poorest survival. Conclusion. Our findings are the first evidence that the increased sialylation of TF-specific Abs combined with a low level of anti-TF IgM is strongly linked to gastric cancer and patients survival, which can be used as a novel biomarker for cancer detection and prognosis. PMID:25276822

  8. Chinese Hamster Ovary (CHO) Host Cell Engineering to Increase Sialylation of Recombinant Therapeutic Proteins by Modulating Sialyltransferase Expression

    PubMed Central

    Lin, Nan; Mascarenhas, Joaquina; Sealover, Natalie R.; George, Henry J.; Brooks, Jeanne; Kayser, Kevin J.; Gau, Brian; Yasa, Isil; Azadi, Parastoo; Archer-Hartmann, Stephanie

    2015-01-01

    N-Glycans of human proteins possess both α2,6- and α2,3-linked terminal sialic acid (SA). Recombinant glycoproteins produced in Chinese hamster overy (CHO) only have α2,3-linkage due to the absence of α2,6-sialyltransferase (St6gal1) expression. The Chinese hamster ST6GAL1 was successfully overexpressed using a plasmid expression vector in three recombinant immunoglobulin G (IgG)-producing CHO cell lines. The stably transfected cell lines were enriched for ST6GAL1 overexpression using FITC-Sambucus nigra (SNA) lectin that preferentially binds α2,6-linked SA. The presence of α2,6-linked SA was confirmed using a novel LTQ Linear Ion Trap Mass Spectrometry (LTQ MS) method including MSn fragmentation in the enriched ST6GAL1 Clone 27. Furthermore, the total SA (mol/mol) in IgG produced by the enriched ST6GAL1 Clone 27 increased by 2-fold compared to the control. For host cell engineering, the CHOZN® GS host cell line was transfected and enriched for ST6GAL1 overexpression. Single-cell clones were derived from the enriched population and selected based on FITC-SNA staining and St6gal1 expression. Two clones (“ST6GAL1 OE Clone 31 and 32”) were confirmed for the presence of α2,6-linked SA in total host cell protein extracts. ST6GAL1 OE Clone 32 was subsequently used to express SAFC human IgG1. The recombinant IgG expressed in this host cell line was confirmed to have α2,6-linked SA and increased total SA content. In conclusion, overexpression of St6gal1 is sufficient to produce recombinant proteins with increased sialylation and more human-like glycoprofiles without combinatorial engineering of other sialylation pathway genes. This work represents our ongoing effort of glycoengineering in CHO host cell lines for the development of “bio-better” protein therapeutics and cell culture vaccine production. PMID:25641927

  9. Lewis rats have greater response impulsivity than Fischer rats.

    PubMed

    Hamilton, Kristen R; Potenza, Marc N; Grunberg, Neil E

    2014-11-01

    Impulsivity, a tendency toward immediate action without consideration of future consequences, is associated with a wide array of problematic behaviors. Response impulsivity, a type of behaviorally-assessed impulsivity characterized by behavioral disinhibition, is also associated with health risk behaviors. Response impulsivity is distinct from choice impulsivity, which is characterized by intolerance for delay. Lewis rats have higher levels of choice impulsivity than Fischer rats (Anderson & Woolverton, 2005; Madden et al., 2008; Stein et al., 2012). However, no studies have examined whether Lewis and Fischer rats have different levels of response impulsivity. The present research examined response impulsivity in the two rat strains. Subjects were 16 male Lewis and Fischer rats. Rats' response impulsivity was measured using the Five Choice Serial Reaction Time Task (5-CSRTT). In addition, their locomotor activity was measured in locomotor activity chambers. Lewis rats had more premature responses than Fischer rats during the 5-CSRTT assessment [F(1, 14)=5.34, p<0.05], indicating higher levels of response impulsivity. Locomotor activity did not differ between rat strain groups [F(1, 14)=3.05, p=.10], suggesting that overall movement did not account for group differences in response impulsivity on the 5-CSRTT. It can be concluded from this research that Lewis rats have higher levels of response impulsivity than Fischer rats, and therefore provide a valid rat model of individual differences in impulsivity. PMID:24613059

  10. The spectrum of cognitive impairment in Lewy body diseases

    PubMed Central

    Goldman, Jennifer G.; Williams-Gray, Caroline; Barker, Roger A.; Duda, John E.; Galvin, James E.

    2014-01-01

    Cognitive impairment represents an important and often defining component of the clinical syndromes of Lewy body disorders: Parkinson’s disease and dementia with Lewy bodies. The spectrum of cognitive deficits in these Lewy body diseases encompasses a broad range of clinical features, severity of impairment, and timing of presentation. Cognitive dysfunction is now recognized to occur not only in more advanced Parkinson’s disease, but also in early, untreated patients, and even in those patients with pre-motor syndromes such as REM behavior disorder and hyposmia. In recent years, the concept of “mild cognitive impairment” as a transitional or pre-dementia state in Parkinson’s disease has emerged. While this has led to much research regarding the diagnosis, prognosis, and underlying neurobiology of mild cognitive impairment in Parkinson’s disease, it has also raised questions regarding the usefulness of this concept and its application in clinical and research settings. In addition, the conundrum of whether Parkinson’s disease dementia and dementia with Lewy bodies represent the same or different entities remains unresolved. While these disorders overlap in many aspects of their presentations and pathophysiology, they differ in other aspects such as timing of cognitive, behavioral, and motor symptoms, medication responses, and neuropathological contributions. This article examines the spectrum and evolution of cognitive impairment in Lewy body disorders and debates these controversial issues in the field using point-counterpoint approaches. PMID:24757110

  11. Direct simulations of premixed turbulent flames with nonunity Lewis numbers

    SciTech Connect

    Rutland, C.J.; Trouve, A. . Dept. of Mechanical Engineering Stanford Univ., Stanford, CA . Center for Turbulence Research)

    1993-07-01

    A principal effect of turbulence on premixed flames in the flamelet regime is to wrinkle the flame fronts. For nonunity Lewis numbers, Le [ne] 1, the local flame structure is altered in curved regions. This effect is examined using direct numerical simulations of three-dimensional isotropic turbulence with constant density, single-step Arrhenius kinetics chemistry. Simulations of Lewis numbers 0.8, 1.0, and 1.2 are compared. At the local level, curvature effects dominated changes to the flame structure while strain effects were insignificant. A strong Lewis-number-dependent correlation was found between surface curvature and the local flame speed. The correlation was positive for Le < 1 and negative for Le > 1. At the global level, strain-related effects were more significant than curvature effects. The turbulent flame speed changed significantly with Lewis number, increasing as Le decreased. This was found to be due to strain effect that have a nonzero mean over the flame surface, rather than to curvature effects that have a nearly zero mean. The mean product temperature was also found to vary with Lewis number, being higher for Le > 1 and lower for Le < 1.

  12. Direct simulations of premixed turbulent flames with nonunity Lewis numbers

    NASA Technical Reports Server (NTRS)

    Rutland, C. J.; Trouve, A.

    1993-01-01

    A principal effect of turbulence on premixed flames in the flamelet regime is to wrinkle the flame fronts. For nonunity Lewis numbers, Le is not equal to 1, the local flame structure is altered in curved regions. This effect is examined using direct numerical simulations of 3D isotropic turbulence with constant density, single-step Arrhenius kinetics chemistry. Simulations of Lewis numbers 0.8, 1.0, and 1.2 are compared. At the local level, curvature effects dominated changes to the flame structure while strain effects were insignificant. A strong Lewis-number-dependent correlation was found between surface curvature and the local flame speed. The correlation was positive for Le less than 1 and negative for Le greater than 1. At the global level, strain-related effects were more significant than curvature effects. The turbulent flame speed changed significantly with Lewis number, increasing as Le decreased. This was found to be due to strain effects that have a nonzero mean over the flame surface, rather than to curvature effects that have a nearly zero mean. The mean product temperature was also found to vary with Lewis number, being higher for Le greater than 1 and lower for Le less than 1.

  13. Cortical Lewy body dementia: clinical features and classification.

    PubMed Central

    Gibb, W R; Luthert, P J; Janota, I; Lantos, P L

    1989-01-01

    Seven patients, aged 65-72 years, are described with dementia and cortical Lewy bodies. In one patient a Parkinsonian syndrome was followed by dementia and motor neuron disease. In the remaining six patients dementia was accompanied by dysphasia, dyspraxia and agnosia. One developed a Parkinsonian syndrome before the dementia, in three cases a Parkinsonian syndrome occurred later, and in two cases not at all. All patients showed Lewy bodies and cell loss in the substantia nigra, locus coeruleus and dorsal vagal nucleus, as in Parkinson's disease. The severity of cell loss in the nucleus basalis varied from mild to severe. Lewy bodies were also present in the parahippocampus and cerebral cortex, but Alzheimer-type pathology was mild or absent, and insufficient for a diagnosis of Alzheimer's disease. Patients with moderate or severe dementia, some with temporal or parietal features, may have cortical Lewy body disease, Alzheimer's disease, or a combination of the two. Cortical Lewy body disease may be associated with dementia in Parkinson's disease more often than realised, but is not necessarily associated with extensive Alzheimer pathology. Images PMID:2467966

  14. Lewy Bodies: A Spectator or Salient Killer?

    PubMed

    Sian-Hulsmann, Jeswinder; Monoranu, Camelia; Strobel, S; Riederer, Peter

    2015-01-01

    Lewy bodies (LBs) are characteristic hallmarks of Parkinson's disease (PD). However, their role in the pathology of PD is not established yet. Are they primary events in the neurodegenerative process or only secondary phenomena? Are they signs of protecting neurons from toxicity or are they toxic per se? How are they are formed? Are LBs targets for therapeutic strategies? Addressing these questions may be of pivotal importance to unravel the basic mechanisms of neurodegeneration in PD. On the basis of current evidence, we intend to elucidate the possible role of LBs as triggers and/or markers of disease progression in PD. We present evidence for the morphogenesis of brain stem and cortical LBs, the role in neuronal cell death mechanisms, which seem to be correlated with the adhesion of LBs to and finally disruption of their inner neuronal membrane. Taken as such, LBs would be salient killers of nerve cells. However, they may also play a neuroprotective role in the early phases of neuronal pathology (LBs as a spectator), yet harmful to neuronal stability in later stages of LB development. Generation of LB pathology in the periphery (early subclinical Braak stage) might be due to reactive oxygen species (ROS) due to (chronic) bacteria-induced and/or otherwise intestinal inflammation, both leading to alpha-synuclein structural changes, oligomerization, seeding and propagation in a prion-like mechanism. If so, LB generation is a secondary process following ROS/inflammation pathology. Therapeutic implication based on LB pathology include drug development to inhibit protein misfolding, templating and transmission or vaccination against LBs, neuron regeneration strategies, anti-inflammatory and anti-biotic drugs as well as nutritional specialities to prevent intestine intoxications. In conclusion, evidence suggests LBs to be secondary hallmarks of PD pathology, induced by ROS/inflammation or other pathological triggers able to modify protein (alpha-synuclein) steric

  15. Risk factors for dementia with Lewy bodies

    PubMed Central

    Boot, Brendon P.; Orr, Carolyn F.; Ahlskog, J. Eric; Ferman, Tanis J.; Roberts, Rosebud; Pankratz, Vernon S.; Dickson, Dennis W.; Parisi, Joseph; Aakre, Jeremiah A.; Geda, Yonas E.; Knopman, David S.; Petersen, Ronald C.

    2013-01-01

    Objective: To determine the risk factors associated with dementia with Lewy bodies (DLB). Methods: We identified 147 subjects with DLB and sampled 2 sex- and age-matched cognitively normal control subjects for each case. We also identified an unmatched comparison group of 236 subjects with Alzheimer disease (AD). We evaluated 19 candidate risk factors in the study cohort. Results: Compared with controls, subjects with DLB were more likely to have a history of anxiety (odds ratio; 95% confidence interval) (7.4; 3.5–16; p < 0.0001), depression (6.0; 3.7–9.5; p < 0.0001), stroke (2.8; 1.3–6.3; p = 0.01), a family history of Parkinson disease (PD) (4.6; 2.5–8.6; p < 0.0001), and carry APOE ε4 alleles (2.2; 1.5–3.3; p < 0.0001), but less likely to have had cancer (0.44; 0.27–0.70; p = 0.0006) or use caffeine (0.29; 0.14–0.57; p < 0.0001) with a similar trend for alcohol (0.65; 0.42–1.0; p = 0.0501). Compared with subjects with AD, subjects with DLB were younger (72.5 vs 74.9 years, p = 0.021) and more likely to be male (odds ratio; 95% confidence interval) (5.3; 3.3–8.5; p < 0.0001), have a history of depression (4.3; 2.4–7.5; p < 0.0001), be more educated (2.5; 1.1–5.6; p = 0.031), have a positive family history of PD (5.0; 2.4–10; p < 0.0001), have no APOE ε4 alleles (0.61; 0.40–0.93; p = 0.02), and to have had an oophorectomy before age 45 years (7.6; 1.5–39; p = 0.015). Conclusion: DLB risk factors are an amalgam of those for AD and PD. Smoking and education, which have opposing risk effects on AD and PD, are not risk factors for DLB; however, depression and low caffeine intake, both risk factors for AD and PD, increase risk of DLB more strongly than in either. PMID:23892702

  16. Galactosyl-Lactose Sialylation Using Trypanosoma cruzi trans-Sialidase as the Biocatalyst and Bovine κ-Casein-Derived Glycomacropeptide as the Donor Substrate

    PubMed Central

    Wilbrink, Maarten H.; ten Kate, Geert A.; van Leeuwen, Sander S.; Sanders, Peter; Sallomons, Erik; Hage, Johannes A.; Kamerling, Johannis P.

    2014-01-01

    trans-Sialidase (TS) enzymes catalyze the transfer of sialyl (Sia) residues from Sia(α2-3)Gal(β1-x)-glycans (sialo-glycans) to Gal(β1-x)-glycans (asialo-glycans). Aiming to apply this concept for the sialylation of linear and branched (Gal)nGlc oligosaccharide mixtures (GOS) using bovine κ-casein-derived glycomacropeptide (GMP) as the sialic acid donor, a kinetic study has been carried out with three components of GOS, i.e., 3′-galactosyl-lactose (β3′-GL), 4′-galactosyl-lactose (β4′-GL), and 6′-galactosyl-lactose (β6′-GL). This prebiotic GOS is prepared from lactose by incubation with suitable β-galactosidases, whereas GMP is a side-stream product of the dairy industry. The trans-sialidase from Trypanosoma cruzi (TcTS) was expressed in Escherichia coli and purified. Its temperature and pH optima were determined to be 25°C and pH 5.0, respectively. GMP [sialic acid content, 3.6% (wt/wt); N-acetylneuraminic acid (Neu5Ac), >99%; (α2-3)-linked Neu5Ac, 59%] was found to be an efficient sialyl donor, and up to 95% of the (α2-3)-linked Neu5Ac could be transferred to lactose when a 10-fold excess of this acceptor substrate was used. The products of the TcTS-catalyzed sialylation of β3′-GL, β4′-GL, and β6′-GL, using GMP as the sialic acid donor, were purified, and their structures were elucidated by nuclear magnetic resonance spectroscopy. Monosialylated β3′-GL and β4′-GL contained Neu5Ac connected to the terminal Gal residue; however, in the case of β6′-GL, TcTS was shown to sialylate the 3 position of both the internal and terminal Gal moieties, yielding two different monosialylated products and a disialylated structure. Kinetic analyses showed that TcTS had higher affinity for the GL substrates than lactose, while the Vmax and kcat values were higher in the case of lactose. PMID:25063655

  17. Effects of non-unity Lewis numbers in diffusion flames

    NASA Technical Reports Server (NTRS)

    Linan, A.; Orlandi, P.; Verzicco, R.; Higuera, F. J.

    1994-01-01

    The purpose of this work is to carry out direct numerical simulations of diffusion controlled combustion with non-unity Lewis numbers for the reactants and products, thus accounting for the differential diffusion effects of the temperature and concentration fields. We use a formulation based on combining the conservation equations in a way to eliminate the reaction terms similar to the method used by Burke and Schumann (1928) for unity Lewis numbers. We present calculations for an axisymmetric fuel jet and for a planar, time evolving mixing layer, leaving out the effects of thermal expansion and variations of the transport coefficients due to the heat release. Our results show that the front of the flame shifts toward the fuel or oxygen sides owing to the effect of the differential diffusion and that the location of maximum temperature may not coincide with the flame. The dependence of the distribution of the reaction products on their Lewis number has been investigated.

  18. Helicopter transmission testing at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Lewicki, David G.; Coy, John J.

    1987-01-01

    The helicopter has evolved into a highly valuable air mobile vehicle for both military and civilian needs. The helicopter transmission requires advanced studies to develop a technology base for future rotorcraft advances. A joint helicopter transmission research program between the NASA Lewis Research Center and the U.S. Army Aviation Systems Command has existed since 1970. Program goals are to reduce weight and noise and to increase life and reliability. The current experimental activities at Lewis consist of full-scale helicopter transmission testing, a base effort in gearing technology, and a future effort in noise reduction technology. The experimental facilities at Lewis for helicopter transmission testing are described. A description of each of the rigs is presented along with some significant results and near-term plans.

  19. Sudden Death: An Uncommon Occurrence in Dementia with Lewy Bodies.

    PubMed

    Molenaar, Joery P; Wilbers, Joyce; Aerts, Marjolein B; Leijten, Quinten H; van Dijk, Jan G; Esselink, Rianne A; Bloem, Bastiaan R

    2016-01-01

    We present a 75-year-old woman with dementia and parkinsonism who developed severe orthostatic hypotension and eventually died. Autopsy revealed extensive Lewy body formation in the midbrain, limbic system, intermediate spinal cord, and medulla oblongata. Furthermore, a vast amount of Lewy bodies was seen in the paravertebral sympathetic ganglia which likely explained the severe autonomic failure. We speculate that this autonomic failure caused sudden death through dysregulation of respiration or heart rhythm, reminiscent of sudden death in multiple system atrophy (MSA). Clinicians should be aware of this complication in patients presenting with parkinsonism and autonomic dysfunction, and that sudden death may occur in dementia with Lewy bodies (DLB) as it does in MSA. PMID:26891177

  20. Lewis Acid Coupled Electron Transfer of Metal-Oxygen Intermediates.

    PubMed

    Fukuzumi, Shunichi; Ohkubo, Kei; Lee, Yong-Min; Nam, Wonwoo

    2015-12-01

    Redox-inactive metal ions and Brønsted acids that function as Lewis acids play pivotal roles in modulating the redox reactivity of metal-oxygen intermediates, such as metal-oxo and metal-peroxo complexes. The mechanisms of the oxidative CH bond cleavage of toluene derivatives, sulfoxidation of thioanisole derivatives, and epoxidation of styrene derivatives by mononuclear nonheme iron(IV)-oxo complexes in the presence of triflic acid (HOTf) and Sc(OTf)3 have been unified as rate-determining electron transfer coupled with binding of Lewis acids (HOTf and Sc(OTf)3 ) by iron(III)-oxo complexes. All logarithms of the observed second-order rate constants of Lewis acid-promoted oxidative CH bond cleavage, sulfoxidation, and epoxidation reactions of iron(IV)-oxo complexes exhibit remarkably unified correlations with the driving forces of proton-coupled electron transfer (PCET) and metal ion-coupled electron transfer (MCET) in light of the Marcus theory of electron transfer when the differences in the formation constants of precursor complexes were taken into account. The binding of HOTf and Sc(OTf)3 to the metal-oxo moiety has been confirmed for Mn(IV) -oxo complexes. The enhancement of the electron-transfer reactivity of metal-oxo complexes by binding of Lewis acids increases with increasing the Lewis acidity of redox-inactive metal ions. Metal ions can also bind to mononuclear nonheme iron(III)-peroxo complexes, resulting in acceleration of the electron-transfer reduction but deceleration of the electron-transfer oxidation. Such a control on the reactivity of metal-oxygen intermediates by binding of Lewis acids provides valuable insight into the role of Ca(2+) in the oxidation of water to dioxygen by the oxygen-evolving complex in photosystem II. PMID:26404482

  1. Analysis of the specificity of sialyltransferases toward mucin core 2, globo, and related structures. identification of the sialylation sequence and the effects of sulfate, fucose, methyl, and fluoro substituents of the carbohydrate chain in the biosynthesis of selectin and siglec ligands, and novel sialylation by cloned alpha2,3(O)sialyltransferase.

    PubMed

    Chandrasekaran, E V; Xue, Jun; Xia, Jie; Chawda, Ram; Piskorz, Conrad; Locke, Robert D; Neelamegham, Sriram; Matta, Khushi L

    2005-11-29

    Sialic acids are key determinants in many carbohydrates involved in biological recognition. We studied the acceptor specificities of three cloned sialyltransferases (STs) [alpha2,3(N)ST, alpha2,3(O)ST, and alpha2,6(N)ST] and another alpha2,3(O)ST present in prostate cancer cell LNCaP toward mucin core 2 tetrasaccharide [Galbeta1,4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-O-Bn] and Globo [Galbeta1,3GalNAcbeta1,3Galalpha-O-Me] structures containing sialyl, fucosyl, sulfo, methyl, or fluoro substituents by identifying the products by electrospray ionization tandem mass spectral analysis and other biochemical methods. The Globo precursor was an efficient acceptor for both alpha2,3(N)ST and alpha2,3(O)ST, whereas only alpha2,3(O)ST used its deoxy analogue (d-Fucbeta1,3GalNAcbeta1,3-Gal-alpha-O-Me); 2-O-MeGalbeta1,3GlcNAc and 4-OMeGalbeta1,4GlcNAc were specific acceptors for alpha2,3(N)ST. Other major findings of this study include: (i) alpha2,3 sialylation of beta1,3Gal in mucin core 2 can proceed even after alpha1,3 fucosylation of beta1,6-linked LacNAc. (ii) Sialylation of beta1,3Gal must precede the sialylation of beta1,4Gal for favorable biosynthesis of mucin core 2 compounds. (iii) alpha2,3 sialylation of the 6-O-sulfoLacNAc moiety in mucin core 2 (e.g., GlyCAM-1) is facilitated when beta1,3Gal has already been alpha2,3 sialylated. (iv) alpha2,6(N)ST was absolutely specific for the beta1,4Gal in mucin core 2. Either alpha1,3 fucosylation or 6-O-sulfation of the GlcNAc moiety reduced the activity. Sialylation of beta1,3Gal in addition to 6-O-sulfation of GlcNAc moiety abolished the activity. (v) Prior alpha2,3 sialylation or 3-O-sulfation of beta1,3Gal would not affect alpha2,6 sialylation of Galbeta1,4GlcNAc of mucin core 2. (vi) A 3- or 4-fluoro substituent in beta1,4Gal resulted in poor acceptors for the cloned alpha2,6(N)ST and alpha2,3(N)ST, whereas 4-fluoro- or 4-OMe-Galbeta1,3GalNAcalpha was a good acceptor for cloned alpha2,3(O)ST. (vii) 4-O-Methylation of beta1

  2. MALDI-MS analysis of sialylated N-glycan linkage isomers using solid-phase two step derivatization method.

    PubMed

    Li, Henghui; Gao, Wenjie; Feng, Xiaojun; Liu, Bi-Feng; Liu, Xin

    2016-06-14

    Sialic acids usually locate at the terminal of many glycan structures in either α(2,3) or α(2,6) linkage, playing different roles in various biological and pathological processes. Several linkage specific carboxyl derivatization methods have been reported to discriminate between α(2,3) and α(2,6)-linked sialic acids by matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Among them, ethyl esterification was recently reported to achieve linkage specific derivatization between α(2,3) and α(2,6)-linked sialic acids with good selectivity. However, the method suffered from the instability of the generated lactones and byproducts of the derivatives. To overcome these shortcomings, a solid-phase two step derivatization method was introduced to convert the α(2,6)-linked sialic acid into ethyl esters and the α(2,3)-inked counterparts into N-methyl amides, respectively. Under the optimized derivatization conditions, our method was able to achieve accurate relative quantification of N-glycan as well as their corresponding sialylated linkage types, superior to the ethyl esterification method. The solid phase derivatization strategy was further applied to investigate N-glycans from biosimilar antibody drug and human serum from patients and healthy volunteers. This method has the potential to be used in the biomarker discovery and pharmaceutical industry. PMID:27181647

  3. Sialylation of neurites inhibits complement-mediated macrophage removal in a human macrophage-neuron Co-Culture System.

    PubMed

    Linnartz-Gerlach, Bettina; Schuy, Christine; Shahraz, Anahita; Tenner, Andrea J; Neumann, Harald

    2016-01-01

    The complement system has been implicated in the removal of dysfunctional synapses and neurites during development and in disease processes in the mouse, but it is unclear how far the mouse data can be transferred to humans. Here, we co-cultured macrophages derived from human THP1 monocytes and neurons derived from human induced pluripotent stem cells, to study the role of the complement system in a human model. Components of the complement system were expressed by the human macrophages and human neuronal culture, while receptors of the complement cascade were expressed by human macrophages as shown via gene transcript analysis and flow cytometry. We mimicked pathological conditions leading to an altered glycocalyx by treatment of human neurons with sialidases. Desialylated human neurites were opsonized by the complement component C1q. Furthermore, human neurites with an intact sialic acid cap remained untouched, while desialylated human neurites were removed and ingested by human macrophages. While blockage of the complement receptor 1 (CD35) had no effect, blockage of CD11b as part of the complement receptor 3 (CR3) reversed the effect on macrophage phagocytosis of desialylated human neurites. Data demonstrate that in the human system sialylation of the neuronal glycocalyx serves as an inhibitory flag for complement binding and CR3-mediated phagocytosis by macrophages. PMID:26257016

  4. The Angelman Syndrome Protein Ube3a/E6AP is Required for Golgi Acidification and Surface Protein Sialylation

    PubMed Central

    Condon, Kathryn H.; Ho, Jianghai; Robinson, Camenzind G.; Hanus, Cyril; Ehlers, Michael D.

    2013-01-01

    Angelman syndrome (AS) is a severe disorder of postnatal brain development caused by neuron-specific loss of the HECT (homologous to E6AP carboxy terminus) domain E3 ubiquitin ligase Ube3a/E6AP. The cellular role of Ube3a remains enigmatic despite recent descriptions of synaptic and behavioral deficits in AS mouse models. Although neuron-specific imprinting is thought to limit the disease to the brain, Ube3a is expressed ubiquitously, suggesting a broader role in cellular function. In the current study, we demonstrate a profound structural disruption and cisternal swelling of the Golgi apparatus (GA) in the cortex of AS (UBE3Am−/p+) mice. In Ube3a knockdown cell lines and UBE3Am−/p+ cortical neurons, the GA is severely under-acidified, leading to osmotic swelling. Both in vitro and in vivo, the loss of Ube3a and corresponding elevated pH of the GA is associated with a marked reduction in protein sialylation, a process highly dependent on intralumenal Golgi pH. Altered ion homeostasis of the GA may provide a common cellular pathophysiology underlying the diverse plasticity and neurodevelopmental deficits associated with AS. PMID:23447592

  5. The Angelman syndrome protein Ube3a/E6AP is required for Golgi acidification and surface protein sialylation.

    PubMed

    Condon, Kathryn H; Ho, Jianghai; Robinson, Camenzind G; Hanus, Cyril; Ehlers, Michael D

    2013-02-27

    Angelman syndrome (AS) is a severe disorder of postnatal brain development caused by neuron-specific loss of the HECT (homologous to E6AP carboxy terminus) domain E3 ubiquitin ligase Ube3a/E6AP. The cellular role of Ube3a remains enigmatic despite recent descriptions of synaptic and behavioral deficits in AS mouse models. Although neuron-specific imprinting is thought to limit the disease to the brain, Ube3a is expressed ubiquitously, suggesting a broader role in cellular function. In the current study, we demonstrate a profound structural disruption and cisternal swelling of the Golgi apparatus (GA) in the cortex of AS (UBE3A(m-/p+)) mice. In Ube3a knockdown cell lines and UBE3A(m-/p+) cortical neurons, the GA is severely under-acidified, leading to osmotic swelling. Both in vitro and in vivo, the loss of Ube3a and corresponding elevated pH of the GA is associated with a marked reduction in protein sialylation, a process highly dependent on intralumenal Golgi pH. Altered ion homeostasis of the GA may provide a common cellular pathophysiology underlying the diverse plasticity and neurodevelopmental deficits associated with AS. PMID:23447592

  6. Space Chemical Propulsion Test Facilities at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Urasek, Donald C.; Calfo, Frederick D.

    1993-01-01

    The NASA Lewis Research Center, located in Cleveland, Ohio, has a number of space chemical propulsion test facilities which constitute a significant national space testing resource. The purpose of this paper is to make more users aware of these test facilities and to encourage their use through cooperative agreements between the government, industry, and universities. Research which is of interest to the government is especially encouraged and often can be done in a cooperative manner that best uses the resources of all parties. An overview of the Lewis test facilities is presented.

  7. Summary of Research Report Lewis Incubator for Technology

    NASA Technical Reports Server (NTRS)

    Zeman, Wayne P.

    2000-01-01

    This report summarizes the work done to establish and operate the Lewis Incubator for Technology (LIFT) for the period July 1996 through September 2000. The Lewis Incubator helps the startup and growth of technology-based businesses with the potential to incorporate technology from the NASA Glenn Research Center. During the grant period, LIFT began operation, met or exceeded all key performance measures, and continues its operation through a new cooperative agreement with NASA Glenn and also through continued funding from the State of Ohio.

  8. A revision of Megalocraerus Lewis, 1902 (Coleoptera, Histeridae: Exosternini)

    PubMed Central

    Caterino, Michael S.; Tishechkin, Alexey K.

    2016-01-01

    Abstract The formely monotypic Neotropical genus Megalocraerus Lewis is revised to include five species, known from southeastern Brazil to Costa Rica: Megalocraerus rubricatus Lewis, Megalocraerus mandibularis sp. n., Megalocraerus chico sp. n., Megalocraerus madrededios sp. n., and Megalocraerus tiputini sp. n. We describe the species, map their distributions, and provide a key for their identification. Their subcylindrical body form and emarginate mesosternum have previously hindered placement to tribe, although their curent assignment to Exosternini now appears well supported by morphological evidence. Nothing is known of the natural history of the species. PMID:26877699

  9. Bibliography of Lewis Research Center technical contributions announced in 1976

    NASA Technical Reports Server (NTRS)

    1977-01-01

    Abstracts of Lewis authored publications and publications resulting from Lewis managed contracts which were announced in the 1976 issues of STAR (Scientific and Technical Aerospace Reports) and IAA (International Aerospace Abstracts) are presented. Research reports, journal articles, conference presentations, patents and patent applications, and these are included. The arrangement is by NASA subject category. Citations indicate report literature (identified by their N-numbers) and the journal and conference presentations (identified by their A-numbers). A grouping of indexes helps locate specific publications by author (including contractor authors), contractor organization, contract number, and report number.

  10. Utilization of NASA Lewis mobile terminals for the Hermes satellite

    NASA Technical Reports Server (NTRS)

    Edelman, E. A.; Fiala, J. L.; Rizzolla, L.

    1977-01-01

    The high power of the Hermes satellite enables two-way television and voice communication with small ground terminals. The Portable Earth Terminal (PET) and the Transportable Earth Terminal (TET) were developed and built by NASA-Lewis to provide communications capability to short-term users. The NASA-Lewis mobile terminals are described in terms of vehicles and onboard equipment, as well as operation aspects, including use in the field. The section on demonstrations divides the uses into categories of medicine, education, technology and government. Applications of special interest within each category are briefly described.

  11. National space test centers - Lewis Research Center Facilities

    NASA Technical Reports Server (NTRS)

    Roskilly, Ronald R.

    1990-01-01

    The Lewis Research Center, NASA, presently has a number of test facilities that constitute a significant national space test resource. It is expected this capability will continue to find wide application in work involving this country's future in space. Testing from basic research to applied technology, to systems development, to ground support will be performed, supporting such activities as Space Station Freedom, the Space Exploration Initiative, Mission to Planet Earth, and many others. The major space test facilities at both Cleveland and Lewis' Plum Brook Station are described. Primary emphasis is on space propulsion facilities; other facilities of importance in space power and microgravity are also included.

  12. Gear and Transmission Research at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Townsend, Dennis P.

    1997-01-01

    This paper is a review of some of the research work of the NASA Lewis Research Center Mechanical Components Branch. It includes a brief review of the NASA Lewis Research Center and the Mechanical Components Branch. The research topics discussed are crack propagation of gear teeth, gear noise of spiral bevel and other gears, design optimization methods, methods we have investigated for transmission diagnostics, the analytical and experimental study of gear thermal conditions, the analytical and experimental study of split torque systems, the evaluation of several new advanced gear steels and transmission lubricants and the evaluation of various aircraft transmissions. The area of research needs for gearing and transmissions is also discussed.

  13. Crystalline, Lewis base-free, cationic phosphoranimines (iminophosphonium salts).

    PubMed

    Dielmann, Fabian; Moore, Curtis E; Rheingold, Arnold L; Bertrand, Guy

    2013-09-25

    Cationic phosphoranimines have been postulated as intermediates in phosphazene polymerization chemistry. However, the high electrophilicity of the phosphorus center has so far prevented their characterization. Here, we report the synthesis of two Lewis base-free iminophosphonium salts, obtained by reaction of a stable phosphinonitrene with methyl trifluoromethanesulfonate and trifluoromethanesulfonic acid. These cationic species were characterized by NMR spectroscopy and single-crystal X-ray diffraction analysis. Using 4-(dimethylamino)pyridine, a corresponding Lewis-base adduct has also been isolated. PMID:24007472

  14. Mach 6 Integrated Systems Tests of Lewis' Hypersonic Tunnel Facility

    NASA Technical Reports Server (NTRS)

    1996-01-01

    A series of 15 integrated systems tests were conducted at the NASA Lewis Research Center's Hypersonic Tunnel Facility (HTF) with test conditions simulating flight up to Mach 6. Facility stagnation conditions up to 3050 R and 1050 psia were obtained with typical test times of 20 to 45 sec.

  15. Bibliography of Lewis Research Center Technical Publications announced in 1991

    NASA Technical Reports Server (NTRS)

    1992-01-01

    This compilation of abstracts describes and indexes the technical reporting that resulted from the scientific engineering work performed and managed by the Lewis Research Center in 1991. All the publications were announced in the 1991 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  16. 175. Photocopy of Photograph (original in Roger Lewis' private collection). ...

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

    175. Photocopy of Photograph (original in Roger Lewis' private collection). Photographer and date unknown. CENTER ISLAND, CRAWFORD WATER WHEEL, TWIN FALLS COUNTY, MILNER, IDAHO; LOOKING DOWNSTREAM FROM DAM SITE. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  17. 174. Photocopy of Photograph (original in Roger Lewis' private collection). ...

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

    174. Photocopy of Photograph (original in Roger Lewis' private collection). Photographer and date unknown. SNAKE RIVER BELOW MILNER DAM SITE, TWIN FALLS COUNTY, MILNER, IDAHO; RAPIDS JUST BELOW MILNER TOWNSITE. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  18. Cholinesterase Inhibitors for Lewy Body Disorders: A Meta-Analysis

    PubMed Central

    Yasue, Ichiro; Iwata, Nakao

    2016-01-01

    Background: We performed a meta-analysis of cholinesterase inhibitors for patients with Lewy body disorders, such as Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies. Methods: The meta-analysis included only randomized controlled trials of cholinesterase inhibitors for Lewy body disorders. Results: Seventeen studies (n = 1798) were assessed. Cholinesterase inhibitors significantly improved cognitive function (standardized mean difference [SMD] = −0.53], behavioral disturbances (SMD = −0.28), activities of daily living (SMD = −0.28), and global function (SMD = −0.52) compared with control treatments. Changes in motor function were not significantly different from control treatments. Furthermore, the cholinesterase inhibitor group had a higher all-cause discontinuation (risk ratio [RR] = 1.48, number needed to harm [NNH] = 14), discontinuation due to adverse events (RR = 1.59, NNH = 20), at least one adverse event (RR = 1.13, NNH = 11), nausea (RR = 2.50, NNH = 13), and tremor (RR = 2.30, NNH = 20). Conclusions: Cholinesterase inhibitors appear beneficial for the treatment of Lewy body disorders without detrimental effects on motor function. However, a careful monitoring of treatment compliance and side effects is required. PMID:26221005

  19. A Legacy of Dandelions: Carolyn Lewis Attneave (1990-1992).

    ERIC Educational Resources Information Center

    Heckman-Stone, Carolyn

    2000-01-01

    Discusses the legacy of Carolyn Lewis Attneave who was, according to T. D. LaFromboise and J. E. Trimble (1966), "undoubtedly the most well-known psychologist of American Indian background." Reviews Attneave's work in organizations across the United States promoting the causes of American Indian families and community mental health and her skill…

  20. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Land Use Policy for Fort Lewis... permits. The group leader permit is not transferable. (3) Events requiring commitment of land must be processed per § 552.166. (f) Aside from the land commitment coordination time requirement in §...

  1. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Land Use Policy for Fort Lewis... permits. The group leader permit is not transferable. (3) Events requiring commitment of land must be processed per § 552.166. (f) Aside from the land commitment coordination time requirement in §...

  2. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Land Use Policy for Fort Lewis... permits. The group leader permit is not transferable. (3) Events requiring commitment of land must be processed per § 552.166. (f) Aside from the land commitment coordination time requirement in §...

  3. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Land Use Policy for Fort Lewis... permits. The group leader permit is not transferable. (3) Events requiring commitment of land must be processed per § 552.166. (f) Aside from the land commitment coordination time requirement in §...

  4. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Land Use Policy for Fort Lewis... permits. The group leader permit is not transferable. (3) Events requiring commitment of land must be processed per § 552.166. (f) Aside from the land commitment coordination time requirement in §...

  5. Seals Related Research at NASA. Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Hendricks, Robert C.

    1991-01-01

    Some current efforts in seal research at the Lewis Research Center include self-sealing linear segmented ceramic configurations, the T700 brush seal engine test, flow and duration characteristics of brush seals and other configurations, cryogenic hydrogen brush seal tests, and a brush seal tester. Information is given in diagram and graphs for a labyrinth seal and a straight cylindrical seal.

  6. Modified NASA-Lewis chemical equilibrium code for MHD applications

    NASA Technical Reports Server (NTRS)

    Sacks, R. A.; Geyer, H. K.; Grammel, S. J.; Doss, E. D.

    1979-01-01

    A substantially modified version of the NASA-Lewis Chemical Equilibrium Code was recently developed. The modifications were designed to extend the power and convenience of the Code as a tool for performing combustor analysis for MHD systems studies. The effect of the programming details is described from a user point of view.

  7. Bibliography of Lewis Research Center technical publications announced in 1983

    NASA Technical Reports Server (NTRS)

    1984-01-01

    This compilation of abstracts describes and indexes over 800 technical publications that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1983. Announced in the 1983 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts), the documents cited include research reports, journal articles, conference presentations, patents and patent applications, and theses.

  8. Effects of Lewis Number on Temperatures of Spherical Diffusion Flames

    NASA Technical Reports Server (NTRS)

    Santa, K. J.; Sun, Z.; Chao, B. H.; Sunderland, P. B.; Axelbaum, R. I.; Urban, D. L.; Stocker, D. P.

    2007-01-01

    Spherical diffusion flames supported on a porous sphere were studied numerically and experimentally. Experiments were performed in 2.2 s and 5.2 s microgravity facilities. Numerical results were obtained from a Chemkin-based program. The program simulates flow from a porous sphere into a quiescent environment, yields both steady-state and transient results, and accounts for optically thick gas-phase radiation. The low flow velocities and long residence times in these diffusion flames lead to enhanced radiative and diffusive effects. Despite similar adiabatic flame temperatures, the measured and predicted temperatures varied by as much as 700 K. The temperature reduction correlates with flame size but characteristic flow times and, importantly, Lewis number also influence temperature. The numerical results show that the ambient gas Lewis number would have a strong effect on flame temperature if the flames were steady and nonradiating. For example, a 10% decrease in Lewis number would increase the steady-state flame temperature by 200 K. However, for these transient, radiating flames the effect of Lewis number is small. Transient predictions of flame sizes are larger than those observed in microgravity experiments. Close agreement could not be obtained without either increasing the model s thermal and mass diffusion properties by 30% or reducing mass flow rate by 25%.

  9. LAPWAI CREEK STUDY, LEWIS AND NEZ PERCE COUNTIES, IDAHO. 1979

    EPA Science Inventory

    During Water Year 1979, a water quality study was conducted on the Lapwai Creek in Nez Perce and Lewis Counties, Idaho (17060306) to obtain background information on nonpoint source pollution impacts and for effluent limitation development. The study involved approximately bi-mo...

  10. Alleged Mercury Discharge by the Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Rosenbluum, L.

    1971-01-01

    Water sample analysis, site visits, and effluent reports are examined in an attempt to identify the sources contributing to mercury pollution of the Great Lakes. Two sources were identified, Lewis Research Center and Dow Chemical of Canada. Tests were made during a period from April to September 1970.

  11. Q & A with Ed Tech Leaders: Interview with Brian Lewis

    ERIC Educational Resources Information Center

    Shaughnessy, Michael F.; Fulgham, Susan M.

    2013-01-01

    Brian Lewis, International Society for Technology in Education (ISTE) chief executive officer, is an education advocate and leader specializing in management and governance, policy, corporate communications, branding, and marketing. He provides leadership to ISTE's Washington, DC, and Eugene, Oregon, offices and directs organizational…

  12. 162. Photocopy of Photograph (original in Roger Lewis' private collection). ...

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

    162. Photocopy of Photograph (original in Roger Lewis' private collection). Photographer and date unknown. MILNER DAM, TWIN FALLS COUNTY, MILNER, IDAHO; NORTH DAM, NORTH VIEW, SHOWS ROCK BEING TAKEN FROM FUTURE NORTHSIDE CANAL SITE. - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  13. 168. Photocopy of Photograph (original in Roger Lewis' private collection). ...

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

    168. Photocopy of Photograph (original in Roger Lewis' private collection). Photographer and date unknown. MILNER DAM TUNNEL CONSTRUCTION, TWIN FALLS COUNTY, MILNER, IDAHO; WORKERS STANDING IN TUNNEL (ONE CAN BE SEEN AT FAR END OF TUNNEL). - Milner Dam & Main Canal: Twin Falls Canal Company, On Snake River, 11 miles West of city of Burley, Idaho, Twin Falls, Twin Falls County, ID

  14. Impact of Predatory Threat on Fear Extinction in Lewis Rats

    ERIC Educational Resources Information Center

    Goswami, Sonal; Cascardi, Michele; Rodriguez-Sierra, Olga E.; Duvarci, Sevil; Pare, Denis

    2010-01-01

    Humans with post-traumatic stress disorder (PTSD) are deficient at extinguishing conditioned fear responses. A study of identical twins concluded that this extinction deficit does not predate trauma but develops as a result of trauma. The present study tested whether the Lewis rat model of PTSD reproduces these features of the human syndrome.…

  15. Bibliography of Lewis Research Center technical publications announced in 1982

    NASA Technical Reports Server (NTRS)

    1983-01-01

    The technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1982 is described. All the publications were announced in the 1982 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  16. Bibliography of Lewis Research Center technical publications announced in 1980

    NASA Technical Reports Server (NTRS)

    1981-01-01

    This compilation of abstracts describes and indexes over 780 research reports, journal articles, conference presentations, patents and patent applications, and theses resulting from the scientific and engineering work performed and managed by the Lewis Research Center in 1980. All the publications were announced in Scientific and Technical Aerospace Reports and/or International Aerospace Abstracts.

  17. Lewis Terman: Genetic Study of Genius--Elementary School Students

    ERIC Educational Resources Information Center

    Jolly, Jennifer L.

    2008-01-01

    Although the field of gifted education generally recognizes the foundational work of Lewis Terman, rarely does one stop to examine the details of his longitudinal study and their connection to present-day gifted education. This article reexamines the beginnings of Terman's longitudinal study with a focus on elementary-school-aged children.…

  18. "Termanal" Science? The Work of Lewis Terman Revisited.

    ERIC Educational Resources Information Center

    Vialle, Wilma

    1994-01-01

    This article place's Lewis Terman's work in the context of his time and space, in response to criticism of biases against women and certain ethnic groups in his work. The paper concludes that, notwithstanding the unacceptability of his ideas on women and race, Terman's work provides an important foundation for the field of gifted education.…

  19. Lewis M. Terman and the "World" of Test Publishing.

    ERIC Educational Resources Information Center

    Minton, Henry L.

    The association between Lewis M. Terman and the World Book Company is traced in order to gain insight about the role of test publishing in the testing movement. The test publisher assumes the position of an intermediary between the test developer and the educational administrator responsible for making decisions about test adoption. Terman began…

  20. Liquid droplet radiator program at the NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Presler, A. F.; Coles, C. E.; Diem-Kirsop, P. S.; White, K. A., III

    1985-01-01

    The NASA Lewis Research Center and the Air Force Rocket Propulsion Laboratory (AFRPL) are jointly engaged in a program for technical assessment of the Liquid Droplet Radiator (LDR) concept as an advanced high performance heat ejection component for future space missions. NASA Lewis has responsibility for the technology needed for the droplet generator, for working fluid qualification, and for investigating the physics of droplets in space; NASA Lewis is also conducting systems/mission analyses for potential LDR applications with candidate space power systems. For the droplet generator technology task, both micro-orifice fabrication techniques and droplet stream formation processes have been experimentally investigated. High quality micro-orifices (to 50 micron diameter) are routinely fabricated with automated equipment. Droplet formation studies have established operating boundaries for the generation of controlled and uniform droplet streams. A test rig is currently being installed for the experimental verification, under simulated space conditions, of droplet radiation heat transfer performance analyses and the determination of the effect radiative emissivity of multiple droplet streams. Initial testing has begun in the NASA Lewis Zero-Gravity Facility for investigating droplet stream behavior in microgravity conditions. This includes the effect of orifice wetting on jet dynamics and droplet formation. Results for both Brayton and Stirling power cycles have identified favorable mass and size comparisons of the LDR with conventional radiator concepts.

  1. Diffuse Lewy body disease with immediate post-partum onset.

    PubMed

    Opeskin, K; Gonzales, M; Borenstein, R; Anderson, R

    1993-01-01

    A previously healthy 27 years-old woman developed psychotic depression and parkinsonism shortly after delivery of her first child. Her neuropsychiatric symptoms progressed to dementia and she died 5 years after onset. Diffuse Lewy body disease was found at autopsy. This case is unusual because of the early age of onset and the abrupt development of symptoms following pregnancy. PMID:8442413

  2. Blood group variation in the Isle of Lewis.

    PubMed

    Clegg, E J; Tills, D; Warlow, A; Wilkinson, J; Marin, A

    1985-01-01

    Blood groups and protein and enzyme polymorphism distributions were studied in 285 residents on the Isle of Lewis, in the Outer Hebrides. As well as gene frequency calculations for individual loci, genetic distance estimations were made and a phylogenetic tree was constructed. The results indicated several major differences from North-west European populations, with high values of R2(CDe), Rz(CDE) and P1. Among protein and enzyme polymorphisms Hp1, EAPA and PGM1(1) had very high frequencies. Genetic distances show Lewis to be unlike both Western and Eastern North European populations, while the phylogenetic tree shows a common, but rather distant, ancestry with Icelanders. This genetic uniqueness of Lewis as a whole is accompanied by a considerable degree of heterogeneity within the island itself, especially in the ABO and Rh systems. Stornoway, with a greater proportion of residents descended from immigrant stock, shows a greater degree of similarity with neighbouring populations. The reasons for both the overall uniqueness and the heterogeneity within Lewis are discussed, but in the absence of a large time-depth and adequate vital records, the various roles of selection, drift and migration in producing them are difficult to establish. PMID:3929670

  3. Beyond "Discovery": Lewis & Clark from an Indigenous Perspective.

    ERIC Educational Resources Information Center

    Littlebear, Richard

    2003-01-01

    Recontextualizes the history of the Lewis and Clark expedition from a Native American perspective. Argues that the success of the expedition hastened killing of American Indians and more firmly entrenched U.S. government policies toward indigenous peoples. Stresses that education, particularly at tribal colleges, is the key to success for…

  4. Ada H. H. Lewis Middle School Curriculum Guide.

    ERIC Educational Resources Information Center

    Philadelphia School District, PA. Office of Curriculum and Instruction.

    This curriculum guide describes the instructional program at the Ada H. H. Lewis Middle School in Philadelphia, Pennsylvania. In brief, the goals of the program are to provide the schools' fifth-grade through eighth-grade students with educational opportunities based on an eclectic team-teaching approach. Four separate "houses" accommodate…

  5. False Recognition in Lewy-Body Disease and Frontotemporal Dementia

    ERIC Educational Resources Information Center

    de Boysson, C.; Belleville, S.; Phillips, N. A.; Johns, E. K.; Goupil, D.; Souchay, C.; Bouchard, R.; Chertkow, H.

    2011-01-01

    The primary goal of this study was to evaluate the false recognition phenomenon in persons with frontotemporal dementia (FTD) and those with Lewy-body disease (LBD). Patients with LBD (n=10) or FTD (n=15) and their corresponding controls (n=30) were subjected to the Deese-Roediger-McDermott (DRM) paradigm to induce false recognition. Patients were…

  6. Telling Lewis Hine's Story: Russell Freedman's "Kids at Work."

    ERIC Educational Resources Information Center

    Zarnowski, Myra

    In "Kids at Work," Russell Freedman explores the world of child labor during the years 1908-1918 when Lewis Hine, "teacher-crusader," worked as an investigative photographer for the National Child Labor Committee (NCLC). Hine's writing and the photos he gathered from across the country revealed a "shocking reality that most Americans had never…

  7. NASA. Lewis Research Center materials research and technology: An overview

    NASA Technical Reports Server (NTRS)

    Grisaffe, Salvatore J.

    1990-01-01

    The Materials Division at the Lewis Research Center has a long record of contributions to both materials and process technology as well as to the understanding of key high-temperature phenomena. This paper overviews the division staff, facilities, past history, recent progress, and future interests.

  8. Research and technology highlights of the Lewis Research Center

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Highlights of research accomplishments of the Lewis Research Center for fiscal year 1984 are presented. The report is divided into four major sections covering aeronautics, space communications, space technology, and materials and structures. Six articles on energy are included in the space technology section.

  9. Who Needs Lewis Structures to Get VSEPR Geometries?

    ERIC Educational Resources Information Center

    Lindmark, Alan F.

    2010-01-01

    Teaching the VSEPR (valence shell electron-pair repulsion) model can be a tedious process. Traditionally, Lewis structures are drawn and the number of "electron clouds" (groups) around the central atom are counted and related to the standard VSEPR table of possible geometries. A simpler method to deduce the VSEPR structure without first drawing…

  10. 75 FR 42460 - Minor Boundary Revision at Lewis and Clark National Historical Park

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-21

    ... National Park Service Minor Boundary Revision at Lewis and Clark National Historical Park AGENCY: National..., pursuant to 16 U.S.C. 460l- (9)(c)(1), the boundary of Lewis and Clark National Historical Park is modified... boundary of the Sunset Beach portion of Lewis and Clark National Historical Park. The boundary revision...

  11. Lewis number effects on turbulent premixed flame structure

    SciTech Connect

    Goix, P.J. , 230 - Mont-Saint-Aignan . URA CORIA); Shepherd, I.G. )

    1992-09-01

    The influence of the Lewis number on turbulent flame front geometry is investigated in a premixed turbulent stagnation point flame. A laser tomography technique is used to obtain the flame shape, a fractal analysis of the multiscale flame edges is performed and the distribution of local flame front curvature is determined. Lean H[sub 2]/Air and C[sub 3]H[sub 8]/Air mixtures with similar burning rates were investigated with Lewis numbers of 0.33 and 1.85 respectively. At the conditions studied the laminar H[sub 2]/Air mixture is unstable and a cellular structure is observed. Turbulence in the reactant is generated by a perforated plate and the turbulent length scale (3mm) and intensity (7%) at the nozzle exit are fixed. The equivalence ratio is set so that the burning velocity is the same for all the cases. Results show clearly that the turbulent flame surface area is dependent on the Lewis number. For a Lewis number less than unity surface area production is observed. The shape of the flame front curvature distribution is not found to be very sensitive to the Lewis number. For the H[sub 2]/Air mixture the distribution is skewed toward the positive values indicating the presence of cusps while for the C[sub 3]H[sub 8]/Air mixture the distribution is more symmetrical. In both cases the average curvature is found to be zero, and if the local burning speed varies linearly with curvature, the local positive and negative burning velocity variations due to curvature will balance.

  12. Lewis number effects on turbulent premixed flame structure

    SciTech Connect

    Goix, P.J.; Shepherd, I.G.

    1992-09-01

    The influence of the Lewis number on turbulent flame front geometry is investigated in a premixed turbulent stagnation point flame. A laser tomography technique is used to obtain the flame shape, a fractal analysis of the multiscale flame edges is performed and the distribution of local flame front curvature is determined. Lean H{sub 2}/Air and C{sub 3}H{sub 8}/Air mixtures with similar burning rates were investigated with Lewis numbers of 0.33 and 1.85 respectively. At the conditions studied the laminar H{sub 2}/Air mixture is unstable and a cellular structure is observed. Turbulence in the reactant is generated by a perforated plate and the turbulent length scale (3mm) and intensity (7%) at the nozzle exit are fixed. The equivalence ratio is set so that the burning velocity is the same for all the cases. Results show clearly that the turbulent flame surface area is dependent on the Lewis number. For a Lewis number less than unity surface area production is observed. The shape of the flame front curvature distribution is not found to be very sensitive to the Lewis number. For the H{sub 2}/Air mixture the distribution is skewed toward the positive values indicating the presence of cusps while for the C{sub 3}H{sub 8}/Air mixture the distribution is more symmetrical. In both cases the average curvature is found to be zero, and if the local burning speed varies linearly with curvature, the local positive and negative burning velocity variations due to curvature will balance.

  13. Liquid-fuel burning with nonunitary Lewis number

    SciTech Connect

    Sirignano, William A.

    2007-02-15

    An analysis is presented for liquid-fuel vaporization and burning with nonunitary Lewis number (i.e., nonsimilar heat and mass diffusion) in a general geometrical situation, e.g., a dense spray. Variable transport properties are considered and only Stefan flow is allowed. The analysis builds on the approach of Imaoka and Sirignano for unitary Lewis number. Fickian diffusion with differing diffusivities for each species is considered. It is shown that the problem can conveniently be separated, using a mass-flux potential function, into a one-dimensional problem for the quasi-steady, gas-phase scalar properties and a three-dimensional problem for the mass-flux potential, which satisfies Laplace's equation. This allows some previous calculations of the potential function for unitary Lewis number to be used for the potential-function solution. The scalar properties are shown to be functions of the mass-flux potential only. It is demonstrated that a mass-flux-weighted sensible specific enthalpy is more natural and convenient than the traditional mass-weighted value. This modification results in a new definition of the Lewis number. A generalization of the classical Spalding heat transfer number is presented. The theory predicts scalar gas-phase profiles, flame position, and vaporization rates. Quantitative results are presented for special cases where the Lewis number is piecewise constant. The thin-flame temperature and the effective latent heat of vaporization can be determined as functions of the liquid-surface temperature via solution of nonlinear algebraic equations; these values do not depend on the specific configuration and therefore have some universality. (author)

  14. Impairment of script comprehension in Lewy body spectrum disorders.

    PubMed

    Gross, Rachel G; Camp, Emily; McMillan, Corey T; Dreyfuss, Michael; Gunawardena, Delani; Cook, Philip A; Morgan, Brianna; Siderowf, Andrew; Hurtig, Howard I; Stern, Matthew B; Grossman, Murray

    2013-06-01

    A disabling impairment of higher-order language function can be seen in patients with Lewy body spectrum disorders such as Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB). We focus on script comprehension in patients with Lewy body spectrum disorders. While scripts unfold sequentially, constituent events are thought to contain an internal organization. Executive dysfunction in patients with Lewy body spectrum disorders may interfere with comprehension of this internal structure. We examined 42 patients (30 non-demented PD and 12 mildly demented PDD/DLB patients) and 12 healthy seniors. We presented 22 scripts (e.g., "going fishing"), each consisting of six events. Pilot data from young controls provided the basis for organizing associated events into clusters and arranging them hierarchically into scripts. We measured accuracy and latency to judge the order of adjacent events in the same cluster versus adjacent events in different clusters. PDD/DLB patients were less accurate in their ordering judgments than PD patients and controls. Healthy seniors and PD patients were significantly faster to judge correctly the order of highly associated within-cluster event pairs relative to less closely associated different-cluster event pairs, while PDD/DLB patients did not consistently distinguish between these event-pair types. This relative insensitivity to the clustered-hierarchical organization of events was related to executive impairment and to frontal atrophy as measured by volumetric MRI. These findings extend prior work on script processing to patients with Lewy body spectrum disorders and highlight the potential impact of frontal/executive dysfunction on the daily lives of affected patients. PMID:23566691

  15. Microgravity noncontact temperature requirements at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Santoro, G.

    1989-01-01

    NASA Lewis Research Center is currently supporting 66 microgravity science and applications projects. The 66 projects are separated into 23 flight projects and 43 ground-based projects. The part of the NASA Lewis program dealing with flight experiments is divided into six areas: Combustion Science, Materials Science, Fluid Physics, Instrumentation/Equipment, Advanced Technology Development, and Space Station Multi-User Facility studies. The part of the NASA Lewis program dealing with ground-based experiments is coincidentally also divided into six areas: Electronic Materials, Combustion Science, Fluid Dynamics and Transport Phenomena, Metals and Alloys, Glasses and Ceramics, and Physics and Chemistry Experiments. Several purposes exist for ground-based experimenting. Preliminary information is necessary before a decision can be made for flight status, the short low gravity durations available in ground facilities are adequate for a particular study, or extensive ground-based research must be conducted to define and support the microgravity science endeavors contemplated for space. Not all of the 66 microgravity science and application projects at NASA Lewis have temperature requirements, but most do. Since space allocation does not permit a review of all the pertinent projects, a decision was made to restrict the coverage to the science flight projects, flight projects minus the advanced technology development, and multiuser facility efforts. Very little is lost by this decision as the types of temperature requirements for science flight projects can be considered representative of those for the ground-based projects. The noncontact temperature needs at NASA Lewis, as represented by the science flight projects are discussed by describing briefly the experiments themselves, by displaying an illustration of each experimental setup, and by specifying their temperature requisites.

  16. Reduced Mucin-7 (Muc7) Sialylation and Altered Saliva Rheology in Sjögren's Syndrome Associated Oral Dryness.

    PubMed

    Chaudhury, Nayab M A; Proctor, Gordon B; Karlsson, Niclas G; Carpenter, Guy H; Flowers, Sarah A

    2016-03-01

    Sjögren's syndrome is a chronic autoimmune disorder characterized by lymphocytic infiltration and hypofunction of salivary and lacrimal glands. This loss of salivary function leads to oral dryness, impaired swallowing and speech, and increased infection and is associated with other autoimmune diseases and an increased risk of certain cancers. Despite the implications of this prevalent disease, diagnosis currently takes years, partly due to the diversity in patient presentation. Saliva is a complicated biological fluid with major constituents, including heavily glycosylated mucins MUC5B and MUC7, important for its viscoelastic and hydrating and lubricating properties. This study investigated Sjögren's patient's perception of dryness (bother index questionnaires) along with the rheological, protein composition, and glycan analysis of whole mouth saliva and the saliva on the mucosal surface (residual mucosal saliva) to understand the properties that most affect patient wellbeing. Sjögren's patients exhibited a statistically significant reduction in residual mucosal saliva, salivary flow rate, and extensional rheology, spinnbarkeit (stringiness). Although the concentration of mucins MUC5B and MUC7 were similar between patients and controls, a comparison of protein Western blotting and glycan staining identified a reduction in mucin glycosylation in Sjögren's, particularly on MUC7. LC-MS/MS analysis of O-glycans released from MUC7 by β-elimination revealed that although patients had an increase in core 1 sulfation, the even larger reduction in sialylation resulted in a global decline of charged glycans. This was primarily due to the loss of the extended core 2 disialylated structure, with and without fucosylation. A decrease in the extended, fucosylated core 2 disialylated structure on MUC7, residual mucosal wetness, and whole mouth saliva flow rate appeared to have a negative and cumulative effect on the perception of oral dryness. The observed changes in MUC7

  17. Expression profile of mucin-associated sialyl-Tn antigen in Chinese patients with different colorectal lesions (adenomas, carcinomas)

    PubMed Central

    Xu, Feng; Fan, Cuizhen; Fan, Shanshan; Liu, Fuquan; Wen, Tao; An, Guangyu; Feng, Guosheng

    2015-01-01

    Background: The sialyl-Tn (sTn) antigen is a mucin-associated carbohydrate antigen expressed by numerous human carcinomas, and is also claimed to be a prognostic factor in colorectal cancer. But the associations between sTn and colorectal cancer remain elusive and controversial. Here, we investigated the expression profile of sTn antigen in a series of human colorectal tissue samples including normal colon, colorectal adenomas, and colorectal carcinomas (CRCs), with an aim to analyzing whether sTn plays a role in the progression and development of Chinese patients with CRCs. Methods: Immunohistochemical staining of sTn antigen was performed in formalin-fixed, paraffin-embedded colonic sections from 4 healthy controls, 44 patients with colorectal adenomas, and 186 patients with primary CRCs. Results: No sTn antigen was detected in normal colonic tissues. There were 41 of 44 patients with colorectal adenomas (93.2%), and 141 of 186 patients with CRCs (75.8%) found to express sTn antigen. The patterns of sTn localization were different in adenomas and carcinomas of colonic tissues. Colorectal adenomas showed predominant supranuclear distribution of sTn antigen, while carcinomas revealed apical membrane, mucin droplet and diffuse cytoplasmic localization. Notably, sTn was significantly associated with the degree of differentiation (P = 0.006) and perineural invasion (P = 0.041) of the tumors, but was independent of age, gender, tumor location, depth of penetration, status of lymph nodes, lymphovascular invasion and TNM stage. Conclusions: These results indicate that sTn may play a role in initiating colorectal carcinogenesis and promoting tumor progression. Determination of sTn expression and localization may assist in evaluating malignant status of colorectal lesions. PMID:26617889

  18. A Panel of Recombinant Mucins Carrying a Repertoire of Sialylated O-Glycans Based on Different Core Chains for Studies of Glycan Binding Proteins.

    PubMed

    Cherian, Reeja Maria; Jin, Chunsheng; Liu, Jining; Karlsson, Niclas G; Holgersson, Jan

    2015-01-01

    Sialylated glycans serve as key elements of receptors for many viruses, bacteria, and bacterial toxins. The microbial recognition and their binding specificity can be affected by the linkage of the terminal sugar residue, types of underlying sugar chains, and the nature of the entire glycoconjugate. Owing to the pathobiological significance of sialylated glycans, we have engineered Chinese hamster ovary (CHO) cells to secrete mucin-type immunoglobulin-fused proteins carrying terminal α2,3- or α2,6-linked sialic acid on defined O-glycan core saccharide chains. Besides stably expressing P-selectin glycoprotein ligand-1/mouse immunoglobulin G2b cDNA (PSGL-1/mIgG2b), CHO cells were stably transfected with plasmids encoding glycosyltransferases to synthesize core 2 (GCNT1), core 3 (B3GNT6), core 4 (GCNT1 and B3GNT6), or extended core 1 (B3GNT3) chains with or without the type 1 chain-encoding enzyme B3GALT5 and ST6GAL1. Western blot and liquid chromatography-mass spectrometry analysis confirmed the presence of core 1, 2, 3, 4, and extended core 1 chains carrying either type 1 (Galb3GlcNAc) or type 2 (Galb4GlcNAc) outer chains with or without α2,6-linked sialic acids. This panel of recombinant mucins carrying a repertoire of sialylated O-glycans will be important tools in studies aiming at determining the fine O-glycan binding specificity of sialic acid-specific microbial adhesins and mammalian lectins. PMID:26274979

  19. A Panel of Recombinant Mucins Carrying a Repertoire of Sialylated O-Glycans Based on Different Core Chains for Studies of Glycan Binding Proteins

    PubMed Central

    Maria Cherian, Reeja; Jin, Chunsheng; Liu, Jining; Karlsson, Niclas G.; Holgersson, Jan

    2015-01-01

    Sialylated glycans serve as key elements of receptors for many viruses, bacteria, and bacterial toxins. The microbial recognition and their binding specificity can be affected by the linkage of the terminal sugar residue, types of underlying sugar chains, and the nature of the entire glycoconjugate. Owing to the pathobiological significance of sialylated glycans, we have engineered Chinese hamster ovary (CHO) cells to secrete mucin-type immunoglobulin-fused proteins carrying terminal α2,3- or α2,6-linked sialic acid on defined O-glycan core saccharide chains. Besides stably expressing P-selectin glycoprotein ligand-1/mouse immunoglobulin G2b cDNA (PSGL-1/mIgG2b), CHO cells were stably transfected with plasmids encoding glycosyltransferases to synthesize core 2 (GCNT1), core 3 (B3GNT6), core 4 (GCNT1 and B3GNT6), or extended core 1 (B3GNT3) chains with or without the type 1 chain-encoding enzyme B3GALT5 and ST6GAL1. Western blot and liquid chromatography-mass spectrometry analysis confirmed the presence of core 1, 2, 3, 4, and extended core 1 chains carrying either type 1 (Galβ3GlcNAc) or type 2 (Galβ4GlcNAc) outer chains with or without α2,6-linked sialic acids. This panel of recombinant mucins carrying a repertoire of sialylated O-glycans will be important tools in studies aiming at determining the fine O-glycan binding specificity of sialic acid-specific microbial adhesins and mammalian lectins. PMID:26274979

  20. Differential chemical derivatization integrated with chromatographic separation for analysis of isomeric sialylated N-glycans: a nano-hydrophilic interaction liquid chromatography-MS platform.

    PubMed

    Tousi, Fateme; Bones, Jonathan; Hancock, William S; Hincapie, Marina

    2013-09-01

    MS analysis of sialylated glycans is challenging due to their low ionization efficiency in positive ion mode as well as the possibility of in-source fragmentation. Chemical derivatization strategies have been developed to address this issue focused on removal of the labile acidic proton prior to MS analysis. Highly sialylated negatively charged glycans also exhibit high retention and unsatisfactory separation efficiency when analyzed by hydrophilic interaction liquid chromatography (HILIC) due to their high polarity. Here, we combined linkage specific derivatization of sialic acids by reaction with the condensation reagent 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM) in methanol with nanoscale liquid chromatographic separation prior to accurate mass Orbitrap MS analysis. Coupling DMT-MM charge neutralization of sialic acids with nano-HILIC-Orbitrap-MS not only allows for linkage specific characterization of sialylated glycans directly from the precursor mass but also improves the preceding HILIC separation by increasing the hydrophobicity and altering the selectivity of the oligosaccharide analytes. We focused on the trisialylated N-glycan fraction from haptoglobin and human plasma, enriched using weak anion exchange chromatography, as this trisialylated fraction has been linked with cancer associated changes in the serum N-glycome. The developed methodology was applied to investigate whether structural alterations in this oligosaccharide pool, enriched from the sera of pathological stage and sex matched patients bearing lung, breast, ovarian, pancreatic, or gastric cancer, demonstrate any degree of cancer specificity or whether changes in expression levels are purely cancer associated. The results of this pilot study indicate limited degrees of cancer specificity, particularly for pancreatic cancer, based on alterations in the relative abundance of specific trisialylated isomers. PMID:23901877

  1. Identification of two highly sialylated human tear-fluid DMBT1 isoforms: the major high-molecular-mass glycoproteins in human tears.

    PubMed Central

    Schulz, Benjamin L; Oxley, David; Packer, Nicolle H; Karlsson, Niclas G

    2002-01-01

    Human open eye tear fluid was separated by low-percentage SDS/PAGE to detect high-molecular-mass protein components. Two bands were found with apparent molecular masses of 330 and 270 kDa respectively. By peptide-mass fingerprinting after tryptic digestion, the proteins were found to be isoforms of the DMBT1 gene product, with over 30% of the predicted protein covered by the tryptic peptides. By using gradient SDS/agarose/polyacrylamide composite gel electrophoresis and staining for glycosylation, it was shown that the two isoforms were the major high-molecular-mass glycoproteins of >200 kDa in human tear fluid. Western blotting showed that the proteins expressed sialyl-Le(a). After the release of oligosaccharides by reductive beta-elimination from protein blotted on to PVDF membrane, it was revealed by liquid chromatography-MS that the O-linked oligosaccharides were comprised mainly of highly sialylated oligosaccharides with up to 16 monosaccharide units. A majority of the oligosaccharides could be described by the formula dHex(0-->2)NeuAc(1-->)(x)Hex(x)HexNAc(x)(-ol), x=1-6, where Hex stands for hexose, dHex for deoxyhexose, HexNAc for N-acetylhexosamine and NeuAc for N-acetylneuraminate. The number of sialic acids in the formula is less than 5. Interpretation of collision-induced fragmentation tandem MS confirmed the presence of sialic acid and suggested the presence of previously undescribed structures carrying the sialyl-Le(a) epitopes. Small amounts of neutral and sulphated species were also present. This is the first time that O-linked oligosaccharides have been detected and described from protein variant of the DMBT1 gene. PMID:12015815

  2. Discovery and expression of 3 siglecs-like in Oreochromis niloticus neutrophil, and their interaction with group B streptococcal sialylated capsular polysaccharides.

    PubMed

    Dong, Junjian; Wei, Yuanzheng; Ye, Xing; Sun, Chengfei; Tian, Yuanyuan; Lu, Maixin; Du, Juanjuan; Chen, Zhihang

    2016-05-01

    Sialic acid - binding immunoglobulin - like lectins (Siglecs) are members of the largest superfamily of immune receptors; they recognize sialic acid and are mainly expressed in immune cells. Studies on mammals indicate that Streptococcus agalactiae (GBS) evade immune reactions by interacting with the host immune cells via the sialic acid of sialylated capsular polysaccharides. However, it is currently unknown if fish-derived GBS can interact with Siglecs to evade host immunity. In this study, we examined the binding of FITC-GBS with neutrophils to determine the presence of receptors that binds with GBS. Furthermore, 3 Siglec-like genes, (OnSiglec-1-like/-4b-like/-14-like) from the neutrophils cDNA were screened by PCR. All the genes had specific domains (immunostimulation and immunosuppression domains), conserved amino acid residues, and sialic acid polysaccharide binding sites that are found in mammalian Siglecs. Flow cytometry of Siglecs-like/COS-7 cells and ELISA of Siglecs/Ex-Fc fusion proteins confirmed that 3 Siglecs-like have high binding activity with GBS. Erythrocytes adhesion assays and sialylated glycans binding assay confirmed that 3 Siglecs-like bind to sialic acid polysaccharides. Siglecs-like had high expression levels in the spleen, gill, and kidney in Oreochromis niloticus by qPCR. After experimental infection, Siglec-1-like/-14-like showed a significant upregulated initially and later downregulated in liver, spleen, kidney, and gill. However, Siglec-4b-like was downregulated in most tissues, except that in liver. The results indicate that 3 OnSiglecs-like may recognize GBS sialylated capsular polysaccharides. GBS infections led to significant changes in Siglecs-like expression in immune-related tissues. However, immunostimulation or immunosuppression via the recognition of GBS by different Siglecs-like molecules requires additional studies. PMID:26847490

  3. Pharmacokinetic properties of IB1001, an investigational recombinant factor IX, in patients with haemophilia B: repeat pharmacokinetic evaluation and sialylation analysis.

    PubMed

    Martinowitz, U; Shapiro, A; Quon, D V; Escobar, M; Kempton, C; Collins, P W; Chowdary, P; Makris, M; Mannucci, P M; Morfini, M; Valentino, L A; Gomperts, E; Lee, M

    2012-11-01

    IB1001 trenacog alfa is an investigational recombinant factor IX (FIX) for the treatment and prevention of bleeding in individuals with haemophilia B. To compare the pharmacokinetics (PK) of IB1001 with nonacog alfa in individuals with haemophilia B and to assess the relationship between sialylation and PK of IB1001 (NCT00768287). A randomized, double-blind, non-inferiority, cross-over study conducted in participants aged ≥ 12 years weighing ≥ 40 kg, with severe or moderately severe haemophilia B (FIX activity ≤ 2 IU dL (-1) ). PK parameters were derived using observed FIX concentration levels and actual PK sampling times, and repeated in a subset of participants who had received IB1001 prophylaxis for 4-18 months. A retrospective analysis was conducted in subgroups according to the sialylation levels of IB1001 (50.8, 57.8-59.0%, or 71.7%). In the 32 adolescent and adult males evaluated, there were no clinically meaningful differences in PK parameters between those receiving IB1001 75 IU kg(-1) or nonacog alfa. The lower limit of the one-sided 95% confidence interval for the ratio of AUC(0-t) and AUC(0-∞) (IB1001/nonacog alfa) was 0.90, establishing non-inferiority. Terminal phase half-lives were similar (29.7 ± 18.2 h for IB1001 and 33.4 ± 21.2 h for nonacog alfa). The PK results were stable for up to 18 months of IB1001 exposure; the impact of sialylation levels was not clinically meaningful. There were no clinically meaningful PK differences between IB1001 and nonacog alfa. IB1001 was well tolerated and without safety concerns. The non-inferiority of IB1001 to nonacog alfa supports IB1001 becoming a useful alternative recombinant agent for the management of haemophilia B. PMID:22764744

  4. Imaging and acetylcholinesterase inhibitor response in dementia with Lewy bodies.

    PubMed

    Graff-Radford, Jonathan; Boeve, Bradley F; Pedraza, Otto; Ferman, Tanis J; Przybelski, Scott; Lesnick, Timothy G; Vemuri, Prashanthi; Senjem, Matthew L; Smith, Glenn E; Knopman, David S; Lowe, Val; Jack, Clifford R; Petersen, Ronald C; Kantarci, Kejal

    2012-08-01

    Acetylcholinesterase inhibitors are commonly used to treat patients with dementia with Lewy bodies. Hippocampal atrophy on magnetic resonance imaging and amyloid-β load on positron emission tomography are associated with the Alzheimer's disease-related pathology in patients with dementia with Lewy bodies. To date, few studies have investigated imaging markers that predict treatment response in patients with dementia with Lewy bodies. Our objective was to determine whether imaging markers of Alzheimer's disease-related pathology such as hippocampal volume, brain amyloid-β load on (11)C Pittsburgh compound B positron emission tomography predict treatment response to acetylcholinesterase inhibitors in patients with dementia with Lewy bodies. We performed a retrospective analysis on consecutive treatment-naive patients with dementia with Lewy bodies (n = 54) from the Mayo Clinic Alzheimer's Disease Research Centre who subsequently received acetylcholinesterase inhibitors and underwent magnetic resonance imaging with hippocampal volumetry. Baseline and follow-up assessments were obtained with the Mattis Dementia Rating Scale. Subjects were divided into three groups (reliable improvement, stable or reliable decline) using Dementia Rating Scale reliable change indices determined previously. Associations between hippocampal volumes and treatment response were tested with analysis of covariance adjusting for baseline Dementia Rating Scale, age, gender, magnetic resonance field strength and Dementia Rating Scale interval. Seven subjects underwent (11)C Pittsburgh compound B imaging within 12 weeks of magnetic resonance imaging. Global cortical (11)C Pittsburgh compound B retention (scaled to cerebellar retention) was calculated in these patients. Using a conservative psychometric method of assessing treatment response, there were 12 patients with reliable decline, 29 stable cases and 13 patients with reliable improvement. The improvers had significantly larger

  5. Space chemical propulsion test facilities at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Urasek, Donald C.; Calfo, Frederick D.

    1993-01-01

    The NASA Lewis Research Center, located in Cleveland, Ohio has a number of space chemical propulsion test facilities which constitute a significant national space testing resource. The purpose of this paper is to make more users aware of these test facilities and to encourage their use through cooperative agreements between the government, industry, and universities. Research which is of interest to the government is especiallly encouraged and often can be done in a cooperative manner that best uses the resources of all parties. This paper presents an overview of the Lewis test facilities. These facilities are clustered into three test areas: the Rocket Engine Test Facilities (RETF), the Rocket Laboratory (RL), and the Cryogenic Components Laboratory (CCL).

  6. The organization of narrative discourse in Lewy body spectrum disorder.

    PubMed

    Ash, Sharon; McMillan, Corey; Gross, Rachel G; Cook, Philip; Morgan, Brianna; Boller, Ashley; Dreyfuss, Michael; Siderowf, Andrew; Grossman, Murray

    2011-10-01

    Narrative discourse is an essential component of day-to-day communication, but little is known about narrative in Lewy body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB). We performed a detailed analysis of a semi-structured speech sample in 32 non-aphasic patients with LBSD, and we related their narrative impairments to gray matter (GM) atrophy using voxel-based morphometry. We found that patients with PDD and DLB have significant difficulty organizing their narrative speech. This was correlated with deficits on measures of executive functioning and speech fluency. Regression analyses associated this deficit with reduced cortical volume in inferior frontal and anterior cingulate regions. These findings are consistent with a model of narrative discourse that includes executive as well as language components and with an impairment of the organizational component of narrative discourse in patients with PDD and DLB. PMID:21689852

  7. The Organization of Narrative Discourse in Lewy Body Spectrum Disorder

    PubMed Central

    Ash, Sharon; McMillan, Corey; Gross, Rachel G.; Cook, Philip; Morgan, Brianna; Boller, Ashley; Dreyfuss, Michael; Siderowf, Andrew; Grossman, Murray

    2011-01-01

    Narrative discourse is an essential component of day-to-day communication, but little is known about narrative in Lewy Body spectrum disorder (LBSD), including Parkinson's disease (PD), Parkinson's disease with dementia (PDD), and dementia with Lewy bodies (DLB). We performed a detailed analysis of a semi-structured speech sample in 32 non-aphasic patients with LBSD, and we related their narrative impairments to gray matter (GM) atrophy using voxel-based morphometry. We found that patients with PDD and DLB have significant difficulty organizing their narrative speech. This was correlated with deficits on measures of executive functioning and speech fluency. Regression analyses associated this deficit with reduced cortical volume in inferior frontal and anterior cingulate regions. These findings are consistent with a model of narrative discourse that includes executive as well as language components and with an impairment of the organizational component of narrative discourse in patients with PDD and DLB. PMID:21689852

  8. Microfluidic studies of CO2 sequestration by frustrated Lewis pairs.

    PubMed

    Voicu, Dan; Abolhasani, Milad; Choueiri, Rachelle; Lestari, Gabriella; Seiler, Caroline; Menard, Gabriel; Greener, Jesse; Guenther, Axel; Stephan, Douglas W; Kumacheva, Eugenia

    2014-03-12

    Frustrated Lewis pairs (FLPs) comprising sterically hindered Lewis acids and bases offer the capability to reversibly capture CO2 under mild reaction conditions. The determination of equilibrium constants and thermodynamic properties of these reactions should enable assessment of the efficiency of a particular FLP system for CO2 sequestration and provide insights for design of new, efficient formulations of FLP catalysts for CO2 capture. We have developed a microfluidic approach to studies of FLP-CO2 reactions, which provides their thermodynamic characterization that is not accessible otherwise. The approach enables the determination of the equilibrium reaction constants at different temperatures, the enthalpy, the entropy, and the Gibbs energy of these reactions, as well as the enhancement factor. The microfluidic methodology has been validated by applying it to the well-characterized reaction of CO2 with a secondary amine. The microfluidic approach can be applied for fundamental thermodynamic studies of other gas-liquid reactions. PMID:24555752

  9. Modeling Lewis acidity of transition aluminas by numerical simulations

    SciTech Connect

    Alvarez, L.J.; Blumenfeld, A.L.; Fripiat, J.J.

    1998-01-01

    The bulk and surface features of an alumina particle obtained by molecular-dynamics simulation are used to support the experimental distribution of aluminums with respect to their coordination number obtained by NMR (nuclear magnetic resonance). This information was obtained by using results of various editing procedures of the {sup 27}Al nuclear magnetic resonance, such as the classical one-pulse (1P) magic angle spinning, the cross polarization (CP) from the protons of chemisorbed ammonia and the 1P or CP rotational echo double resonance (REDOR). Because the REDOR technique revealed that the acid Lewis sites are constituted by pairs of four or fivefold coordinated aluminum atoms about 3 {Angstrom} apart, these pairs were counted in the simulated particle. The agreement with experimental surface density of Lewis sites is satisfactory. {copyright} {ital 1998 American Institute of Physics.}

  10. Familial Dementia With Lewy Bodies With an Atypical Clinical Presentation

    PubMed Central

    Bonner, Lauren T.; Tsuang, Debby W.; Cherrier, Monique M.; Eugenio, Charisma J.; Du, Jennifer Q.; Steinbart, Ellen J.; Limprasert, Pornprot; La Spada, Albert R.; Seltzer, Benjamin; Bird, Thomas D.; Leverenz, James B.

    2006-01-01

    The authors report a case of a 64-year-old male with Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) pathology at autopsy who did not manifest the core symptoms of DLB until very late in his clinical course. His initial presentation of early executive and language dysfunction suggested a cortical dementia similar to frontotemporal lobar degeneration (FTLD). Core symptoms of DLB including dementia, hallucination, and parkinsonian symptoms were not apparent until late in the course of his illness. Autopsy revealed both brainstem and cortical Lewy bodies and AD pathology. Family history revealed 7 relatives with a history of dementia including 4 with possible or probable DLB. This case is unique because of the FTLD-like presentation, positive family history of dementia, and autopsy confirmation of DLB. PMID:12641375

  11. Engines and innovation: Lewis Laboratory and American propulsion technology

    NASA Technical Reports Server (NTRS)

    Dawson, Virginia Parker

    1991-01-01

    This book is an institutional history of the NASA Lewis Research Center, located in Cleveland, Ohio, from 1940, when Congress authorized funding for a third laboratory for the National Advisory Committee for Aeronautics, through the 1980s. The history of the laboratory is discussed in relation to the development of American propulsion technology, with particular focus on the transition in the 1940s from the use of piston engines in airplanes to jet propulsion and that from air-breathing engines to rocket technology when the National Aeronautics and Space Administration was established in 1958. The personalities and research philosophies of the people who shaped the history of the laboratory are discussed, as is the relationship of Lewis Research Center to the Case Institute of Technology.

  12. Review of recent thermophotovoltaic (TPV) research at Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L.; Good, Brian S.; Wilt, David M.; Lowe, Roland A.; Fatemi, Navid S.; Hoffman, Richard H.; Scheiman, David

    1996-01-01

    Thermophotovoltaic (TPV) research at NASA Lewis Research Center that began in the late 1980's is reviewed. This work has been concentrated on low bandgap indium gallium arsenide (InGaAs) PV cells and rare earth yttrium aluminum garnet (YAG) thin film selective emitters, as well as, TPV system studies. An emittance theory has been developed for the thin film emitters. Experimental spectral emittance results for erbium Er-YAG and holmium Ho-YAG show excellent emittance (greater than or equal to .7) within the emission bands. The .75 eV InGaAs PV cells fabricated at Lewis have excellent quantum efficiency. An efficiency of 13% has been measured for this cell coupled to an Er-YAG selective emitter and a short pass IR filter.

  13. Review of Recent Thermophotovoltaic (TPV) Research at Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Chubb, Donald L.; Good, Brian S.; Wilt, David M.; Lowe, Roland A.; Fatemi, Navid S.; Hoffman, Richard H.; Scheiman, David

    1995-01-01

    Thermophotovoltaic (TPV) research at NASA Lewis Research Center that began in the late 1980's is reviewed. This work has been concentrated on low bandgap indium gallium arsenide (InGaAs) PV calls and rare earth - yttrium aluminum garnet (YAG) thin film selective emitters, as well as, TPV system studies. An emittance theory has been developed for the thin film emitters. Experimental spectral emittance results for erbium Er-YAG and holmium Ho-YAG show excellent emittance (greater than or equal to 0.7) within the emission bands. The 0.75 eV InGaAs PV cells fabricated at Lewis have excellent quantum efficiency. An efficiency of 130% has been measured for this cell coupled to an Er-YAG selective emitter and a short pass IR filter.

  14. Chemical Inventory Management at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Kraft, Shirley S.; Homan, Joseph R.; Bajorek, Michael J.; Dominguez, Manuel B.; Smith, Vanessa L.

    1997-01-01

    The Chemical Management System (CMS) is a client/server application developed with Power Builder and Sybase for the Lewis Research Center (LeRC). Power Builder is a client-server application development tool, Sybase is a Relational Database Management System. The entire LeRC community can access the CMS from any desktop environment. The multiple functions and benefits of the CMS are addressed.

  15. Update to the NASA Lewis Ice Accretion Code LEWICE

    NASA Technical Reports Server (NTRS)

    Wright, William B.

    1994-01-01

    This report is intended as an update to NASA CR-185129 'User's Manual for the NASA Lewis Ice Accretion Prediction Code (LEWICE).' It describes modifications and improvements made to this code as well as changes to the input and output files, interactive input, and graphics output. The comparison of this code to experimental data is shown to have improved as a result of these modifications.

  16. Lewis Structures Technology, 1988. Volume 1: Structural Dynamics

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The specific purpose of the symposium was to familiarize the engineering structures community with the depth and range of research performed by the Structures Division of the Lewis Research Center and its academic and industrial partners. Sessions covered vibration control, fracture mechanics, ceramic component reliability, parallel computing, nondestructive testing, dynamical systems, fatigue and damage, wind turbines, hot section technology, structural mechanics codes, computational methods for dynamics, structural optimization, and applications of structural dynamics.

  17. Bibliography of Lewis Research Center technical publications announced in 1985

    NASA Technical Reports Server (NTRS)

    1986-01-01

    This compilation of abstracts describes and indexes the technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1985. All the publications were announced in the 1985 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  18. Bibliography of Lewis Research Center technical publications announced in 1993

    NASA Technical Reports Server (NTRS)

    1994-01-01

    This compilation of abstracts describes and indexes the technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1993. All the publications were announced in the 1993 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  19. Bibliography of Lewis Research Center technical publications announced in 1984

    NASA Technical Reports Server (NTRS)

    1985-01-01

    This compilation of abstracts describes and indexes the technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1984. All the publications were announced in the 1984 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  20. Bibliography of Lewis Research Center technical publications announced in 1981

    NASA Technical Reports Server (NTRS)

    1982-01-01

    Technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1981 are indexed and abstracted. All the publications were announced in the 1981 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patent applications, and theses. A total of 384 technical publications is listed.

  1. A Comparison of Lead Abatement Technologies at Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Jeziorowski, Luz Y.; Calla, Joanne

    1997-01-01

    In 1995, Lewis participated in a pilot test of Lead Specifications. The Specifications were sponsored by the Center to Protect Worker's Rights (CPWR). Entitled "Model Specifications for the Protection of Worker's from Lead on Steel Structures", one aspect of this endeavor was to test and compare several lead abatement technologies. The project overview, objectives, team, and requirements as well as abatement methods and materials are outlined.

  2. Ion Thruster Development at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Sovey, James S.; Hamley, John A.; Patterson, Michael J.; Rawlin, Vincent K.; Sarver-Verhey, Timothy R.

    1992-01-01

    Recent ion propulsion technology efforts at NASA's Lewis Research Center including development of kW-class xenon ion thrusters, high power xenon and krypton ion thrusters, and power processors are reviewed. Thruster physical characteristics, performance data, life projections, and power processor component technology are summarized. The ion propulsion technology program is structured to address a broad set of mission applications from satellite stationkeeping and repositioning to primary propulsion using solar or nuclear power systems.

  3. Bibliography of Lewis Research Center technical publications announced in 1988

    NASA Technical Reports Server (NTRS)

    1989-01-01

    This bibliography contains abstracts of the technical reports that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1988. Subject, author, and corporate source indexes are also included. All the publications were announced in the 1988 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  4. Bibliography of Lewis Research Center Technical Publications announced in 1979

    NASA Technical Reports Server (NTRS)

    1980-01-01

    This compilation of over 1100 abstracts describes and indexes the technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1979. All the publications were announced in the 1979 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Research reports, journal articles, conference presentations, patents and patent applications, and theses are included. Subject, author, corporate source, contract number, and report number indexes are provided.

  5. Bibliography of Lewis Research Center technical publications announced in 1977

    NASA Technical Reports Server (NTRS)

    1978-01-01

    This compilation of abstracts describes and indexes over 780 technical reports resulting from the scientific and engineering work performed and managed by the Lewis Research Center in 1977. All the publications were announced in the 1977 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Documents cited include research reports, journal articles, conference presentations, patents and patent applications, and theses.

  6. Bibliography of Lewis Research Center technical publications announced in 1987

    NASA Technical Reports Server (NTRS)

    1988-01-01

    This compilation of abstracts describes and indexes the technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1987. All the publications were announced in the 1987 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  7. Bibliography of Lewis Research Center technical publications announced in 1992

    NASA Technical Reports Server (NTRS)

    1993-01-01

    This compilation of abstracts describes and indexes the technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1992. All the publications were announced in the 1992 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  8. Bibliography of Lewis Research Center technical publications announced in 1989

    NASA Technical Reports Server (NTRS)

    1990-01-01

    This compilation of abstracts describes and indexes the technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1989. All the publications were announced in the 1989 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  9. Bibliography of Lewis Research Center technical publications announced in 1990

    NASA Technical Reports Server (NTRS)

    1991-01-01

    This compilation of abstracts describes and indexes the technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1990. All the publications were announced in the 1990 issues of STAR (Scientific and Technical Aerospace Reports) and/or IAA (International Aerospace Abstracts). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  10. Structure Of Flame Balls At Low Lewis-number (SOFBALL)

    NASA Technical Reports Server (NTRS)

    Ronney, Paul D.

    1995-01-01

    The work has encompassed several topics related to the experimental and theoretical study of combustion limits in premixed flames at microgravity. These topics include (1) flame structure and stability at low Lewis number (which is the basis for the SOFBALL space flight experiment), (2) flame propagation and extinction in cylindrical tubes, and (3) experimental simulation of combustion processes using autocatalytic chemical reactions. Progress on each of these topics is outlined.

  11. Structure Of Flame Balls At Low Lewis-numbers (SOFBALL)

    NASA Technical Reports Server (NTRS)

    2004-01-01

    Structure Of Flame Balls At Low Lewis-numbers (SOFBALL) Experiment Mounting Structure (EMS) was used to conduct the SOFBALL experiment on Combustion Module-1. The EMS was inserted into the CM-1 combustion chamber. The chamber was filled with a lean fuel/oxidizer mixture and a spark igniter on the EMS ignited the gas. Very small, weak flames, in the shape of spheres, were formed and studied.

  12. Bibliography of Lewis Research Center technical publications announced in 1986

    NASA Technical Reports Server (NTRS)

    1987-01-01

    This compilation of abstracts describes and indexes the technical reporting that resulted from the scientific and engineering work performed and managed by the Lewis Research Center in 1986. All the publications were announced in the 1986 issues of Scientific and Technical Aerospace Reports (STAR) and/or International Aerospace Abstracts (IAA). Included are research reports, journal articles, conference presentations, patents and patent applications, and theses.

  13. Therapeutic Targeting of Endothelial Ligands for L-selectin (PNAd) in a Sheep Model of Asthma

    PubMed Central

    Rosen, Steven D.; Tsay, Durwin; Singer, Mark S.; Hemmerich, Stefan; Abraham, William M.

    2005-01-01

    The homing of lymphocytes to peripheral lymph nodes is initiated by an adhesive interaction between L-selectin on lymphocytes and PNAd, a set of sialomucins that are constitutively displayed on high endothelial venules of lymph nodes. PNAd is defined by monoclonal antibody MECA-79 that recognizes a sulfated oligosaccharide carried by the sialomucins. This epitope overlaps with 6-sulfo sialyl Lewis x, a recognition determinant for L-selectin. Previous work has shown that administration of a L-selectin monoclonal antibody blocks both late-phase airway responses and airway hyperresponsiveness in a sheep model of asthma. We show here that airway-associated lymphoid collections from lungs of allergic sheep exhibited PNAd+ venules as detected by immunostaining with MECA-79. The same vessels also expressed a GlcNAc-6-O-sulfotransferase known as HEC-GlcNAc6ST, which is known to contribute to the formation of the MECA-79 epitope in high endothelial venules of mouse lymph nodes. Intravenous administration of MECA-79 to allergic sheep significantly blunted both the late-phase airway response and airway hyperresponsiveness induced by airway allergen challenge. Furthermore, MECA-79 inhibited the accumulation of all classes of leukocytes in bronchoalveolar lavage fluid. These findings represent the first demonstration that targeting of PNAd has therapeutic efficacy in an inflammatory disease. PMID:15743804

  14. Lewis' Educational and Research Collaborative Intership Program Grant Closeout Report

    NASA Technical Reports Server (NTRS)

    2003-01-01

    The Lewis' Educational and Research Collaborative Internship Program (LERCIP) is a collaborative undertaking by the Office of Educational Programs at NASA Glenn Research Center at Lewis Field (formerly NASA Lewis Research Center) and the Ohio Aerospace Institute. This program provides 10-week internships and 10 or 12-week fellowships for undergraduate/graduate students and secondary school teachers. Approximately 130 interns are selected to participate in this program each year and begin arriving the second week in May. The internships provide students with introductory professional experiences to complement their academic programs. The interns are given assignments on research and development projects under the personal guidance of NASA professional staff members. Each intern is assigned a NASA mentor who facilitates a research assignment. In addition to the research assignment, the summer program includes a strong educational component that enhances the professional stature of the participants. The educational activities include a research symposium and a variety of workshops, lectures and short courses. An important aspect of the program is that it includes students with diverse social, cultural and economic backgrounds.

  15. Lewis and Clark: Pioneering Meteorological Observers in the American West.

    NASA Astrophysics Data System (ADS)

    Solomon, Susan; Daniel, John S.

    2004-09-01

    The technical achievements of Lewis and Clark have been celebrated in fields ranging from cartography to zoology. As America commemorates the bicentennial of their historic journey across the continent, this paper shows that their meteorological data and personal weather-related observations also are worthy of celebration. While the primary goal of the mission, as described by then-President Jefferson to the Congress, was economic and strategic, both Jefferson and cocaptains Lewis and Clark showed an interest in and capacity for scientific understanding of the meteorology of the then-unknown West. The seasonal evolution and variability of temperatures recorded for the first time by Lewis and Clark on the High Plains can now be shown to be quite close to average, thanks to many decades of collection of modern data by the U.S. Cooperative Observer Network stations along their route. While the diets, lives, and experiences of these early explorers and their men were profoundly different from those of modern Americans, the climate that they documented for the first time with care and accuracy remains familiar to us today.

  16. Lewis Wolpert discusses development and depression. Interview by Joanne Clough.

    PubMed

    Wolpert, Lewis

    2004-06-01

    Lewis Wolpert is Professor of Biology as Applied to Medicine in the Department of Anatomy and Developmental Biology at University College, London, UK. His research interests focus on the mechanisms that are involved in embryonic development. Lewis originally trained as a civil engineer in South Africa but in 1955 made the move to research in cellular biology at King's College, London. He was made a Fellow of the Royal Society in 1980 and awarded the CBE in 1990. Lewis was also made a Fellow of the Royal Society of Literature in 1999 and has presented science on both radio and TV for several years. He was awarded The Royal Society Michael Faraday Prize in 2000 for his contribution to the public understanding of science, most notably through his Chairmanship of the Committee for the Public Understanding of Science (COPUS; 1993-1998). He is the author of numerous books, including Malignant Sadness: The Anatomy of Depression, Principles of Development, The Unnatural Nature of Science and The Triumph of the Embryo. He also writes a regular column for The Independent. PMID:15149619

  17. Anaplasma phagocytophilum Infects Mast Cells via α1,3-Fucosylated but Not Sialylated Glycans and Inhibits IgE-Mediated Cytokine Production and Histamine Release ▿

    PubMed Central

    Ojogun, Nore; Barnstein, Brian; Huang, Bernice; Oskeritzian, Carole A.; Homeister, Jonathon W.; Miller, Daniel; Ryan, John J.; Carlyon, Jason A.

    2011-01-01

    Mast cells are sentinels for infection. Upon exposure to pathogens, they release their stores of proinflammatory cytokines, chemokines, and histamine. Mast cells are also important for the control of certain tick-borne infections. Anaplasma phagocytophilum is an obligate intracellular tick-transmitted bacterium that infects neutrophils to cause the emerging disease granulocytic anaplasmosis. A. phagocytophilum adhesion to and infection of neutrophils depend on sialylated and α1,3-fucosylated glycans. We investigated the hypotheses that A. phagocytophilum invades mast cells and inhibits mast cell activation. We demonstrate that A. phagocytophilum binds and/or infects murine bone marrow-derived mast cells (BMMCs), murine peritoneal mast cells, and human skin-derived mast cells. A. phagocytophilum infection of BMMCs depends on α1,3-fucosylated, but not sialylated, glycans. A. phagocytophilum binding to and invasion of BMMCs do not elicit proinflammatory cytokine secretion. Moreover, A. phagocytophilum-infected cells are inhibited in the release of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), IL-13, and histamine following stimulation with IgE or antigen. Thus, A. phagocytophilum mitigates mast cell activation. These findings potentially represent a novel means by which A. phagocytophilum usurps host defense mechanisms and shed light on the interplay between mast cells and vector-borne bacterial pathogens. PMID:21536789

  18. Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response

    PubMed Central

    Carlin, Aaron F.; Uchiyama, Satoshi; Chang, Yung-Chi; Lewis, Amanda L.; Nizet, Victor

    2009-01-01

    Human neutrophil Siglec-9 is a lectin that recognizes sialic acids (Sias) via an amino-terminal V-set Ig domain and possesses tyrosine-based inhibitory motifs in its cytoplasmic tail. We hypothesized that Siglec-9 recognizes host Sias as “self,” including in cis interactions with Sias on the neutrophil's own surface, thereby dampening unwanted neutrophil reactivity. Here we show that neutrophils presented with immobilized multimerized Siaα2-3Galβ1-4GlcNAc units engage them in trans via Siglec-9. The sialylated capsular polysaccharide of group B Streptococcus (GBS) also presents terminal Siaα2-3Galβ1-4GlcNAc units, and similarly engages neutrophil Siglec-9, dampening neutrophil responses in a Sia- and Siglec-9–dependent manner. Reduction in the neutrophil oxidative burst, diminished formation of neutrophil extracellular DNA traps, and increased bacterial survival are also facilitated by GBS sialylated capsular polysaccharide interactions with Siglec-9. Thus, GBS can impair neutrophil defense functions by coopting a host inhibitory receptor via sialoglycan molecular mimicry, a novel mechanism of bacterial immune evasion. PMID:19196661

  19. Differences in the sialylation patterns of membrane stress proteins in chemical carcinogen-induced tumors developed in BALB/c and IL-1alpha deficient mice.

    PubMed

    Avidan, Avi; Perlmutter, Michal; Tal, Smadar; Oraki, Omer; Kapp, Tsachi; Krelin, Yacov; Elkabets, Moshe; Dotan, Shahar; Apte, Ron N; Lichtenstein, Rachel G

    2009-12-01

    We evaluated the patterns of sialylation on fibrosarcoma cell lines arising following 3-methylcholanthrene treatments of wild-type and IL-1alpha-deficient mice; the former induced progressive tumors, whereas the latter cell lines induced regressing tumors or failed to develop into tumors in mice due to immune rejection. In regressing tumors, terminating alpha2-6-Neu5Ac residues were present at lower levels than in progressively growing tumors. In both tumor cells, the amount of alpha2-6-Neu5Ac residues was higher by an order of magnitude relative to the amount expressed in primary fibroblasts harvested from IL-1alpha-deficient and wild-type mice. We focused on membrane proteins, which may interact with the immune system. Interestingly, HSP65, grp75, and gp96 were found on the surfaces of malignant cells and were shown to possess sialylated N-glycans. The amount of trisialylated glycans on gp96 and HSP65 and monosialylated glycans on grp75 of regressing cells was significantly lower than in progressively growing cells, suggesting a dependency of these specific glycoforms on anti-tumor immunity. PMID:19430902

  20. Gilbert Newton Lewis: his influence on physical-organic chemists at Berkeley

    SciTech Connect

    Calvin, M.

    1982-03-01

    A review is presented of the historical contributions of Gilbert N. Lewis to science and a discussion of the influence of Lewis on the research of the members of the physical-organic staff at Berkeley, including Melvin Calvin, during the twenties, thirties and forties. Some specific examples are discussed. Also, the effect of Lewis, his science and administrative concepts in the creation of excellence in a department of chemistry are reviewed.

  1. P53 and Cancer-Associated Sialylated Glycans Are Surrogate Markers of Cancerization of the Bladder Associated with Schistosoma haematobium Infection

    PubMed Central

    Lima, Luís; Tavares, Ana; Peixoto, Andreia; Parreira, Beatriz; Correia da Costa, José Manuel; Brindley, Paul J.; Lopes, Carlos

    2014-01-01

    Background Bladder cancer is a significant health problem in rural areas of Africa and the Middle East where Schistosoma haematobium is prevalent, supporting an association between malignant transformation and infection by this blood fluke. Nevertheless, the molecular mechanisms linking these events are poorly understood. Bladder cancers in infected populations are generally diagnosed at a late stage since there is a lack of non-invasive diagnostic tools, hence enforcing the need for early carcinogenesis markers. Methodology/Principal Findings Forty-three formalin-fixed paraffin-embedded bladder biopsies of S. haematobium-infected patients, consisting of bladder tumours, tumour adjacent mucosa and pre-malignant/malignant urothelial lesions, were screened for bladder cancer biomarkers. These included the oncoprotein p53, the tumour proliferation rate (Ki-67>17%), cell-surface cancer-associated glycan sialyl-Tn (sTn) and sialyl-Lewisa/x (sLea/sLex), involved in immune escape and metastasis. Bladder tumours of non-S. haematobium etiology and normal urothelium were used as controls. S. haematobium-associated benign/pre-malignant lesions present alterations in p53 and sLex that were also found in bladder tumors. Similar results were observed in non-S. haematobium associated tumours, irrespectively of their histological nature, denoting some common molecular pathways. In addition, most benign/pre-malignant lesions also expressed sLea. However, proliferative phenotypes were more prevalent in lesions adjacent to bladder tumors while sLea was characteristic of sole benign/pre-malignant lesions, suggesting it may be a biomarker of early carcionogenesis associated with the parasite. A correlation was observed between the frequency of the biomarkers in the tumor and adjacent mucosa, with the exception of Ki-67. Most S. haematobium eggs embedded in the urothelium were also positive for sLea and sLex. Reinforcing the pathologic nature of the studied biomarkers, none was observed

  2. Lewis Acid Catalyzed Selective Reactions of Donor-Acceptor Cyclopropanes with 2-Naphthols.

    PubMed

    Kaicharla, Trinadh; Roy, Tony; Thangaraj, Manikandan; Gonnade, Rajesh G; Biju, Akkattu T

    2016-08-16

    Lewis acid-catalyzed reactions of 2-substituted cyclopropane 1,1-dicarboxylates with 2-naphthols is reported. The reaction exhibits tunable selectivity depending on the nature of Lewis acid employed and proceed as a dearomatization/rearomatization sequence. With Bi(OTf)3 as the Lewis acid, a highly selective dehydrative [3+2] cyclopentannulation takes place leading to the formation of naphthalene-fused cyclopentanes. Interestingly, engaging Sc(OTf)3 as the Lewis acid, a Friedel-Crafts-type addition of 2-naphthols to cyclopropanes takes place, thus affording functionalized 2-naphthols. Both reactions furnished the target products in high regioselectivity and moderate to high yields. PMID:27391792

  3. Reduced striatal tyrosine hydroxylase in incidental Lewy body disease

    PubMed Central

    Adler, Charles H.; Sue, Lucia I.; Peirce, Jeffrey B.; Bachalakuri, Jyothi; Dalsing-Hernandez, Jessica E.; Lue, Lih Fen; Caviness, John N.; Connor, Donald J.; Sabbagh, Marwan N.; Walker, Douglas G.

    2009-01-01

    Incidental Lewy body disease (ILBD) is the term used when Lewy bodies are found in the nervous system of subjects without clinically documented parkinsonism or dementia. The prevalence of ILBD in the elderly population has been estimated at between 3.8 and 30%, depending on subject age and anatomical site of sampling. It has been speculated that ILBD represents the preclinical stage of Parkinson’s disease (PD) and/or dementia with Lewy bodies (DLB). Studies of ILBD could potentially identify early diagnostic signs of these disorders. At present, however, it is impossible to know whether ILBD is a precursor to PD or DLB or is just a benign finding of normal aging. We hypothesized that, if ILBD represents an early stage of PD or DLB, it should be associated with depletion of striatal dopaminergic markers. Eleven subjects with ILBD and 27 control subjects were studied. The ILBD subjects ranged in age from 74 to 96 years (mean 86.5) while the control subjects’ age ranged from 75 to 102 years (mean 86.7). Controls and subjects did not differ in terms of age, postmortem interval, gender distribution, medical history conditions, brain weight, neuritic plaque density or Braak neurofibrillary stage. Quantitative ELISA measurement of striatal tyrosine hydroxylase (TH), the principal enzyme for dopamine synthesis, showed a 49.8% (P = 0.01) reduction in ILBD cases, as compared with control cases. The finding suggests that ILBD is not a benign condition but is likely a precursor to PD and/or DLB. PMID:17985144

  4. NASA Lewis and Ohio Company Hit Hole in One

    NASA Technical Reports Server (NTRS)

    1998-01-01

    Ben Hogan Company's Golf Ball Division, which is based in Elyria, Ohio, had developed concepts and prototypes for new golf balls but was unable to determine exact performance characteristics. Specifically, the company's R&D department wanted to measure the spin rates of experimental golf balls. After the Golf Ball Division requested assistance, researchers and technicians from the NASA Lewis Research Center went to Elyria and conducted several days worth of tests. Ben Hogan is using the test results to improve the spin characteristics of a new ball it plans to introduce to the market.

  5. Imaging in Dementia With Lewy Bodies: An Overview.

    PubMed

    Watson, Rosie; Colloby, Sean J

    2016-09-01

    Dementia with Lewy bodies (DLB) while common in older age can present a diagnostic challenge to clinicians and is often misdiagnosed as Alzheimer disease (AD). Imaging studies have improved our understanding of the neurobiological changes in DLB during life and how they differ from AD. This has led to significant advances in the development of new techniques, such as dopaminergic imaging, which can aid the clinical diagnosis. Other functional imaging methods also show promise in helping to assess the influence of differing pathologies in DLB, most notably, AD-related and vascular pathology during life. This article will provide an overview of the main imaging findings in DLB. PMID:27502300

  6. NASA Lewis H2-O2 MHD program

    NASA Technical Reports Server (NTRS)

    Smith, M.; Nichols, L. D.; Seikel, G. R.

    1974-01-01

    Performance and power costs of H2-O2 combustion powered steam-MHD central power systems are estimated. Hydrogen gas is assumed to be transmitted by pipe from a remote coal gasifier into the city and converted to electricity in a steam MHD plant having an integral gaseous oxygen plant. These steam MHD systems appear to offer an attractive alternative to both in-city clean fueled conventional steam power plants and to remote coal fired power plants with underground electric transmission into the city. Status and plans are outlined for an experimental evaluation of H2-O2 combustion-driven MHD power generators at NASA Lewis Research Center.

  7. Fluctuation spectra in the NASA Lewis bumpy-torus plasma

    NASA Technical Reports Server (NTRS)

    Singh, C. M.; Krawczonek, W. M.; Roth, J. R.; Hong, J. Y.; Powers, E. J.

    1978-01-01

    The electrostatic potential fluctuation spectrum in the NASA Lewis bumpy-torus plasma was studied with capacitive probes in the low pressure (high impedance) mode and in the high pressure (low impedance) mode. Under different operating conditions, the plasma exhibited electrostatic potential fluctuations (1) at a set of discrete frequencies, (2) at a continuum of frequencies, and (3) as incoherent high-frequency turbulence. The frequencies and azimuthal wave numbers were determined from digitally implemented autopower and cross-power spectra. The azimuthal dispersion characteristics of the unstable waves were examined by varying the electrode voltage, the polarity of the voltage, and the neutral background density at a constant magnetic field strength.

  8. Structures Of Flameballs at Low-Lewis number

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The potential for investigating combustion at the limits of flammability, and the implications for spacecraft fire safety, led to the Structures Of Flame Balls At Low Lewis-number (SOFBALL) experiment flown twice aboard the Space Shuttle in 1997. The success there led to reflight on STS-107 Research 1 mission plarned for 2002. All the combustion in a flame ball takes place in a razor-thin reaction zone that depends on diffusion to keep the ball alive. Such a fragile balance is impossible on Earth. The principal investigator is Dr. Paul Ronney of the University of Southern California, Los Angeles. Glenn Research in Cleveland, OH, manages the project.

  9. Telecommuting (Work-At-Home) at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Srinidhi, Saragur M.

    1994-01-01

    This report presents a study in evaluating the viability of providing a work-at-home (telecommuting) program for Lewis Research Center's corporate employees using Integrated Services Digital Network (ISDN). Case studies have been presented for a range of applications from casual data access to interactive access. The network performance of telemedia applications were studied against future requirements for such level of remote connectivity. Many of the popular ISDN devices were characterized for network and service functionality. A set of recommendations to develop a telecommuting policy have been proposed.

  10. NASA Lewis advanced IPV nickel-hydrogen technology

    NASA Astrophysics Data System (ADS)

    Smithrick, John J.; Britton, Doris L.

    1993-11-01

    Individual pressure vessel (IPV) nickel-hydrogen technology was advanced at NASA Lewis and under Lewis contracts. Some of the advancements are as follows: to use 26 percent potassium hydroxide electrolyte to improve cycle life and performance, to modify the state of the art cell design to eliminate identified failure modes and further improve cycle life, and to develop a lightweight nickel electrode to reduce battery mass, hence reduce launch and/or increase satellite payload. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen battery cells was reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 accelerated LEO cycles at 80 percent DOD compared to 3,500 cycles for cells containing 31 percent KOH. Results of the boiler plate cell tests have been validated at NWSC, Crane, Indiana. Forty-eight ampere-hour flight cells containing 26 and 31 percent KOH have undergone real time LEO cycle life testing at an 80 percent DOD, 10 C. The three cells containing 26 percent KOH failed on the average at cycle 19,500. The three cells containing 31 percent KOH failed on the average at cycle 6,400. Validation testing of NASA Lewis 125 Ah advanced design IPV nickel-hydrogen flight cells is also being conducted at NWSC, Crane, Indiana under a NASA Lewis contract. This consists of characterization, storage, and cycle life testing. There was no capacity degradation after 52 days of storage with the cells in the discharged state, on open circuit, 0 C, and a hydrogen pressure of 14.5 psia. The catalyzed wall wick cells have been cycled for over 22,694 cycles with no cell failures in the continuing test. All three of the non-catalyzed wall wick cells failed (cycles 9,588; 13,900; and 20,575). Cycle life test results of the Fibrex nickel electrode has demonstrated the feasibility of an improved nickel electrode giving a higher specific energy nickel-hydrogen cell. A nickel-hydrogen boiler plate cell using an 80

  11. Lewis Structures Technology, 1988. Volume 2: Structural Mechanics

    NASA Technical Reports Server (NTRS)

    1988-01-01

    Lewis Structures Div. performs and disseminates results of research conducted in support of aerospace engine structures. These results have a wide range of applicability to practitioners of structural engineering mechanics beyond the aerospace arena. The engineering community was familiarized with the depth and range of research performed by the division and its academic and industrial partners. Sessions covered vibration control, fracture mechanics, ceramic component reliability, parallel computing, nondestructive evaluation, constitutive models and experimental capabilities, dynamic systems, fatigue and damage, wind turbines, hot section technology (HOST), aeroelasticity, structural mechanics codes, computational methods for dynamics, structural optimization, and applications of structural dynamics, and structural mechanics computer codes.

  12. Structure of Flame Balls at Low Lewis-Number

    NASA Technical Reports Server (NTRS)

    Weiland, Karen J.; Ronney, Paul

    1998-01-01

    The Structure of Flame Balls at Low Lewis-Number (SOFBALL) experiment explored the behavior of a newly discovered flame phenomena called "flame balls." These spherical, stable, stationary flame structures, observed only in microgravity, provide a unique opportunity to study the interactions of the two most important processes necessary for combustion (chemical reaction and heat and mass transport) in the simplest possible configuration. The previously unobtainable experimental data provided a comparison with models of flame stability and flame propagation limits that are crucial both in assessing fire safety and in designing efficient, clean-burning combustion engines.

  13. Hall current effects in the Lewis magnetohydrodynamic generator.

    NASA Technical Reports Server (NTRS)

    Nichols, L. D.; Sovie, R. J.

    1972-01-01

    Data obtained in the Lewis MHD generator are compared with theoretical values calculated using the Dzung (1966) theory. The generator is operated with cesium seeded argon as the working fluid. The gas temperature varies from 1800 to 2100 K, the gas pressure from 19 to 22 N/sq cm, the Mach number from .3 to .5, and the magnetic field strength from .2 to 1.6 tesla. The analysis indicates that there is incomplete seed vaporization and that Hall current shorting paths (through the working fluid to ground at both the entrance and exit of the channel) are limiting generator performance.

  14. Additional Improvements to the NASA Lewis Ice Accretion Code LEWICE

    NASA Technical Reports Server (NTRS)

    Wright, William B.; Bidwell, Colin S.

    1995-01-01

    Due to the feedback of the user community, three major features have been added to the NASA Lewis ice accretion code LEWICE. These features include: first, further improvements to the numerics of the code so that more time steps can be run and so that the code is more stable; second, inclusion and refinement of the roughness prediction model described in an earlier paper; third, inclusion of multi-element trajectory and ice accretion capabilities to LEWICE. This paper will describe each of these advancements in full and make comparisons with the experimental data available. Further refinement of these features and inclusion of additional features will be performed as more feedback is received.

  15. NASA Lewis advanced IPV nickel-hydrogen technology

    NASA Technical Reports Server (NTRS)

    Smithrick, John J.; Britton, Doris L.

    1993-01-01

    Individual pressure vessel (IPV) nickel-hydrogen technology was advanced at NASA Lewis and under Lewis contracts. Some of the advancements are as follows: to use 26 percent potassium hydroxide electrolyte to improve cycle life and performance, to modify the state of the art cell design to eliminate identified failure modes and further improve cycle life, and to develop a lightweight nickel electrode to reduce battery mass, hence reduce launch and/or increase satellite payload. A breakthrough in the LEO cycle life of individual pressure vessel nickel-hydrogen battery cells was reported. The cycle life of boiler plate cells containing 26 percent KOH electrolyte was about 40,000 accelerated LEO cycles at 80 percent DOD compared to 3,500 cycles for cells containing 31 percent KOH. Results of the boiler plate cell tests have been validated at NWSC, Crane, Indiana. Forty-eight ampere-hour flight cells containing 26 and 31 percent KOH have undergone real time LEO cycle life testing at an 80 percent DOD, 10 C. The three cells containing 26 percent KOH failed on the average at cycle 19,500. The three cells containing 31 percent KOH failed on the average at cycle 6,400. Validation testing of NASA Lewis 125 Ah advanced design IPV nickel-hydrogen flight cells is also being conducted at NWSC, Crane, Indiana under a NASA Lewis contract. This consists of characterization, storage, and cycle life testing. There was no capacity degradation after 52 days of storage with the cells in the discharged state, on open circuit, 0 C, and a hydrogen pressure of 14.5 psia. The catalyzed wall wick cells have been cycled for over 22,694 cycles with no cell failures in the continuing test. All three of the non-catalyzed wall wick cells failed (cycles 9,588; 13,900; and 20,575). Cycle life test results of the Fibrex nickel electrode has demonstrated the feasibility of an improved nickel electrode giving a higher specific energy nickel-hydrogen cell. A nickel-hydrogen boiler plate cell using an 80

  16. Visual cortical excitability in dementia with Lewy bodies.

    PubMed

    Taylor, John-Paul; Firbank, Michael; O'Brien, John T

    2016-05-01

    Alterations in the visual system may underlie visual hallucinations in dementia with Lewy bodies (DLB). However, cortical excitability as measured by transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) activation of lower visual areas (V1-3) to visual stimuli appear normal in DLB. We explored the relationship between TMS-determined phosphene threshold and fMRI-related visual activation and found a positive relationship between the two in controls but a negative one in DLB. This double dissociation suggests a loss of inhibition in the visual system in DLB, which may predispose individuals to visual dysfunction and visual hallucinations. PMID:26541688

  17. Engine component instrumentation development facility at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Bruckner, Robert J.; Buggele, Alvin E.; Lepicovsky, Jan

    1992-01-01

    The Engine Components Instrumentation Development Facility at NASA Lewis is a unique aeronautics facility dedicated to the development of innovative instrumentation for turbine engine component testing. Containing two separate wind tunnels, the facility is capable of simulating many flow conditions found in most turbine engine components. This facility's broad range of capabilities as well as its versatility provide an excellent location for the development of novel testing techniques. These capabilities thus allow a more efficient use of larger and more complex engine component test facilities.

  18. Structure of Flame Balls at Low Lewis Number (SOFBALL) Video

    NASA Technical Reports Server (NTRS)

    2003-01-01

    The Structure of Flame Balls at Low Lewis (SOFBALL) experiment, was run on Space Shuttle Columbia in 2003 for STS-107. The experiment tested various fuel-oxygen-inert gas mixtures in microgravity to produce flame balls, which are spherical steady flames that reveal combustion processes hidden by the volatile effects of gravity on Earth. In this video, a hydrogen-oxygen-sulfur hexafluoride gas mixture produced nine flame balls, the most ever created at once, one of which lasted 81 minutes making it the longest lasting flame ball ever burned in space.

  19. Visual cortical excitability in dementia with Lewy bodies

    PubMed Central

    Taylor, John-Paul; Firbank, Michael; O'Brien, John T.

    2016-01-01

    Alterations in the visual system may underlie visual hallucinations in dementia with Lewy bodies (DLB). However, cortical excitability as measured by transcranial magnetic stimulation (TMS) and functional magnetic resonance imaging (fMRI) activation of lower visual areas (V1–3) to visual stimuli appear normal in DLB. We explored the relationship between TMS-determined phosphene threshold and fMRI-related visual activation and found a positive relationship between the two in controls but a negative one in DLB. This double dissociation suggests a loss of inhibition in the visual system in DLB, which may predispose individuals to visual dysfunction and visual hallucinations. PMID:26541688

  20. Separation of 8-aminonaphthalene-1,3,6-trisulfonic acid-labelled neutral and sialylated N-linked complex oligosaccharides by capillary electrophoresis.

    PubMed

    Klockow, A; Amadò, R; Widmer, H M; Paulus, A

    1995-11-17

    Complex oligosaccharides, both neutral and sialylated, were derivatized with 8-aminonaphthalene-1,3,6-trisulfonic acid (ANTS) and separated by capillary electrophoresis. The derivatization reaction was carried out in a total reaction volume of 2 microliters. The separated peaks were detected by laser-induced fluorescence detection using the 325-nm line of a He-Cd laser. Concentration and mass detection limits of 5 x 10(-8) M and 500 amol, respectively, could be achieved. The limiting step for higher sensitivity is not the detector performance, however, but the chemistry with a derivatization limit of 2.5 x 10(-6) M. Two labelling protocols were established, one with overnight reaction at 40 degrees C and the other with a 2.5-h derivatization time at 80 degrees C. Neutral oligosaccharides could be labelled with either protocol. However, sialylated oligosaccharides hydrolysed when labeled at 80 degrees C. Low nanomole to picomole amounts of oligomannose-type and complex-type oligosaccharide mixtures were derivatized and separated in less than 8 min with excellent resolution using a phosphate background electrolyte at pH 2.5. The linear relationship between the electrophoretic mobility and the charge-to-mass ratios of the ANTS conjugates was used for peak assignment. Further, the influence of the three-dimensional structure of the complex oligosaccharides on their migration behaviour is discussed. The suitability of the ANTS derivatization and the subsequent separation for the analysis of complex oligosaccharide patterns is demonstrated with oligosaccharide libraries derived from ovalbumin and bovine fetuin. For peak assignment the patterns are compared with those of the oligomannose and the complex-type oligosaccharide mixtures.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8574387

  1. Transmission diagnostic research at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Zakrajsek, J. J.; Townsend, D. P.; Lewicki, D. G.; Decker, H. J.; Handschuh, R. F.

    1995-01-01

    The NASA Lewis Research Center and the U.S. Army Research Laboratory are involved in a joint research program to advance the technology of aerospace transmissions. Within the last six years, a transmission diagnostics research team was formed to address current and future technology barriers in transmission diagnostics. The diagnostics team conducted a survey to determine critical needs of the diagnostics community. Survey results indicated that experimental verification of gear and bearing fault detection methods and damage magnitude assessment were considered the two most critical research areas of a highly reliable health and usage monitoring system. A plan was implemented by the diagnostics team to address these key research areas, by in-house research and university grants. A variety of transmission fault detection methods were applied to experimentally obtained fatigue data. Failure modes of the fatigue tests include a variety of gear pitting failures, tooth wear, tooth fracture, and bearing spalling failures. Accomplishments to date include verification of several specific gear diagnostic methods, verification of a new pattern recognition method to determine failure, and development of a new method to model gear tooth damage. This paper presents the results of these accomplishments in transmission diagnostics research at NASA Lewis Research Center.

  2. Applied imaging at the NASA Lewis Research Center

    NASA Astrophysics Data System (ADS)

    Slater, Howard A.; Owens, Jay C.

    1993-01-01

    NASA Lewis Research Center in Cleveland, Ohio has just completed the celebration of its 50th anniversary. `During the past 50 years, Lewis helped win World War II, made jet aircraft safer and more efficient, helped Americans land on the Moon ... and engaged in the type of fundamental research that benefits all of us in our daily lives.' As part of the center's long history, the Photographic and Printing Branch has continued to develop and meet the center's research imaging requirements. As imaging systems continue to advance and researchers more clearly understand the power of imaging, investigators are relying more and more on imaging systems to meet program objectives. Today, the Photographic and Printing Branch supports a research community of over 5,000 including advocacy for NASA Headquarters and other government agencies. Complete classified and unclassified imaging services include high- speed image acquisition, technical film and video documentaries, still imaging, and conventional and unconventional photofinishing operations. These are the foundation of the branch's modern support function. This paper provides an overview of the varied applied imaging programs managed by the Photographic and Printing Branch. Emphasis is placed on recent imaging projects including icing research, space experiments, and an on-line image archive.

  3. Expression of Lewis antigenic determinants in colorectal adenocarcinomas.

    PubMed

    Blasco, E; Torrado, J; Cosme, A; Alvarez, E; Zugasti, A; Gutierrez-Hoyos, A; Arenas, J I

    1989-01-01

    Expression of type 1 and type 2 chain Lewis antigens was studied in 32 rectal adenocarcinoma specimens; the results were correlated with the patients' Lewis phenotype and secretor status. In addition, the pattern of expression of these antigens was analyzed in adjacent and distant normal mucosa. We used an indirect immunofluorescence technique with p-phenylenediamine counterstaining (Oriol technique) and a panel of monoclonal antibodies directed against the different antigenic specificities. Normal distal colonic mucosa only expresses monofucosylated structures (Lea and X) arising from activity of the alpha 1-3,4-fucosyltransferase coded by the Le gene. Rectal adenocarcinomas also show Lea and X, but also reexpress blood group antigens ABH and exhibit difucosylated determinants (Leb and Y). The accumulation of mono- and difucosylated type 2 chain in neoplastic processes, independently of the Le and Se genes, could be due to the enzymes coded by reactivation of the H and X genes. Blood group antigens form a complex signal code, genetically regulated, which intervenes in differentiation, growth and cellular recognition processes, and which may undergo important modifications during malignant transformation. These alterations could be useful in the diagnosis and prognosis of some types of carcinoma. PMID:2476347

  4. F119 Nozzle Flaps Tested at Lewis' CE-22 Facility

    NASA Technical Reports Server (NTRS)

    2005-01-01

    The next generation of aircraft fighters requires higher engine performance and enhanced stealth characteristics for air superiority. A Lockheed-Martin/Boeing aircraft with a Pratt & Whitney F119 engine was selected by the Air Force for the next advanced tactical fighter (ATF). As part of this program, the NASA Lewis Research Center entered into a cooperative test program with Pratt & Whitney along with the Air Force to study the performance for various advanced nozzle concepts for the F119 engine. The area of interest was to measure the internal performance (both thrust and flow coefficients) of nozzle flaps redesigned for low observability with minimal performance loss. The experimental program was successfully completed May 1995 in Lewis' CE-22 facility. The models were tested over a wide range of geometric variations and nozzle pressure ratios. Results confirmed that the redesigned nozzle flaps had an insignificant effect on the thrust performance and that the resulting flow patterns should not be a problem in the cooling flow design. The results also agreed well with Pratt & Whitney's computational fluid dynamics analysis. The data obtained from this test were added to the current data base to help validate other performance prediction methodology.

  5. Impairments of Speech Fluency in Lewy Body Spectrum Disorder

    PubMed Central

    Ash, Sharon; McMillan, Corey; Gross, Rachel G.; Cook, Philip; Gunawardena, Delani; Morgan, Brianna; Boller, Ashley; Siderowf, Andrew; Grossman, Murray

    2011-01-01

    Few studies have examined connected speech in demented and non-demented patients with Parkinson’s disease (PD). We assessed the speech production of 35 patients with Lewy body spectrum disorder (LBSD), including non-demented PD patients, patients with PD dementia (PDD), and patients with dementia with Lewy bodies (DLB), in a semi-structured narrative speech sample in order to characterize impairments of speech fluency and to determine the factors contributing to reduced speech fluency in these patients. Both demented and non-demented PD patients exhibited reduced speech fluency, characterized by reduced overall speech rate and long pauses between sentences. Reduced speech rate in LBSD correlated with measures of between-utterance pauses, executive functioning, and grammatical comprehension. Regression analyses related non-fluent speech, grammatical difficulty, and executive difficulty to atrophy in frontal brain regions. These findings indicate that multiple factors contribute to slowed speech in LBSD, and this is mediated in part by disease in frontal brain regions. PMID:22099969

  6. Coupling of Carbon Monoxide with Nitrogen Monoxide at a Frustrated Lewis Pair Template.

    PubMed

    Ye, Ke-Yin; Kehr, Gerald; Daniliuc, Constantin G; Liu, Lei; Grimme, Stefan; Erker, Gerhard

    2016-08-01

    Coupling of carbon monoxide with nitrogen monoxide was achieved at a frustrated Lewis pair template. This unique reaction uses hydride as an auxiliary, which reductively activates carbon monoxide at the frustrated Lewis pair. The CO/NO coupling reaction then takes place through a pathway involving a radical reaction in which the hydrogen atom auxiliary is eventually removed again. PMID:27328914

  7. LewiSpace: An Exploratory Study with a Machine Learning Model in an Educational Game

    ERIC Educational Resources Information Center

    Ghali, Ramla; Ouellet, Sébastien; Frasson, Claude

    2016-01-01

    The use of educational games as a tool for providing learners with a playful and educational aspect is widespread. In this paper, we present an educational game that we developed to teach a chemistry lesson, namely drawing a Lewis diagram. Our game is a 3D environment known as LewiSpace and aims at balancing between playful and educational…

  8. The Lewis and Clark Expedition. The Constitution Community: Expansion and Reform (1801-1861).

    ERIC Educational Resources Information Center

    Perry, Douglas

    In 1803, President Thomas Jefferson guided a piece of foreign diplomacy through the U.S. Senate, the purchase of Louisiana territory from France. Jefferson chose Meriwether Lewis, his personal secretary, who possessed frontiersman skills to explore the territory. Lewis, in turn, solicited the help of William Clark, whose abilities as a draftsman…

  9. On the Trail of Lewis and Clark: A Journey up the Missouri River.

    ERIC Educational Resources Information Center

    Lourie, Peter

    In 1804, Lewis and Clark and a band of adventurers called the Corps of Discovery embarked on one of the great expeditions in history, the exploration of the newly purchased Louisiana Territory. Much of their time was spent on the Missouri River. Two hundred years later, four friends follow Lewis and Clark's path up the Missouri. Their journey…

  10. 32 CFR Appendix C to Part 552 - Authorized Activities for Fort Lewis Maneuver Area Access

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 3 2011-07-01 2009-07-01 true Authorized Activities for Fort Lewis Maneuver Area Access C Appendix C to Part 552 National Defense Department of Defense (Continued) DEPARTMENT OF.... 552, App. C Appendix C to Part 552—Authorized Activities for Fort Lewis Maneuver Area Access...

  11. An Integrated Perspective of Humanism and Supernaturalism for Education: C. S. Lewis's Version of Education

    ERIC Educational Resources Information Center

    Lee, Seung Chun

    2013-01-01

    This paper explores some theoretical reflections on the connection between C. S. Lewis's thoughts on the purpose and process of education and his understanding of supernatural human nature which has been relatively little explored. An introduction about Lewis's career as a college teacher blends into the background of this paper. It is followed by…

  12. Sentence Processing in Lewy Body Spectrum Disorder: The Role of Working Memory

    ERIC Educational Resources Information Center

    Gross, Rachel G.; McMillan, Corey T.; Chandrasekaran, Keerthi; Dreyfuss, Michael; Ash, Sharon; Avants, Brian; Cook, Philip; Moore, Peachie; Libon, David J.; Siderowf, Andrew; Grossman, Murray

    2012-01-01

    Prior work has related sentence processing to executive deficits in non-demented patients with Parkinson's disease (PD). We extended this investigation to patients with dementia with Lewy bodies (DLB) and PD dementia (PDD) by examining grammatical and working memory components of sentence processing in the full range of patients with Lewy body…

  13. Unprecedented synergistic effects between weak Lewis and Brønsted acids in Prins cyclization.

    PubMed

    Borkar, Prashant; van de Weghe, Pierre; Reddy, B V Subba; Yadav, J S; Grée, René

    2012-09-25

    Novel synergistic effects between Lewis and Brønsted acids in Prins cyclization are reported. Non-reactive Lewis acids and non-reactive Brønsted acids, which failed to perform Prins cyclization when used alone, have shown remarkable synergistic effects when used in combination to perform the reaction successfully. PMID:22885680

  14. The First Confirmed Case of Down Syndrome with Dementia with Lewy Bodies

    ERIC Educational Resources Information Center

    Prasher, V. P.; Airuehia, E.; Carey, M.

    2010-01-01

    Dementia with Lewy bodies (DLB) is the second commonest cause of dementia in the general population. Several researches have established an association between Down syndrome (DS) and Alzheimer's disease. Very few studies have however showed such an association between dementia with Lewy bodies and Down syndrome. The occurrence of DLB in persons…

  15. 33 CFR 117.899 - Youngs Bay and Lewis and Clark River.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 33 Navigation and Navigable Waters 1 2013-07-01 2013-07-01 false Youngs Bay and Lewis and Clark... SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements Oregon § 117.899 Youngs Bay and Lewis and Clark River. (a) The draw of the US101 (New Youngs Bay) highway bridge, mile 0.7,...

  16. Adele Parot: Beacon of the Dioclesian Lewis School of Gymnastic Expression in the American West.

    ERIC Educational Resources Information Center

    Barney, Robert Knight

    In the late 1800's, Dioclesian Lewis developed and introduced into the schools his new concept of physical education. Dr. Lewis thought in terms of preventing illness and maintaining bodily strength and health through physical fitness. His "new gymnastics" were based on programs of exercise movements. Employing light equipment suitable for use by…

  17. Oral Interpretation of C.S. Lewis'"Narnia Tales": A Refracting of "Pictures."

    ERIC Educational Resources Information Center

    Keefe, Carolyn

    "The Chronicles of Narnia" are a series of seven fairy tales written by C.S. Lewis that have become popular with both children and adults. Lewis points to five aspects of the fairy tale form that made the form suitable for expressing the images he saw. The aspects are: (1) no love interest; (2) no close psychology; (3) severe restraints on…

  18. Enthalpy Costs of Making and Breaking Bonds: A Game of Generating Molecules with Proper Lewis Structures

    ERIC Educational Resources Information Center

    Bell, Peter T.; Adkins, Alyssa D.; Gamble, Rex J.; Schultz, Linda D.

    2009-01-01

    "Enthalpy Costs" is a simple card game created to assist students in developing proper Lewis structure drawing skills. Score keeping is accomplished by tracking the enthalpy changes associated with bond-making and bond-breaking processes during formation of molecules represented by proper Lewis structures. Playing the game requires the student to…

  19. Motor and cognitive function in Lewy body dementia: comparison with Alzheimer's and Parkinson's diseases.

    PubMed Central

    Gnanalingham, K K; Byrne, E J; Thornton, A; Sambrook, M A; Bannister, P

    1997-01-01

    OBJECTIVE: Motor and cognitive function were compared in patients with Lewy body dementia, Parkinson's disease, or Alzheimer's disease, to identify features that may be clinically useful in differentiating Lewy body dementia from Alzheimer's disease and Parkinson's disease. METHODS: A range of neuropsychological function and extrapyrimidal signs (EPS) was assessed in 16 patients with Lewy body dementia, 15 with Parkinson's disease, 25 with Alzheimer's disease, and 22 control subjects. RESULTS: The severity of total motor disability scores increased in the following order: controls approximately = Alzheimer's disease << Parkinson's disease < Lewy body dementia. Compared with patients with Parkinson's disease, patients with Lewy body dementia had greater scores for rigidity and deficits in the finger tapping test, but rest tremor and left/right asymmetry in EPS were more evident in Parkinson's disease. Patients with Lewy body dementia were also less likely to present with left/right asymmetry in EPS at the onset of their parkinsonism. "Sensitivity" to neuroleptic drugs was noted in 33% of patients with Lewy body dementia. Alzheimer's disease and Lewy body dementia groups had greater severity of dementia compared with the Parkinson's disease group and controls. Neuropsychological evaluation disclosed severe but similar degrees of impaired performances in tests of attention (digit span), frontal lobe function (verbal fluency, category, and Nelson card sort test) and motor sequencing in both Lewy body dementia and Alzheimer's disease groups, than Parkinson's disease and controls. In the clock face test, improved performance was noted in the "copy" compared to "draw" part of the test in controls, patients with Alzheimer's disease, and those with Parkinson's disease, but not in the patients with Lewy body dementia, who achieved equally poor scores in both parts of the test. CONCLUSIONS: EPS in Lewy body dementia resemble those seen in idiopathic Parkinson's disease

  20. Tuning Lewis acidity using the reactivity of "frustrated Lewis pairs": facile formation of phosphine-boranes and cationic phosphonium-boranes.

    PubMed

    Welch, Gregory C; Cabrera, Lourdes; Chase, Preston A; Hollink, Emily; Masuda, Jason D; Wei, Pingrong; Stephan, Douglas W

    2007-08-21

    The concept of "frustrated Lewis pairs" involves donor and acceptor sites in which steric congestion precludes Lewis acid-base adduct formation. In the case of sterically demanding phosphines and boranes, this lack of self-quenching prompts nucleophilic attack at a carbon para to B followed by fluoride transfer affording zwitterionic phosphonium borates [R(3)P(C(6)F(4))BF(C(6)F(5))(2)] and [R(2)PH(C(6)F(4))BF(C(6)F(5))(2)]. These can be easily transformed into the cationic phosphonium-boranes [R(3)P(C(6)F(4))B(C(6)F(5))(2)](+) and [R(2)PH(C(6)F(4))B(C(6)F(5))(2)](+) or into the neutral phosphino-boranes R(2)P(C(6)F(4))B(C(6)F(5))(2). This new reactivity provides a modular route to a family of boranes in which the steric features about the Lewis acidic center remains constant and yet the variation in substitution provides a facile avenue for the tuning of the Lewis acidity. Employing the Gutmann-Beckett and Childs methods for determining Lewis acid strength, it is demonstrated that the cationic boranes are much more Lewis acidic than B(C(6)F(5))(3), while the acidity of the phosphine-boranes is diminished. PMID:17664977

  1. Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras

    SciTech Connect

    van Bruggen, M.C.; van den Broek, M.F.; van den Berg, W.B. )

    1991-09-01

    Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis. Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant. In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease. In this communication the authors describe their studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras. By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction. F344 rats reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection. For AA comparable results were obtained. These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation.

  2. Exercise for Individuals with Lewy Body Dementia: A Systematic Review

    PubMed Central

    Inskip, Michael; Mavros, Yorgi; Sachdev, Perminder S.; Fiatarone Singh, Maria A.

    2016-01-01

    Background Individuals with Lewy body Dementia (LBD), which encompasses both Parkinson disease dementia (PDD) and Dementia with Lewy Bodies (DLB) experience functional decline through Parkinsonism and sedentariness exacerbated by motor, psychiatric and cognitive symptoms. Exercise may improve functional outcomes in Parkinson’s disease (PD), and Alzheimer’s disease (AD). However, the multi-domain nature of the LBD cluster of symptoms (physical, cognitive, psychiatric, autonomic) results in vulnerable individuals often being excluded from exercise studies evaluating physical function in PD or cognitive function in dementia to avoid confounding results. This review evaluated existing literature reporting the effects of exercise interventions or physical activity (PA) exposure on cluster symptoms in LBD. Methods A high-sensitivity search was executed across 19 databases. Full-length articles of any language and quality, published or unpublished, that analysed effects of isolated exercise/physical activity on indicative Dementia with Lewy Bodies or PD-dementia cohorts were evaluated for outcomes inclusive of physical, cognitive, psychiatric, physiological and quality of life measures. The protocol for this review (Reg. #: CRD42015019002) is accessible at http://www.crd.york.ac.uk/PROSPERO/. Results 111,485 articles were initially retrieved; 288 full articles were reviewed and 89.6% subsequently deemed ineligible due to exclusion of participants with co-existence of dementia and Parkinsonism. Five studies (1 uncontrolled trial, 1 randomized controlled trial and 3 case reports) evaluating 16 participants were included. Interventions were diverse and outcome homogeneity was low. Habitual gait speed outcomes were measured in 13 participants and increased (0.18m/s, 95% CI -0.02, 0.38m/s), exceeding moderate important change (0.14m/s) for PD cohorts. Other outcomes appeared to improve modestly in most participants. Discussion Scarce research investigating exercise in LBD

  3. Ransom, Religion, and Red Giants: C.S. Lewis and Fred Hoyle

    NASA Astrophysics Data System (ADS)

    Larsen, Kristine

    2010-01-01

    Famed fantasy writer C.S. Lewis (1898-1963) was known to friends as a well-read astronomy aficionado. However, this medieval scholar and Christian apologist embraced a pre-Copernican universe (with its astrological overtones) in his Chronicles of Narnia series and defended the beauty and relevance of the geocentric model in his final academic work, "The Discarded Image". In the "Ransom Trilogy” ("Out of the Silent Planet", "Perelandra", and "That Hideous Strength") philologist Ransom (loosely based on Lewis's close friend J.R.R. Tolkien) travels to Lewis's visions of Mars and Venus, where he interacts with intelligent extraterrestrials, battles with evil scientists, and aids in the continuation of extraterrestrial Christian values. In the final book, Ransom is joined by a handful of colleagues in open warfare against the satanic N.I.C.E. (National Institute for Coordinated Experiments). Geneticist and evolutionary biologist J.B.S. Haldane criticized Lewis for his scientifically inaccurate descriptions of the planets, and his disdain for the scientific establishment. Lewis responded to the criticism in essays of his own. Another of Lewis's favorite scientific targets was atheist Fred Hoyle, whom he openly criticized for anti-Christian statements in Hoyle's BBC radio series. Writer and Lewis friend Dorothy L. Sayers voiced her own criticism of Hoyle. In a letter, Lewis dismissed Hoyle as "not a great philosopher (and none of my scientific colleagues think much of him as a scientist.” Given Lewis's lack of respect for Hoyle, and use of creative license in describing the planets, and the flat-earth, "geocentric” Narnia, it is surprising that Lewis very carefully includes an astronomically correct description of red giants in two novels in the Narnia series ("The Magician's Nephew" and "The Last Battle"). This inclusion is even more curious given that Fred Hoyle is well-known as one of the pioneers in the field of stellar death and the properties of red giants.

  4. Design of the NASA Lewis 4-Port Wave Rotor Experiment

    NASA Technical Reports Server (NTRS)

    Wilson, Jack

    1997-01-01

    Pressure exchange wave rotors, used in a topping stage, are currently being considered as a possible means of increasing the specific power, and reducing the specific fuel consumption of gas turbine engines. Despite this interest, there is very little information on the performance of a wave rotor operating on the cycle (i.e., set of waves) appropriate for use in a topping stage. One such cycle, which has the advantage of being relatively easy to incorporate into an engine, is the four-port cycle. Consequently, an experiment to measure the performance of a four-port wave rotor for temperature ratios relevant to application as a topping cycle for a gas turbine engine has been designed and built at NASA Lewis. The design of the wave rotor is described, together with the constraints on the experiment.

  5. Structures Of Flameballs at Low-Lewis number

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The potential for investigating combustion at the limits of flammability, and the implications for spacecraft fire safety, led to the Structures Of Flame Balls At Low Lewis-number (SOFBALL) experiment flown twice aboard the Space Shuttle in 1997. The success there led to reflight on STS-107 Research 1 mission plarned for 2002. Theory does not always predict behavior, thus the need for experiments. Three different published chemical reaction models (lines) for hydrogen-airflame balls proved to be quite different from what was observed (dots) during SOFBALL tests in space. The principal investigator is Dr. Paul Ronney of the University of Southern California, Los Angeles. Glenn Research in Cleveland, OH, manages the project.

  6. Disease-modifying therapeutic directions for Lewy-Body dementias

    PubMed Central

    Zhang, Qiang; Kim, Young-Cho; Narayanan, Nandakumar S.

    2015-01-01

    Dementia with Lewy bodies (DLB) is the second leading cause of dementia following Alzheimer's disease (AD) and accounts for up to 25% of all dementia. DLB is distinct from AD in that it involves extensive neuropsychiatric symptoms as well as motor symptoms, leads to enormous societal costs in terms of direct medical care and is associated with high financial and caregiver costs. Although, there are no disease-modifying therapies for DLB, we review several new therapeutic directions in treating DLB. We discuss progress in strategies to decrease the level of alpha-synuclein, to prevent the cell to cell transmission of misfolded alpha-synuclein, and the potential of brain stimulation in DLB. PMID:26347604

  7. Lewy body dementia: the impact on patients and caregivers

    PubMed Central

    2014-01-01

    Lewy body dementia (LBD) is the second most common neurodegenerative dementia in older adults, yet there remains a delay in diagnosis that limits healthcare providers’ ability to maximize therapeutic outcomes and enhance patient and caregiver quality of life. The impact of LBD on patients includes limiting the potential exposure to medications that may cause adverse outcomes, and addressing how the disease manifestations, such as autonomic features and behavior, affect quality of life. LBD impact on caregivers has been discussed to a greater degree in the literature, and there is clear evidence of caregiver burden and grief associated with disease manifestations. Other common caregiving concerns, such as access to care, prevention of hospitalization, managing behavior, and reviewing prognosis and nursing home placement, are important to comprehensively address the needs of patients with LBD and their caregivers. PMID:25031635

  8. Materials research and applications at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Probst, H. B.

    1987-01-01

    The facilities and instruments of the Lewis Research Center specialized for materials research are discussed. The main objectives of the Center are to provide R & D relevant to main propulsion plants and auxiliary power systems for aeronautics, space, and energy conversion applications. The Center is concerned with microstructure-property relations and their effect on processing; intermetallic compounds and high temperature metal matrix composites; ceramics with improved reliability for use in heat engines; polymer matrix composites for aerospace applcations; understanding the high temperature corrosive attack in the hostile environments of aircraft, rockets, and other heat engines; high temperature lubrication and wear; and microgravity materials research. The various types of schemes and techniques, provided by the Center, for analyzing data are described.

  9. A Neutral Silicon/Phosphorus Frustrated Lewis Pair.

    PubMed

    Waerder, Benedikt; Pieper, Martin; Körte, Leif A; Kinder, Timo A; Mix, Andreas; Neumann, Beate; Stammler, Hans-Georg; Mitzel, Norbert W

    2015-11-01

    Frustrated Lewis pairs (FLPs) have a great potential for activation of small molecules. Most known FLP systems are based on boron or aluminum atoms as acid functions, few on zinc, and only two on boron-isoelectronic silicenium cation systems. The first FLP system based on a neutral silane, (C2F5)3SiCH2P(tBu)2 (1), was prepared from (C2F5)3SiCl with C2F5 groups of very high electronegativity and LiCH2P(tBu)2. 1 is capable of cleaving hydrogen, and adds CO2 and SO2. Hydrogen splitting was confirmed by H/D scrambling reactions. The structures of 1, its CO2 and SO2 adducts, and a decomposition product with CO2 were elucidated by X-ray diffraction. PMID:26423202

  10. Transport Coefficients for the NASA Lewis Chemical Equilibrium Program

    NASA Technical Reports Server (NTRS)

    Svehla, Roger A.

    1995-01-01

    The new transport property data that will be used in the NASA Lewis Research Center's Chemical Equilibrium and Applications Program (CEA) is presented. It complements a previous publication that documented the thermodynamic and transport property data then in use. Sources of the data and a brief description of the method by which the data were obtained are given. Coefficients to calculate the viscosity, thermal conductivity, and binary interactions are given for either one, or usually, two temperature intervals, typically 300 to 1000 K and 1000 to 5000 K. The form of the transport equation is the same as used previously. The number of species was reduced from the previous database. Many species for which the data were estimated were eliminated from the database. Some ionneutral interactions were added.

  11. Magnetic-field measurements for the Lewis Research Center cyclotron

    NASA Technical Reports Server (NTRS)

    Fessler, T. E.

    1973-01-01

    The magnetic field of the Lewis Center cyclotron was mapped by using a Hall-effect magnetic-field transducer. Main-field Fourier coefficients were determined on a polar mesh of 40 radii for each of seven levels of main-field coil current. Incremental fields for eight sets of trim coils and two sets of harmonic coils were also determined at four of these main-field levels. A stored-program, digital computer was used to perform the measurements. The process was entirely automatic; all data-taking and data-reduction activities were specified by the computer programs. A new method for temperature compensation of a Hall element was used. This method required no temperature control of the element. Measurements of the Hall voltage and Hall-element resistance were sufficient to correct for temperature effects.

  12. The NASA Lewis Strain Gauge Laboratory: An update

    NASA Technical Reports Server (NTRS)

    Hobart, H. F.

    1986-01-01

    Efforts continue in the development and evaluation of electrical resistance strain gauges of the thin film and small diameter wire type. Results obtained early in 1986 on some Chinese gauges and Kanthal A-1 gauges mounted on a Hastelloy-X substrate are presented. More recent efforts include: (1) the determination of the uncertainty in the ability to establish gauge factor, (2) the evaluation of sputtered gauges that were fabricated at Lewis, (3) an investigation of the efficacy of dual element temperature compensated gauges when using strain gauge alloys having large thermal coefficients of resistance, and (4) an evaluation of the practical methods of stabilizing gauges whose apparent strain is dependent on cooling rate (e.g., FeCrAl gauges).

  13. Disease-modifying therapeutic directions for Lewy-Body dementias.

    PubMed

    Zhang, Qiang; Kim, Young-Cho; Narayanan, Nandakumar S

    2015-01-01

    Dementia with Lewy bodies (DLB) is the second leading cause of dementia following Alzheimer's disease (AD) and accounts for up to 25% of all dementia. DLB is distinct from AD in that it involves extensive neuropsychiatric symptoms as well as motor symptoms, leads to enormous societal costs in terms of direct medical care and is associated with high financial and caregiver costs. Although, there are no disease-modifying therapies for DLB, we review several new therapeutic directions in treating DLB. We discuss progress in strategies to decrease the level of alpha-synuclein, to prevent the cell to cell transmission of misfolded alpha-synuclein, and the potential of brain stimulation in DLB. PMID:26347604

  14. Lower hybrid emission diagnostics on the NASA Lewis bumpy torus

    NASA Technical Reports Server (NTRS)

    Mallavarpu, R.

    1977-01-01

    The feasibility of using RF emission near the lower hybrid frequency of the NASA Lewis Bumpy Torus plasma for diagnostic purposes is examined. The emission is detected using a spectrum analyzer and a 50 omega miniature coaxial antenna that is sensitive to the polarization of the incoming signal. The frequency shift of the lower hybrid emission peak is monitored as a function of the background pressure, electrode voltage, electrode ring configuration and the strength of the toroidal dc magnetic field. Simultaneous measurements of the average plasma density are made with a polarization diplexing microwave interferometer. Data derived from the experiment are discussed with reference to the following: (1) the strength of the dc magnetic field in the emitting region; (2) comparison of the lower hybrid plasma density with the average plasma density; and (3) validity of the cold plasma lower hybrid resonance formula in the high density operating regime of the bumpy torus plasma.

  15. The NASA Lewis integrated propulsion and flight control simulator

    NASA Technical Reports Server (NTRS)

    Bright, Michelle M.; Simon, Donald L.

    1991-01-01

    A new flight simulation facility was developed at NASA-Lewis. The purpose of this flight simulator is to allow integrated propulsion control and flight control algorithm development and evaluation in real time. As a preliminary check of the simulator facility capabilities and correct integration of its components, the control design and physics models for a short take-off and vertical landing fighter aircraft model were shown, with their associated system integration and architecture, pilot vehicle interfaces, and display symbology. The initial testing and evaluation results show that this fixed based flight simulator can provide real time feedback and display of both airframe and propulsion variables for validation of integrated flight and propulsion control systems. Additionally, through the use of this flight simulator, various control design methodologies and cockpit mechanizations can be tested and evaluated in a real time environment.

  16. The NASA Lewis Research Center SBIR program: An assessment

    NASA Technical Reports Server (NTRS)

    Grimes, Hubert H.; Metzger, Marie E.; Kim, Walter S.

    1993-01-01

    An assessment was made of the NASA Lewis Small Business Innovation Research (SBIR) Program for the years 1983 to 1989. The assessment was based on the study of 99 Phase 1 contracts and 39 Phase 2 contracts. The overall impact of SBIR was found to be very positive, contributing strongly to many NASA programs. In addition, many successful efforts were commercialized benefiting the small business, federal agencies, and the aerospace industry. The program was evaluated in terms of contract quality, innovativeness, comparison to the state-of-the-art, achievement of goals, difficulty, and impact. Program difficulties were also identified, which could suggest possible program improvements. Much of the information gained in this assessment provided a basis for a SBIR data base which will be updated every year. This data base is computerized and will provide an excellent source of information about past SBIR efforts and company capabilities.

  17. Stable Borocyclic Radicals via Frustrated Lewis Pair Hydrogenations.

    PubMed

    Longobardi, Lauren E; Liu, Lei; Grimme, Stefan; Stephan, Douglas W

    2016-03-01

    The synthesis and isolation of stable main group radicals remains an ongoing challenge. Here we report the application of frustrated Lewis pair chemistry to the synthesis of boron-containing radicals. H2 activation with polyaromatic diones and B(C6F5)3 leads to radical formation in good yields. These radicals are robust; they do not decompose on silica gel or react with O2 and are stable at 35 °C under N2 indefinitely. The mechanism of formation is explored experimentally, with support from DFT calculations. EPR and UV/vis spectroscopy as well as cyclic voltammetry data are provided, and the radicals are shown to react with cobaltocenes in one-electron chemical reductions to their corresponding borate anions. PMID:26846796

  18. Lewis Carroll and psychoanalysis: why nothing adds up in wonderland.

    PubMed

    Lane, Christopher

    2011-08-01

    Each generation of psychoanalyst has found different things to value and sometimes to censure in Lewis Carroll's remarkable fiction and flights of fancy. But what does Carroll's almost 'surrealist' perspective in the Alice stories tell us about the rituals and symbols that govern life beyond Wonderland and Looking-Glass World? Arguing that Carroll's strong interest in meaning and nonsense in these and later works helps make the world strange to readers, the better to show it off-kilter, this essay focuses on Jacques Lacan's Carroll - the writer-logician who stressed, as Lacan did, the difficulty and price of adapting to the symbolic order. By reconsidering Lacan's 1966 homage to the eccentric Victorian, I argue that Carroll's insight into meaning and interpretation remains of key interest to psychoanalysts intent on hearing all that he had to say about psychic life. PMID:21843247

  19. Enhanced Attitude Control Experiment for SSTI Lewis Spacecraft

    NASA Technical Reports Server (NTRS)

    Maghami, Peoman G.

    1997-01-01

    The enhanced attitude control system experiment is a technology demonstration experiment on the NASA's small spacecraft technology initiative program's Lewis spacecraft to evaluate advanced attitude control strategies. The purpose of the enhanced attitude control system experiment is to evaluate the feasibility of designing and implementing robust multi-input/multi-output attitude control strategies for enhanced pointing performance of spacecraft to improve the quality of the measurements of the science instruments. Different control design strategies based on modern and robust control theories are being considered for the enhanced attitude control system experiment. This paper describes the experiment as well as the design and synthesis of a mixed H(sub 2)/H(sub infinity) controller for attitude control. The control synthesis uses a nonlinear programming technique to tune the controller parameters and impose robustness and performance constraints. Simulations are carried out to demonstrate the feasibility of the proposed attitude control design strategy. Introduction

  20. NASA Lewis Propulsion Systems Laboratory Customer Guide Manual

    NASA Technical Reports Server (NTRS)

    Soeder, Ronald H.

    1994-01-01

    This manual describes the Propulsion Systems Laboratory (PSL) at NASA Lewis Research Center. The PSL complex supports two large engine test cells (PSL-3 and PSL-4) that are capable of providing flight simulation to altitudes of 70,000 ft. Facility variables at the engine or test-article inlet, such as pressure, temperature, and Mach number (up to 3.0 for PSL-3 and up to 6.0 planned for PSL-4), are discussed. Support systems such as the heated and cooled combustion air systems; the altitude exhaust system; the hydraulic system; the nitrogen, oxygen, and hydrogen systems; hydrogen burners; rotating screen assemblies; the engine exhaust gas-sampling system; the infrared imaging system; and single- and multiple-axis thrust stands are addressed. Facility safety procedures are also stated.

  1. Dementia with Lewy bodies: disease concept and genetics.

    PubMed

    Graeber, Manuel B; Müller, Ulrich

    2003-08-01

    Dementia with Lewy bodies (DLB) was first recognized as a clinicopathological entity about 20 years ago. It is the second most-common degenerative dementia after Alzheimer's disease. Clinically, DLB differs from Alzheimer's disease in that disease symptoms are prone to fluctuate and patients often suffer from visual hallucinations, while short-term memory is relatively preserved. As many as 70% of patients have parkinsonism and up to 50% are sensitive to the extrapyramidal side effects of neuroleptic drugs. About 3 million Europeans will be affected by DLB in 2020 if no cure or effective treatment is found. This article reviews the current disease concept, as well as existing problems concerning classification and delineation of DLB from other conditions with dementia. The literature on genetic findings in this complex disease is critically discussed. PMID:12898286

  2. NASA Lewis Research Center Workshop on Forced Response in Turbomachinery

    NASA Technical Reports Server (NTRS)

    Stefko, George L. (Compiler); Murthy, Durbha V. (Compiler); Morel, Michael (Compiler); Hoyniak, Dan (Compiler); Gauntner, Jim W. (Compiler)

    1994-01-01

    A summary of the NASA Lewis Research Center (LeRC) Workshop on Forced Response in Turbomachinery in August, 1993 is presented. It was sponsored by the following NASA organizations: Structures, Space Propulsion Technology, and Propulsion Systems Divisions of NASA LeRC and the Aeronautics and Advanced Concepts & Technology Offices of NASA Headquarters. In addition, the workshop was held in conjunction with the GUIde (Government/Industry/Universities) Consortium on Forced Response. The workshop was specifically designed to receive suggestions and comments from industry on current research at NASA LeRC in the area of forced vibratory response of turbomachinery blades which includes both computational and experimental approaches. There were eight presentations and a code demonstration. Major areas of research included aeroelastic response, steady and unsteady fluid dynamics, mistuning, and corresponding experimental work.

  3. Update on results of SPRE testing at NASA Lewis

    NASA Astrophysics Data System (ADS)

    Cairelli, James E.; Swec, Diane M.; Wong, Wayne A.; Doeberling, Thomas J.; Madi, Frank J.

    The Space Power Research Engine (SPRE), a free-piston Stirling engine with a linear alternator, is being tested at NASA Lewis Research Center as part of the Civilian Space Technology Initiative (CSTI) as a candidate for high capacity space power. Results are presented from recent SPRE tests designed to investigate the effects of variation in the displacer seal clearance and piston centering port area on engine performance and dynamics. The effects of these variations on PV power and efficiency are presented. Comparisons of the displacer seal clearance test results with HFAST code predictions show good agreement for PV power but poor agreement for PV efficiency. Correlations are presented relating the piston mid-stroke position to the dynamic Delta P across the piston and the centering port area. Test results indicate that a modest improvement in PV power and efficiency may be realized with a reduction in piston centering port area.

  4. Juvenile cannabinoid treatment induces frontostriatal gliogenesis in Lewis rats.

    PubMed

    Bortolato, Marco; Bini, Valentina; Frau, Roberto; Devoto, Paola; Pardu, Alessandra; Fan, Yijun; Solbrig, Marylou V

    2014-06-01

    Cannabis abuse in adolescence is associated with a broad array of phenotypical consequences, including a higher risk for schizophrenia and other mental disturbances related to dopamine (DA) imbalances. The great variability of these sequelae likely depends on the key influence of diverse genetic vulnerability factors. Inbred rodent strains afford a highly informative tool to study the contribution of genetic determinants to the long-term effects of juvenile cannabinoid exposure. In this study, we analyzed the phenotypical impact of the synthetic cannabinoid agonist WIN 55,212-2 (WIN; 2mg/kg/day from postnatal day 35-48) in adolescent Lewis rats, an inbred strain exhibiting resistance to psychotomimetic effects of environmental manipulations. At the end of this treatment, WIN-injected animals displayed increased survival of new cells (mainly oligodendroglia precursors) in the striatum and prefrontal cortex (PFC), two key terminal fields of DAergic pathways. To test whether these changes may be associated with enduring behavioral alterations, we examined the consequences of adolescent WIN treatment in adulthood (postnatal days 60-70), with respect to DA levels and metabolism as well as multiple behavioral paradigms. Rats injected with WIN exhibited increased turnover, but not levels, of striatal DA. In addition, cannabinoid-treated animals displayed increases in acoustic startle latency and novel-object exploration; however, WIN treatment failed to induce overt deficits of sensorimotor gating and social interaction. These results indicate that, in Lewis rats, juvenile cannabinoid exposure leads to alterations in frontostriatal gliogenesis, as well as select behavioral alterations time-locked to high DAergic metabolism, but not overt schizophrenia-related deficits. PMID:24630433

  5. Columbia River Fishes of the Lewis and Clark Expedition

    SciTech Connect

    Dauble, Dennis D.

    2007-06-21

    The Lewis and Clark expedition crossed the Continental Divide in 1805 on the way west to the Pacific Ocean. Based on journal entries, members of the expedition probably encountered two species of resident salmonids and four of the six species of anadromous salmonids and steelhead (Family Salmonidae, genus Oncorhynchus). The salmonid species were called common salmon (now known as Chinook salmon O. tshawytscha), red char (sockeye salmon O.nerka) white salmon trout (coho salmon [also known as silver salmon] O. kisutch), salmon trout (steelhead O. mykiss), and spotted trout (cutthroat trout O. clarkii). There was no evidence of the expedition encountering pink salmon O. gorbuscha, chum salmon O. keta, or species of true char Salvelinus spp. Common fishes procured from Indian tribes living along the lower Columbia River included eulachon Thaleichthys pacificus and white sturgeon Acipenser transmontanus. The identity of three additional resident freshwater species is questionable. Available descriptions suggest that what they called mullet were largescale sucker Catastomus macrocheilus, and that chubb were peamouth Mylocheilus caurinus. The third questionable fish, which they called bottlenose, was probably mountain whitefish Prosopium williamsoni, although there is no evidence that the species was observed in the Columbia River drainage. Missing from the species list were more than 20 other fishes known to Sahaptin-speaking people from the mid-Columbia region. More complete documentation of the icthyofauna of the Pacific Northwest region did not occur until the latter half of the 19th century. However, journals from the Lewis and Clark expedition provide the first documentation of Columbia River fishes.

  6. Identification of biomarkers in Lewy-body disorders.

    PubMed

    Warr, L; Walker, Z

    2012-02-01

    Dementia with Lewy bodies (DLB) may account for up to 30% of all dementia cases. The symptoms of DLB can be difficult to disentangle from other dementia subtypes, particularly Alzheimer's disease (AD). AD and DLB pathologies often overlap within individuals. Like DLB, Parkinson's disease dementia (PDD) also shares common features with DLB. Currently, whether an individual is diagnosed with PDD or DLB depends solely on the timing of symptom onset. Early, accurate diagnosis is needed for optimal management and treatment. It is hoped that the development of existing and new Lewy body disorders biomarkers will facilitate more accurate diagnosis. Reduced dopamine transporter levels in DLB as shown with [123I]FP-CIT-SPECT currently appears to be the most reliable and valid biomarker, although other (predominantly imaging-based) methods also appear to have the high sensitivity and specificity required for a good biomarker. This includes (in DLB compared to AD) reduced cardiac 123I-MIBG uptake, occipital hypometabolism on FDG-PET and preservation of medial temporal lobe structures on CT/MRI. Perfusion SPECT, cerebrospinal fluid protein levels (amyloid, tau and α-synuclein), electroencephalography, saccadic eye movement tracking and 11C-PiB amyloid imaging also hold promise as biomarkers in terms of differentiating DLB, AD, PDD and other neurodegenerative disorders, although findings are less consistent. Studies utilising a combination approach in which two or more potential biomarkers are compared seem to provide very good sensitivity and specificity. In general, longitudinal studies, pathological confirmation of diagnosis and the combined approach may hold the most promise for the identification of biomarkers. PMID:22460159

  7. Can we clinically diagnose dementia with Lewy bodies yet?

    PubMed Central

    2013-01-01

    Dementia with Lewy Bodies (DLB) was initially identified and confirmed primarily by pathology, but is soon to be incorporated into the Diagnostic and Statistical Manual criteria as a clinical disease entity. Despite these advances over more than 20 years, current data suggest that the sensitivity of accurate clinical diagnosis of DLB is still very low, although there is mounting evidence that supportive features may increase diagnostic accuracy. Although DLB remains easy to identify pathologically with different cellular pathologies differentiating it from other dementia syndromes, pathological identification using only Lewy body pathology has been shown to be inaccurate due to overlap with patients without dementia symptoms. A number of studies now suggest that a combination of cellular pathologies, which include α-synuclein and β-amyloid deposition as well as dopamine denervation, assist with differentiating this dementia syndrome from others. The clinical and pathological overlap with the tauopathy of Alzheimer’s disease still remains to be clarified. To determine more robust and independent clinicopathological correlates from Alzheimer’s disease, longitudinal prospective studies, using specific clinical batteries on dementia patients reaching the proposed criteria for DLB, with post-mortem assessment of the multiple pathologies associated with dementia, are required. Identifying genetic causes for DLB is another approach to investigate the pathogenesis of DLB. However this approach has been hindered to date by difficulties with identifying DLB clinically. The use of novel techniques is likely to advance knowledge on the pathogenesis of DLB and assist with redefining clinical and pathologic diagnostic criteria. To achieve the goal of more accurate clinical diagnosis of DLB, breakthroughs are necessary on the pathogenesis of DLB. PMID:23398715

  8. Alcohol consumption, Lewis phenotypes, and risk of ischemic heart disease

    SciTech Connect

    Hein, H.O.; Suadicani, P.; Gyntelberg, F. . Epidemiological Research Unit); Sorenson, H. . Dept. of Chemical Immunology); Hein, H.O. . Dept. of Internal Medicine)

    1993-02-13

    The authors have previously found an increased risk of ischemic heart disease (IHD) in men with the Lewis phenotype Le(a[minus]b[minus]) and suggested that the Lewis blood group has a close genetic relation with insulin resistance. The authors have investigated whether any conventional risk factors explain the increased risk in Le(a[minus]b[minus]) men. 3,383 men aged 53-75 years were examined in 1985-86, and morbidity and mortality during the next 4 years were recorded. At baseline, the authors excluded 343 men with a history of myocardial infarction, angina pectoris, intermittent claudication, or stroke. The potential risk factors examined were alcohol consumption, physical activity, tobacco smoking, serum cotinine, serum lipids, body-mass index, blood pressure, prevalence of hypertension and non-insulin-dependent diabetes mellitus, and social class. In 280 (9.6%) men with Le(a[minus]b[minus]), alcohol was the only risk factor significantly associated with risk of IHD. There was a significant inverse dose-effect relation between alcohol consumption and risk; trend tests, with adjustment for age, were significant for fatal IHD (p=0.02), all IHD (p=0.03), and all causes of death (p=0.02). In 2649 (90.4%) men with other phenotypes, there was a limited negative association with alcohol consumption. In Le(a[minus]b[minus]) men, a group genetically at high risk of IHD, alcohol consumption seems to be especially protective. The authors suggest that alcohol consumption may modify insulin resistance in Le(a[minus]b[minus]) men.

  9. Mars Pathfinder Rover-Lewis Research Center Technology Experiments Program

    NASA Technical Reports Server (NTRS)

    Stevenson, Steven M.

    1997-01-01

    An overview of NASA's Mars Pathfinder Program is given and the development and role of three technology experiments from NASA's Lewis Research Center and carried on the Mars Pathfinder rover is described. Two recent missions to Mars were developed and managed by the Jet Propulsion Laboratory, and launched late last year: Mars Global Surveyor in November 1996 and Mars Pathfinder in December 1996. Mars Global Surveyor is an orbiter which will survey the planet with a number of different instruments, and will arrive in September 1997, and Mars Pathfinder which consists of a lander and a small rover, landing on Mars July 4, 1997. These are the first two missions of the Mars Exploration Program consisting of a ten year series of small robotic martian probes to be launched every 26 months. The Pathfinder rover will perform a number of technology and operational experiments which will provide the engineering information necessary to design and operate more complex, scientifically oriented surface missions involving roving vehicles and other machinery operating in the martian environment. Because of its expertise in space power systems and technologies, space mechanisms and tribology, Lewis Research Center was asked by the Jet Propulsion Laboratory, which is heading the Mars Pathfinder Program, to contribute three experiments concerning the effects of the martian environment on surface solar power systems and the abrasive qualities of the Mars surface material. In addition, rover static charging was investigated and a static discharge system of several fine Tungsten points was developed and fixed to the rover. These experiments and current findings are described herein.

  10. Surface properties of turbulent premixed propane/air flames at various Lewis numbers

    SciTech Connect

    Lee, T.W.; North, G.L.; Santavicca, D.A. )

    1993-06-01

    Surface properties of turbulent premixed flames including the wrinkled flame perimeter, fraction of the flame pocket perimeter, flame curvature, and orientation distributions have been measured for propane-air flames at Lewis numbers ranging from 0.98 to 1.86 and u[prime]/S[sub L] = 1.42-5.71. The wrinkled flame perimeter is found to be greater for the thermodiffusively unstable Lewis number (Le < 1) by up to 30% in comparison to the most stable condition (Le = 1.86) tested, while the fraction of the flame pocket perimeter shows a similar tendency to be greater for Le < 1. The flame curvature probability density functions are nearly symmetric with respect to the zero mean at all Lewis numbers throughout the range of u[prime]/S[sub L] tested, and show a much stronger dependence on the turbulence condition than on the Lewis number. Similarly, the flame orientation distributions show a trend from anisotropy toward a more uniform distribution with increasing u[prime]/S[sub L] at a similar rate for all Lewis numbers. Thus, for turbulent premixed propane/air flames for a practical range of Lewis number from 0.98 to 1.86, the effect of Lewis number is primarily to affect the flame structures and thereby flame surface areas and flame pocket areas, while the flame curvature and orientation statistics are essentially determined by the turbulence properties.

  11. Visual hallucinations in dementia with Lewy bodies: transcranial magnetic stimulation study

    PubMed Central

    Taylor, John-Paul; Firbank, Michael; Barnett, Nicola; Pearce, Sarah; Livingstone, Anthea; Mosimann, Urs; Eyre, Janet; McKeith, Ian G.; O’Brien, John T.

    2011-01-01

    Background The aetiology of visual hallucinations is poorly understood in dementia with Lewy bodies. Pathological alterations in visual cortical excitability may be one contributory mechanism. Aims To determine visual cortical excitability in people with dementia with Lewy bodies compared with aged-matched controls and also the relationship between visual cortical excitability and visual hallucinations in dementia with Lewy bodies. Method Visual cortical excitability was determined by using transcranial magnetic stimulation (TMS) applied to the occiput to elicit phosphenes (transient subjective visual responses) in 21 patients with dementia with Lewy bodies and 19 age-matched controls. Results Phosphene parameters were similar between both groups. However, in the patients with dementia with Lewy bodies, TMS measures of visual cortical excitability correlated strongly with the severity of visual hallucinations (P = 0.005). Six patients with dementia with Lewy bodies experienced visual hallucination-like phosphenes (for example, seeing people or figures on stimulation) compared with none of the controls (P = 0.02). Conclusions Increased visual cortical excitability in dementia with Lewy bodies does not appear to explain visual hallucinations but it may be a marker for their severity. PMID:22016436

  12. Highly Lewis Acidic Arylboronate Esters Capable of Colorimetric Turn-On Response.

    PubMed

    Oehlke, Alexander; Auer, Alexander A; Schreiter, Katja; Friebe, Nadine; Spange, Stefan

    2015-12-01

    A series of boronate-π-acceptor compounds containing different types of π bridges (1,4-phenylen or thien-2,5-diyl or furan-2,5-diyl) that link the switchable boronate ester group with the efficient TCF acceptor group (TCF=2-dicyanomethylen-3-cyano-4,5,5-trimethyl-2,5-dihydrofuran) has been synthesized. A TCF chromophore of this type undergoes transition to a donor-π-acceptor compound upon coordination of Lewis bases at the Lewis acidic boron center, which is accompanied by an enhanced intramolecular charge-transfer interaction. The Lewis acid character has been investigated by spectroscopic measurements (UV/Vis, NMR spectroscopies) as well as DFT and ab initio-based calculations. It is shown that the TCF acceptor group and thiophene or furan π-bridges directly bound to the boron atom cooperatively increase the Lewis acidity. UV/Vis titration experiments confirm fluoride binding constants in the range of up to 10(8)  M(-1) in CH2 Cl2 . In addition to the strong boron fluoride binding motif, Lewis interactions also occur with weaker Lewis bases, such as pyridine or aliphatic alcohols. The unique combination of chromophoric and Lewis acidic properties is responsible for the intense colorimetric turn-on response detectable after complex formation. PMID:26489784

  13. Lewis pair polymerization by classical and frustrated Lewis pairs: acid, base and monomer scope and polymerization mechanism.

    PubMed

    Zhang, Yuetao; Miyake, Garret M; John, Mallory G; Falivene, Laura; Caporaso, Lucia; Cavallo, Luigi; Chen, Eugene Y-X

    2012-08-14

    Classical and frustrated Lewis pairs (LPs) of the strong Lewis acid (LA) Al(C(6)F(5))(3) with several Lewis base (LB) classes have been found to exhibit exceptional activity in the Lewis pair polymerization (LPP) of conjugated polar alkenes such as methyl methacrylate (MMA) as well as renewable α-methylene-γ-butyrolactone (MBL) and γ-methyl-α-methylene-γ-butyrolactone (γ-MMBL), leading to high molecular weight polymers, often with narrow molecular weight distributions. This study has investigated a large number of LPs, consisting of 11 LAs as well as 10 achiral and 4 chiral LBs, for LPP of 12 monomers of several different types. Although some more common LAs can also be utilized for LPP, Al(C(6)F(5))(3)-based LPs are far more active and effective than other LA-based LPs. On the other hand, several classes of LBs, when paired with Al(C(6)F(5))(3), can render highly active and effective LPP of MMA and γ-MMBL; such LBs include phosphines (e.g., P(t)Bu(3)), chiral chelating diphosphines, N-heterocyclic carbenes (NHCs), and phosphazene superbases (e.g., P(4)-(t)Bu). The P(4)-(t)Bu/Al(C(6)F(5))(3) pair exhibits the highest activity of the LP series, with a remarkably high turn-over frequency of 9.6 × 10(4) h(-1) (0.125 mol% catalyst, 100% MMA conversion in 30 s, M(n) = 2.12 × 10(5) g mol(-1), PDI = 1.34). The polymers produced by LPs at RT are typically atactic (P(γ)MMBL with ∼47% mr) or syndio-rich (PMMA with ∼70-75% rr), but highly syndiotactic PMMA with rr ∼91% can be produced by chiral or achiral LPs at -78 °C. Mechanistic studies have identified and structurally characterized zwitterionic phosphonium and imidazolium enolaluminates as the active species of the current LPP system, which are formed by the reaction of the monomer·Al(C(6)F(5))(3) adduct with P(t)Bu(3) and NHC bases, respectively. Kinetic studies have revealed that the MMA polymerization by the (t)Bu(3)P/Al(C(6)F(5))(3) pair is zero-order in monomer concentration after an initial

  14. Deletion of antigens of the Lewis a/b blood group family in human prostatic carcinoma.

    PubMed Central

    Young, W. W.; Mills, S. E.; Lippert, M. C.; Ahmed, P.; Lau, S. K.

    1988-01-01

    The expression of antigens of the blood group Lewis a/b family were studied in a series of 42 prostatectomy specimens from patients with adenocarcinoma clinically confined to the prostate; 19 of these were later reclassified as pathologic Stage C. Staining of normal or hyperplastic versus neoplastic epithelium was assessed in routinely processed, paraffin-embedded tissue using murine monoclonal antibodies and an avidin-biotin immunoperoxidase technique. Antigens screened and the antibodies used to recognize them were Lewis a (CF4C4), Lewis b and Type 1 H (NS10), monosialosyl Lewis a I (19.9), and disialosyl Lewis a and monosialosyl Lewis a II (FH7). FH7 strongly stained the benign epithelium of all 39 Lewis positive cases, suggesting that the sialyltransferase responsible for synthesis of FH7-reactive determinants is highly active in benign prostatic tissue. When compared to the reactivity of benign epithelium in Lewis positive cases, the staining of the carcinomas was markedly reduced in 18 cases (46%) and absent in 16 cases (41%). This reduction or loss of staining of the malignant epithelium was observed for all antibodies that stained the corresponding benign epithelium of each case. In only five of the cases (13%) was the intensity of staining in the carcinoma equal to that of the surrounding benign epithelium. No cases in this latter group had recurrence of disease, whereas in the other staining groups 25-33% of the cases had recurrences; median follow-up for the entire group was 78 months. No correlation was apparent between Gleason score and the staining pattern with these antigens. In summary, antigens of the Lewis a/b family are deleted in a high percentage of cases of prostatic adenocarcinoma. Images Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 PMID:2454582

  15. Activation of Carbonyl-Containing Molecules with Solid Lewis Acids in Aqueous Media

    SciTech Connect

    Román-Leshkov, Yuriy; Davis, Mark E.

    2011-09-28

    Current interest in reacting carbonyl-containing molecules in aqueous media is primarily due to the growing emphasis on conversion of biomass to fuels and chemicals. Recently, solid Lewis acids have been shown to perform catalytic reactions with carbonyl-containing molecules such as sugars in aqueous media. Here, catalysis mediated by Lewis acids is briefly discussed, Lewis acid solids that perform catalysis in aqueous media are then described, and the review is concluded with a few comments on the outlook for the future.

  16. Plans and status of the NASA-Lewis Research Center wind energy project

    NASA Technical Reports Server (NTRS)

    Thomas, R.; Puthoff, R.; Savino, J.; Johnson, W.

    1975-01-01

    This report describes that portion of the national five-year wind energy program that is being managed by the NASA-Lewis Research Center for the ERDA. The Lewis Research Center's Wind Power Office, its organization and plans and status are briefly described. The three major elements of the wind energy project at Lewis are the experimental 100 kW wind-turbine generator; the first generation industry-built and user-operated wind turbine generators; and the supporting research and technology tasks which are each briefly described.

  17. A note on generalization of the Lewis invariant and the Ermakov systems

    NASA Astrophysics Data System (ADS)

    Simic, Srboljub S.

    2000-08-01

    In this paper we examine several possible generalizations of the well known Lewis invariant and the Ermakov systems. The analysis relies on the application of the theorem of Emmy Noether. The problem of constructing Lewis-type invariants is reduced to a problem of solving a single partial differential equation - the so-called potential equation. Within this approach, the role of the auxiliary equation is clarified by an analysis of linear systems. Generalization of the Ermakov-type procedure for derivation of the Lewis invariant is also discussed. Moreover, different forms of general solution of the problem will be provided, which extend the range of possible applications of the analysis.

  18. Rapid Dihydrogen Cleavage by Persistent Nitroxide Radicals under Frustrated Lewis Pair Conditions.

    PubMed

    Tao, Xin; Kehr, Gerald; Wang, Xiaowu; Daniliuc, Constantin G; Grimme, Stefan; Erker, Gerhard

    2016-07-01

    Persistent radicals undergo hydrogen atom abstraction reactions with a great variety of substrates, but not with dihydrogen. It has now been found that the TEMPO radical splits dihydrogen under mild conditions in the presence of the strong bulky B(C6 F5 )3 boron Lewis acid. The reaction is thought to proceed by a typical frustrated Lewis pair mechanism with the TEMPO radical acting as the active Lewis base. The reaction was analyzed by DFT, which indicates that no significant spin density on the hydrogen atoms is accumulated along the H2 splitting reaction path. PMID:27189745

  19. Survey on Cosmogenic 26Al in Lewis Cliff Meteorites

    NASA Astrophysics Data System (ADS)

    Welten, K. C.; Alderliesten, C.; Lindner, L.

    1992-07-01

    INTRODUCTION: We have embarked upon a ^26Al gamma-ray survey of meteorites selected from about 2000 samples recently recovered from the Lewis Cliff Ice Fields (84 degrees 18'S/161 degrees 20'E). Due to its 705-ka half-life ^26Al can be used for estimating terrestrial ages and thus contribute to further characterization of Antarctic meteorites in addition to their classification and thermoluminescence (TL) properties. The ^26Al survey is also useful for identifying meteorites with unusual exposure histories, which merit additional measurements of cosmogenic radionuclides (by AMS) and noble gases. In addition, it provides clues on possible pairings. METHOD: Low-level gamma-ray spectroscopy is well suited for ^26Al survey work, since bulk meteorite samples can be measured routinely and nondestructively without any previous sample preparation. The required size of the samples (30-500 g) makes the method relatively independent of depth effects and compositional inhomogeneities. The use of a high-resolution GeLi detector also allows the determination of the natural ^40K activity and thus the K content of the samples, which can be used as an additional pairing criterion for ordinary chondrites. Also ^137Cs, a fall-out surface contamination [1], is simultaneously measured; low values may be characteristic for meteorites recently fallen or released from the ablating ice. For the detector an efficiency calibration curve has been made that adequately accounts for differences in size and shape of the meteorite samples. RESULTS and DISCUSSION: TERRESTRIAL AGES: So far, we have measured over 30 Lewis Cliff equilibrated H and L chondrites, collected from widely differing locations. Normalized to L-chondrite composition, the ^26Al contents range from 27 to 110 dpm/kg with peaks around 43 and 53 dpm/kg. This bimodal ^26Al distribution is reminiscent of that observed for Allan Hills ordinary chondrites [2]. Tentative terrestrial ages, calculated on the basis of ^26Al saturation

  20. Survey on Cosmogenic 26Al in Lewis Cliff Meteorites

    NASA Astrophysics Data System (ADS)

    Welten, K. C.; Alderliesten, C.; Lindner, L.

    1992-07-01

    INTRODUCTION: We have embarked upon a ^26Al gamma-ray survey of meteorites selected from about 2000 samples recently recovered from the Lewis Cliff Ice Fields (84 degrees 18'S/161 degrees 20'E). Due to its 705-ka half-life ^26Al can be used for estimating terrestrial ages and thus contribute to further characterization of Antarctic meteorites in addition to their classification and thermoluminescence (TL) properties. The ^26Al survey is also useful for identifying meteorites with unusual exposure histories, which merit additional measurements of cosmogenic radionuclides (by AMS) and noble gases. In addition, it provides clues on possible pairings. METHOD: Low-level gamma-ray spectroscopy is well suited for ^26Al survey work, since bulk meteorite samples can be measured routinely and nondestructively without any previous sample preparation. The required size of the samples (30-500 g) makes the method relatively independent of depth effects and compositional inhomogeneities. The use of a high-resolution GeLi detector also allows the determination of the natural ^40K activity and thus the K content of the samples, which can be used as an additional pairing criterion for ordinary chondrites. Also ^137Cs, a fall-out surface contamination [1], is simultaneously measured; low values may be characteristic for meteorites recently fallen or released from the ablating ice. For the detector an efficiency calibration curve has been made that adequately accounts for differences in size and shape of the meteorite samples. RESULTS and DISCUSSION: TERRESTRIAL AGES: So far, we have measured over 30 Lewis Cliff equilibrated H and L chondrites, collected from widely differing locations. Normalized to L-chondrite composition, the ^26Al contents range from 27 to 110 dpm/kg with peaks around 43 and 53 dpm/kg. This bimodal ^26Al distribution is reminiscent of that observed for Allan Hills ordinary chondrites [2]. Tentative terrestrial ages, calculated on the basis of ^26Al saturation

  1. Essential Domains of Anaplasma phagocytophilum Invasins Utilized to Infect Mammalian Host Cells

    PubMed Central

    Seidman, David; Hebert, Kathryn S.; Truchan, Hilary K.; Miller, Daniel P.; Tegels, Brittney K.; Marconi, Richard T.; Carlyon, Jason A.

    2015-01-01

    Anaplasma phagocytophilum causes granulocytic anaplasmosis, an emerging disease of humans and domestic animals. The obligate intracellular bacterium uses its invasins OmpA, Asp14, and AipA to infect myeloid and non-phagocytic cells. Identifying the domains of these proteins that mediate binding and entry, and determining the molecular basis of their interactions with host cell receptors would significantly advance understanding of A. phagocytophilum infection. Here, we identified the OmpA binding domain as residues 59 to 74. Polyclonal antibody generated against a peptide spanning OmpA residues 59 to 74 inhibited A. phagocytophilum infection of host cells and binding to its receptor, sialyl Lewis x (sLex-capped P-selectin glycoprotein ligand 1. Molecular docking analyses predicted that OmpA residues G61 and K64 interact with the two sLex sugars that are important for infection, α2,3-sialic acid and α1,3-fucose. Amino acid substitution analyses demonstrated that K64 was necessary, and G61 was contributory, for recombinant OmpA to bind to host cells and competitively inhibit A. phagocytophilum infection. Adherence of OmpA to RF/6A endothelial cells, which express little to no sLex but express the structurally similar glycan, 6-sulfo-sLex, required α2,3-sialic acid and α1,3-fucose and was antagonized by 6-sulfo-sLex antibody. Binding and uptake of OmpA-coated latex beads by myeloid cells was sensitive to sialidase, fucosidase, and sLex antibody. The Asp14 binding domain was also defined, as antibody specific for residues 113 to 124 inhibited infection. Because OmpA, Asp14, and AipA each contribute to the infection process, it was rationalized that the most effective blocking approach would target all three. An antibody cocktail targeting the OmpA, Asp14, and AipA binding domains neutralized A. phagocytophilum binding and infection of host cells. This study dissects OmpA-receptor interactions and demonstrates the effectiveness of binding domain-specific antibodies

  2. Summary of the NASA Lewis component technology program for Stirling power converters

    NASA Astrophysics Data System (ADS)

    Thieme, Lanny G.; Swec, Diane M.

    1992-10-01

    An update is presented on the NASA Lewis Stirling component technology program. The component technology program has been organized as part of the NASA Lewis effort to develop Stirling converter technology for space power applications. The Stirling space power project is part of the High Capacity Power element of the NASA Civil Space Technology Initiative (CSTI). Lewis is also providing technical management of a DOE funded project to develop Stirling converter systems for distributed dish solar terrestrial power applications. The primary contractors for the space power and solar terrestrial projects develop component technologies directly related to their project goals. This Lewis component technology program, while coordinated with these main projects, is aimed at longer term issues, advanced technologies, and independent assessments. Topics to be discussed include bearings, linear alternators, controls and load interaction, materials/life assessment, and heat exchangers.

  3. Development of an eluotropic series for the chromatography of Lewis bases on zirconium oxide.

    PubMed

    Blackwell, J A; Carr, P W

    1992-04-15

    Ligand-exchange interactions, which dominate the retention characteristics of Lewis base solutes on zirconium oxide, can be strongly attenuated by the addition of a competing Lewis base to the eluent. The chromatographic effects of these competing bases vary significantly in their thermodynamics and kinetics depending on their structure and Lewis basicity. An eluotropic scale of mobile-phase strength for ligand-exchange/ion-exchange chromatography on zirconia has been developed which ranks the overall elution strength of a variety of Lewis bases in terms of their ability to elute a wide variety of benzoic acid derivatives. This series generally holds true for similar solutes; however, deviations are noted with some solutes and eluents where chelation and steric factors alter the kinetic and thermodynamic characteristics of the retention process. PMID:1622000

  4. Stable Isotope Systematics of Cryogenic Evaporite Deposits from Lewis Cliff Ice Tongue, Antarctica: A Mars Analog

    NASA Astrophysics Data System (ADS)

    Socki, R. A.; Harvey, R. P.; Bish, D. L.; Tonui, E.; Bao, H.

    2008-03-01

    We report stable isotope results of evaporite mounds and associated moraine materials from Lewis Cliff, Antarctica. Data suggest evaporite mineral formation likely occurred sub-glacially, influenced by secondary glacial ice and/or moraine lake water.

  5. Advocacy, education, and the role of not-for-profit organizations in Lewy body dementias

    PubMed Central

    2014-01-01

    Lewy body dementias (LBDs) represent a spectrum of dementias that are associated with the presence of Lewy bodies in the brain and that dramatically impact both the person diagnosed and the family caregiver. LBD charities provide education of the public and health-care professionals, emotional support to families, and advocacy to policy-makers on the needs of LBD families and advance research. The US-based Lewy Body Dementia Association and the Lewy Body Society in the UK play an important role in reducing the burden that LBD places on families and society and provide leadership on issues affecting LBD families. Health-care providers are encouraged to refer families upon diagnosis to LBD charities as an additional resource to clinical care. PMID:26082807

  6. Synergistic effects between Lewis and Brønsted acids: application to the Prins cyclization.

    PubMed

    Breugst, Martin; Grée, René; Houk, K N

    2013-10-01

    Brønsted and Lewis acids can catalyze the Prins cyclization, an efficient method for the synthesis of tetrahydropyrans from homoallylic alcohols and carbonyl compounds. Synergistic effects between weak Brønsted and Lewis acids in these reactions have been analyzed by density functional theory [M06-L/def2-QZVP/IEFPCM(CH2Cl2)//M06-L/6-311+G(2df,2p)]. In order to characterize the reactivities of the employed Lewis acids, methyl anion and hydroxide affinities were determined. On the basis of our calculations, we found that the coordination of Lewis acids to carboxylic and sulfonic acids results in a significant increase in the Brønsted acidities of the latter. PMID:23984760

  7. Organo-Lewis acid as cocatalyst for cationic homogenous metallocene Ziegler-Natta olefin polymerizations

    DOEpatents

    Marks, Tobin J.; Chen, You-Xian

    2000-01-01

    The synthesis of the organo-Lewis acid perfluorobiphenylborane (PBB) and the activation of metallocenes for the formation of a variety of highly active homogeneous Ziegler-Natta metallocene olefin polymerization, copolymerization and ring-opening polymerization catalysts is described.

  8. Lewis Research Center studies of multiple large wind turbine generators on a utility network

    NASA Technical Reports Server (NTRS)

    Gilbert, L. J.; Triezenberg, D. M.

    1979-01-01

    A NASA-Lewis program to study the anticipated performance of a wind turbine generator farm on an electric utility network is surveyed. The paper describes the approach of the Lewis Wind Energy Project Office to developing analysis capabilities in the area of wind turbine generator-utility network computer simulations. Attention is given to areas such as, the Lewis Purdue hybrid simulation, an independent stability study, DOE multiunit plant study, and the WEST simulator. Also covered are the Lewis mod-2 simulation including analog simulation of a two wind turbine system and comparison with Boeing simulation results, and gust response of a two machine model. Finally future work to be done is noted and it is concluded that the study shows little interaction between the generators and between the generators and the bus.

  9. Decreased vasopressin content in parvocellular CRH neurosecretory system of Lewis rats.

    PubMed

    Whitnall, M H; Anderson, K A; Lane, C A; Mougey, E H; Neta, R; Perlstein, R S

    1994-08-15

    Rats possess stress-responsive, vasopressin (VP)-expressing and stress-nonresponsive, VP-deficient subpopulations of parvocellular corticotropin-releasing hormone (CRH) neurosecretory cells. Both subpopulations are activated by bacterial lipopolysaccharide (LPS) and cytokines. Lewis rats exhibit hyporesponsive hypothalamo-pituitary-adrenocortical axes (HPAAs). The Lewis CRH neurosecretory system has been reported to be defective in females and normal in males. We used post-embedding electron microscopic (EM) immunocytochemistry to study baseline levels and LPS-stimulated depletion of neurosecretory vesicles. Male Lewis rats possessed normal numbers of CRH+/VP- varicosities and low numbers of CRH+/VP+ varicosities, indicating abnormally low release of VP into portal blood. This defect contrasts with the reported increase in VP content and release in magnocellular neurosecretory cells in Lewis rats. PMID:7819536

  10. Advocacy, education, and the role of not-for-profit organizations in Lewy body dementias.

    PubMed

    Taylor, Angela; Yardley, Cecilia

    2014-01-01

    Lewy body dementias (LBDs) represent a spectrum of dementias that are associated with the presence of Lewy bodies in the brain and that dramatically impact both the person diagnosed and the family caregiver. LBD charities provide education of the public and health-care professionals, emotional support to families, and advocacy to policy-makers on the needs of LBD families and advance research. The US-based Lewy Body Dementia Association and the Lewy Body Society in the UK play an important role in reducing the burden that LBD places on families and society and provide leadership on issues affecting LBD families. Health-care providers are encouraged to refer families upon diagnosis to LBD charities as an additional resource to clinical care. PMID:26082807

  11. Summary of the NASA Lewis component technology program for Stirling power converters

    NASA Technical Reports Server (NTRS)

    Thieme, Lanny G.; Swec, Diane M.

    1992-01-01

    An update is presented on the NASA Lewis Stirling component technology program. The component technology program has been organized as part of the NASA Lewis effort to develop Stirling converter technology for space power applications. The Stirling space power project is part of the High Capacity Power element of the NASA Civil Space Technology Initiative (CSTI). Lewis is also providing technical management of a DOE funded project to develop Stirling converter systems for distributed dish solar terrestrial power applications. The primary contractors for the space power and solar terrestrial projects develop component technologies directly related to their project goals. This Lewis component technology program, while coordinated with these main projects, is aimed at longer term issues, advanced technologies, and independent assessments. Topics to be discussed include bearings, linear alternators, controls and load interaction, materials/life assessment, and heat exchangers.

  12. How Lewis acidic is your cation? Putting phosphenium ions on the fluoride ion affinity scale.

    PubMed

    Slattery, John M; Hussein, Sharifa

    2012-02-14

    The fluoride ion affinities (FIAs) of 33 phosphenium ions with a range of substituents were calculated using ab inito and DFT methods. The use of these FIA data as a measure of the Lewis acidities of phosphenium ions is described and the FIAs of the species studied here are compared to FIA data for more commonly encountered Lewis acids. Phosphenium ions are often stronger Lewis acids than neutral species, but in many cases are less Lewis acidic than highly electrophilic cations such as [Me(3)C](+) or [Me(3)Si](+). The impact of mesomeric, inductive and steric substituent effects on FIAs are discussed and related to the underlying electronic structures of different cation types. A comparison between the FIAs of known "free" phosphenium ions with those that are currently unknown and other highly electrophilic cations suggests that some diaryl- and dialkylphosphenium ions may yet be accessible under the right conditions. PMID:22159000

  13. [Book review] The youngest science: notes of a medicine-watcher, by Lewis Thomas

    USGS Publications Warehouse

    Johnson, D.H.

    1984-01-01

    Review of: The youngest science: notes of a medicine-watcher. Alfred P. Sloan Foundation Series. Lewis Thomas. Penguin Books, 1995. Pennsylvania State University. 270 pp. ISBN: 0140243275, 9780140243277.

  14. Sialic acid and sialyl-lactose glyco-conjugates: design, synthesis and binding assays to lectins and swine influenza H1N1 virus.

    PubMed

    Zevgiti, Stella; Zabala, Juliana Gonzalez; Darji, Ayub; Dietrich, Ursula; Panou-Pomonis, Eugenia; Sakarellos-Daitsiotis, Maria

    2012-01-01

    The terminal parts of the influenza hemagglutinin (HA) receptors α2,6- and α2,3-sialyllactoses were conjugated to an artificial carrier, named sequential oligopeptide carrier (SOC(4) ), to formulate human and avian receptor mimics, respectively. SOC(4) , formed by the tripeptide unit Lys-Aib-Gly, adopts a rigid helicoids-type conformation, which enables the conjugation of biomolecules to the Lys-N(ε) H(2) groups. By doing so, it preserves their initial conformations and functionalities of the epitopes. We report that SOC(4) -glyco-conjugate bearing two copies of the α2,6-sialyllactose is specifically recognized by the biotinylated Sambucus nigra (elderberry) bark lectin, which binds preferentially to sialic acid in an α2,6-linkage. SOC(4) -glyco-conjugate bearing two copies of the α2,3-sialyllactose was not recognized by the biotinylated Maackia amurensis lectin, despite its well-known α2,3-sialyl bond specificity. However, preliminary immune blot assays showed that H1N1 virus binds to both the SOC(4) -glyco-conjugates immobilized onto nitrocellulose membrane. It is concluded that Ac-SOC(4) [(Ac)(2) ,(3'SL-Aoa)(2) ]-NH(2) 5 and Ac-SOC(4) [(Ac)(2) ,(6'SL-Aoa)(2) ]-NH(2) 6 mimic the HA receptors. These findings could be useful for easy screening of binding and inhibition assays of virus-receptor interactions. PMID:22052803

  15. A MALDI-TOF MS method for the simultaneous and quantitative analysis of neutral and sialylated glycans of CHO-expressed glycoproteins.

    PubMed

    Tep, Samnang; Hincapie, Marina; Hancock, William S

    2012-01-10

    The development of a MALDI-TOF MS method for the quantitative analysis of the glycosylation of CHO-expressed biotherapeutic glycoproteins shall be presented. The method utilizes a well-established chemistry, reductive amination of glycans, to derivatize glycans with either a light analog ((12)C(7) anthranilic acid) or a heavy analog ((13)C(7) anthranilic acid) to allow for the direct comparison of the alternately-labeled glycans by MALDI-TOF MS. The method allows for the simultaneous analysis of neutral and sialylated glycans and displays a linear dynamic range over two orders of magnitude with sub-picomolar sensitivity. Additionally, because the glycans are derivatized with anthranilic acid, which is a very sensitive fluorophore, the glycans can be analyzed by chromatography with fluorescence detection. The need for this type of method is highlighted by the biotechnology/biopharmaceutical industry's continuous drive towards fully understanding process control. By providing this type of quantitative data, glycosylation changes of the expressed protein can be easily observed thereby helping to further advance the understanding of a major aspect of the biopharmaceutical process. PMID:22138464

  16. Liquid Chromatography-Selected Reaction Monitoring (LC-SRM) Approach for the Separation and Quantitation of Sialylated N-Glycans Linkage Isomers

    PubMed Central

    2015-01-01

    The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. PMID:25299151

  17. Liquid chromatography-selected reaction monitoring (LC-SRM) approach for the separation and quantitation of sialylated N-glycans linkage isomers.

    PubMed

    Tao, Shujuan; Huang, Yining; Boyes, Barry E; Orlando, Ron

    2014-11-01

    The study of N-linked glycans is among the most challenging bioanalytical tasks because of their complexity and variety. The presence of glycoform families that differ only in branching and/or linkage position makes the identification and quantitation of individual glycans exceedingly difficult. Quantitation of these individual glycans is important because changes in the abundance of these isomers are often associated with significant biomedical events. For instance, previous studies have shown that the ratio of α2-3 to α2-6 linked sialic acid (SA) plays an important role in cancer biology. Consequently, quantitative methods to detect alterations in the ratios of glycans based on their SA linkages could serve as a diagnostic tool in oncology, yet traditional glycomic profiling cannot readily differentiate between these linkage isomers. Here, we present a liquid chromatography-selected reaction monitoring (LC-SRM) approach that we demonstrate is capable of quantitating the individual SA linkage isomers. The LC method is capable of separating sialylated N-glycan isomers differing in α2-3 and α2-6 linkages using a novel superficially porous particle (Fused-Core) Penta-HILIC (hydrophilic interaction liquid chromatography) column. SRM detection provides the relative quantitation of each SA linkage isomer, and minimizes interferences from coeluting glycans that are problematic for UV/Fluorescence based quantitation. With our approach, the relative quantitation of each SA linkage isomer is obtained from a straightforward liquid chromatography-mass spectrometry (LC-MS) experiment. PMID:25299151

  18. Sialylated and O-glycosidically linked glycans in prion protein deposits in a case of Gerstmann-Sträussler-Scheinker disease.

    PubMed

    Zomosa-Signoret, Viviana; Mayoral, Miguel; Limón, Daniel; Espinosa, Blanca; Calvillo, Minerva; Zenteno, Edgar; Martínez, Victor; Guevara, Jorge

    2011-04-01

    Prion diseases are caused by an abnormal form of the prion protein (PrP(Sc)). We identified, with lectins, post-translational modifications of brain proteins due to glycosylation in a Gerstmann-Sträussler-Scheinker (GSS) patient. The lectin Amaranthus leucocarpus (ALL), specific for mucin type O-glycosylated structures (Galß1,3 GalNAcα1,0 Ser/Thr or GalNAcα1,0 Ser/Thr), and Sambucus nigra agglutinin (SNA), specific for Neu5Acα2,6 Gal/GalNAc, showed positive labeling in all the prion deposits and in the core of the PrP(Sc) deposits, respectively, indicating specific distribution of O-glycosylated and sialylated structures. Lectins from Maackia amurensis (MAA, Neu5Acα2,3), Macrobrachium rosenbergii (MrL, Neu5,9Ac2-specific) and Arachis hypogaea (PNA, Gal-specific) showed low staining of prion deposits. Immunohistochemistry colocalization with prion antibody indicated that all lectins stained prion protein deposits. These results show that specific modifications in the glycosylation pattern are closely related to the hallmark lesions and might be an early event in neuronal degeneration in GSS disease. PMID:20667006

  19. An Engineering Approach to Management of Occupational and Community Noise Exposure at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Cooper, Beth A.

    1997-01-01

    Workplace and environmental noise issues at NASA Lewis Research Center are effectively managed via a three-part program that addresses hearing conservation, community noise control, and noise control engineering. The Lewis Research Center Noise Exposure Management Program seeks to limit employee noise exposure and maintain community acceptance for critical research while actively pursuing engineered controls for noise generated by more than 100 separate research facilities and the associated services required for their operation.

  20. Thioarsenides: A case for long-range Lewis acid-base-directed van der Waals interactions

    SciTech Connect

    Gibbs, Gerald V.; Wallace, Adam F.; Downs, R. T.; Ross, Nancy L.; Cox, David F.; Rosso, Kevin M.

    2011-04-01

    Electron density distributions, bond paths, Laplacian and local energy density properties have been calculated for a number of As4Sn (n = 3,4,5) thioarsenide molecular crystals. On the basis of the distributions, the intramolecular As-S and As-As interactions classify as shared bonded interactions and the intermolecular As-S, As-As and S-S interactions classify as closed-shell van der Waals bonded interactions. The bulk of the intermolecular As-S bond paths link regions of locally concentrated electron density (Lewis base regions) with aligned regions of locally depleted electron density (Lewis acid regions) on adjacent molecules. The paths are comparable with intermolecular paths reported for several other molecular crystals that link aligned Lewis base and acid regions in a key-lock fashion, interactions that classified as long range Lewis acid-base directed van der Waals interactions. As the bulk of the intermolecular As-S bond paths (~70%) link Lewis acid-base regions on adjacent molecules, it appears that molecules adopt an arrangement that maximizes the number of As-S Lewis acid-base intermolecular bonded interactions. The maximization of the number of Lewis acid-base interactions appears to be connected with the close-packed array adopted by molecules: distorted cubic close-packed arrays are adopted for alacránite, pararealgar, uzonite, realgar and β-AsS and the distorted hexagonal close-packed arrays adopted by α- and β-dimorphite. A growth mechanism is proposed for thioarsenide molecular crystals from aqueous species that maximizes the number of long range Lewis acid-base vdW As-S bonded interactions with the resulting directed bond paths structuralizing the molecules as a molecular crystal.

  1. Thioarsenides: a case for long-range Lewis acid-base-directed van der Waals interactions

    NASA Astrophysics Data System (ADS)

    Gibbs, G. V.; Wallace, A. F.; Downs, R. T.; Ross, N. L.; Cox, D. F.; Rosso, K. M.

    2011-04-01

    Electron density distributions, bond paths, Laplacian and local-energy density properties have been calculated for a number of As4S n ( n = 3, 4 and 5) thioarsenide molecular crystals. On the basis of the distributions, the intramolecular As-S and As-As interactions classify as shared bonded interactions, and the intermolecular As-S, As-As and S-S interactions classify as closed-shell van der Waals (vdW) bonded interactions. The bulk of the intermolecular As-S bond paths link regions of locally concentrated electron density (Lewis-base regions) with aligned regions of locally depleted electron density (Lewis-acid regions) on adjacent molecules. The paths are comparable with intermolecular paths reported for several other molecular crystals that link aligned Lewis base and acid regions in a key-lock fashion, interactions that classified as long-range Lewis acid-base-directed vdW interactions. As the bulk of the intermolecular As-S bond paths (~70%) link Lewis acid-base regions on adjacent molecules, it appears that molecules adopt an arrangement that maximizes the number of As-S Lewis acid-base intermolecular bonded interactions. The maximization of the number of Lewis acid-base interactions appears to be connected with the close-packed array adopted by molecules: distorted cubic close-packed arrays are adopted for alacránite, pararealgar, uzonite, realgar and β-AsS and the distorted hexagonal close-packed arrays adopted by α- and β-dimorphite. A growth mechanism is proposed for thioarsenide molecular crystals from aqueous species that maximizes the number of long-range Lewis acid-base vdW As-S bonded interactions with the resulting directed bond paths structuralizing the molecules as a molecular crystal.

  2. Plans and status of the NASA-Lewis Research Center wind energy project

    NASA Technical Reports Server (NTRS)

    Thomas, R.; Puthoff, R.; Savino, J.; Johnson, W.

    1975-01-01

    Wind energy is investigated as a source of energy. The wind energy program that is managed by the NASA-Lewis Research Center is described. The Lewis Research Center's Wind Power Office, its organization, plans, and status are discussed. Major elements of the wind power project included are: an experimental 100 kW wind-turbine generator; first generation industry-built and user-operated wind turbine generators; and supporting research and technology tasks.

  3. Shell shock at Queen Square: Lewis Yealland 100 years on

    PubMed Central

    Jones, Edgar; Lees, Andrew J.

    2013-01-01

    This article reviews the treatment of functional neurological symptoms during World War I by Lewis Yealland at the National Hospital for the Paralysed and Epileptic in London. Yealland was among the first doctors in Britain to incorporate electricity in the systematic treatment of shell shock. Our analysis is based on the original case records of his treatment of 196 soldiers with functional motor and sensory symptoms, functional seizures and somatoform disorders. Yealland’s treatment approach integrated peripheral and central electrical stimulation with a variety of other—psychological and physical—interventions. A combination of electrical stimulation of affected muscles with suggestion of imminent improvement was the hallmark of his approach. Although his reported success rates were high, Yealland conducted no formal follow-up. Many of the principles of his treatment, including the emphasis on suggestion, demonstration of preserved function and the communication of a physiological illness model, are encountered in current therapeutic approaches to functional motor and sensory symptoms. Yealland has been attacked for his use of electrical stimulation and harsh disciplinary procedures in popular and scientific literature during and after World War I. This criticism reflects changing views on patient autonomy and the social role of doctors and directly impacts on current debates on ethical justification of suggestive therapies. We argue that knowledge of the historical approaches to diagnosis and management of functional neurological syndromes can inform both aetiological models and treatment concepts for these challenging conditions. PMID:23384604

  4. NASA Lewis steady-state heat pipe code users manual

    NASA Technical Reports Server (NTRS)

    Tower, Leonard K.; Baker, Karl W.; Marks, Timothy S.

    1992-01-01

    The NASA Lewis heat pipe code was developed to predict the performance of heat pipes in the steady state. The code can be used as a design tool on a personal computer or with a suitable calling routine, as a subroutine for a mainframe radiator code. A variety of wick structures, including a user input option, can be used. Heat pipes with multiple evaporators, condensers, and adiabatic sections in series and with wick structures that differ among sections can be modeled. Several working fluids can be chosen, including potassium, sodium, and lithium, for which monomer-dimer equilibrium is considered. The code incorporates a vapor flow algorithm that treats compressibility and axially varying heat input. This code facilitates the determination of heat pipe operating temperatures and heat pipe limits that may be encountered at the specified heat input and environment temperature. Data are input to the computer through a user-interactive input subroutine. Output, such as liquid and vapor pressures and temperatures, is printed at equally spaced axial positions along the pipe as determined by the user.

  5. NASA Lewis Research Center's Preheated Combustor and Materials Test Facility

    NASA Technical Reports Server (NTRS)

    Nemets, Steve A.; Ehlers, Robert C.; Parrott, Edith

    1995-01-01

    The Preheated Combustor and Materials Test Facility (PCMTF) in the Engine Research Building (ERB) at the NASA Lewis Research Center is one of two unique combustor facilities that provide a nonvitiated air supply to two test stands, where the air can be used for research combustor testing and high-temperature materials testing. Stand A is used as a research combustor stand, whereas stand B is used for cyclic and survivability tests of aerospace materials at high temperatures. Both stands can accommodate in-house and private industry research programs. The PCMTF is capable of providing up to 30 lb/s (pps) of nonvitiated, 450 psig combustion air at temperatures ranging from 850 to 1150 g F. A 5000 gal tank located outdoors adjacent to the test facility can provide jet fuel at a pressure of 900 psig and a flow rate of 11 gal/min (gpm). Gaseous hydrogen from a 70,000 cu ft (CF) tuber is also available as a fuel. Approximately 500 gpm of cooling water cools the research hardware and exhaust gases. Such cooling is necessary because the air stream reaches temperatures as high as 3000 deg F. The PCMTF provides industry and Government with a facility for studying the combustion process and for obtaining valuable test information on advanced materials. This report describes the facility's support systems and unique capabilities.

  6. Altered neurofilament expression does not contribute to Lewy body formation.

    PubMed Central

    Bergeron, C.; Petrunka, C.; Weyer, L.; Pollanen, M. S.

    1996-01-01

    Lewy bodies (LBs) are cytoskeletal alterations found in several neurodegenerative disorders. Although neurofilaments are the main constituent of the LB, the precise mechanisms that underlie their formation remain speculative. To examine the pathogenesis of this inclusion, we measured the mRNA level of the low molecular weight neurofilament subunit in the nigral dopaminergic neurons of patients with LB disorders and neurologically normal controls. We found a small but significant decrease in the mean mRNA values in the LB group as compared with controls. However, a comparison of LB-bearing and non-LB-bearing neurons on the same section showed no significant difference between these two neuronal populations. We conclude that altered neurofilament expression is not a major contributory event in the pathogenesis of the LB. The decrease in neurofilament mRNA expression observed in the overall nigral dopaminergic neuronal population of LB disorders probably represents a nonspecific response to neuronal injury independent of LB formation. Images Figure 1 PMID:8546215

  7. Fort Lewis electric energy baseline and efficiency resource assessment

    SciTech Connect

    Secrest, T.J.; Currie, J.W.; DeSteese, J.G.; Dirks, J.A.; Marseille, T.J.; Parker, G.B.; Richman, E.E.; Shankle, S.A.

    1991-10-01

    In support of the US DOE Federal Energy Management Program, the Pacific Northwest Laboratory is developing a fuel-neutral approach for identifying, evaluating, and acquiring all cost-effective energy projects at federal installations. Fort Lewis, a US Army installation near Tacoma, Washington, was selected as the pilot site for developing this approach. This site was chosen in conjunction with the interests of the Bonneville Power Administration to develop programs for its federal sector customers and the Army Forces Command to develop an in-house program to upgrade the energy efficiency of its installations. This report documents the electricity assessment portion of the approach, providing an estimate of the electricity use baseline and efficiency improvement potential for major sectors and end uses at the Fort. Although the assessment did not identify all possible efficiency improvement opportunities, it is estimated that electricity use can be reduced by at least 20% cost-effectively at the $0.045/kWh marginal cost of electricity in the Pacific Northwest. 12 refs., 3 figs., 7 tabs.

  8. Prodromal clinical manifestations of neuropathologically confirmed Lewy body disease.

    PubMed

    Jicha, G A; Schmitt, F A; Abner, E; Nelson, P T; Cooper, G E; Smith, C D; Markesbery, W R

    2010-10-01

    The mild cognitive impairment (MCI) stage of dementia with Lewy bodies (MCI-DLB) has not yet been defined, but is likely to differ in the MCI stage of Alzheimer's disease (MCI-AD). To determine whether clinical features distinguish MCI-DLB and MCI-AD, 9 cases of neuropathologically confirmed MCI-DLB and 12 cases of MCI-AD were compared. No significant differences were found between MCI-DLB and MCI-AD cases in age at death, gender, ApoE status, education, time followed while clinically normal, or duration of MCI. MCI-DLB and MCI-AD cases differed clinically in the expression of Parkinsonism (P=0.012), provoked hallucinations or delirium (P=0.042), or the presence of any of these noncognitive symptoms of DLB (P<0.0001). Letter fluency (P=0.007) was significantly lower and Wechsler Logical Memory I (P=0.019) was significantly higher in MCI-DLB compared to MCI-AD cases. These data demonstrate the feasibility of differentiating underlying pathologic processes responsible for cognitive decline in the preclinical disease state and suggest that further refinement in diagnostic criteria may allow more accurate early detection of prodromal DLB and AD. PMID:19026468

  9. NASA Lewis Research Center's combustor test facilities and capabilities

    NASA Technical Reports Server (NTRS)

    Bianco, Jean

    1995-01-01

    NASA Lewis Research Center (LeRC) presently accommodates a total of six combustor test facilities with unique capabilities. The facilities are used to evaluate combustor and afterburner concepts for future engine applications, and also to test the survivability and performance of innovative high temperature materials, new instrumentation, and engine components in a realistic jet engine environment. The facilities provide a variety of test section interfaces and lengths to allow for flametube, sector and component testing. The facilities can accommodate a wide range of operating conditions due to differing capabilities in the following areas: inlet air pressure, temperature, and flow; fuel flow rate, pressure, and fuel storage capacity; maximum combustion zone temperature; cooling water flow rate and pressure; types of exhaust - atmospheric or altitude; air heater supply pressure; and types of air heaters - vitiated or nonvitiated. All of the facilities have provisions for standard gas (emissions) analysis, and a few of the facilities are equipped with specialized gas analysis equipment, smoke and particle size measurement devices, and a variety of laser systems. This report will present some of the unique features of each of the high temperature/high pressure combustor test facilities at NASA LeRC.

  10. Cyclic Oxidation Testing and Modelling: A NASA Lewis Perspective

    NASA Technical Reports Server (NTRS)

    Smialek, J. L.; Nesbitt, J. A.; Barrett, C. A.; Lowell, C. E.

    2000-01-01

    The Materials Division of the NASA Lewis Research Center has been heavily involved in the cyclic oxidation of high temperature materials for 30 years. Cyclic furnace and burner rig apparati have been developed, refined, and replicated to provide a large scale facility capable of evaluating many materials by a standard technique. Material behavior is characterized by weight change data obtained throughout the test, which has been modelled in a step-wise process of scale growth and spallation. This model and a coupled diffusion model have successfully described cyclic behavior for a number of systems and have provided insights regarding life prediction and variations in the spalling process. Performance ranking and mechanistic studies are discussed primarily for superalloys and coating alloys. Similar cyclic oxidation studies have been performed on steels, intermetallic compounds, thermal barrier coatings, ceramics, and ceramic composites. The most common oxidation test was performed in air at temperatures ranging from 800 deg. to 1600 C, for times up to 10000 h, and for cycle durations of 0.1 to 1000 h. Less controlled, but important, test parameters are the cooling temperature and humidity level. Heating and cooling rates are not likely to affect scale spallation. Broad experience has usually allowed for considerable focus and simplification of these test parameters, while still revealing the principal aspects of material behavior and performance. Extensive testing has been performed to statistically model the compositional effects of experimental alloys and to construct a comprehensive database of complex commercial alloys.

  11. Cerebrospinal Fluid Biomarkers for Dementia with Lewy Bodies

    PubMed Central

    Mukaetova-Ladinska, Elizabeta B.; Monteith, Rachael; Perry, Elaine K.

    2010-01-01

    More than 750,000 of the UK population suffer from some form of cognitive impairment and dementia. Of these, 5–20% will have Dementia with Lewy Bodies (DLB). Clinico-pathological studies have shown that it is the low frequency of DLB clinical core features that makes the DLB diagnosis hardly recognisable during life, and easily misdiagnosed for other forms of dementia. This has an impact on the treatment and long-term care of the affected subjects. Having a biochemical test, based on quantification of a specific DLB biomarker within Cerebrospinal Fluid (CSF) could be an effective diagnostic method to improve the differential diagnosis. Although some of the investigated DLB CSF biomarkers are well within the clinical criteria for sensitivity and specificity (>90%), they all seem to be confounded by the contradictory data for each of the major groups of biomarkers (α-synuclein, tau and amyloid proteins). However, a combination of CSF measures appear to emerge, that may well be able to differentiate DLB from other dementias: α-synuclein reduction in early DLB, a correlation between CSF α-synuclein and Aβ42 measures (characteristic for DLB only), and t-tau and p-tau181 profile (differentiating AD from DLB). PMID:21048932

  12. Lewis-Riesenfeld invariants and transitionless quantum driving

    SciTech Connect

    Chen Xi; Torrontegui, E.; Muga, J. G.

    2011-06-15

    Different methods have been recently put forward and implemented experimentally to inverse engineer the time-dependent Hamiltonian of a quantum system and accelerate slow adiabatic processes via nonadiabatic shortcuts. In the ''transitionless quantum driving'' proposed by Berry, shortcut Hamiltonians are designed so that the system follows exactly, in an arbitrarily short time, the approximate adiabatic path defined by a reference Hamiltonian. A different approach is based on first designing a Lewis-Riesenfeld invariant to carry the eigenstates of a Hamiltonian from specified initial to final configurations, again in an arbitrary time, and then constructing from the invariant the transient Hamiltonian that connects these boundary configurations. We show that the two approaches, apparently quite different in form and so far in results, are, in fact, strongly related and potentially equivalent, so that the inverse-engineering operations in one of them can be reinterpreted and understood in terms of the concepts and operations of the other one. We study, as explicit examples, expansions of time-dependent harmonic traps and the state preparation of two-level systems.

  13. Enamine/butadienylborane cycloaddition in the frustrated Lewis pair regime.

    PubMed

    Chen, Guo-Qiang; Türkyilmaz, Fatma; Daniliuc, Constantin G; Bannwarth, Christoph; Grimme, Stefan; Kehr, Gerald; Erker, Gerhard

    2015-11-14

    The dienylborane 2a was prepared by regioselective alkyne hydroboration of the conjugated enyne 1a with Piers' borane [HB(C6F5)2]. Its reaction with a series of acetophenone derived enamines 3 resulted in the formation of the strong enamine β-carbon adduct with the borane Lewis acid (4). In contrast B-C adduct formation between the dienylborane 2a and a series of much more bulky cyclohexanone derived enamines (6) is rapidly reversible above ca.-30 °C and then leads to the formation of the [4 + 2]cycloaddition products 8. A DFT study revealed that this reaction is probably taking a stepwise route, proceeding by means of enamine addition to the dienylborane terminus to generate a zwitterionic borata-alkene/iminium ion intermediate that undergoes rapid subsequent ring closure. Heating of the products 8 led to amidoborane elimination from the vicinal amino/borane pair at the product framework to give the respective hexahydronaphthalene product 10. Subsequent treatment with TEMPO (2 equiv.) resulted in selective oxidation of the unsaturated ring to give the respective tetrahydronaphthalene derivative 12. PMID:26330093

  14. Activities of the Structures Division, Lewis Research Center

    NASA Technical Reports Server (NTRS)

    1990-01-01

    The purpose of the NASA Lewis Research Center, Structures Division's 1990 Annual Report is to give a brief, but comprehensive, review of the technical accomplishments of the Division during the past calendar year. The report is organized topically to match the Center's Strategic Plan. Over the years, the Structures Division has developed the technology base necessary for improving the future of aeronautical and space propulsion systems. In the future, propulsion systems will need to be lighter, to operate at higher temperatures and to be more reliable in order to achieve higher performance. Achieving these goals is complex and challenging. Our approach has been to work cooperatively with both industry and universities to develop the technology necessary for state-of-the-art advancement in aeronautical and space propulsion systems. The Structures Division consists of four branches: Structural Mechanics, Fatigue and Fracture, Structural Dynamics, and Structural Integrity. This publication describes the work of the four branches by three topic areas of Research: (1) Basic Discipline; (2) Aeropropulsion; and (3) Space Propulsion. Each topic area is further divided into the following: (1) Materials; (2) Structural Mechanics; (3) Life Prediction; (4) Instruments, Controls, and Testing Techniques; and (5) Mechanisms. The publication covers 78 separate topics with a bibliography containing 159 citations. We hope you will find the publication interesting as well as useful.

  15. NASA Lewis steady-state heat pipe code users manual

    SciTech Connect

    Tower, L.K.; Baker, K.W.; Marks, T.S.

    1992-06-01

    The NASA Lewis heat pipe code has been developed to predict the performance of heat pipes in the steady state. The code can be used as a design tool on a personal computer or, with a suitable calling routine, as a subroutine for a mainframe radiator code. A variety of wick structures, including a user input option, can be used. Heat pipes with multiple evaporators, condensers, and adiabatic sections in series and with wick structures that differ among sections can be modeled. Several working fluids can be chosen, including potassium, sodium, and lithium, for which the monomer-dimer equilibrium is considered. The code incorporates a vapor flow algorithm that treats compressibility and axially varying heat input. This code facilitates the determination of heat pipe operating temperatures and heat pipe limits that may be encountered at the specified heat input and environment temperature. Data are input to the computer through a user-interactive input subroutine. Output, such as liquid and vapor pressures and temperatures, is printed at equally spaced axial positions along the pipe as determined by the user.

  16. LSENS, The NASA Lewis Kinetics and Sensitivity Analysis Code

    NASA Technical Reports Server (NTRS)

    Radhakrishnan, K.

    2000-01-01

    A general chemical kinetics and sensitivity analysis code for complex, homogeneous, gas-phase reactions is described. The main features of the code, LSENS (the NASA Lewis kinetics and sensitivity analysis code), are its flexibility, efficiency and convenience in treating many different chemical reaction models. The models include: static system; steady, one-dimensional, inviscid flow; incident-shock initiated reaction in a shock tube; and a perfectly stirred reactor. In addition, equilibrium computations can be performed for several assigned states. An implicit numerical integration method (LSODE, the Livermore Solver for Ordinary Differential Equations), which works efficiently for the extremes of very fast and very slow reactions, is used to solve the "stiff" ordinary differential equation systems that arise in chemical kinetics. For static reactions, the code uses the decoupled direct method to calculate sensitivity coefficients of the dependent variables and their temporal derivatives with respect to the initial values of dependent variables and/or the rate coefficient parameters. Solution methods for the equilibrium and post-shock conditions and for perfectly stirred reactor problems are either adapted from or based on the procedures built into the NASA code CEA (Chemical Equilibrium and Applications).

  17. Rapid reconstitution of functionally active 6-sulfoLacNAc+ dendritic cells (slanDCs) of donor origin following allogeneic haematopoietic stem cell transplant

    PubMed Central

    Mimiola, E; Marini, O; Perbellini, O; Micheletti, A; Vermi, W; Lonardi, S; Costantini, C; Meneghelli, E; Andreini, A; Bonetto, C; Vassanelli, A; Cantini, M; Zoratti, E; Massi, D; Zamo', A; Leso, A; Quaresmini, G; Benedetti, F; Pizzolo, G; Cassatella, M A; Tecchio, C

    2014-01-01

    The role of dendritic cells (DCs) and macrophages in allogeneic haematopoietic stem cell transplant (HSCT) is critical in determining the extent of graft-versus-host response. The goal of this study was to analyse slanDCs, a subset of human proinflammatory DCs, in haematopoietic stem cell (HSC) sources, as well as to evaluate their 1-year kinetics of reconstitution, origin and functional capacities in peripheral blood (PB) and bone marrow (BM) of patients who have undergone HSCT, and their presence in graft-versus-host disease (GVHD) tissue specimens. slanDCs were also compared to myeloid (m)DCs, plasmacytoid (p)DCs and monocytes in HSC sources and in patients' PB and BM throughout reconstitution. slanDCs accounted for all HSC sources. In patients' PB and BM, slanDCs were identified from day +21, showing median frequencies comparable to healthy donors, donor origin and kinetics of recovery similar to mDCs, pDCs, and monocytes. Under cyclosporin treatment, slanDCs displayed a normal pattern of maturation, and maintained an efficient chemotactic activity and capacity of releasing tumour necrosis factor (TNF)-α upon lipopolysaccharide (LPS) stimulation. None the less, they were almost undetectable in GVHD tissue specimens, being present only in intestinal acute GVHD samples. slanDCs reconstitute early, being donor-derived and functionally competent. The absence of slanDCs from most of the GVHD-targeted tissue specimens seems to rule out the direct participation of these cells in the majority of the local reactions characterizing GVHD. PMID:24853271

  18. [Study of nucleic acid structure by immunochemical methods. I. Antibodies specific for 6-sulfo-5,6-dihydro-4-methoxyaminopyrimidinone-2].

    PubMed

    Poverennyĭ, A M; Podgorodnichenko, V K; Monastyrskaia, G S; Bryskina, L E; Sverdlov, E D

    1978-01-01

    Immunization of animals with DNA modified by a mixture of bisulphite and O-methylhydroxylamine and methylated bovine serum albumin results in production of antibodies mainly reacting with modified DNA. Antibodies that react with denatured DNA were produced in minute quantity. It was shown that elicited antibodies possess a high specificity and have the ability to recognize only nucleotides with a double modification. The immune sera were fractionated by Sephadex G-200 column chromatography and the antibody activity was demonstrable in the 19S and 7S fractions. The attempts to induce synthesis of antibodies by injection of DNA modified by O-methylhydroxylamine failed. PMID:79979

  19. Main Group Lewis Acid-Mediated Transformations of Transition-Metal Hydride Complexes.

    PubMed

    Maity, Ayan; Teets, Thomas S

    2016-08-10

    This Review highlights stoichiometric reactions and elementary steps of catalytic reactions involving cooperative participation of transition-metal hydrides and main group Lewis acids. Included are reactions where the transition-metal hydride acts as a reactant as well as transformations that form the metal hydride as a product. This Review is divided by reaction type, illustrating the diverse roles that Lewis acids can play in mediating transformations involving transition-metal hydrides as either reactants or products. We begin with a discussion of reactions where metal hydrides form direct adducts with Lewis acids, elaborating the structure and dynamics of the products of these reactions. The bulk of this Review focuses on reactions where the transition metal and Lewis acid act in cooperation, and includes sections on carbonyl reduction, H2 activation, and hydride elimination reactions, all of which can be promoted by Lewis acids. Also included is a section on Lewis acid-base secondary coordination sphere interactions, which can influence the reactivity of hydrides. Work from the past 50 years is included, but the majority of this Review focuses on research from the past decade, with the intent of showcasing the rapid emergence of this field and the potential for further development into the future. PMID:27164024

  20. Current wind tunnel capability and planned improvements at Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Bowditch, D. N.

    1986-01-01

    As the propulsion and power generation center of NASA, Lewis has designed its wind tunnels for propulsion research. Therefore, the 8 by 6 Foot Supersonic Wind Tunnel and the 10 by 10 Foot Supersonic Wind Tunnel provide the capability to test operating propulsion systems from Mach 0.4 to 3.5. The 9 by 15 Foot Wind Tunnel can investigate propulsion installation problems at the lower takeoff and landing speeds and provides an excellent anechoic environment to measure propeller and fan noise. The Lewis Central Air System provides steady air supplies to 450 psi, and exhaust to 3 in. of mercury absolute, which are available to the wind tunnels for simulation of jets and engine induced flows. The Lewis Icing Research Tunnel is the largest in the free world that can produce icing conditions throughout the year. Rehabilitation of the Altitude Wind Tunnel at Lewis would allow testing of propulsion systems in the upper left hand corner which would be a unique capability. Also, in a mothballed state at Lewis, the Hypersonic Tunnel Facility could provide the best simulation of nonvitiated Mach 5-7 test conditions available. Studies are currently being made of the Lewis facilities to identify enhancements of their research potential for the 1990's and beyond.

  1. Helicobacter pylori Does Not Require Lewis X or Lewis Y Expression To Colonize C3H/HeJ mice

    PubMed Central

    Takata, Tohru; El-Omar, Emad; Camorlinga, Margarita; Thompson, Stuart A.; Minohara, Yutaka; Ernst, Peter B.; Blaser, Martin J.

    2002-01-01

    Helicobacter pylori strains frequently express Lewis X (Lex) and/or Ley on their cell surfaces as constituents of the O antigens of their lipopolysaccharide molecules. To assess the effect of Lex and Ley expression on the ability of H. pylori to colonize the mouse stomach and to adhere to epithelial cells, isogenic mutants were created in which fucT1 alone or fucT1 and fucT2, which encode the fucosyl transferases necessary for Lex and Ley expression, were deleted. C3H/HeJ mice were experimentally challenged with either wild-type 26695 H. pylori or its isogenic mutants. All strains, whether passaged in the laboratory or recovered after mouse passage, colonized the mice well and without consistent differences. During colonization by the mutants, there was no reversion to wild type. Similarly, adherence to AGS and KatoIII cells was unaffected by the mutations. Together, these findings indicate that Le expression is not necessary for mouse gastric colonization or for H. pylori adherence to epithelial cells. PMID:12011000

  2. The NASA Lewis Research Center: An Economic Impact Study

    NASA Technical Reports Server (NTRS)

    Austrian, Ziona

    1996-01-01

    The NASA Lewis Research Center (LeRC), established in 1941, is one of ten NASA research centers in the country. It is situated on 350 acres of land in Cuyahoga County and occupies more than 140 buildings and over 500 specialized research and test facilities. Most of LeRC's facilities are located in the City of Cleveland; some are located within the boundaries of the cities of Fairview Park and Brookpark. LeRC is a lead center for NASA's research, technology, and development in the areas of aeropropulsion and selected space applications. It is a center of excellence for turbomachinery, microgravity fluid and combustion research, and commercial communication. The base research and technology disciplines which serve both aeronautics and space areas include materials and structures, instrumentation and controls, fluid physics, electronics, and computational fluid dynamics. This study investigates LeRC's economic impact on Northeast Ohio's economy. It was conducted by The Urban Center's Economic Development Program in Cleveland State University's Levin College of Urban Affairs. The study measures LeRC's direct impact on the local economy in terms of jobs, output, payroll, and taxes, as well as the indirect impact of these economic activities when they 'ripple' throughout the economy. To fully explain LeRC's overall impact on the region, its contributions in the areas of technology transfer and education are also examined. The study uses a highly credible and widely accepted research methodology. First, regional economic multipliers based on input-output models were used to estimate the effect of LERC spending on the Northeast Ohio economy. Second, the economic models were complemented by interviews with industrial, civic, and university leaders to qualitatively assess LeRC's impact in the areas of technology transfer and education.

  3. Thoracoscopic purse string technique for minimally invasive Ivor Lewis esophagectomy

    PubMed Central

    Kang, Ningning; Xia, Wanli; Che, Yun; Wan, Jun; Yu, Zaicheng

    2014-01-01

    Objective Thoracolaparoscopic esophagectomy with chest anastomosis (TLE-chest) is increasingly performed for middle and lower esophageal cancer; however, gastroesophageal anastomosis for this surgery remains both challenging and inefficient. To address this issue, we previously reported our MIE technique with Ivor-Lewis anastomosis. Here we present the video to introduce our TLE-chest operation procedures. Methods TLE-chest with a combined thoracoscopic and laparoscopic technique was performed by one group of surgeons. From October 2011 to September 2013, 80 esophageal cancer patients were treated with TLE-chest using this improved anastomotic technique. Results The surgery was successful for all patients, although the anastomosis in one patient required intraoperative manual repair. No patients required open conversion. In this video, dissociation of stomach, and dissection of lymph nodes, creation of gastric tube and staple line embedding, jejunostomy were carried out by laparoscopic surgery. Dissection of esophageal cancer and mediastinal lymph nodes were done through rib 3 or 4 by a 3-4 cm video-assisted right anterior minithoracotomy, then esophago-gastric anastomosis was performed in right thoracic cavity This video shows the R0 resection of T3N0M0 esophageal cancer. Totally, 36 lymph nodes were dissected, including 21 mediastinal lymph nodes and 15 abdominal lymph nodes. The patient recovered well and was discharged on day 8 after the surgery, with good short term outcomes. Conclusions A safe, cost effective purse string stapled anastomotic technique has been presented for TLE-chest in our video. It is consistent with the oncology principles. PMID:24605229

  4. Expression of hPNAS-4 Radiosensitizes Lewis Lung Cancer

    SciTech Connect

    Zeng Hui; Yuan Zhu; Zhu Hong; Li Lei; Shi Huashan; Wang Zi; Fan Yu; Deng Qian; Zeng Jianshuang; He Yinbo; Xiao Jianghong; Li Zhiping

    2012-11-15

    Purpose: This study aimed to transfer the hPNAS-4 gene, a novel apoptosis-related human gene, into Lewis lung cancer (LL2) and observe its radiosensitive effect on radiation therapy in vitro and in vivo. Methods and Materials: The hPNAS-4 gene was transfected into LL2 cells, and its expression was detected via western blot. Colony formation assay and flow cytometry were used to detect the growth and apoptosis of cells treated with irradiation/PNAS-4 in vitro. The hPNAS-4 gene was transferred into LL2-bearing mice through tail vein injection of the liposome/gene complex. The tumor volumes were recorded after radiation therapy. Proliferating cell nuclear antigen (PCNA) immunohistochemistry staining and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay were performed to detect the tumor cell growth and apoptosis in vivo. Results: The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue, and its overexpressions were confirmed via western blot analysis. Compared with the control, empty plasmid, hPNAS-4, radiation, and empty plasmid plus radiation groups, the hPNAS-4 plus radiation group more significantly inhibited growth and enhanced apoptosis of LL2 cells in vitro and in vivo (P<.05). Conclusions: The hPNAS-4 gene was successfully transferred into LL2 cells and tumor tissue and was expressed in both LL2 cell and tumor tissue. The hPNAS-4 gene therapy significantly enhanced growth inhibition and apoptosis of LL2 tumor cells by radiation therapy in vitro and in vivo. Therefore, it may be a potential radiosensitive treatment of radiation therapy for lung cancer.

  5. Historical perspectives - The role of the NASA Lewis Research Center in the national space nuclear power programs

    NASA Technical Reports Server (NTRS)

    Bloomfield, H. S.; Sovie, R. J.

    1991-01-01

    The history of the NASA Lewis Research Center's role in space nuclear power programs is reviewed. Lewis has provided leadership in research, development, and the advancement of space power and propulsion systems. Lewis' pioneering efforts in nuclear reactor technology, shielding, high temperature materials, fluid dynamics, heat transfer, mechanical and direct energy conversion, high-energy propellants, electric propulsion and high performance rocket fuels and nozzles have led to significant technical and management roles in many natural space nuclear power and propulsion programs.

  6. Historical perspectives: The role of the NASA Lewis Research Center in the national space nuclear power programs

    NASA Technical Reports Server (NTRS)

    Bloomfield, H. S.; Sovie, R. J.

    1991-01-01

    The history of the NASA Lewis Research Center's role in space nuclear power programs is reviewed. Lewis has provided leadership in research, development, and the advancement of space power and propulsion systems. Lewis' pioneering efforts in nuclear reactor technology, shielding, high temperature materials, fluid dynamics, heat transfer, mechanical and direct energy conversion, high-energy propellants, electric propulsion and high performance rocket fuels and nozzles have led to significant technical and management roles in many national space nuclear power and propulsion programs.

  7. A new method for detection of tumor driver-dependent changes of protein sialylation in a colon cancer cell line reveals nectin-3 as TGFBR2 target.

    PubMed

    Lee, Jennifer; Warnken, Uwe; Schnölzer, Martina; Gebert, Johannes; Kopitz, Jürgen

    2015-10-01

    Protein-linked glycans play key roles in cell differentiation, cell-cell interactions, cell growth, adhesion and immune response. Aberrant glycosylation is a characteristic feature of tumor cells and is involved in tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. It can serve as cancer biomarker and treatment target. To enable comprehensive screening for the impact of tumor driving mutations in colorectal cancer cells we present a method for specific analysis of tumor driver-induced glycome changes. The strategy is based on a combination of three technologies, that is recombinase-mediated cassette exchange (RMCE), Click-It chemistry and mass spectrometry. The new method is exemplified by the analysis of the impact of inactivating mutations of the TGF-ß-receptor type II (TGFBR2) on sialic acid incorporation into protein-linked glycans of the colon cancer cell line HCT116. Overall, 70 proteins were found to show de novo sialic acid incorporation exclusively upon TGFBR2 expression whereas 7 proteins lost sialylation upon TGFBR2 reconstitution. Validation of detected candidate glycoproteins is demonstrated with the cell surface glycoprotein nectin-3 known to be involved in metastasis, invasion and prognosis of various cancers. Altogether, our new approach can help to systematically puzzle out the influence of tumor-specific mutations in a major signaling pathway, as exemplified by the TGFBR2 tumor suppressor, on the tumor glycome. It facilitates the identification of glycan-based tumor markers that could be used for diagnostic and therapeutic applications. In principle the outlined strategy can be adapted to any cancer cell line, tumor driver mutation and several glycan-building blocks. PMID:26177744

  8. Reducing CO₂ to methanol using frustrated Lewis pairs: on the mechanism of phosphine-borane-mediated hydroboration of CO₂.

    PubMed

    Courtemanche, Marc-André; Légaré, Marc-André; Maron, Laurent; Fontaine, Frédéric-Georges

    2014-07-30

    The full mechanism of the hydroboration of CO2 by the highly active ambiphilic organocatalyst 1-Bcat-2-PPh2-C6H4 (Bcat = catecholboryl) was determined using computational and experimental methods. The intramolecular Lewis pair was shown to be involved in every step of the stepwise reduction. In contrast to traditional frustrated Lewis pair systems, the lack of steric hindrance around the Lewis basic fragment allows activation of the reducing agent while moderate Lewis acidity/basicity at the active centers promotes catalysis by releasing the reduction products. Simultaneous activation of both the reducing agent and carbon dioxide is the key to efficient catalysis in every reduction step. PMID:24948159

  9. Clinicians' ability to diagnose dementia with Lewy bodies is not affected by β-amyloid load

    PubMed Central

    Attems, Johannes; Thomas, Alan; Brown, Andrew; Jaros, Evelyn; Lett, Debbie J.; Ossola, Maria; Perry, Robert H.; Ramsay, Lynne; Walker, Lauren; McKeith, Ian G.

    2015-01-01

    Objective: To investigate whether an increasing load of β-amyloid and/or neuritic plaques influences the phenotype, and thus the clinical diagnostic accuracy, of dementia with Lewy bodies (DLB). Methods: A series of 64 subjects with autopsy-proven DLB was studied. Last diagnosis before death was used to determine the clinical diagnostic accuracy of DLB in relation to Lewy body distribution and extent of Alzheimer β-amyloid and/or neuritic pathology. DLB pathologic diagnosis was made according to consensus criteria, using α-synuclein immunostaining for Lewy body identification. β-Amyloid immunostaining was used for quantifying β-amyloid deposits. The Consortium to Establish a Registry for Alzheimer's Disease criteria and Braak stage were applied for semiquantitative grading of neuritic plaque and neurofibrillary tangle pathology. Results: Overall clinical diagnostic accuracy for the entire DLB cohort was high (80%), reflecting the high prevalence of core clinical features (fluctuations [81%], parkinsonism [77%], visual hallucinations [70%]). Lower frequencies of core clinical features of DLB, resulting in lower accuracy of its clinical diagnosis, were associated with decreasing Lewy body distribution (p < 0.0001) and with increasing neuritic plaque pathology (p = 0.035), but not with the number of β-amyloid plaque deposits. Conclusions: The likelihood of occurrence of the DLB clinical syndrome is positively related to the extent of Lewy body pathology and negatively related to the severity of Alzheimer neuritic pathology, while β-amyloid load has no effect. PMID:25552579

  10. Effects of Lewis number on turbulent scalar transport and its modelling in turbulent premixed flames

    SciTech Connect

    Chakraborty, Nilanjan; Cant, R.S.

    2009-07-15

    The behaviour of the turbulent scalar flux in premixed flames has been studied using Direct Numerical Simulation (DNS) with emphasis on the effects of Lewis number in the context of Reynolds-averaged closure modelling. A database was obtained from DNS of three-dimensional freely propagating statistically planar turbulent premixed flames with simplified chemistry and a range of global Lewis numbers from 0.34 to 1.2. Under the same initial conditions of turbulence, flames with low Lewis numbers are found to exhibit counter-gradient transport, whereas flames with higher Lewis numbers tend to exhibit gradient transport. The Reynolds-averaged transport equation for the turbulent scalar flux is analysed in detail and the performance of existing models for the unclosed terms is assessed with respect to corresponding quantities extracted from DNS data. Based on this assessment, existing models which are able to address the effects of non-unity Lewis number on turbulent scalar flux transport are identified, and new or modified models are suggested wherever necessary. In this way, a complete set of closure models for the scalar flux transport equation is prescribed for use in Reynolds-Averaged Navier-Stokes simulations. (author)

  11. Neural correlates of attention‐executive dysfunction in lewy body dementia and Alzheimer's disease

    PubMed Central

    Kobeleva, Xenia; Cherry, George; Killen, Alison; Gallagher, Peter; Burn, David J.; Thomas, Alan J.; O'Brien, John T.; Taylor, John‐Paul

    2015-01-01

    Abstract Attentional and executive dysfunction contribute to cognitive impairment in both Lewy body dementia and Alzheimer's disease. Using functional MRI, we examined the neural correlates of three components of attention (alerting, orienting, and executive/conflict function) in 23 patients with Alzheimer's disease, 32 patients with Lewy body dementia (19 with dementia with Lewy bodies and 13 with Parkinson's disease with dementia), and 23 healthy controls using a modified Attention Network Test. Although the functional MRI demonstrated a similar fronto‐parieto‐occipital network activation in all groups, Alzheimer's disease and Lewy body dementia patients had greater activation of this network for incongruent and more difficult trials, which were also accompanied by slower reaction times. There was no recruitment of additional brain regions or, conversely, regional deficits in brain activation. The default mode network, however, displayed diverging activity patterns in the dementia groups. The Alzheimer's disease group had limited task related deactivations of the default mode network, whereas patients with Lewy body dementia showed heightened deactivation to all trials, which might be an attempt to allocate neural resources to impaired attentional networks. We posit that, despite a common endpoint of attention‐executive disturbances in both dementias, the pathophysiological basis of these is very different between these diseases. Hum Brain Mapp 37:1254–1270, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:26705763

  12. Deubiquitinase Usp8 regulates α-synuclein clearance and modifies its toxicity in Lewy body disease.

    PubMed

    Alexopoulou, Zoi; Lang, Johannes; Perrett, Rebecca M; Elschami, Myriam; Hurry, Madeleine E D; Kim, Hyoung Tae; Mazaraki, Dimitra; Szabo, Aron; Kessler, Benedikt M; Goldberg, Alfred Lewis; Ansorge, Olaf; Fulga, Tudor A; Tofaris, George K

    2016-08-01

    In Parkinson's disease, misfolded α-synuclein accumulates, often in a ubiquitinated form, in neuronal inclusions termed Lewy bodies. An important outstanding question is whether ubiquitination in Lewy bodies is directly relevant to α-synuclein trafficking or turnover and Parkinson's pathogenesis. By comparative analysis in human postmortem brains, we found that ubiquitin immunoreactivity in Lewy bodies is largely due to K63-linked ubiquitin chains and markedly reduced in the substantia nigra compared with the neocortex. The ubiquitin staining in cells with Lewy bodies inversely correlated with the content and pathological localization of the deubiquitinase Usp8. Usp8 interacted and partly colocalized with α-synuclein in endosomal membranes and, both in cells and after purification, it deubiquitinated K63-linked chains on α-synuclein. Knockdown of Usp8 in the Drosophila eye reduced α-synuclein levels and α-synuclein-induced eye toxicity. Accordingly, in human cells, Usp8 knockdown increased the lysosomal degradation of α-synuclein. In the dopaminergic neurons of the Drosophila model, unlike knockdown of other deubiquitinases, Usp8 protected from α-synuclein-induced locomotor deficits and cell loss. These findings strongly suggest that removal of K63-linked ubiquitin chains on α-synuclein by Usp8 is a critical mechanism that reduces its lysosomal degradation in dopaminergic neurons and may contribute to α-synuclein accumulation in Lewy body disease. PMID:27444016

  13. Storable Propellant Combustion Instability Program at Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Tabata, William K.; Antl, Robert J.; Vincent, David W.

    1966-01-01

    An experimental program at Lewis Research Center investigates acoustical-mode combustion instability in liquid propellant rockets. One phase of this program is concerned with nitrogen tetroxide and a 50-50 fuel blend of hydrazine-UDMH. Effects on combustor stability and performance by variations in injection velocities, impingement angle and distance, amd thrust per element of triplet injectors were studied in a 10.77-inch- diameter cylindrical combustor at chamber pressures of 100 and 300 psia. Nominal thrust levels were 6700 and 20 000 pounds. Stability rating was accomplished by the use of various size RDX explosive charges to generate tangential pressure disturbances. The injection velocity effect correlated by using a ratio V(sub o)/V(sub f). Stability correlation with V(sub o)/V(sub f) resulted in a sharply humped curve with maximum stability at a ratio of 1.2. Performance decreased with increase in V(sub o)/V(sub f) after a maximum at 0.7, which agreed fairly well with the "uniform mixture ratio distribution" criteria of the Jet Propulsion Laboratory. Variation of impingement angle from 38 deg to 120 deg indicated that performance correlated with the absolute velocity ratio V(sub o)/V(sub f), but stability correlation appeared to be best with a velocity ratio using the radial component of the fuel injection velocity V(sub o)/V(sub fr). Impingement distances from 0.5 to 1.0 inch appeared to have only slight effect on stability and performance. Investigation of injector thrust per element for V(sub o)/V(sub fr) ranging from 0.8 to 2.8 yielded convex maxima curves. Acoustic liners were also tested to improve a liner design computer program, to obtain design criteria, and to develop flight-type liners. A marginally stable and spontaneously unstable combustor were used to evaluate linear configurations. All liners were effective in the marginally stable configuration, and only liners with large theoretical absorptivity were successful in the spontaneously

  14. Composition, texture and methane potential of cellulosic residues from Lewis acids organosolv pulping of wheat straw.

    PubMed

    Constant, Sandra; Barakat, Abdellatif; Robitzer, Mike; Di Renzo, Francesco; Dumas, Claire; Quignard, Françoise

    2016-09-01

    Cellulosic pulps have been successfully isolated from wheat straw through a Lewis acids organosolv treatment. The use of Lewis acids with different hardness produced pulps with different delignification degrees. The cellulosic residue was characterised by chemical composition, X-ray diffraction, FT-IR spectroscopy, N2 physisorption, scanning electron microscopy and potential for anaerobic digestibility. Surface area and pore volume increased with the hardness of the Lewis acid, in correspondence with the decrease of the amount of lignin and hemicellulose in the pulp. The non linearity of the correlation between porosity and composition suggests that an agglomeration of cellulose fibrils occurs in the early stages of pulping. All organosolv pulps presented a significantly higher methane potential than the parent straw. A methane evolution of 295Ncm(3)/g OM was reached by a moderate improvement of the accessibility of the native straw. PMID:27295251

  15. NASA-ASEE Summer Faculty Fellowship Program at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Prahl, Joseph M.; Keith, Theo G., Jr.; Montegani, Francis J.

    1996-01-01

    During the summer of 1996, a ten-week Summer Faculty Fellowship Program was conducted at the NASA Lewis Research Center (LeRC) in collaboration with Case Western Reserve University (CWRU), and the Ohio Aerospace Institute (OAI). This is the thirty-third summer of this program at Lewis. It was one of nine summer programs sponsored by NASA in 1996, at various field centers under the auspices of the American Society for Engineering Education (ASEE). The objectives of the program are: (1) to further the professional knowledge of qualified engineering and science educators, (2) to stimulate an exchange of ideas between participants and NASA, (3) to enrich and refresh the research activities of participants' institutions. (4) to contribute to the research objectives of LeRC. This report is intended to recapitulate the activities comprising the 1996 Lewis Summer Faculty Fellowship Program, to summarize evaluations by the participants, and to make recommendations regarding future programs.

  16. End of Frustration: Catalytic Precision Polymerization with Highly Interacting Lewis Pairs.

    PubMed

    Knaus, Maximilian G M; Giuman, Marco M; Pöthig, Alexander; Rieger, Bernhard

    2016-06-22

    Herein we report on the catalytic polymerization of diverse Michael-type monomers with high precision by using simple but highly active combinations of phosphorus-containing Lewis bases and organoaluminum compounds. The interacting Lewis pair catalysts enable the control of molecular weight and microstructure of the produced polymers. The reactions show a linear Mn vs consumption plot thus proving a living type polymerization. The initiation has been investigated by end-group analysis with ESI mass spectrometric analysis. With these main-group element Lewis acid base pairs, it is not only possible to polymerize sterically demanding, functionalized as well as heteroatom containing monomers but also, for the first time, to catalytically polymerize extended Michael systems, like 4-vinylpyridine. PMID:27254134

  17. On the behaviour of biradicaloid [P(μ-NTer)]2 towards Lewis acids and bases.

    PubMed

    Hinz, Alexander; Schulz, Axel; Villinger, Alexander

    2016-05-01

    The well-known diphosphadiazane-1,3-diyl [P(μ-NTer)]2 (Ter = 2,6-bis(2,4,6-trimethyl-phenyl)-phenyl) was treated with Lewis bases such as N-heterocyclic carbenes and Lewis acids e.g. gold(i) chloride complexes. In the reaction with the Lewis base, fragmentation of the P2N2 framework was observed, yielding a salt of the type [(NHC)2P](+)[(TerN)2P](-) in a clean reaction. The reaction of [P(μ-NTer)]2 with gold(i) chloride afforded 1 : 1 and 1 : 2 complexes. The dinuclear complex [(ClAu)2P(μ-NTer)2P] displays a bridging P atom between both gold centers, as has been observed for P based zwitterions. PMID:27086655

  18. Lewis-Acid/Base Effects on Gallium Volatility in Molten Chlorides

    SciTech Connect

    Williams, D.F.

    2001-02-26

    It has been proposed that GaCl{sub 3} can be removed by direct volatilization from a Pu-Ga alloy that is dissolved in a molten chloride salt. Although pure GaCl{sub 3} is quite volatile (boiling point, 201 C), the behavior of GaCl{sub 3} dissolved in chloride salts is different due to solution effects and is critically dependent on the composition of the solvent salt (i.e., its Lewis-acid/base character). In this report, the behavior of gallium in prototypical Lewis-acid and Lewis-base salts is compared. It was found that gallium volatility is suppressed in basic melts and enhanced in acidic melts. The implications of these results on the potential for simple gallium removal in molten salt systems are significant.

  19. The NASA Langley building solar project and the supporting Lewis solar technology program

    NASA Technical Reports Server (NTRS)

    Ragsdale, R. G.; Namkoong, D.

    1974-01-01

    The use of solar energy to heat and cool a new office building that is now under construction is reported. Planned for completion in December 1975, the 53,000 square foot, single story building will utilize 15,000 square feet of various types of solar collectors in a test bed to provide nearly all of the heating demand and over half of the air conditioning demand. Drawing on its space-program-developed skills and resources in heat transfer, materials, and systems studies, NASA-Lewis will provide technology support for the Langley building project. A solar energy technology program underway at Lewis includes solar collector testing in an indoor solar simulator facility and in an outdoor test facility, property measurements of solar panel coatings, and operation of a laboratory-scale solar model system test facility. Based on results obtained in this program, NASA-Lewis will select and procure the solar collectors for the Langley test bed.

  20. Lewis Basicity of Nitrogen-Doped Graphite Observed by CO2 Chemisorption.

    PubMed

    Kiuchi, Hisao; Shibuya, Riku; Kondo, Takahiro; Nakamura, Junji; Niwa, Hideharu; Miyawaki, Jun; Kawai, Maki; Oshima, Masaharu; Harada, Yoshihisa

    2016-12-01

    The characteristics of CO2 adsorption sites on a nitrogen-doped graphite model system (N-HOPG) were investigated by X-ray photoelectron and absorption spectroscopy and infrared reflection absorption spectroscopy. Adsorbed CO2 was observed lying flat on N-HOPG, stabilized by a charge transfer from the substrate. This demonstrated that Lewis base sites were formed by the incorporation of nitrogen via low-energy nitrogen-ion sputtering. The possible roles of twofold coordinated pyridinic N and threefold coordinated valley N (graphitic N) sites in Lewis base site formation on N-HOPG are discussed. The presence of these nitrogen species focused on the appropriate interaction strength of CO2 indicates the potential to fine-tune the Lewis basicity of carbon-based catalysts. PMID:26951127