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Sample records for 6-sulfo sialyl lewis

  1. Glycoforms of human endothelial CD34 that bind L-selectin carry sulfated sialyl Lewis x capped O- and N-glycans

    PubMed Central

    Mir, Gerard Hernandez; Helin, Jari; Skarp, Kari-Pekka; Cummings, Richard D.; Mäkitie, Antti; Renkonen, Risto

    2009-01-01

    Endothelial sialomucin CD34 functions as an L-selectin ligand mediating lymphocyte extravasation only when properly glycosylated to express a sulfated carbohydrate epitope, 6-sulfo sialyl Lewis x (6-sulfo SLex). It is thought that multivalent 6-sulfo SLex expression promotes high-affinity binding to L-selectin by enhancing avidity. However, the reported low amount of 6-sulfo SLex in total human CD34 is inconsistent with this model and prompted us to re-evaluate CD34 glycosylation. We separated CD34 into 2 glycoforms, the L-selectin–binding and nonbinding glycoforms, L-B-CD34 and L-NB-CD34, respectively, and analyzed released O- and N-glycans from both forms. L-B-CD34 is relatively minor compared with L-NB-CD34 and represented less than 10% of total tonsillar CD34. MECA-79, a mAb to sulfated core-1 O-glycans, bound exclusively to L-B-CD34 and this form contained all sulfated and fucosylated O-glycans. 6-Sulfo SLex epitopes occur on core-2 and extended core-1 O-glycans with approximately 20% of total L-B-CD34 O-glycans expressing 6-sulfo SLex. N-glycans containing potential 6-sulfo SLex epitopes were also present in L-B-CD34, but their removal did not abolish binding to L-selectin. Thus, a minor glycoform of CD34 carries relatively abundant 6-sulfo SLex epitopes on O-glycans that are important for its recognition by L-selectin. PMID:19359410

  2. Increased expression of sialyl Lewis A and sialyl Lewis X in liver metastases of human colorectal carcinoma.

    PubMed

    Yamada, N; Chung, Y S; Maeda, K; Sawada, T; Ikehara, T; Nishino, H; Okuno, M; Sowa, M

    1995-01-01

    Sialyl Lewis A (SLA) and sialyl Lewis X (SLX) have been shown to be specific ligands for endothelial leukocyte adhesion molecule-1 (ELAM-1), and may be involved in the process of adhesion between cancer cells and endothelium. We used immunohistochemical methods to study the expression of SLA, SLX and CEA in both primary tumors and matched metastatic liver lesions of colorectal carcinomas. Specimens from primary tumors and matched liver metastases from 24 patients with colorectal carcinomas were studied immunohistochemically. The degree of expression of CEA in liver metastases was similar to that in primary tumors, but SLA and SLX were expressed on a larger proportion of tumor cells in liver metastases than in primary tumors. Our findings suggest that colorectal carcinoma cells expressing SLA and/or SLX form metastatic liver tumors. They also suggest that expression of SLA and SLX in primary of colorectal carcinoma can be used as a prognostic indicator of metastasis.

  3. Discovery of sialyl Lewis A and Lewis X modified protein cancer biomarkers using high density antibody arrays

    PubMed Central

    Rho, Jung-hyun; Mead, Judson R.; Wright, W. Shea; Brenner, Dean E.; James, W. Stave; Gildersleeve, Jeffrey C.; Lampe, Paul D.

    2013-01-01

    We report on a high-dimensional method to globally profile glycoproteins that are modified with sialyl Lewis A or Lewis X glycans. Specifically, glycoproteins in serum or plasma are fractionated on a high-density antibody microarray (i.e., each are localized to their specific antibody spot) and are specifically detected via fluorescently labeled anti-sialyl Lewis A or anti- Lewis X antibodies with quantification in a microarray scanner. Non-glycosylated proteins or glycoproteins with other glycan motifs do not interfere with this assay. The whole process is very rapid and applicable for high-throughput screening without the need for purification of glycoproteins from the samples. Using these methods, sialyl Lewis A or Lewis X moieties were found to be expressed on many previously unreported secreted or membrane associated proteins. Furthermore, the combination of sialyl Lewis A or Lewis X content with protein level increased the ability of certain glycoproteins to distinguish 30 patients with stage III and IV colon cancer from 60 control samples. Thus, this highly sensitive method is capable of discovering novel specific glycan modifications on proteins, many of which will likely be useful for disease detection and monitoring. PMID:24185138

  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

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

    2015-06-12

    Sialyl Lewis X (sLe(x)) 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-sLe(x) monoclonal antibodies (mAbs) with mouse tissues. Here, we developed novel anti-sLe(x) mAbs, termed F1 and F2, which react well with both human and mouse sLe(x), by immunizing fucosyltransferase (FucT)-IV and FucT-VII doubly deficient mice with 6-sulfo-sLe(x)-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 sLe(x) as well as 6-sulfo-sLe(x), 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-sLe(x) 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 sLe(x) antigen under physiological and pathological conditions.

  5. Human L-selectin preferentially binds synthetic glycosulfopeptides modeled after endoglycan and containing tyrosine sulfate residues and sialyl Lewis x in core 2 O-glycans

    PubMed Central

    Leppänen, Anne; Parviainen, Ville; Ahola-Iivarinen, Elina; Kalkkinen, Nisse; Cummings, Richard D

    2010-01-01

    Endoglycan is a mucin-like glycoprotein expressed by endothelial cells and some leukocytes and is recognized by L-selectin, a C-type lectin important in leukocyte trafficking and extravasation during inflammation. Here, we show that recombinant L-selectin and human T lymphocytes expressing L-selectin bind to synthetic glycosulfopeptides (GSPs). These synthetic glycosulfopeptides contain 37 amino acid residues modeled after the N-terminus of human endoglycan and contain one or two tyrosine sulfates (TyrSO3) along with a nearby core-2-based Thr-linked O-glycan with sialyl Lewis x (C2-SLex). TyrSO3 at position Y118 was more critical for binding than at Y97. C2-SLex at T124 was required for L-selectin recognition. Interestingly, under similar conditions, neither L-selectin nor T lymphocytes showed appreciable binding to the sulfated carbohydrate epitope 6-sulfo-SLex. P-selectin also bound to endoglycan-based GSPs but with lower affinity than toward GSPs modeled after PSGL-1, the physiological ligand for P- and L-selectin that is expressed on leukocytes. These results demonstrate that TyrSO3 residues in association with a C2-SLex moiety within endoglycan and PSGL-1 are preferentially recognized by L-selectin. PMID:20507883

  6. 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

  7. Expression of the carcinoma markers: the sialylated Lewis A and X carbohydrate antigens in normal laryngeal surface epithelium and submucosal glands from old humans.

    PubMed

    Kirkeby, Svend; Moe, Dennis

    2013-03-01

    Aberrant surface expression of the carbohydrate ABH and Lewis antigens are often used as markers for the diagnosis of cancer, but while the distribution of these histo-blood group antigens is relatively well-described in tissues and organs from young and middle-aged humans little is known of their expression in old age. The objective for this study was to estimate if the Lewis A and X antigens together with their sialylated modifications, are expressed in sections of normal laryngeal tissue from old humans. Antibodies directed against the tumor markers Sialyl Lewis A and Sialyl Lewis X showed positive reaction in the surface epithelia from normal larynx autopsies obtained from people aged 77-90 years. The sialylated and non-sialylated Lewis A antigens were more frequently expressed in the pseudostratified epithelium than in squamous surface epithelium. Both the sialylated and the non-sialylated carbohydrates were stained in the submucosal glands in all the autopsies. In conclusion, visualization of Lewis tumor markers in the larynx should be interpreted with great care, as they may be present in normal laryngeal epithelial cells from old humans.

  8. Sialyl Lewis X mimetics attenuate E-selectin-mediated adhesion of leukocytes to irradiated human endothelial cells.

    PubMed

    Hallahan, D E; Kuchibhotla, J; Wyble, C

    1997-01-01

    Ionizing radiation causes histological changes in normal tissues that resemble those resulting from the inflammatory response. Inflammation is a multistep process requiring expression of adhesion molecules on the surface of endothelial cells which results in leukocyte extravasation. E-selectin is an adhesion molecule that mediates leukocyte "rolling" on the endothelium and is required for the inflammatory response. We quantified E-selectin expression and selectin-dependent adhesion of leukocytes to human endothelial cells after X irradiation to determine whether E-selectin participates in the radiation-mediated inflammation-like response. Immunofluorescence staining of irradiated endothelial cells demonstrated expression of E-selectin on the cell surface similar to that elicited by treatment with interleukin-1 (IL-1). Radiation-mediated expression of E-selectin was dependent on dose and time and occurred at doses as low as 0.5 Gy. Furthermore, the increased adhesion of leukocytes to irradiated endothelial cells was prevented by an E-selectin-blocking antibody. Sialyl Lewis X is one of the molecules on the surface of leukocytes that adheres to E-selectin. The anti-inflammatory agents glycyrrhizin and carminic acid, which are structural analogues of sialyl Lewis X, attenuated adhesion of leukocytes to endothelial cells treated with X rays or IL-1. These data implicate a new class of anti-inflammatory agents in the prevention of adhesions of leukocytes to the irradiated vascular endothelium. PMID:8989368

  9. Total synthesis of trifluorobutyryl-modified, globally protected sialyl Lewis x by a convergent [2+2] approach

    PubMed Central

    Akçay, Gizem; Ramphal, John Y.; d’Alarcao, Marc; Kumar, Krishna

    2014-01-01

    Structural and quantitative changes in the expression of sialic acid residues on the surface of eukaryotic cells profoundly influence a broad range of biological processes including inflammation, antigen recognition, microbial attachment, and tumor metastasis. Uptake and incorporation of sialic acid analogues in mammalian cells enable structure-function studies and perturbation of specific recognition events. Our group has recently shown that a trifluorobutyryl-modified sialic acid metabolite diminishes the adhesion of mammalian cells to E and P-selectin, presumably by leading to the expression of fluorinated sLex epitopes on cell surfaces, and interfering with the sLex-selectin interactions that are well known in mediating tumor cell migration.1 For studies directed towards understanding the molecular basis of this reduced adhesion, chemical synthesis of trifluorobutyrylated sialyl Lewis x (C4F3--sLex) was crucial. We have developed a highly efficient [2+2] approach for the assembly of C4F3-sLex on a preparative scale that contains versatile protective groups allowing the glycan to be surface immobilized or solubilized as needed for biophysical studies to investigate selectin interactions. This strategy can, in principle, be used for preparation of other N-modified sLex analogues. PMID:25530638

  10. Expression of sialyl-Lewis X, an E-selectin ligand, in inflammation, immune processes, and lymphoid tissues.

    PubMed Central

    Munro, J. M.; Lo, S. K.; Corless, C.; Robertson, M. J.; Lee, N. C.; Barnhill, R. L.; Weinberg, D. S.; Bevilacqua, M. P.

    1992-01-01

    The carbohydrate structure sialyl-Lewis X (SLex) can function as a ligand for E-selectin, formerly known as endothelial leukocyte adhesion molecule-1 (ELAM-1). This study was performed to analyze the expression of SLex by leukocytes and other cell types in the context of inflammatory and immune processes. Human peripheral blood cells were examined by flow cytometry using monoclonal antibody CSLEX1 directed against SLex. Cell surface SLex was found in abundance on nearly all isolated polymorphonuclear leukocytes (PMN) and monocytes, and at low levels on a substantial portion (up to 40%) of natural killer cells. This moiety was expressed also on approximately 10% of peripheral blood T cells. Immunohistochemistry was performed on various human tissues involved in inflammatory or immune processes and on secondary lymphoid tissues. In acute appendicitis, endothelial cells of postcapillary venules expressed E-selectin, and most PMN, both within vessels and extravasated, expressed SLex. A substantial number of monocytes/macrophages in inflamed appendiceal, synovial, and dermal tissues also reacted with antibody CSLEX1; however, only rare tissue macrophages in uninflamed nonlymphoid sites showed expression of SLex. These observations are consistent with the concept that SLex on circulating PMN and monocytes functions as a ligand for endothelial E-selectin in the development of inflammatory reactions. SLex-positive lymphocytes also were seen, notably, T lymphocytes in inflamed skin. An unexpected finding was that the CSLEX1 antibody also reacted with venular endothelium in certain lymphoid tissues and in inflamed appendix, but not with endothelium in normal appendix. Whether the SLex antigen identified on endothelium represents de novo expression or passive adsorption remains to be determined. Images Figure 2 Figure 3 Figure 4 Figure 5 PMID:1281620

  11. 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

  12. 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.

  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. [Basic and clinical evaluation of an immunoradiometric competitive inhibition assay for 2----6 sialyl Lewis a antigen--1. Evaluation of assay conditions and normal values].

    PubMed

    Imura, H; Takahashi, T; Matsuda, T; Yoshida, O; Ohkura, H; Seitetsu, Y; Seino, Y; Ishii, M; Kuwabara, M; Ariyoshi, Y

    1989-06-01

    We describe an immunoradiometric competitive inhibition assay of the serum levels of the 2----6 sialyl Lewisa antigen, using "SLA 2-6 Otsuka" kits. The assay required only duplicate 50-microliters samples, and the concentration of 2----6 sialyl Lewisa antigen in serum was determined by reference to a standard curve ranging from 0 to 160 arbitrary U/ml. The intra- and inter-assays reproducibilities were good and analytical recovery of antigen were excellent. The serum levels of the antigen were highly dependent on the Lewis blood types of the tested individuals; i.e., the levels of the antigen in the sera of the Lewisa-b- individuals were significantly lower than those of the antigen obtained with the Lewisa+b- and Lewisa-b+ individuals. The cut-off value (42 U/ml) was obtained as mean + 2SD, which was carefully calculated from the antigen levels in sera of the non-Lewisa-b- individuals.

  15. Lewis(x) and alpha2,3-sialyl glycans and their receptors TAG-1, Contactin, and L1 mediate CD24-dependent neurite outgrowth.

    PubMed

    Lieberoth, Annika; Splittstoesser, Frauke; Katagihallimath, Nainesh; Jakovcevski, Igor; Loers, Gabriele; Ranscht, Barbara; Karagogeos, Domna; Schachner, Melitta; Kleene, Ralf

    2009-05-20

    Although carbohydrates have been implicated in cell interactions in the nervous system, the molecular bases of their functions have remained largely obscure. Here, we show that promotion or inhibition of neurite outgrowth of cerebellar or dorsal root ganglion neurons, respectively, induced by the mucin-type adhesion molecule CD24 depends on alpha2,3-linked sialic acid and Lewis(x) present on glia-specific CD24 glycoforms. Alpha2,3-sialyl residues of CD24 bind to a structural motif in the first fibronectin type III domain of the adhesion molecule L1. Following the observation that the adhesion molecules TAG-1 and Contactin show sequence homologies with fucose-specific lectins, we obtained evidence that TAG-1 and Contactin mediate Lewis(x)-dependent CD24-induced effects on neurite outgrowth. Thus, L1, TAG-1, and Contactin function as lectin-like neuronal receptors. Their cis interactions with neighboring adhesion molecules, e.g., Caspr1 and Caspr2, and with their triggered signal transduction pathways elicit cell type-specific promotion or inhibition of neurite outgrowth induced by glial CD24 in a glycan-dependent trans interaction. PMID:19458237

  16. Increased sialyl Lewis A expression and fucosyltransferase activity with acquisition of a high metastatic capacity in a colon cancer cell line.

    PubMed

    Yamada, N; Chung, Y S; Takatsuka, S; Arimoto, Y; Sawada, T; Dohi, T; Sowa, M

    1997-01-01

    A human colon cancer cell line, OCUC-LM1(LM), was established from a liver metastasis in our laboratory. Intrasplenic injection of LM into nude mice was repeated three and five times, and the daughter cell lines were designated as LM-H3 and LM-H5 respectively. The level of sialyl Lewis A (SLA) in the supernatant of LM-H3 and LM-H5 was 3 and 4.5 times higher than that of LM respectively. Flow cytometric analysis of SLA expression showed that the peak channel for LM was 113; for LM-H3, 126; and for LM-H5, 146. The mean fluorescence intensity of LM was 102.3 +/- 43.5; for LM-H3, 126.2 +/- 28.4; and for LM-H5, 144.8 +/- 23.4. In endothelial cell adhesion assays, the percentages of adherent LM-H3 and LM-H5 cells were significantly higher than for LM. The activity of alpha1-->4 fucosyltransferase was higher in LM-H3 and LM-H5 than in LM, but there was no difference in alpha2-->3 sialyltransferase activities for type 1 chain among the cell lines. Our results suggest that SLA expression is associated with acquisition of a high capacity for liver metastasis of colon cancer; increased SLA expression is due mainly to increased fucosyltransferase activity.

  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. [Basic and clinical evaluation of an immunoradiometric competitive inhibition assay for 2----6 sialyl Lewis a antigen--2. Evaluation of clinical significance].

    PubMed

    Imura, H; Takahashi, T; Matsuda, T; Yoshida, O; Ohkura, H; Seitetsu, Y; Seino, Y; Ishii, M; Kuwabara, M; Ariyoshi, Y

    1989-06-01

    The clinical significance of serum 2----6 sialyl Lewisa antigen was evaluated using "SLA 2----6 Otsuka" kits. Results indicated that the antigen was frequently elevated in sera obtained from patients with various cancers, including pancreas (73%), liver (67%), bilialy tract (66%), uterus (35%), and stomach (33%). Among other tumor markers examined, CA 19-9 (2----3 sialyl Lewisa) had a very similar cancer spectrum as 2----6 sialyl Lewisa. In the sera of patients with malignant disorders of digestive and respiratory organs, including stomach, intestine, pancreas, biliary tract and lung, the serum levels of CA19-9 tended to be higher than those of 2----6 sialyl Lewisa, usually exceeded those of CA19-9. This suggests that the 2----6 sialylation of Lewisa antigen is equally observed in malignant and non-malignant diseases, while the 2----3 sialylation is relatively specific to cancers. As a result, the ratio of the two antigens, CA 19-9: 2----6 sialyl Lewisa antigen ratio, exceeded 2.0 in most of the sera obtained from patients with malignancy, whereas the ratio was below 2.0 in most of patients with corresponding non-malignant diseases of those organs. The determination of the ratio may be clinically useful in the differential diagnosis of the malignant and non-malignant diseases in those organs.

  20. 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

  1. Human Monoclonal Antibodies to Sialyl-Lewis a (CA19.9) with Potent CDC, ADCC and Anti-Tumor Activity

    PubMed Central

    Sawada, Ritsuko; Sun, Shu-Man; Wu, Xiaohong; Hong, Feng; Ragupathi, Govind; Livingston, Philip O.; Scholz, Wolfgang W.

    2011-01-01

    Purpose The carbohydrate antigen sialyl-Lewis A (sLea), also known as CA19.9, is widely expressed on epithelial tumors of the gastrointestinal tract and breast, and on small cell lung cancers. Since over-expression of sLea appears to be a key event in invasion and metastasis of many tumors and results in susceptibility to antibody mediated lysis, sLea is an attractive molecular target for tumor therapy. Experimental Design We generated and characterized fully human monoclonal antibodies (mAbs) from blood lymphocytes from individuals immunized with a sLea –KLH vaccine. Results Several mAbs were selected based on ELISA and FACS including two mAbs with high affinity for sLea (5B1 and 7E3, binding affinities 0.14 nM and 0.04 nM, respectively) and further characterized. Both antibodies were specific for Neu5Acα2-3Galβ1-3(Fucα1-4)GlcNAcβ as determined by glycan array analysis. Complement dependent cytotoxicity against DMS-79 cells was higher for r7E3 (IgM) compared to r5B1 (IgG1), (EC50 0.1 μg/ml vs 1.7 μg/ml). In addition, r5B1 antibodies showed high level ADCC activity on DMS-79 cells with human NK cells or peripheral blood mononuclear cells. To evaluate in vivo efficacy, the antibodies were tested in a xenograft model with Colo205 tumor cells engrafted into SCID mice. Treatment during the first 21 days with 4 doses r5B1 (100 μg/dose) doubled the median survival time to 207 days, and 3/5 animals survived with 6 doses. Conclusion Based on the potential of sLea as a target for immune attack and their affinity, specificity and effector functions, 5B1and 7E3 may have clinical utility. PMID:21343375

  2. 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.

  3. Accumulation of tolerogenic human 6-sulfo LacNAc dendritic cells in renal cell carcinoma is associated with poor prognosis

    PubMed Central

    Toma, Marieta; Wehner, Rebekka; Kloß, Anja; Hübner, Linda; Fodelianaki, Georgia; Erdmann, Kati; Füssel, Susanne; Zastrow, Stefan; Meinhardt, Matthias; Seliger, Barbara; Brech, Dorothee; Noessner, Elfriede; Tonn, Torsten; Schäkel, Knut; Bornhäuser, Martin; Bachmann, Michael P; Wirth, Manfred P; Baretton, Gustavo; Schmitz, Marc

    2015-01-01

    Dendritic cells (DCs) essentially contribute to the induction and regulation of innate and adaptive immunity. Based on these important properties, DCs may profoundly influence tumor progression in patients. However, little is known about the role of distinct human DC subsets in primary tumors and their impact on clinical outcome. In the present study, we investigated the characteristics of human 6-sulfo LacNAc (slan) DCs in clear cell renal cell carcinoma (ccRCC). slanDCs have been shown to display various tumor-directed properties and to accumulate in tumor-draining lymph nodes from patients. When evaluating 263 ccRCC and 227 tumor-free tissue samples, we found increased frequencies of slanDCs in ccRCC tissues compared to tumor-free tissues. slanDCs were also detectable in the majority of 24 metastatic lymph nodes and 67 distant metastases from ccRCC patients. Remarkably, a higher density of slanDCs was significantly associated with a reduced progression-free, tumor-specific or overall survival of ccRCC patients. Tumor-infiltrating slanDCs displayed an immature phenotype expressing interleukin-10. ccRCC cells efficiently impaired slanDC-induced T-cell proliferation and programming as well as natural killer (NK) cell activation. In conclusion, these findings indicate that higher slanDC numbers in ccRCC tissues are associated with poor prognosis. The induction of a tolerogenic phenotype in slanDCs leading to an insufficient activation of innate and adaptive antitumor immunity may represent a novel immune escape mechanism of ccRCC. These observations may have implications for the design of therapeutic strategies that harness tumor-directed functional properties of DCs against ccRCC. PMID:26155414

  4. 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

  5. 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

  6. 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

  7. 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

  8. Deficits in sialylation impair podocyte maturation.

    PubMed

    Weinhold, Birgit; Sellmeier, Melanie; Schaper, Wiebke; Blume, Linda; Philippens, Brigitte; Kats, Elina; Bernard, Ulrike; Galuska, Sebastian P; Geyer, Hildegard; Geyer, Rudolf; Worthmann, Kirstin; Schiffer, Mario; Groos, Stephanie; Gerardy-Schahn, Rita; Münster-Kühnel, Anja K

    2012-08-01

    The role of sialylation in kidney biology is not fully understood. The synthesis of sialoglycoconjugates, which form the outermost structures of animal cells, requires CMP-sialic acid, which is a product of the nuclear enzyme CMAS. We used a knock-in strategy to create a mouse with point mutations in the canonical nuclear localization signal of CMAS, which relocated the enzyme to the cytoplasm of transfected cells without affecting its activity. Although insufficient to prevent nuclear entry in mice, the mutation led to a drastically reduced concentration of nuclear-expressed enzyme. Mice homozygous for the mutation died from kidney failure within 72 hours after birth. The Cmas(nls) mouse exhibited podocyte foot process effacement, absence of slit diaphragms, and massive proteinuria, recapitulating features of nephrin-knockout mice and of patients with Finnish-type congenital nephrotic syndrome. Although the Cmas(nls) mouse displayed normal sialylation in all organs including kidney, a critical shortage of CMP-sialic acid prevented sialylation of nephrin and podocalyxin in the maturing podocyte where it is required during the formation of foot processes. Accordingly, the sialylation defects progressed with time and paralleled the morphologic changes. In summary, sialylation is critical during the development of the glomerular filtration barrier and required for the proper function of nephrin. Whether altered sialylation impairs nephrin function in human disease requires further study.

  9. 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

  10. 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

  11. 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 ...

  12. Lewy bodies

    PubMed Central

    Shults, Clifford W.

    2006-01-01

    Lewy bodies (LB) in the substantia nigra are a cardinal pathological feature of Parkinson's disease, but they occur in a number of neurodegenerative diseases and can be widespread in the nervous system. The characteristics, locations, and composition of LB are reviewed, with particular attention to α-synuclein (α-SYN), which appears to be the major component of LB. The propensity for α-SYN, a presynaptic protein widely expressed in the brain, to aggregate is because of an amyloidogenic central region. The factors that favor the aggregation of α-SYN and mechanisms of toxicity are examined, and a mechanism through which aggregates of α-SYN could induce mitochondrial dysfunction and/or release of proapoptotic molecules is proposed. PMID:16449387

  13. Sialylation regulates brain structure and function

    PubMed Central

    Yoo, Seung-Wan; Motari, Mary G.; Susuki, Keiichiro; Prendergast, Jillian; Mountney, Andrea; Hurtado, Andres; Schnaar, Ronald L.

    2015-01-01

    Every cell expresses a molecularly diverse surface glycan coat (glycocalyx) comprising its interface with its cellular environment. In vertebrates, the terminal sugars of the glycocalyx are often sialic acids, 9-carbon backbone anionic sugars implicated in intermolecular and intercellular interactions. The vertebrate brain is particularly enriched in sialic acid-containing glycolipids termed gangliosides. Human congenital disorders of ganglioside biosynthesis result in paraplegia, epilepsy, and intellectual disability. To better understand sialoglycan functions in the nervous system, we studied brain anatomy, histology, biochemistry, and behavior in mice with engineered mutations in St3gal2 and St3gal3, sialyltransferase genes responsible for terminal sialylation of gangliosides and some glycoproteins. St3gal2/3 double-null mice displayed dysmyelination marked by a 40% reduction in major myelin proteins, 30% fewer myelinated axons, a 33% decrease in myelin thickness, and molecular disruptions at nodes of Ranvier. In part, these changes may be due to dysregulation of ganglioside-mediated oligodendroglial precursor cell proliferation. Neuronal markers were also reduced up to 40%, and hippocampal neurons had smaller dendritic arbors. Young adult St3gal2/3 double-null mice displayed impaired motor coordination, disturbed gait, and profound cognitive disability. Comparisons among sialyltransferase mutant mice provide insights into the functional roles of brain gangliosides and sialoglycoproteins consistent with related human congenital disorders.—Yoo, S.-W., Motari, M. G., Susuki, K., Prendergast, J., Mountney, A., Hurtado, A., Schnaar, R. L. Sialylation regulates brain structure and function. PMID:25846372

  14. Lewy Body Dementia Association

    MedlinePlus

    ... promoting scientific advances. Featured LBD Stories & Tributes Dad's Dementia Journey It's been years since my father passed ... I received an email from the Lewy Body Dementia Association about a benefit... Read Story The Lewy ...

  15. 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 ...

  16. 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 ...

  17. Altered expression of Lewis blood group and related antigens in fetal, normal adult and malignant tissues of the uterine endometrium.

    PubMed

    Inoue, M; Nakayama, M; Tanizawa, O

    1990-01-01

    The expression of the Lewis blood group and its related antigens in fetal, normal adult and malignant tissues of the uterine endometrium was examined immunohistochemically using a panel of mouse monoclonal antibodies with specificities for Lewis-a (La), Sialyl Lewis-a (SLa), Lewis-b (Lb), Lewis-X (LX), Sialyl Lewis-X (SLX) and Lewis-Y (LY) antigens. La, SLa and SLX having one fucose residue were detected in a small number of fetal tissues, while Lb and LY having two fucose residues were found in most cases. In the adult endometrium, expression of Lb and LY was considerably lower than those in fetal tissues, although expression of La and SLa was not different between these two tissues. Expression of LX and SLX was pronounced in adult when compared with fetal tissues. Malignant endometrial glands expressed La, SLa, Lb and LY, extensively, while LX and SLX were expressed less than in normal tissues. Lb and LY can thus be considered oncofetal antigens, extensively expressed in fetal and malignant tissues but not in normal adult tissues. Expression of Lb and LY was greater than that of La and SLA in carcinoma; an increase in the activity of fucose transferase might be associated with malignant transformation in the uterine endometrium.

  18. Novel interactions of complex carbohydrates with peanut (PNA), Ricinus communis (RCA-I), Sambucus nigra (SNA-I) and wheat germ (WGA) agglutinins as revealed by the binding specificities of these lectins towards mucin core-2 O-linked and N-linked glycans and related structures.

    PubMed

    Chandrasekaran, E V; Xue, Jun; Xia, Jie; Khaja, Siraj D; Piskorz, Conrad F; Locke, Robert D; Neelamegham, Sriram; Matta, Khushi L

    2016-10-01

    Plant lectins through their multivalent quaternary structures bind intrinsically flexible oligosaccharides. They recognize fine structural differences in carbohydrates and interact with different sequences in mucin core 2 or complex-type N-glycan chain and also in healthy and malignant tissues. They are used in characterizing cellular and extracellular glycoconjugates modified in pathological processes. We study here, the complex carbohydrate-lectin interactions by determining the effects of substituents in mucin core 2 tetrasaccharide Galβ1-4GlcNAcβ1-6(Galβ1-3)GalNAcα-O-R and fetuin glycopeptides on their binding to agarose-immobilized lectins PNA, RCA-I, SNA-I and WGA. Briefly, in mucin core 2 tetrasaccharide (i) structures modified by α2-3/6-Sialyl LacNAc, LewisX and α1-3-Galactosyl LacNAc resulted in regular binding to PNA whereas compounds with 6-sulfo LacNAc displayed no-binding; (ii) strucures bearing α2-6-sialyl 6-sulfo LacNAc, or 6-sialyl LacdiNAc carbohydrates displayed strong binding to SNA-I; (iii) structures with α2-3/6-sialyl, α1-3Gal LacNAc or LewisX were non-binder to RCA-I and compounds with 6-sulfo LacNAc only displayed weak binding; (iv) structures containing LewisX, 6-Sulfo LewisX, α2-3/6-sialyl LacNAc, α2-3/6-sialyl 6-sulfo LacNAc and GalNAc Lewis-a were non-binding to WGA, those with α1-2Fucosyl, α1-3-Galactosyl LacNAc, α2-3-sialyl T-hapten plus 3'/6'sulfo LacNAc displayed weak binding, and compounds with α2-3-sialyl T-hapten, α2.6-Sialyl LacdiNAc, α2-3-sialyl D-Fucβ1-3 GalNAc and Fucα-1-2 D-Fucβ-1-3GalNAc displaying regular binding and GalNAc LewisX and LacdiNAc plus D-Fuc β-1-3 GalNAcα resulting in tight binding. RCA-I binds Fetuin triantennary asialoglycopeptide 100 % after α-2-3 and 25 % after α-2-6 sialylation, 30 % after α-1-2 and 100 % after α-1-3 fucosylation, and 50 % after α-1-3 galactosylation. WGA binds 3-but not 6-Fucosyl chitobiose core. Thus, information on the influence of complex carbohydrate

  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. Post-conversion sialylation of prions in lymphoid tissues.

    PubMed

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

    2015-12-01

    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 (PrP(Sc)) changes with colonization of secondary lymphoid organs (SLOs). As a result, spleen-derived PrP(Sc) is more sialylated than brain-derived PrP(Sc). Enhanced sialylation of PrP(Sc) is recapitulated in vitro by incubating brain-derived PrP(Sc) 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 PrP(Sc). 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

  1. 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

  2. Human synovial lubricin expresses sialyl Lewis x determinant and has L-selectin ligand activity.

    PubMed

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

    2012-10-19

    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.

  3. 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…

  4. Carbohydrate antigen expression in primary tumors, metastatic lesions, and serous effusions from patients diagnosed with epithelial ovarian carcinoma: evidence of up-regulated Tn and Sialyl Tn antigen expression in effusions.

    PubMed

    Davidson, B; Berner, A; Nesland, J M; Risberg, B; Kristensen, G B; Tropé, C G; Bryne, M

    2000-09-01

    The object of this study was the investigation of carbohydrate antigen expression in malignant epithelial cells and benign mesothelial cells in serous effusions from patients diagnosed with epithelial ovarian carcinomas. In addition, to compare antigen expression in carcinoma cells in effusions with those of corresponding primary tumors and metastatic lesions. Sections from 63 malignant effusions from ovarian carcinoma patients and 15 reactive effusions were immunohistochemically stained, using 5 monoclonal antibodies for Lewis(y), Sialyl Lewis(x), Tn, and Sialyl Tn antigens. Tissue sections (n = 97) from corresponding primary ovarian carcinomas and metastatic lesions, as well as from 12 malignant mesotheliomas, were additionally stained using the above panel. Staining for the 4 antigens was seen in carcinoma cells in serous effusions in the majority of cases (range = 71% to 85%). In contrast, immunoreactivity was detected in mesothelial cells in only 6% to 23% of the specimens studied (P < .001 for all 5 markers). With the exception of B3 antibody against Lewis(y) antigen, malignant mesotheliomas stained negative, infrequently showing focal immunoreactivity. An up-regulation of Tn and Sialyl Tn expression was detected in carcinoma cells in effusions when compared with both primary tumors (P < .003 and P < .007, respectively) and metastatic lesions (P < .034 and .041, respectively). Cancer-associated carbohydrate antigens can thus be used as an adjunct in the differentiation between malignant epithelial and reactive mesothelial cells. Ovarian carcinoma cells in effusions show up-regulation of Tn and Sialyl Tn, possibly representing a transient phenotypic alteration facilitating metastasis. PMID:11014575

  5. Reversible sialylation: synthesis of cytidine 5'-monophospho-N-acetylneuraminic acid from cytidine 5'-monophosphate with alpha2,3-sialyl O-glycan-, glycolipid-, and macromolecule-based donors yields diverse sialylated products.

    PubMed

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

    2008-01-01

    Sialyltransferases transfer sialic acid from cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NeuAc) to an acceptor molecule. Trans-sialidases of parasites transfer alpha2,3-linked sialic acid from one molecule to another without the involvement of CMP-NeuAc. Here we report another type of sialylation, termed reverse sialylation, catalyzed by mammalian sialyltransferase ST3Gal-II. This enzyme synthesizes CMP-NeuAc by transferring NeuAc from the NeuAcalpha2,3Galbeta1,3GalNAcalpha unit of O-glycans, 3-sialyl globo unit of glycolipids, and sialylated macromolecules to 5'-CMP. CMP-NeuAc produced in situ is utilized by the same enzyme to sialylate other O-glycans and by other sialyltransferases such as ST6Gal-I and ST6GalNAc-I, forming alpha2,6-sialylated compounds. ST3Gal-II also catalyzed the conversion of 5'-uridine monophosphate (UMP) to UMP-NeuAc, which was found to be an inactive sialyl donor. Reverse sialylation proceeded without the need for free sialic acid, divalent metal ions, or energy. Direct sialylation with CMP-NeuAc as well as the formation of CMP-NeuAc from 5'-CMP had a wide optimum range (pH 5.2-7.2 and 4.8-6.4, respectively), whereas the entire reaction comprising in situ production of CMP-NeuAc and sialylation of acceptor had a sharp optimum at pH 5.6 (activity level 50% at pH 5.2 and 6.8, 25% at pH 4.8 and 7.2). Several properties distinguish forward/conventional versus reverse sialylation: (i) sodium citrate inhibited forward sialylation but not reverse sialylation; (ii) 5'-CDP, a potent forward sialyltransferase inhibitor, did not inhibit the conversion of 5'-CMP to CMP-NeuAc; and (iii) the mucin core 2 compound 3-O-sulfoGalbeta1,4GlcNAcbeta1,6(Galbeta1,3)GalNAcalpha-O-benzyl, an efficient acceptor for ST3Gal-II, inhibited the conversion of 5'-CMP to CMP-NeuAc. A significant level of reverse sialylation activity is noted in human prostate cancer cell lines LNCaP and PC3. Overall, the study demonstrates that the sialyltransferase reaction is

  6. 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

  7. Production of Highly Sialylated Recombinant Glycoproteins Using Ricinus communis Agglutinin-I-Resistant CHO Glycosylation Mutants.

    PubMed

    Goh, John S Y; Chan, Kah Fai; Song, Zhiwei

    2015-01-01

    The degree of sialylation of therapeutic glycoproteins affects its circulatory half-life and efficacy because incompletely sialylated glycoproteins are cleared from circulation by asialoglycoprotein receptors present in the liver cells. Mammalian expression systems, often employed in the production of these glycoprotein drugs, produce heterogeneously sialylated products. Here, we describe how to produce highly sialylated glycoproteins using a Chinese hamster ovary (CHO) cell glycosylation mutant called CHO-gmt4 with human erythropoietin (EPO) as a model glycoprotein. The protocol describes how to isolate and characterize the CHO glycosylation mutants and how to assess the sialylation of the recombinant protein using isoelectric focusing (IEF). It further describes how to inactivate the dihydrofolate reductase (DHFR) gene in these cells using zinc finger nuclease (ZFN) technology to enable gene amplification and the generation of stable cell lines producing highly sialylated EPO.

  8. 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

  9. Sialylation regulates peripheral tolerance in CD4+ T cells.

    PubMed

    Brennan, Patrick J; Saouaf, Sandra J; Van Dyken, Steve; Marth, Jamey D; Li, Bin; Bhandoola, Avinash; Greene, Mark I

    2006-05-01

    Decreased binding by the 6C10 auto-antibody serves as a unique marker for CD4+ T cell unresponsiveness after the induction of T cell tolerance in Vbeta8.1 TCR transgenic mice. We further define the nature of the epitope recognized by the 6C10 antibody to be a subset of Thy-1 bearing incompletely sialylated N-linked glycans, and furthermore, we demonstrate that tolerant CD4+ T cells have an increased degree of cell-surface sialylation. To test the significance of the altered glycosylation state identified by the 6C10 auto-antibody in the tolerant CD4+ T cell population, surface sialic acid was cleaved enzymatically. Treatment of purified peripheral CD4+ T cells with Vibrio cholerae sialidase (VCS) leads to increased 6C10 binding, significantly enhances proliferation in the tolerant CD4+ population and corrects defects in phosphotyrosine signaling observed in the tolerant CD4+ T cell. Furthermore, in vivo administration of VCS enhances proliferation in both tolerant and naive CD4+ T cell subsets. These studies suggest that sialylation of glycoproteins on the surface of the CD4+ T cell contributes to the regulation of T cell responsiveness in the tolerant state. PMID:16291658

  10. 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

  11. 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

  12. 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 ...

  13. Postnatal changes in sialylation of glycoproteins in rat liver.

    PubMed Central

    Oda-Tamai, S; Kato, S; Akamatsu, N

    1991-01-01

    Glycoproteins containing N-linked oligosaccharides were prepared from plasma and liver microsomes of rats aged 0-5 weeks, and galactose and sialic acid content were determined. The sialic acid/galactose ratios in plasma membrane N-glycans remained at about 1 throughout the postnatal period, suggesting that most of the galactose residues are sialylated. In the same way, it was suggested that most of the galactose residues of microsomal N-glycans were sialylated at 0, 4 and 5 weeks of age, but that the degree of sialylation was lower at the other ages, with a minimum at 2 weeks. When the activities of sialyltransferase and galactosyltransferase in liver Golgi membranes were determined, age-dependent changes were found, not only in the specific activities of the enzymes, but also in the Golgi membrane content per g of liver. The activity of galactosyltransferase per g of liver increased immediately after birth, whereas that of sialyltransferase remained at a low level for 2 weeks and then increased to a constant level at 4 weeks. It is probable that this delayed increase in the activity of sialyltransferase results in the decreased sialylation of microsomal N-glycans at 1, 2 and 3 weeks. Sialyltransferase was solubilized from the liver microsomes of rats aged 2, 3 and 4 weeks and characterized. Phosphocellulose column chromatography separated the activity into two subfractions, designated transferase I and transferase II in the order of elution. The increase in total sialyltransferase activity during this period was caused mainly by an increase in transferase I. Rechromatography of each transferase from 3-week-old rats after neuraminidase treatment showed that transferase I but not transferase II contained sialic acid residue(s) and that desialylated transferase I was eluted in a similar way as transferase II. Although the apparent Km value for CMP-N-acetylneuraminic acid and the heat stability of transferase I were different from those of transferase II, the

  14. Rediscovering Lewis and Clark.

    ERIC Educational Resources Information Center

    Large, Arlen

    1994-01-01

    Discusses the efforts of the Lewis and Clark expedition to conduct what amounted to the first national biological survey. A sidebar examines current U.S. Department of Interior plans to create the National Biological Survey to record every species of plant and animal in the country. (LZ)

  15. 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

  16. Differences in sialyl-Tn antigen expression between keratoacanthomas and cutaneous squamous cell carcinomas.

    PubMed

    Jensen, P; Clausen, O P; Bryne, M

    1999-04-01

    Keratoacanthoma and squamous cell carcinoma are common skin tumors, especially in immunosuppressed transplant recipients, but the distinction between these two types of epidermal neoplasia may be difficult. Sialyl-Tn (Sia-GalNAc-O-Ser/Thr) is a cell surface carbohydrate associated with hyperplasia in squamous epithelium, and correlated with poor prognosis in several human adenocarcinomas. Twenty-seven keratoacanthomas and 29 cutaneous squamous cell carcinomas were examined for the expression of sialyl-Tn and of the Ki67 epitope, the latter a marker for cell proliferation. By immunohistochemistry, basaloid tumor cells at the periphery of tumor nests showed some degree of sialyl-Tn expression in 16 keratoacanthomas (59%), while only three squamous cell carcinomas (10%) showed sialyl-Tn-positive basaloid tumor cells (p<0.001). Keratinized, differentiated tumor cells were more often sialyl-Tn-positive in keratoacanthomas (89%) than in squamous cell carcinomas (31%) (p<0.001). A striking sialyl-Tn-positivity in the basal cell layer was found in a border zone directly adjacent to most tumors of both types (88 and 88%). By immunohistochemical examination of parallel sections and by double immunofluorescence, sialyl-Tn antigen expression was primarily seen in cells that did not express Ki67, although some overlap was present. Keratoacanthomas from transplant recipients did not differ in sialyl-Tn expression compared to those from non-immunosuppressed patients. The results indicate that sialyl-Tn expression is not directly related to cell proliferation, but rather to cellular features of post-mitotic cells, and that sialyl-Tn is not associated with a malignant phenotype. Sialyl-Tn may be linked to tumor regression, as seen in keratoacanthomas. PMID:10335895

  17. Identification of sialylated glycoproteins in Doxorubicin-treated hepatoma cells with glycoproteomic analyses.

    PubMed

    Azuma, Kanako; Serada, Satoshi; Takamatsu, Shinji; Terao, Naoko; Takeishi, Shunsaku; Kamada, Yoshihiro; Naka, Tetsuji; Miyoshi, Eiji

    2014-11-01

    Sialylation is one of the most important types of glycosylation involved in carcinogenesis and establishment of cancer stemness. We previously showed that increased sialylation is a characteristic glycan change in cancer stem cells (CSCs) from hepatocellular carcinoma. However, the identities of glycoproteins targeted for sialylation remain unknown. In the present study, we identified glycoproteins targeted for sialylation in doxorubicin (DXR)-treated hepatocarcinoma cell line, Huh7, using glycoproteomic analyses. Since CSCs constitute a small subset of cells within carcinoma cell lines, it is difficult to identify sialylated proteins using general glycoproteomic strategies. It is known that treatment with anticancer drug can condense CSCs, we used DXR to concentrate CSCs. In DXR-treated Huh7 cells, isobaric tag for relative and absolute quantitation (iTRAQ) analysis identified 17 sialylated glycoproteins. Most of the identified glycoproteins were cancer-associated proteins. Furthermore, two proteins of approximately 70 kDa were detected using Sambucus sieboldoana agglutinin (SSA) blot analysis and identified as beta-galactosidase and alpha-2-HS-glycoprotein (fetuin-A) by SSA precipitation followed by liquid chromatography-tandem mass spectrometry analyses. Sialylation levels of fetuin-A were increased in DXR-treated Huh7 cell lysates. These changes in sialylation of glycoproteins might be involved in the establishment of cancer stemness.

  18. 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

  19. 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

  20. A high-throughput capillary isoelectric focusing immunoassay for fingerprinting protein sialylation.

    PubMed

    Markely, Lam Raga Anggara; Cheung, Lila; Choi, Young Jun; Ryll, Thomas; Estes, Scott; Prajapati, Shashi; Turyan, Iva; Frenkel, Ruth; Sosic, Zoran; Lambropoulos, James; Tescione, Lia; Ryll, Thomas; Berman, Melissa

    2016-01-01

    The serum half-life, biological activity, and solubility of many recombinant glycoproteins depend on their sialylation. Monitoring glycoprotein sialylation during cell culture manufacturing is, therefore, critical to ensure product efficacy and safety. Here a high-throughput method for semi-quantitative fingerprinting of glycoprotein sialylation using capillary isoelectric focusing immunoassay on NanoPro (Protein Simple) platform was developed. The method was specific, sensitive, precise, and robust. It could analyze 2 μL of crude cell culture samples without protein purification, and could automatically analyze from 8 samples in 4 h to 96 samples in 14 h without analyst supervision. Furthermore, its capability to detect various changes in sialylation fingerprints during cell culture manufacturing process was indispensable to ensure process robustness and consistency. Moreover, the changes in the sialylation fingerprints analyzed by this method showed strong correlations with intact mass analysis using liquid chromatography and mass spectrometry. PMID:26588060

  1. 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

  2. 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.

  3. A Pasteurella multocida sialyltransferase displaying dual trans-sialidase activities for production of 3'-sialyl and 6'-sialyl glycans.

    PubMed

    Guo, Yao; Jers, Carsten; Meyer, Anne S; Arnous, Anis; Li, Haiying; Kirpekar, Finn; Mikkelsen, Jørn D

    2014-01-20

    This study examined a recombinant Pasteurella multocida sialyltransferase exhibiting dual trans-sialidase activities. The enzyme catalyzed trans-sialylation using either 2-O-(p-nitrophenyl)-α-d-N-acetylneuraminic acid or casein glycomacropeptide (whey protein) as the sialyl donor and lactose as the acceptor, resulting in production of both 3'-sialyllactose and 6'-sialyllactose. This is the first study reporting α-2,6-trans-sialidase activity of this sialyltransferase (EC 2.4.99.1 and 2.4.99.4). A response surface design was used to evaluate the effects of three reaction parameters (pH, temperature, and lactose concentration) on enzymatic production of 3'- and 6'-sialyllactoses using 5% (w/v) casein glycomacropeptide (equivalent to 9mM bound sialic acid) as the donor. The maximum yield of 3'-sialyllactose (2.75±0.35mM) was achieved at a reaction condition with pH 6.4, 40°C, 100mM lactose after 6h; and the largest concentration of 6'-sialyllactose (3.33±0.38mM) was achieved under a condition with pH 5.4, 40°C, 100mM lactose after 8h. 6'-sialyllactose was presumably formed from α-2,3 bound sialic acid in the casein glycomacropeptide as well as from 3'-sialyllactose produced in the reaction. The kcat/Km value for the enzyme using 3'-sialyllactose as the donor for 6'-sialyllactose synthesis at pH 5.4 and 40°C was determined to be 23.22±0.7M(-1)s(-1). Moreover, the enzyme was capable of catalyzing the synthesis of both 3'- and 6'-sialylated galactooligosaccharides, when galactooligosaccharides served as acceptors.

  4. Meriwether Lewis: was it suicide?

    PubMed

    Westefeld, John S; Less, Aaron

    2004-01-01

    Even 200 years following the conclusion of the Lewis and Clark Expedition, questions remain about whether Meriwether Lewis' death was a suicide. The purpose of this article is to consider this issue by examining historical evidence from a psychological perspective. A risk factor model for suicide assessment (Sanchez, 2001) is employed to evaluate the nature of Lewis' historical, personal, psychosocial environmental, and clinical risk factors as well as protective factors. The authors conclude that though there is some evidence to support a theory of murder, Lewis was at a high suicide risk at the time of his death, and that the preponderance of the evidence indicates that he died by his own hand.

  5. Lewis base activation of Lewis acids: development of a Lewis base catalyzed selenolactonization.

    PubMed

    Denmark, Scott E; Collins, William R

    2007-09-13

    The concept of Lewis base activation of Lewis acids has been applied to the selenolactonization reaction. Through the use of substoichiometric amounts of Lewis bases with "soft" donor atoms (S, Se, P) significant rate enhancements over the background reaction are seen. Preliminary mechanistic investigations have revealed the resting state of the catalyst as well as the significance of a weak Brønsted acid promoter.

  6. Association of IgA secretory component sialylation with leucocytospermia of infertile men - a pilot study.

    PubMed

    Kratz, E M; Ferens-Sieczkowska, M

    2014-12-01

    The aim of our pilot study was to check whether the differences in IgA secretory component (SC) sialylation are associated with leucocytospermia. In normozoospermic and leucocytospermic seminal plasmas, 78-kDa and 63-kDa SC immunoreactive bands were observed. The SC sialylation was analysed by lectin blotting, using sialo-specific lectins MAA (Maackia amurensis agglutinin) and SNA (Sambucus nigra agglutinin). Specific reactivity of 63-kDa SC with MAA and SNA was higher than 78-kDa SC in both analysed seminal groups. The analysis of seminal SC sialylation might be a valuable diagnosis tools for the evaluation of fertility problems related with leucocytospermia.

  7. Evidence for sialylated type 1 blood group chains on human erythrocyte membranes revealed by agglutination of neuraminidase-treated erythrocytes with Waldenström's macroglobulin IgMWOO and hybridoma antibody FC 10.2.

    PubMed

    Picard, J K; Loveday, D; Feizi, T

    1985-01-01

    Haemagglutination studies have been performed with untreated and neuraminidase-treated human erythrocytes of the three Lewis antigen types Le(a-b-), Le(a+b-) and Le(a-b+) using two monoclonal antibodies, IgMWOO and FC 10.2, which were previously shown to recognize the type 1 based blood group chains: Gal beta 1----3GlcNAc beta 1----3Gal beta 1----4Glc/GlcNAc (for explanation of abbreviations see table IV legend). Both antibodies behaved as cold agglutinins with neuraminidase-treated but not with untreated erythrocytes of the three Lewis antigen types. Neuraminidase-treated erythrocytes of i antigen type were similarly agglutinated. This haemagglutination was specifically inhibited by the type 1 based milk oligosaccharide lacto-N-tetraose. Thus, there is strong evidence for the occurrence of sialylated type 1 chains on human erythrocyte membranes of I and i antigen types. In addition, evidence for the presence of type 1 chains which are both sialylated and fucosylated was obtained by (1) haemagglutination of Le(a+b-) erythrocytes with the monoclonal antibody 19.9; (2) increased haemagglutination of neuraminidase-treated erythrocytes with anti-H antibodies of Bombay serum; (3) increased haemagglutination of neuraminidase-treated Le(a+b-) cells with anti-Lea antibodies, and (4) the appearance of Lea antigen activity on neuraminidase-treated erythrocytes of Le(a-b+) type.

  8. Meriwether Lewis: Was it Suicide?

    ERIC Educational Resources Information Center

    Westefeld, John S.; Less, Aaron

    2004-01-01

    Even 200 years following the conclusion of the Lewis and Clark Expedition, questions remain about whether Meriwether Lewis' death was a suicide. The purpose of this article is to consider this issue by examining historical evidence from a psychological perspective. A risk factor model for suicide assessment (Sanchez, 2001) is employed to evaluate…

  9. 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.

  10. The Uncontrolled Sialylation is Related to Chemoresistant Metastatic Breast Cancer.

    PubMed

    Roncati, Luca; Barbolini, Giuseppe; Gatti, Antonietta Morena; Pusiol, Teresa; Piscioli, Francesco; Maiorana, Antonio

    2016-10-01

    Among the scientific communities, there is a convergence of results supporting a direct relationship between dysregulated sialylation and poor prognosis in many human cancers. For this reason, we have retrospectively investigated 169 cases of invasive ductal carcinoma of the breast, coming from female patients aged between 31 and 76 years old. The whole series was subdivided into two prognostic groups: the first group consisted of 138 patients, who showed a post-treatment survival time more than 5 years, while the second group was made up by 31 patients, died within 5 years despite of chemotherapy. All the surgical specimens were fixed in 10 % neutral buffered formalin, paraffin embedded and, then, submitted to routinely haematoxylin/eosin staining and to a further histochemical (Alcian Blue, DDD-Fast Blue B, Mercury Orange), immunohistochemical (ST3GAL5 sialyltransferase, Ki67, c-erbB2, ER, PR) and chemico-elemental characterization. In the 31 cases of breast cancer belonging to the second group, an overexpression of sialomucins and sialyltransferases has been detected. Our results lead us to support that in aggressive chemoresistant breast cancers, the altered expression of sialic acid, due to an uncontrolled sialylation, creates an excessive negative charge on cell membranes, which stimulates repulsion between neoplastic cells and their subsequent access into the blood stream. This event implies an early metastatization and a rapid disease progression with fatal outcome. The early application of Alcian Blue stain on diagnostic biopsies of breast cancer is able to cheaply reveal the sialomucin accumulations, providing for the disease course. PMID:27037559

  11. [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

  12. Sialyl-lactotetra, a novel cell surface marker of undifferentiated human pluripotent stem cells.

    PubMed

    Barone, Angela; Säljö, Karin; Benktander, John; Blomqvist, Maria; Månsson, Jan-Eric; Johansson, Bengt R; Mölne, Johan; Aspegren, Anders; Björquist, Petter; Breimer, Michael E; Teneberg, Susann

    2014-07-01

    Cell surface glycoconjugates are used as markers for undifferentiated pluripotent stem cells. Here, antibody binding and mass spectrometry characterization of acid glycosphingolipids isolated from a large number (1 × 10(9) cells) of human embryonic stem cell (hESC) lines allowed identification of several novel acid glycosphingolipids, like the gangliosides sialyl-lactotetraosylceramide and sialyl-globotetraosylceramide, and the sulfated glycosphingolipids sulfatide, sulf-lactosylceramide, and sulf-globopentaosylceramide. A high cell surface expression of sialyl-lactotetra on hESC and human induced pluripotent stem cells (hiPSC) was demonstrated by flow cytometry, immunohistochemistry, and electron microscopy, whereas sulfated glycosphingolipids were only found in intracellular compartments. Immunohistochemistry showed distinct cell surface anti-sialyl-lactotetra staining on all seven hESC lines and three hiPSC lines analyzed, whereas no staining of hESC-derived hepatocyte-like or cardiomyocyte-like cells was obtained. Upon differentiation of hiPSC into hepatocyte-like cells, the sialyl-lactotetra epitope was rapidly down-regulated and not detectable after 14 days. These findings identify sialyl-lactotetra as a promising marker of undifferentiated human pluripotent stem cells.

  13. Sialyl-lactotetra, a Novel Cell Surface Marker of Undifferentiated Human Pluripotent Stem Cells*

    PubMed Central

    Barone, Angela; Säljö, Karin; Benktander, John; Blomqvist, Maria; Månsson, Jan-Eric; Johansson, Bengt R.; Mölne, Johan; Aspegren, Anders; Björquist, Petter; Breimer, Michael E.; Teneberg, Susann

    2014-01-01

    Cell surface glycoconjugates are used as markers for undifferentiated pluripotent stem cells. Here, antibody binding and mass spectrometry characterization of acid glycosphingolipids isolated from a large number (1 × 109 cells) of human embryonic stem cell (hESC) lines allowed identification of several novel acid glycosphingolipids, like the gangliosides sialyl-lactotetraosylceramide and sialyl-globotetraosylceramide, and the sulfated glycosphingolipids sulfatide, sulf-lactosylceramide, and sulf-globopentaosylceramide. A high cell surface expression of sialyl-lactotetra on hESC and human induced pluripotent stem cells (hiPSC) was demonstrated by flow cytometry, immunohistochemistry, and electron microscopy, whereas sulfated glycosphingolipids were only found in intracellular compartments. Immunohistochemistry showed distinct cell surface anti-sialyl-lactotetra staining on all seven hESC lines and three hiPSC lines analyzed, whereas no staining of hESC-derived hepatocyte-like or cardiomyocyte-like cells was obtained. Upon differentiation of hiPSC into hepatocyte-like cells, the sialyl-lactotetra epitope was rapidly down-regulated and not detectable after 14 days. These findings identify sialyl-lactotetra as a promising marker of undifferentiated human pluripotent stem cells. PMID:24841197

  14. Meriwether Lewis: was it suicide?

    PubMed

    Westefeld, John S; Less, Aaron

    2004-01-01

    Even 200 years following the conclusion of the Lewis and Clark Expedition, questions remain about whether Meriwether Lewis' death was a suicide. The purpose of this article is to consider this issue by examining historical evidence from a psychological perspective. A risk factor model for suicide assessment (Sanchez, 2001) is employed to evaluate the nature of Lewis' historical, personal, psychosocial environmental, and clinical risk factors as well as protective factors. The authors conclude that though there is some evidence to support a theory of murder, Lewis was at a high suicide risk at the time of his death, and that the preponderance of the evidence indicates that he died by his own hand. PMID:15385176

  15. 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

  16. SabA Is the H. pylori Hemagglutinin and Is Polymorphic in Binding to Sialylated Glycans

    PubMed Central

    Nordén, Jenny; Sondén, Berit; Lundberg, Carina; Sjöström, Rolf; Altraja, Siiri; Odenbreit, Stefan; Haas, Rainer; Wadström, Torkel; Engstrand, Lars; Semino-Mora, Cristina; Liu, Hui; Dubois, André; Teneberg, Susann; Arnqvist, Anna; Borén, Thomas

    2006-01-01

    Adherence of Helicobacter pylori to inflamed gastric mucosa is dependent on the sialic acid–binding adhesin (SabA) and cognate sialylated/fucosylated glycans on the host cell surface. By in situ hybridization, H. pylori bacteria were observed in close association with erythrocytes in capillaries and post-capillary venules of the lamina propria of gastric mucosa in both infected humans and Rhesus monkeys. In vivo adherence of H. pylori to erythrocytes may require molecular mechanisms similar to the sialic acid–dependent in vitro agglutination of erythrocytes (i.e., sialic acid–dependent hemagglutination). In this context, the SabA adhesin was identified as the sialic acid–dependent hemagglutinin based on sialidase-sensitive hemagglutination, binding assays with sialylated glycoconjugates, and analysis of a series of isogenic sabA deletion mutants. The topographic presentation of binding sites for SabA on the erythrocyte membrane was mapped to gangliosides with extended core chains. However, receptor mapping revealed that the NeuAcα2–3Gal-disaccharide constitutes the minimal sialylated binding epitope required for SabA binding. Furthermore, clinical isolates demonstrated polymorphism in sialyl binding and complementation analysis of sabA mutants demonstrated that polymorphism in sialyl binding is an inherent property of the SabA protein itself. Gastric inflammation is associated with periodic changes in the composition of mucosal sialylation patterns. We suggest that dynamic adaptation in sialyl-binding properties during persistent infection specializes H. pylori both for individual variation in mucosal glycosylation and tropism for local areas of inflamed and/or dysplastic tissue. PMID:17121461

  17. Production of α2,6-sialylated IgG1 in CHO cells

    PubMed Central

    Raymond, Céline; Robotham, Anna; Spearman, Maureen; Butler, Michael; Kelly, John; Durocher, Yves

    2015-01-01

    The presence of α2,6-sialic acids on the Fc N-glycan provides anti-inflammatory properties to the IgGs through a mechanism that remains unclear. Fc-sialylated IgGs are rare in humans as well as in industrial host cell lines such as Chinese hamster ovary (CHO) cells. Facilitated access to well-characterized α2,6-sialylated IgGs would help elucidate the mechanism of this intriguing IgG's effector function. This study presents a method for the efficient Fc glycan α2,6-sialylation of a wild-type and a F243A IgG1 mutant by transient co-expression with the human α2,6-sialyltransferase 1 (ST6) and β1,4-galactosyltransferase 1 (GT) in CHO cells. Overexpression of ST6 alone only had a moderate effect on the glycoprofiles, whereas GT alone greatly enhanced Fc-galactosylation, but not sialylation. Overexpression of both GT and ST6 was necessary to obtain a glycoprofile dominated by α2,6-sialylated glycans in both antibodies. The wild-type was composed of the G2FS(6)1 glycan (38%) with remaining unsialylated glycans, while the mutant glycoprofile was essentially composed of G2FS(6)1 (25%), G2FS(3,6)2 (16%) and G2FS(6,6)2 (37%). The α2,6-linked sialic acids represented over 85% of all sialic acids in both antibodies. We discuss how the limited sialylation level in the wild-type IgG1 expressed alone or with GT results from the glycan interaction with Fc's amino acid residues or from intrinsic galactosyl- and sialyl-transferases substrate specificities. PMID:25875452

  18. 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

  19. Sialylation is modulated through maturation in hemocytes from Macrobrachium rosenbergii.

    PubMed

    Sierra, C; Guevara, J; Lascurain, R; Pérez, A; Agundis, C; Zenteno, E; Vázquez, L

    2001-10-01

    In this work we identified in adult and juvenile freshwater prawn, Macrobrachium rosenbergii, three major type of circulating hemocytes: fusiform; rounded; and large ovoid hemocytes. Rounded and large hemocytes represent the first defense line, since this type of cells exerts phagocytic activity as well as lectin synthesis. Considering that glycosylation plays important roles in cell communication and as a target for pathogenic microorganisms, in this report was also described the main glycosidic modifications that occur in the large and rounded hemocytes from the freshwater prawn during maturation as determined with lectins. Neu5Acalpha2,6Gal, was identified homogeneously distributed in the membrane in 90% of hemocytes from juvenile organisms. Maturation of the freshwater prawn induced a decrease or complete loss of Neu5Acalpha2,6Gal residues that were replaced with Neu5Acalpha2,3 molecules in practically all hemocytes from adult organisms. This change was paralleled by a diminution in 9-O-acetyl-neuraminic acid (Neu5,9Ac(2)) expression. T and Tn antigens (Galbetal,3 GalNAcalpha1-0-Ser/Thr or GalNAcalpha1-0-Ser/Thr, respectively), as well as N-glycosidically linked glycans, seem to be highly conserved throughout maturation. Our results show that sialylation of freshwater prawn hemocytes is modulated throughout the maturation process.

  20. 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.

  1. 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

  2. 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.

  3. The trans-sialidase from Trypanosoma cruzi triggers apoptosis by target cell sialylation.

    PubMed

    Mucci, Juan; Risso, Marikena G; Leguizamón, M Susana; Frasch, Alberto C C; Campetella, Oscar

    2006-07-01

    The trans-sialidase, a modified sialidase that transfers sialyl residues among macromolecules, is a unique enzymatic activity expressed by some parasitic trypanosomes being essential for their survival in the mammalian host and/or in the insect vector. The enzyme from Trypanosoma cruzi, the agent of Chagas disease, is found in blood and able to act far from the infection site by inducing apoptosis in cells from the immune system. A central and still unsolved question is whether trans-sialidase-mediated addition or removal of sialic acid to/from host acceptor molecules is the event associated with the apoptosis induced by the enzyme. Here we show that lactitol, a competitive inhibitor that precluded the transference of the sialyl residue to endogenous acceptors but not the hydrolase activity of the enzyme, prevented ex vivo and in vivo the apoptosis caused by the trans-sialidase. By lectin histochemistry, the transference of sialyl residue to the cell surface was demonstrated in vivo and found associated with the apoptosis induction. The sialylation of the CD43 mucin, a key molecule involved in trans-sialidase-apoptotic process, was readily detected and also prevented by lactitol on thymocytes. Therefore, lesions induced by trans-sialidase on the immune system are due to the sialylation of endogenous acceptor molecules. PMID:16819962

  4. 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

  5. Linear synthesis and immunological properties of a fully synthetic vaccine candidate containing a sialylated MUC1 glycopeptide†

    PubMed Central

    Thompson, Pamela; Lakshminarayanan, Vani; Supekar, Nitin T.; Bradley, Judy M.; Cohen, Peter A.; Wolfert, Margreet A.

    2015-01-01

    A strategy for the linear synthesis of a sialylated glycolipopeptide cancer vaccine candidate has been developed using a strategically designed sialyl-Tn building block and microwave-assisted solid-phase peptide synthesis. The glycolipopeptide elicited potent humoral and cellular immune responses. T-cells primed by such a vaccine candidate could be restimulated by tumor-associated MUC1. PMID:26022217

  6. 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.

  7. 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

  8. 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.

  9. Lewis Structure Skills: Taxonomy and Difficulty Levels.

    ERIC Educational Resources Information Center

    Brady, Joseph A.; And Others

    1990-01-01

    Discussed is the performance of college students on the task of solving chemistry problems involving Lewis structures. Difficulty of the task and of individual problems is described. A taxonomy of skills associated with Lewis structures is presented. (CW)

  10. 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…

  11. 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,…

  12. 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.

  13. 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.

  14. Gonococcal lipooligosaccharide sialylation prevents complement-dependent killing by immune sera.

    PubMed

    Wetzler, L M; Barry, K; Blake, M S; Gotschlich, E C

    1992-01-01

    Previous investigators have demonstrated that a sialic acid residue is added to the terminal galactose moiety of gonococcal lipooligosaccharide (LOS) when incubated with 5'-CMP-N-acetylneuraminic acid. When this in vitro sialylation occurs, gonococci become resistant to the bactericidal activity of normal human serum. This is believed to result because the added sialic acid residue blocks the binding of bactericidal anti-LOS antibodies present in normal human serum. We extend these studies by demonstrating that sialylated gonococci also become resistant to the bactericidal effect of immune sera containing antibodies that recognize exposed components of the outer membrane besides LOS. Prevention of antibody binding to the organism was not the cause, since the same percentage of bactericidal antibodies to the major outer membrane protein, Protein I, can be absorbed with sialylated organisms as with wild-type organisms. In addition, gonococcal sialylation prevents opsonophagocytosis by antigonococcal antisera. The negative effect of sialic acid on the complement pathway might be the reason for the findings in this study.

  15. 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.

  16. 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.

  17. Sialylation of outer membrane porin protein D: a mechanistic basis of antibiotic uptake in Pseudomonas aeruginosa.

    PubMed

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

    2014-06-01

    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

  18. 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

  19. 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

  20. A Sialylated Glycan Microarray Reveals Novel Interactions of Modified Sialic Acids with Proteins and Viruses*

    PubMed Central

    Song, Xuezheng; Yu, Hai; Chen, Xi; Lasanajak, Yi; Tappert, Mary M.; Air, Gillian M.; Tiwari, Vinod K.; Cao, Hongzhi; Chokhawala, Harshal A.; Zheng, Haojie; Cummings, Richard D.; Smith, David F.

    2011-01-01

    Many glycan-binding proteins in animals and pathogens recognize sialic acid or its modified forms, but their molecular recognition is poorly understood. Here we describe studies on sialic acid recognition using a novel sialylated glycan microarray containing modified sialic acids presented on different glycan backbones. Glycans terminating in β-linked galactose at the non-reducing end and with an alkylamine-containing fluorophore at the reducing end were sialylated by a one-pot three-enzyme system to generate α2–3- and α2–6-linked sialyl glycans with 16 modified sialic acids. The resulting 77 sialyl glycans were purified and quantified, characterized by mass spectrometry, covalently printed on activated slides, and interrogated with a number of key sialic acid-binding proteins and viruses. Sialic acid recognition by the sialic acid-binding lectins Sambucus nigra agglutinin and Maackia amurensis lectin-I, which are routinely used for detecting α2–6- and α2–3-linked sialic acids, are affected by sialic acid modifications, and both lectins bind glycans terminating with 2-keto-3-deoxy-d-glycero-d-galactonononic acid (Kdn) and Kdn derivatives stronger than the derivatives of more common N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc). Three human parainfluenza viruses bind to glycans terminating with Neu5Ac or Neu5Gc and some of their derivatives but not to Kdn and its derivatives. Influenza A virus also does not bind glycans terminating in Kdn or Kdn derivatives. An especially novel aspect of human influenza A virus binding is its ability to equivalently recognize glycans terminated with either α2–6-linked Neu5Ac9Lt or α2–6-linked Neu5Ac. Our results demonstrate the utility of this sialylated glycan microarray to investigate the biological importance of modified sialic acids in protein-glycan interactions. PMID:21757734

  1. 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

  2. Enzymatic sialylation of IgA1 O-glycans: implications for studies of IgA nephropathy.

    PubMed

    Takahashi, Kazuo; Raska, Milan; Stuchlova Horynova, Milada; Hall, Stacy D; Poulsen, Knud; Kilian, Mogens; Hiki, Yoshiyuki; Yuzawa, Yukio; Moldoveanu, Zina; Julian, Bruce A; Renfrow, Matthew B; Novak, Jan

    2014-01-01

    Patients with IgA nephropathy (IgAN) have elevated circulating levels of IgA1 with some O-glycans consisting of galactose (Gal)-deficient N-acetylgalactosamine (GalNAc) with or without N-acetylneuraminic acid (NeuAc). We have analyzed O-glycosylation heterogeneity of naturally asialo-IgA1 (Ale) myeloma protein that mimics Gal-deficient IgA1 (Gd-IgA1) of patients with IgAN, except that IgA1 O-glycans of IgAN patients are frequently sialylated. Specifically, serum IgA1 of healthy controls has more α2,3-sialylated O-glycans (NeuAc attached to Gal) than α2,6-sialylated O-glycans (NeuAc attached to GalNAc). As IgA1-producing cells from IgAN patients have an increased activity of α2,6-sialyltransferase (ST6GalNAc), we hypothesize that such activity may promote premature sialylation of GalNAc and, thus, production of Gd-IgA1, as sialylation of GalNAc prevents subsequent Gal attachment. Distribution of NeuAc in IgA1 O-glycans may play an important role in the pathogenesis of IgAN. To better understand biological functions of NeuAc in IgA1, we established protocols for enzymatic sialylation leading to α2,3- or α2,6-sialylation of IgA1 O-glycans. Sialylation of Gal-deficient asialo-IgA1 (Ale) myeloma protein by an ST6GalNAc enzyme generated sialylated IgA1 that mimics the Gal-deficient IgA1 glycoforms in patients with IgAN, characterized by α2,6-sialylated Gal-deficient GalNAc. In contrast, sialylation of the same myeloma protein by an α2,3-sialyltransferase yielded IgA1 typical for healthy controls, characterized by α2,3-sialylated Gal. The GalNAc-specific lectin from Helix aspersa (HAA) is used to measure levels of Gd-IgA1. We assessed HAA binding to IgA1 sialylated at Gal or GalNAc. As expected, α2,6-sialylation of IgA1 markedly decreased reactivity with HAA. Notably, α2,3-sialylation also decreased reactivity with HAA. Neuraminidase treatment recovered the original HAA reactivity in both instances. These results suggest that binding of a GalNAc-specific lectin

  3. Enzymatic Sialylation of IgA1 O-Glycans: Implications for Studies of IgA Nephropathy

    PubMed Central

    Takahashi, Kazuo; Raska, Milan; Stuchlova Horynova, Milada; Hall, Stacy D.; Poulsen, Knud; Kilian, Mogens; Hiki, Yoshiyuki; Yuzawa, Yukio; Moldoveanu, Zina; Julian, Bruce A.; Renfrow, Matthew B.; Novak, Jan

    2014-01-01

    Patients with IgA nephropathy (IgAN) have elevated circulating levels of IgA1 with some O-glycans consisting of galactose (Gal)-deficient N-acetylgalactosamine (GalNAc) with or without N-acetylneuraminic acid (NeuAc). We have analyzed O-glycosylation heterogeneity of naturally asialo-IgA1 (Ale) myeloma protein that mimics Gal-deficient IgA1 (Gd-IgA1) of patients with IgAN, except that IgA1 O-glycans of IgAN patients are frequently sialylated. Specifically, serum IgA1 of healthy controls has more α2,3-sialylated O-glycans (NeuAc attached to Gal) than α2,6-sialylated O-glycans (NeuAc attached to GalNAc). As IgA1-producing cells from IgAN patients have an increased activity of α2,6-sialyltransferase (ST6GalNAc), we hypothesize that such activity may promote premature sialylation of GalNAc and, thus, production of Gd-IgA1, as sialylation of GalNAc prevents subsequent Gal attachment. Distribution of NeuAc in IgA1 O-glycans may play an important role in the pathogenesis of IgAN. To better understand biological functions of NeuAc in IgA1, we established protocols for enzymatic sialylation leading to α2,3- or α2,6-sialylation of IgA1 O-glycans. Sialylation of Gal-deficient asialo-IgA1 (Ale) myeloma protein by an ST6GalNAc enzyme generated sialylated IgA1 that mimics the Gal-deficient IgA1 glycoforms in patients with IgAN, characterized by α2,6-sialylated Gal-deficient GalNAc. In contrast, sialylation of the same myeloma protein by an α2,3-sialyltransferase yielded IgA1 typical for healthy controls, characterized by α2,3-sialylated Gal. The GalNAc-specific lectin from Helix aspersa (HAA) is used to measure levels of Gd-IgA1. We assessed HAA binding to IgA1 sialylated at Gal or GalNAc. As expected, α2,6-sialylation of IgA1 markedly decreased reactivity with HAA. Notably, α2,3-sialylation also decreased reactivity with HAA. Neuraminidase treatment recovered the original HAA reactivity in both instances. These results suggest that binding of a GalNAc-specific lectin

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. Lewis Mars Pathfinder Microrover Experiments

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The NASA Lewis Research Center has a prime role in the Mars Pathfinder mission, the first in the series of Discovery-class missions, sponsored by NASA Headquarter's Office of Space Science. Mars Pathfinder is an engineering proof-of-concept mission intended to demonstrate the successful deployment of scientific instruments, including a small rover, on a planetary body and to gain engineering design information for follow-on systems. The mission was launched in December 1996 and will land on Mars on July 4, 1997.

  10. Fluorescent mimetics of CMP-Neu5Ac are highly potent, cell-permeable polarization probes of eukaryotic and bacterial sialyltransferases and inhibit cellular sialylation.

    PubMed

    Preidl, Johannes J; Gnanapragassam, Vinayaga S; Lisurek, Michael; Saupe, Jörn; Horstkorte, Rüdiger; Rademann, Jörg

    2014-05-26

    Oligosaccharides of the glycolipids and glycoproteins at the outer membranes of human cells carry terminal neuraminic acids, which are responsible for recognition events and adhesion of cells, bacteria, and virus particles. The synthesis of neuraminic acid containing glycosides is accomplished by intracellular sialyl transferases. Therefore, the chemical manipulation of cellular sialylation could be very important to interfere with cancer development, inflammations, and infections. The development and applications of the first nanomolar fluorescent inhibitors of sialyl transferases are described herein. The obtained carbohydrate-nucleotide mimetics were found to bind all four commercially available and tested eukaryotic and bacterial sialyl transferases in a fluorescence polarization assay. Moreover, it was observed that the anionic mimetics intruded rapidly and efficiently into cells in vesicles and translocated to cellular organelles surrounding the nucleus of CHO cells. The new compounds inhibit cellular sialylation in two cell lines and open new perspectives for investigations of cellular sialylation.

  11. CMP-Sialic Acid Synthetase: The Point of Constriction in the Sialylation Pathway.

    PubMed

    Sellmeier, Melanie; Weinhold, Birgit; Münster-Kühnel, Anja

    2015-01-01

    Sialoglycoconjugates form the outermost layer of animal cells and play a crucial role in cellular communication processes. An essential step in the biosynthesis of sialylated glycoconjugates is the activation of sialic acid to the monophosphate diester CMP-sialic acid. Only the activated sugar is transported into the Golgi apparatus and serves as a substrate for the linkage-specific sialyltransferases. Interference with sugar activation abolishes sialylation and is embryonic lethal in mammals. In this chapter we focus on the enzyme catalyzing the activation of sialic acid, the CMP-sialic acid synthetase (CMAS), and compare the enzymatic properties of CMASs isolated from different species. Information concerning the reaction mechanism and active site architecture is included. Moreover, the unusual nuclear localization of vertebrate CMASs as well as the biotechnological application of bacterial CMAS enzymes is addressed.

  12. 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

  13. Dual modifications strategy to quantify neutral and sialylated N-glycans simultaneously by MALDI-MS.

    PubMed

    Zhou, Hui; Warren, Peter G; Froehlich, John W; Lee, Richard S

    2014-07-01

    Differences in ionization efficiency among neutral and sialylated glycans prevent direct quantitative comparison by their respective mass spectrometric signals. To overcome this challenge, we developed an integrated chemical strategy, Dual Reactions for Analytical Glycomics (DRAG), to quantitatively compare neutral and sialylated glycans simultaneously by MALDI-MS. Initially, two glycan samples to be compared undergo reductive amination with 2-aminobenzoic acid and 2-(13)[C6]-aminobenzoic acid, respectively. The different isotope-incorporated glycans are then combined and subjected to the methylamidation of the sialic acid residues in one mixture, homogenizing the ionization responses for all neutral and sialylated glycans. By this approach, the expression change of relevant glycans between two samples is proportional to the ratios of doublet signals with a static 6 Da mass difference in MALDI-MS and the change in relative abundance of any glycan within samples can also be determined. The strategy was chemically validated using well-characterized N-glycans from bovine fetuin and IgG from human serum. By comparing the N-glycomes from a first morning (AM) versus an afternoon (PM) urine sample obtained from a single donor, we further demonstrated the ability of DRAG strategy to measure subtle quantitative differences in numerous urinary N-glycans.

  14. 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.

  15. Simplified Lewis Structure Drawing for Nonscience Majors.

    ERIC Educational Resources Information Center

    Miburo, Barnabe B.

    1998-01-01

    Argues that Lewis diagrams can be easily done by students using a minimal number of clues. Presents a method to draw the Lewis structure of molecules, polyatomic ions, and radicals whereby students no longer need to move bonds or lone pairs of electrons. (DDR)

  16. Drawing Lewis Structures without Anticipating Octets.

    ERIC Educational Resources Information Center

    Carroll, James Allen

    1986-01-01

    After noting the grounds for labelling structures as incorrect, the guidelines for selecting which Lewis structures are most important for a molecule are introduced. Several examples of appropriate Lewis structures and the fine structural predictions that are possible are included. (JN)

  17. 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…

  18. 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

  19. 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

  20. Multivalent sialylation of β-thio-glycoclusters by Trypanosoma cruzi trans sialidase and analysis by high performance anion exchange chromatography.

    PubMed

    Agustí, Rosalía; Cano, María Emilia; Cagnoni, Alejandro J; Kovensky, José; de Lederkremer, Rosa M; Uhrig, María Laura

    2016-10-01

    The synthesis of multivalent sialylated glycoclusters is herein addressed by a chemoenzymatic approach using the trans-sialidase of Trypanosoma cruzi (TcTS). Multivalent β-thio-galactopyranosides and β-thio-lactosides were used as acceptor substrates and 3'-sialyllactose as the sialic acid donor. High performance anion exchange chromatography with pulsed amperometric detection (HPAEC-PAD) was shown to be an excellent technique for the analysis of the reaction products. Different eluting conditions were optimized to allow the simultaneous resolution of the sialylated species, as well as their neutral precursors. The TcTS efficiently transferred sialyl residues to di, tri, tetra and octa β-thiogalactosides. In the case of an octavalent thiolactoside, up to six polysialylated compounds could be resolved. Preparative sialylation reactions were performed using the tetravalent and octavalent acceptor substrates. The main sialylated derivatives could be unequivocally assigned by MALDI mass spectrometry. Inhibition of the transfer to the natural substrate, N-acetyllactosamine, was also studied. The octalactoside caused 82 % inhibition of sialic acid transfer when we used equimolar concentrations of donor, acceptor and inhibitor.

  1. [Dementia: Where are the Lewy bodies?].

    PubMed

    Lebouvier, T; Delrieu, J; Evain, S; Pallardy, A; Sauvaget, A; Letournel, F; Chevrier, R; Lepetit, M; Vercelletto, M; Boutoleau-Bretonnière, C; Derkinderen, P

    2013-11-01

    Dementia with Lewy bodies (DLB) is the second cause of degenerative dementia in autopsy studies. In clinical pratice however, the prevalence of DLB is much lower with important intercenter variations. Among the reasons for this low sensitivity of DLB diagnosis are (1) the imprecision and subjectivity of the diagnostic criteria; (2) the underestimation of non-motor symptoms (REM-sleep behavior disorder, dysautonomia, anosmia); mostly (3) the nearly constant association of Lewy bodies with Alzheimer's disease pathology, which dominates the clinical phenotype. With the avenue of targeted therapies against the protein agregates, new clinical scales able to apprehend the coexistence of Lewy pathology in Alzheimer's disease are expected.

  2. Lipooligosaccharide locus class of Campylobacter jejuni: sialylation is not needed for invasive infection.

    PubMed

    Ellström, P; Feodoroff, B; Hänninen, M-L; Rautelin, H

    2014-06-01

    Campylobacter jejuni is a highly diverse enteropathogen that is commonly detected worldwide. It can sometimes cause bacteraemia, but the bacterial characteristics facilitating bloodstream infection are not known. A total of 73 C. jejuni isolates, consecutively collected from blood-borne infections during a 10-year period all over Finland and for which detailed clinical information of the patients were available, were included. We screened the isolates by PCR for the lipooligosaccharide (LOS) locus class and for the presence of the putative virulence genes ceuE, ciaB, fucP, and virB11. The isolates were also tested for γ-glutamyl transpeptidase production. The results were analysed with respect to the clinical characteristics of the patients, and the multilocus sequence types (MLSTs) and serum resistance of the isolates. LOS locus classes A, B, and C, which carry genes for sialylation of LOS, were detected in only 23% of the isolates. These isolates were not more resistant to human serum than those with the genes of non-sialylated LOS locus classes, but were significantly more prevalent among patients with underlying diseases (p 0.02). The fucose permease gene fucP was quite uncommon, but was associated with the isolates with the potential to sialylate LOS (p <0.0001). LOS locus classes and some of the putative virulence factors were associated with MLST clonal complexes. Although some of the bacterial characteristics studied here have been suggested to be important for the invasiveness of C. jejuni, they did not explain why the clinical isolates in the present study were able to cause bacteraemia.

  3. 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,…

  4. 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.

  5. 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.

  6. 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)

  7. 90 Seconds of Discovery: Frustrated Lewis Pairs

    ScienceCinema

    Kathmann, Shawn; Schenter, Greg; Autrey, Tom

    2016-07-12

    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.

  8. 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.

  9. 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)

  10. 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)

  11. Lewis A. Conner: Cornell's Osler.

    PubMed

    Fisher, J

    2000-08-29

    Lewis A. Conner, MD (1867 to 1950), was a pioneer in public health cardiology, cardiac rehabilitation, and cardiac psychology. He helped establish the Burke Rehabilitation Hospital and was the founding president of the New York and American Heart Associations (AHA). Dr Conner was the founder of the American Heart Journal, America's first medical subspecialty journal, and the official publication of the American Heart Association until 1950, when CIRCULATION: was created. Conner spent more than a half-century on the staff of the New York Hospital and Cornell University Medical College and was Chairman of Medicine from 1916 to 1932. During this time, he created the innovative Cornell Pay Clinic and united the "old" New York Hospital with the new and scientifically-oriented Cornell University Medical College on a modern and inspiring urban campus. An extraordinary clinician and a humanist with great equanimity, Conner devoted his career to the Oslerian tradition of scholarship, leadership, and organization in the quest for improved patient care. This article contains newly discovered biographic material on Dr Conner and explores his professional and personal connection to Sir William Osler. PMID:10961973

  12. Effect of sialylation of lipopolysaccharide of Neisseria gonorrhoeae on recognition and complement-mediated killing by monoclonal antibodies directed against different outer-membrane antigens.

    PubMed

    de la Paz, H; Cooke, S J; Heckels, J E

    1995-04-01

    Growth of gonococci in the presence of CMP-N-acetylneuraminic acid (CMP-NANA) has previously been shown to induce resistance to the bactericidal effect of normal human serum and is accompanied by sialylation of the gonococcal lipopolysaccharide (LPS). We have used monoclonal antibodies (mAbs) to compare the effect of LPS sialylation on recognition of gonococci and complement-mediated killing by antibodies directed either against LPS or against defined epitopes on outer-membrane protein PI. Despite differences in binding to sialylated LPS on Western blots, all three mAbs directed against LPS showed considerably reduced binding to gonococci grown in the presence of CMP-NANA and a concomitant reduction in ability to promote complement-mediated killing. In contrast, mAbs directed against previously defined epitopes on a surface exposed loop of PI showed little difference in binding between sialylated and non-sialylated gonococci and promoted killing of the sialylated gonococci. Similarly a mAb directed against an epitope on a loop of the outer-membrane Rmp protein, which had previously been shown to block killing by antibodies directed against other surface antigens, also exerted a blocking effect with sialylated gonococci. Thus in the present study the continued biological effect of mAbs was correlated with the ability of the antibody to recognize surface-exposed epitopes on sialylated gonococci. Despite the presence of the sialylation which is likely to occur in vivo, it should be possible to induce complement-mediated killing by focusing the immune response to those surface-exposed epitopes which are least susceptible to the potential inhibitory effect of LPS sialylation.

  13. 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.

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

    PubMed

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

    2015-01-01

    Prion or PrP(Sc) is a proteinaceous infectious agent that consists of a misfolded and aggregated form of a sialoglycoprotein called prion protein or PrP(C). PrP(C) has two sialylated N-linked carbohydrates. In PrP(Sc), 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 PrP(Sc) glycoform ratio. In support of this hypothesis, here we show that diglycosylated PrP(C) molecules that have more sialic groups per molecule than monoglycosylated PrP(C) were preferentially excluded from conversion. However, when partially desialylated PrP(C) was used as a substrate, recruitment of three glycoforms into PrP(Sc) 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 PrP(C) 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

  15. 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

  16. Synthetic glycoprotein mimics inhibit L-selectin-mediated rolling and promote L-selectin shedding.

    PubMed

    Mowery, Patricia; Yang, Zhi-Qiang; Gordon, Eva J; Dwir, Oren; Spencer, Andrew G; Alon, Ronen; Kiessling, Laura L

    2004-05-01

    L-selectin is a leukocyte cell-surface protein that facilitates the rolling of leukocytes along the endothelium, a process that leads to leukocyte migration to a site of infection. Preventing L-selectin-mediated rolling minimizes leukocyte adhesion and extravasation; therefore, compounds that inhibit rolling may act as anti-inflammatory agents. To investigate the potential role of multivalent ligands as rolling inhibitors, compounds termed neoglycopolymers were synthesized that possess key structural features of physiological L-selectin ligands. Sulfated neoglycopolymers substituted with sialyl Lewis x derivatives (3',6-disulfo Lewis x or 6-sulfo sialyl Lewis x) or a sulfatide analog (3,6-disulfo galactose) inhibited L-selectin-mediated rolling of lymphoid cells. Functional analysis of the inhibitory ligands indicates that they also induce proteolytic release of L-selectin. Thus, their inhibitory potency may arise from their ability to induce shedding. Our data indicate that screening for compounds that promote L-selectin release can identify ligands that inhibit rolling.

  17. Frustrated Lewis pairs: metal-free hydrogen activation and more.

    PubMed

    Stephan, Douglas W; Erker, Gerhard

    2010-01-01

    Sterically encumbered Lewis acid and Lewis base combinations do not undergo the ubiquitous neutralization reaction to form "classical" Lewis acid/Lewis base adducts. Rather, both the unquenched Lewis acidity and basicity of such sterically "frustrated Lewis pairs (FLPs)" is available to carry out unusual reactions. Typical examples of frustrated Lewis pairs are inter- or intramolecular combinations of bulky phosphines or amines with strongly electrophilic RB(C(6)F(5))(2) components. Many examples of such frustrated Lewis pairs are able to cleave dihydrogen heterolytically. The resulting H(+)/H(-) pairs (stabilized for example, in the form of the respective phosphonium cation/hydridoborate anion salts) serve as active metal-free catalysts for the hydrogenation of, for example, bulky imines, enamines, or enol ethers. Frustrated Lewis pairs also react with alkenes, aldehydes, and a variety of other small molecules, including carbon dioxide, in cooperative three-component reactions, offering new strategies for synthetic chemistry. PMID:20025001

  18. Impact of a human CMP-sialic acid transporter on recombinant glycoprotein sialylation in glycoengineered insect cells.

    PubMed

    Mabashi-Asazuma, Hideaki; Shi, Xianzong; Geisler, Christoph; Kuo, Chu-Wei; Khoo, Kay-Hooi; Jarvis, Donald L

    2013-02-01

    Insect cells are widely used for recombinant glycoprotein production, but they cannot provide the glycosylation patterns required for some biotechnological applications. This problem has been addressed by genetically engineering insect cells to express mammalian genes encoding various glycoprotein glycan processing functions. However, for various reasons, the impact of a mammalian cytosine-5'-monophospho (CMP)-sialic acid transporter has not yet been examined. Thus, we transformed Spodoptera frugiperda (Sf9) cells with six mammalian genes to generate a new cell line, SfSWT-4, that can produce sialylated glycoproteins when cultured with the sialic acid precursor, N-acetylmannosamine. We then super-transformed SfSWT-4 with a human CMP-sialic acid transporter (hCSAT) gene to isolate a daughter cell line, SfSWT-6, which expressed the hCSAT gene in addition to the other mammalian glycogenes. SfSWT-6 cells had higher levels of cell surface sialylation and also supported higher levels of recombinant glycoprotein sialylation, particularly when cultured with low concentrations of N-acetylmannosamine. Thus, hCSAT expression has an impact on glycoprotein sialylation, can reduce the cost of recombinant glycoprotein production and therefore should be included in ongoing efforts to glycoengineer the baculovirus-insect cell system. The results of this study also contributed new insights into the endogenous mechanism and potential mechanisms of CMP-sialic acid accumulation in the Golgi apparatus of lepidopteran insect cells.

  19. 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.

  20. Molecular cloning and characterization of an N-acetylglucosamine-6-O-sulfotransferase.

    PubMed

    Uchimura, K; Muramatsu, H; Kadomatsu, K; Fan, Q W; Kurosawa, N; Mitsuoka, C; Kannagi, R; Habuchi, O; Muramatsu, T

    1998-08-28

    We isolated a cDNA clone encoding mouse N-acetylglucosamine-6-O-sulfotransferase based on sequence homology to the previously cloned mouse chondroitin 6-sulfotransferase. The cDNA clone contained an open reading frame that predicts a type II transmembrane protein composed of 483 amino acid residues. The expressed enzyme transferred sulfate to the 6 position of nonreducing GlcNAc in GlcNAcbeta1-3Galbeta1-4GlcNAc. Galbeta1-4GlcNAcbeta1-3Galbeta1-4GlcNAc and various glycosaminoglycans did not serve as acceptors. Expression of the cDNA in COS-7 cells resulted in production of a cell-surface antigen, the epitope of which was NeuAcalpha2-3Galbeta1-4(SO4-6)GlcNAc; double transfection with fucosyltransferase IV yielded Galbeta1-4(Fucalpha1-3)(SO4-6)GlcNAc antigen. The sulfotransferase mRNA was strongly expressed in the cerebrum, cerebellum, eye, pancreas, and lung of adult mice. In situ hybridization revealed that the mRNA was localized in high endothelial venules of mesenteric lymph nodes. The sulfotransferase was concluded to be involved in biosynthesis of glycoconjugates bearing the 6-sulfo N-acetyllactosamine structure such as 6-sulfo sialyl Lewis X. The products of the sulfotransferase probably include glycoconjugates with intercellular recognition signals; one candidate of such a glycoconjugate is an L-selectin ligand.

  1. Monocyte B7 and Sialyl Lewis X modulates the efficacy of IL-10 down-regulation of LPS-induced monocyte tissue factor in whole blood.

    PubMed

    Warnes, G; Biggerstaff, J P; Francis, J L

    1998-07-01

    Recent studies have investigated the use of anti-inflammatory cytokine, interleukin 10 (IL-10) to control the development of disseminated intravascular coagulation (DIC) in sepsis by down-regulation of monocyte tissue factor (MTF) induced by lipopolysaccharide (LPS) in the initial phase of the disease. In vitro and in vivo human studies have shown that a minimal (<1 h) delay in IL-10 treatment significantly reduces the cytokines ability to inhibit LPS-induced MTF expression and the end products of coagulation. In this whole blood in vitro study we investigated the role of lymphocyte and platelet interactions with monocytes to up-regulate MTF expression in the presence of IL-10 in the initial phase of exposure to LPS. Individual blockade of monocyte B7 or platelet P-selectin significantly (35%) reduced MTF expression (P<0.05). IL-10 showed a dose-dependent inhibition of LPS (0.1 microg/ml) induced MTF expression, with 56% inhibition at 1 ng/ml, maximizing at 5 ng/ml IL-10 (75%; P<0.05). Simultaneous exposure to LPS and IL-10 (1 ng/ml) or addition of IL-10 1 h after LPS, with individual B7 and P-selectin blockade significantly enhanced the inhibition of MTF expression by IL-10 (P<0.05). We conclude that the efficacy of IL-10 to control DIC could be enhanced by a simultaneous B7 and P-selectin blockade.

  2. Monocyte B7 and Sialyl Lewis X modulates the efficacy of IL-10 down-regulation of LPS-induced monocyte tissue factor in whole blood.

    PubMed

    Warnes, G; Biggerstaff, J P; Francis, J L

    1998-07-01

    Recent studies have investigated the use of anti-inflammatory cytokine, interleukin 10 (IL-10) to control the development of disseminated intravascular coagulation (DIC) in sepsis by down-regulation of monocyte tissue factor (MTF) induced by lipopolysaccharide (LPS) in the initial phase of the disease. In vitro and in vivo human studies have shown that a minimal (<1 h) delay in IL-10 treatment significantly reduces the cytokines ability to inhibit LPS-induced MTF expression and the end products of coagulation. In this whole blood in vitro study we investigated the role of lymphocyte and platelet interactions with monocytes to up-regulate MTF expression in the presence of IL-10 in the initial phase of exposure to LPS. Individual blockade of monocyte B7 or platelet P-selectin significantly (35%) reduced MTF expression (P<0.05). IL-10 showed a dose-dependent inhibition of LPS (0.1 microg/ml) induced MTF expression, with 56% inhibition at 1 ng/ml, maximizing at 5 ng/ml IL-10 (75%; P<0.05). Simultaneous exposure to LPS and IL-10 (1 ng/ml) or addition of IL-10 1 h after LPS, with individual B7 and P-selectin blockade significantly enhanced the inhibition of MTF expression by IL-10 (P<0.05). We conclude that the efficacy of IL-10 to control DIC could be enhanced by a simultaneous B7 and P-selectin blockade. PMID:9695978

  3. 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.

  4. 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.

  5. 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

  6. A Lewis acid-promoted Pinner reaction

    PubMed Central

    Pfaff, Dominik; Nemecek, Gregor

    2013-01-01

    Summary Carbonitriles and alcohols react in a Lewis acid-promoted Pinner reaction to carboxylic esters. Best results are obtained with two equivalents of trimethylsilyl triflate as Lewis acid. Good yields are achieved with primary alcohols and aliphatic or benzylic carbonitriles, but the straightforward synthesis of acrylates and benzoates starting with acrylonitrile and benzonitrile, respectively, is similarly possible. Phenols are not acylated under these reaction conditions. The method has been used for the first total synthesis of the natural product monaspilosin. In the reaction of benzyl alcohols variable amounts of amides are formed in a Ritter-type side reaction. PMID:23946857

  7. 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.

  8. Transferrin Sialylation in Smoking and Non-Smoking Pregnant Women with Intrauterine Growth Restriction.

    PubMed

    Wrześniak, Marta; Kepinska, Marta; Bizoń, Anna; Milnerowicz-Nabzdyk, Ewa; Milnerowicz, Halina

    2015-01-01

    Transferrin (Tf) is a glycosylated protein responsible for transporting iron. Various sialylation levels of Tf are observed during physiological and pathological processes. We studied if the changes in iron stores as well as tobacco smoke may have an impact on foetal development and in consequence lead to intrauterine growth restriction (IUGR). In the third trimester of pregnancy, lower levels of 4-sialoTf isoform and higher levels of 5-sialoTf were observed in the serum of non-smoking women with IUGR in comparison to the control group. On the day of labour, level of 2-sialoTf was significantly lower and level of 3-sialo was Tf higher in the serum of non-smoking women. Level of 4-sialo was found lower in the serum of smoking women with IUGR than in the control group. The observed changes may suggest a connection between iron stores, transport of iron to the foetus and foetal development.

  9. Localization and imaging of sialylated glycosphingolipids in brain tissue sections by MALDI mass spectrometry

    PubMed Central

    Colsch, Benoit; Woods, Amina S.

    2010-01-01

    In this study, we describe a simple and efficient method for mapping the distribution and localization of all sialylated sphingoglycolipids present in coronal mouse brain sections using a conventional axial matrix-assisted laser desorption/ionization time of flight. A single scan of a histological tissue section gives a complete profile of ganglioside species without derivatization or labeling. We have developed and tested a new matrix preparation (2,6-dihydroxyacetophenone [DHA]/ammonium sulfate/heptafluorobutyric acid [HFBA]) to maximize the detection of all ganglioside species; the ammonium sulfate limits the formation of salt adducts, while the addition of HFBA increases the stability of DHA in a vacuum, thus facilitating imaging applications. Our results, in both extracted samples and whole tissue sections using negative ion reflectron and linear modes, show differences in localization in several brain regions depending on the sialic acids and the ceramide-associated core gangliosides. PMID:20190299

  10. 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

  11. Engineering of Sialylated Mucin-type O-Glycosylation in Plants*

    PubMed Central

    Castilho, Alexandra; Neumann, Laura; Daskalova, Sasha; Mason, Hugh S.; Steinkellner, Herta; Altmann, Friedrich; Strasser, Richard

    2012-01-01

    Proper N- and O-glycosylation of recombinant proteins is important for their biological function. Although the N-glycan processing pathway of different expression hosts has been successfully modified in the past, comparatively little attention has been paid to the generation of customized O-linked glycans. Plants are attractive hosts for engineering of O-glycosylation steps, as they contain no endogenous glycosyltransferases that perform mammalian-type Ser/Thr glycosylation and could interfere with the production of defined O-glycans. Here, we produced mucin-type O-GalNAc and core 1 O-linked glycan structures on recombinant human erythropoietin fused to an IgG heavy chain fragment (EPO-Fc) by transient expression in Nicotiana benthamiana plants. Furthermore, for the generation of sialylated core 1 structures constructs encoding human polypeptide:N-acetylgalactosaminyltransferase 2, Drosophila melanogaster core 1 β1,3-galactosyltransferase, human α2,3-sialyltransferase, and Mus musculus α2,6-sialyltransferase were transiently co-expressed in N. benthamiana together with EPO-Fc and the machinery for sialylation of N-glycans. The formation of significant amounts of mono- and disialylated O-linked glycans was confirmed by liquid chromatography-electrospray ionization-mass spectrometry. Analysis of the three EPO glycopeptides carrying N-glycans revealed the presence of biantennary structures with terminal sialic acid residues. Our data demonstrate that N. benthamiana plants are amenable to engineering of the O-glycosylation pathway and can produce well defined human-type O- and N-linked glycans on recombinant therapeutics. PMID:22948156

  12. Playing around in Lewis Carroll's "Alice" Books

    ERIC Educational Resources Information Center

    Susina, Jan

    2010-01-01

    Mathematician Charles Dodgson's love of play and his need for rules came together in his use of popular games as part of the structure of the two famous children's books, "Alice in Wonderland" and "Through the Looking-Glass," he wrote under the pseudonym Lewis Carroll. The author of this article looks at the interplay between…

  13. 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…

  14. 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)

  15. 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.

  16. Lewis materials research and technology: An overview

    NASA Technical Reports Server (NTRS)

    Grisaffe, Salvatore J.

    1987-01-01

    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. An overview of the division staff, facilities, past history, recent progress, and future interests is presented.

  17. Interview with Richard Lewis, Part Two.

    ERIC Educational Resources Information Center

    Mercogliano, Chris; Leue, Mary

    1997-01-01

    Richard Lewis, founder and director of the Touchstone Center (New York City), discusses how the move toward national education standards works against individualism and expressive learning. He suggests that teachers get so involved in meeting standards and goals that they fail to obey the natural laws of learning. (LP)

  18. 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)

  19. 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…

  20. 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…

  1. 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…

  2. 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…

  3. 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.

  4. Sialylation analysis of O-glycosylated sialylated peptides from urine of patients suffering from Schindler's disease by Fourier transform ion cyclotron resonance mass spectrometry and sustained off-resonance irradiation collision-induced dissociation.

    PubMed

    Froesch, Martin; Bindila, Laura; Zamfir, Alina; Peter-Katalinić, Jasna

    2003-01-01

    A strategy based on Fourier transform ion cyclotron resonance mass spectrometry (FTICR-MS) for screening of complex glycoconjugate mixtures containing O-linked glycopeptides and O-glycosylated amino acids with alpha-N-acetylgalactosaminyl residues is presented. To detect and identify O-glycoforms present in urine of patients suffering from hereditary N-acetylhexosaminidase deficiency (known as Schindler's disease), present at 100 times higher concentrations than in urine of healthy controls, new accurate methods for mapping and sequencing were required. In the mass spectrometric analysis particular attention has to be paid to original sialylation patterns, because of the potential lability of the sialic acid moiety during the desorption/ionization process. Negative ion nanoelectrospray ionization (nanoESI) FTICR-MS at 9.4 T is shown here to represent a method of choice for identification of single components in such complex glycomixtures due to high resolution and mass accuracy. By optimization of sustained off-resonance irradiation collision-induced dissociation tandem mass spectrometry (SORI-CID-MS(2)) in the negative ion mode, the type and sequence of the sialylated glycopeptide components were determined from their fragmentation patterns. Additionally, implementation of SORI-CID-MS(3) provides detailed information for sialylation analysis. The potential diagnostic value of this approach is discussed.

  5. 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

  6. 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.

  7. Glycosylation and Sialylation of Macrophage-derived Human Apolipoprotein E Analyzed by SDS-PAGE and Mass Spectrometry

    PubMed Central

    Lee, Youra; Kockx, Maaike; Raftery, Mark J.; Jessup, Wendy; Griffith, Renate; Kritharides, Leonard

    2010-01-01

    Apolipoprotein E (apoE) is a 34-kDa glycoprotein secreted from various cells including hepatocytes and macrophages and plays an important role in remnant lipoprotein clearance, immune responses, Alzheimer disease, and atherosclerosis. Cellular apoE and plasma apoE exist as multiple glycosylated and sialylated glycoforms with plasma apoE being less glycosylated/sialylated than cell-derived apoE. Some of the glycan structures on plasma apoE are characterized; however, the more complicated structures on plasma and cellular/secreted apoE remain unidentified. We investigated glycosylation and sialylation of cellular and secreted apoE from primary human macrophages by one- and two-dimensional gel electrophoresis and mass spectrometry. Our results identify eight different glycoforms with (HexNAc)2-Hex2-(NeuAc)2 being the most complex glycan detected on Thr194 in both cellular and secreted apoE. Four additional glycans were identified on apoE(283–299), and using β-elimination/alkylation by methylamine in vitro, we identified Ser290 as a novel site of glycan attachment. Comparison of plasma and cellular/secreted apoE from the same donor confirmed that cell-derived apoE is more extensively sialylated than plasma apoE. Given the importance of the C terminus of apoE in regulating apoE solubility, stability, and lipid binding, these results may have important implications for our understanding of apoE biochemistry. PMID:20511397

  8. 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

  9. Role of sialylation in determining the pharmacokinetics of neutrophil inhibitory factor (NIF) in the Fischer 344 rat.

    PubMed

    Webster, R; Taberner, J; Edgington, A; Guhan, S; Varghese, J; Feeney, H; Blocker, L; Jezequel, S G

    1999-11-01

    1. Recombinant neutrophil inhibitory factor (NIF) is a glycoprotein. Its amino acid sequence remains constant and has a molecular weight of 28.9 kD. However, approximately 40% of the total molecular weight consists of glycans with variable structure. 2. The pharmacokinetics of 11 different NIF batches with varying extents and patterns of sialylation have been investigated in the Fischer 344 rat following intravenous administration. These data indicate that reducing the extent of NIF sialylation reduces the half-life of the molecule due to an increase in the systemic clearance. Also, an increase in the number of unsialylated or neutral glycans may increase the volume of distribution of NIF, although this effect is marginal. 3. Isolated perfused rat liver (IPRL) investigations have shown that sialylated NIF has a low hepatic extraction (< 1%), while asialo NIF has an extraction that is > 20-fold higher. Co-administration of asialo NIF with asialo fetuin (a protein cleared by hepatic asialoglycoprotein receptor (possibly galactose)-mediated uptake reduced the hepatic extraction of asialo NIF. 4. These data suggest that NIF molecules that have free sugar moieties (possibly galactose) interact with an asialoglycoprotein receptor (possibly galactose-mediated) in the liver (parenchymal cells/hepatocytes). Interaction with this receptor leads to cellular internalization and degradation.

  10. Sialylation of prion protein controls the rate of prion amplification, the cross-species barrier, the ratio of PrPSc glycoform and prion infectivity.

    PubMed

    Katorcha, Elizaveta; Makarava, Natallia; Savtchenko, Regina; D'Azzo, Alessandra; Baskakov, Ilia V

    2014-09-01

    The central event underlying prion diseases involves conformational change of the cellular form of the prion protein (PrP(C)) into the disease-associated, transmissible form (PrP(Sc)). Pr(PC) is a sialoglycoprotein that contains two conserved N-glycosylation sites. Among the key parameters that control prion replication identified over the years are amino acid sequence of host PrP(C) and the strain-specific structure of PrPSc. The current work highlights the previously unappreciated role of sialylation of PrP(C) glycans in prion pathogenesis, including its role in controlling prion replication rate, infectivity, cross-species barrier and PrP(Sc) glycoform ratio. The current study demonstrates that undersialylated PrP(C) is selected during prion amplification in Protein Misfolding Cyclic Amplification (PMCAb) at the expense of oversialylated PrP(C). As a result, PMCAb-derived PrP(Sc) was less sialylated than brain-derived PrP(Sc). A decrease in PrPSc sialylation correlated with a drop in infectivity of PMCAb-derived material. Nevertheless, enzymatic de-sialylation of PrP(C) using sialidase was found to increase the rate of PrP(Sc) amplification in PMCAb from 10- to 10,000-fold in a strain-dependent manner. Moreover, de-sialylation of PrP(C) reduced or eliminated a species barrier of for prion amplification in PMCAb. These results suggest that the negative charge of sialic acid controls the energy barrier of homologous and heterologous prion replication. Surprisingly, the sialylation status of PrP(C) was also found to control PrP(Sc) glycoform ratio. A decrease in Pr(PC) sialylation levels resulted in a higher percentage of the diglycosylated glycoform in PrP(Sc). 2D analysis of charge distribution revealed that the sialylation status of brain-derived PrP(C) differed from that of spleen-derived PrP(C). Knocking out lysosomal sialidase Neu1 did not change the sialylation status of brain-derived PrP(C), suggesting that Neu1 is not responsible for desialylation of Pr

  11. 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

  12. 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.

  13. NASA Lewis' IITA K-12 Program

    NASA Technical Reports Server (NTRS)

    1996-01-01

    The NASA Lewis Research Center's Information Infrastructure Technology and Applications for Kindergarten to 12th Grade (IITA K-12) Program is designed to introduce into school systems computing and communications technology that benefits math and science studies. By incorporating this technology into K-12 curriculums, we hope to increase the proficiency and interest in math and science subjects by K-12 students so that they continue to study technical subjects after their high school careers are over.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. Challenges in Antibody Development against Tn and Sialyl-Tn Antigens

    PubMed Central

    Loureiro, Liliana R.; Carrascal, Mylène A.; Barbas, Ana; Ramalho, José S.; Novo, Carlos; Delannoy, Philippe; Videira, Paula A.

    2015-01-01

    The carbohydrate antigens Tn and sialyl-Tn (STn) are expressed in most carcinomas and usually absent in healthy tissues. These antigens have been correlated with cancer progression and poor prognosis, and associated with immunosuppressive microenvironment. Presently they are used in clinical trials as therapeutic vaccination, but with limited success due to their low immunogenicity. Alternatively, anti-Tn and/or STn antibodies may be used to harness the immune system against tumor cells. Whilst the development of antibodies against these antigens had a boost two decades ago for diagnostic use, so far no such antibody entered into clinical trials. Possible limitations are the low specificity and efficiency of existing antibodies and that novel antibodies are still necessary. The vast array of methodologies available today will allow rapid antibody development and novel formats. Following the advent of hybridoma technology, the immortalization of human B cells became a methodology to obtain human monoclonal antibodies with better specificity. Advances in molecular biology including phage display technology for high throughput screening, transgenic mice and more recently molecularly engineered antibodies enhanced the field of antibody production. The development of novel antibodies against Tn and STn taking advantage of innovative technologies and engineering techniques may result in innovative therapeutic antibodies for cancer treatment. PMID:26270678

  19. 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.

  20. Ultrasensitive electrochemical biosensor based on graphite oxide, Prussian blue, and PTC-NH2 for the detection of α2,6-sialylated glycans in human serum.

    PubMed

    Gao, Liuliu; He, Junlin; Xu, Wailan; Zhang, Jing; Hui, Junmin; Guo, Yanlei; Li, Wenjuan; Yu, Chao

    2014-12-15

    α2,6-Sialylated glycans are crucial molecular targets for cancer diagnosis and clinical research. In this work, a novel ultrasensitive electrochemical biosensor was fabricated based on a graphite oxide (GO), Prussian blue (PB), and PTC-NH2 (an ammonolysis product of 3,4,9,10-perylenetetracarboxylic dianhydride) nanocomposite for the selective detection of α2,6-sialylated glycans. To increase the sensitivity of the electrochemical biosensor, gold nanoparticles (GNPs) were immobilized on a GO-PB-PTC-NH2 modified glassy carbon electrode (GCE). Sambucus nigra agglutinins (SNAs), which specifically bind with α2,6-sialylated glycans, were covalently immobilized on GNPs for the sensitive detection of α2,6-sialylated glycans in serum. This proposed method can be applied to human serum, and it worked well over a broad linear range (0.1 pg mL(-1)-500 ng mL(-1)) with detection limits of 0.03 pg mL(-1). Moreover, recovery of the spiked samples ranged from 100.2% to 105.0%, suggesting that this excellent electrochemical biosensor can be used for the practical detection of α2,6-sialylated glycans.

  1. Cooperative Lewis acid/N-heterocyclic carbene catalysis

    PubMed Central

    Cohen, Daniel T.; Scheidt, Karl A.

    2015-01-01

    Lewis acid activation with N-heterocyclic carbene (NHC) catalysis has presented new opportunities for enantioselective reaction development. Recent findings illustrate that Lewis acids can play an important role in homoenolate annulations by: enhancement of the reactivity, reversal of the diastereo- or regioselectivity, and activation of previously inactive electrophiles. Additionally, the incorporation of a Lewis acid into Brønsted base-catalyzed conjugate addition allowed for an increase in yields. PMID:26413259

  2. 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.

  3. 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

  4. NEU3 activity enhances EGFR activation without affecting EGFR expression and acts on its sialylation levels.

    PubMed

    Mozzi, Alessandra; Forcella, Matilde; Riva, Alice; Difrancesco, Carlotta; Molinari, Francesca; Martin, Vittoria; Papini, Nadia; Bernasconi, Barbara; Nonnis, Simona; Tedeschi, Gabriella; Mazzucchelli, Luca; Monti, Eugenio; Fusi, Paola; Frattini, Milo

    2015-08-01

    Several studies performed over the last decade have focused on the role of sialylation in the progression of cancer and, in particular, on the association between deregulation of sialidases and tumorigenic transformation. The plasma membrane-associated sialidase NEU3 is often deregulated in colorectal cancer (CRC), and it was shown that this enzyme co-immunoprecipitates in HeLa cells with epidermal growth factor receptor (EGFR), the molecular target of most recent monoclonal antibody-based therapies against CRC. To investigate the role of NEU3 sialidase on EGFR deregulation in CRC, we first collected data on NEU3 gene expression levels from a library of commercial colon cell lines, demonstrating that NEU3 transcription is upregulated in these cell lines. We also found EGFR to be hyperphosphorylated in all cell lines, with the exception of SW620 cells and the CCD841 normal intestinal cell line. By comparing the effects induced by overexpression of either the wild-type or the inactive mutant form of NEU3 on EGFR, we demonstrated that the active form of NEU3 enhanced receptor activation without affecting EGFR mRNA or protein expression. Moreover, through western blots and mass spectrometry analysis, we found that EGFR immunoprecipitated from cells overexpressing active NEU3, unlike the receptor from mock cells and cells overexpressing inactive NEU3, is desialylated. On the whole, our data demonstrate that, besides the already reported indirect EGFR activation through GM3, sialidase NEU3 could also play a role on EGFR activation through its desialylation. PMID:25922362

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

    PubMed Central

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

    1990-01-01

    We 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 [3H]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 (2.9- to 7.4-fold increase for TSH-alpha; 15.1- to 25.5-fold increase for TSH-beta). 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. These changes were specific for TSH because glycosylation of free alpha subunit (synthesized by the thyrotroph and gonadotroph) and of total glycoproteins was minimally altered by hypothyroidism. 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. Specifically, such posttranslational changes may be an important adaptive response to prevent the consequences of endocrine deficiency during early development. PMID:1692623

  6. The Role of Sialyl Glycan Recognition in Host Tissue Tropism of the Avian Parasite Eimeria tenella

    PubMed Central

    Garnett, James; Campanero-Rhodes, Maria A.; Blake, Damer P.; Palma, Angelina S.; Chai, Wengang; Ferguson, David J. P.; Simpson, Peter; Feizi, Ten; Tomley, Fiona M.; Matthews, Stephen

    2011-01-01

    Eimeria spp. are a highly successful group of intracellular protozoan parasites that develop within intestinal epithelial cells of poultry, causing coccidiosis. As a result of resistance against anticoccidial drugs and the expense of manufacturing live vaccines, it is necessary to understand the relationship between Eimeria and its host more deeply, with a view to developing recombinant vaccines. Eimeria possesses a family of microneme lectins (MICs) that contain microneme adhesive repeat regions (MARR). We show that the major MARR protein from Eimeria tenella, EtMIC3, is deployed at the parasite-host interface during the early stages of invasion. EtMIC3 consists of seven tandem MAR1-type domains, which possess a high specificity for sialylated glycans as shown by cell-based assays and carbohydrate microarray analyses. The restricted tissue staining pattern observed for EtMIC3 in the chicken caecal epithelium indicates that EtMIC3 contributes to guiding the parasite to the site of invasion in the chicken gut. The microarray analyses also reveal a lack of recognition of glycan sequences terminating in the N-glycolyl form of sialic acid by EtMIC3. Thus the parasite is well adapted to the avian host which lacks N-glycolyl neuraminic acid. We provide new structural insight into the MAR1 family of domains and reveal the atomic resolution basis for the sialic acid-based carbohydrate recognition. Finally, a preliminary chicken immunization trial provides evidence that recombinant EtMIC3 protein and EtMIC3 DNA are effective vaccine candidates. PMID:22022267

  7. Blood Plasma-Derived Anti-Glycan Antibodies to Sialylated and Sulfated Glycans Identify Ovarian Cancer Patients

    PubMed Central

    Pochechueva, Tatiana; Chinarev, Alexander; Schoetzau, Andreas; Fedier, André; Bovin, Nicolai V.; Hacker, Neville F.; Jacob, Francis; Heinzelmann-Schwarz, Viola

    2016-01-01

    Altered levels of naturally occurring anti-glycan antibodies (AGA) circulating in human blood plasma are found in different pathologies including cancer. Here the levels of AGA directed against 22 negatively charged (sialylated and sulfated) glycans were assessed in high-grade serous ovarian cancer (HGSOC, n = 22) patients and benign controls (n = 31) using our previously developed suspension glycan array (SGA). Specifically, the ability of AGA to differentiate between controls and HGSOC, the most common and aggressive type of ovarian cancer with a poor outcome was determined. Results were compared to CA125, the commonly used ovarian cancer biomarker. AGA to seven glycans that significantly (P<0.05) differentiated between HGSOC and control were identified: AGA to top candidates SiaTn and 6-OSulfo-TF (both IgM) differentiated comparably to CA125. The area under the curve (AUC) of a panel of AGA to 5 glycans (SiaTn, 6-OSulfo-TF, 6-OSulfo-LN, SiaLea, and GM2) (0.878) was comparable to CA125 (0.864), but it markedly increased (0.985) when combined with CA125. AGA to SiaTn and 6-OSulfo-TF were also valuable predictors for HGSOC when CA125 values appeared inconclusive, i.e. were below a certain threshold. AGA-glycan binding was in some cases isotype-dependent and sensitive to glycosidic linkage switch (α2–6 vs. α2–3), to sialylation, and to sulfation of the glycans. In conclusion, plasma-derived AGA to sialylated and sulfated glycans including SiaTn and 6-OSulfo-TF detected by SGA present a valuable alternative to CA125 for differentiating controls from HGSOC patients and for predicting the likelihood of HGSOC, and may be potential HGSOC tumor markers. PMID:27764122

  8. Fraction A of armadillo submandibular glycoprotein and its desialylated product as sialyl-Tn and Tn receptors for lectins.

    PubMed

    Wu, A M; Shen, F; Herp, A; Song, S C; Wu, J H

    1995-02-27

    Fraction A of the armadillo submandibular glycoprotein (ASG-A) is one of the simplest glycoproteins among mammalian salivary mucins. The carbohydrate side chains of this mucous glycoprotein have one-third of the NeuAc alpha 2-->6GalNAc (sialyl-Tn) sequence and two thirds of Tn (GalNAc alpha-->Ser/Thr) residues. Those of the desialylated product (ASG-Tn) are almost exclusively unsubstituted GalNAc residues (Tn determinant). When the binding properties of these glycoproteins were tested by a precipitin assay with Gal, GalNAc and GlcNAc specific lectins, it was found that ASG-Tn reacted strongly with all of the Tn-active lectins and completely precipitated Vicia villosa (VVL both B4 and mixture of A and B), Maclura pomifera (MPA), and Artocarpus integrifolia (jacalin) lectins. However, it precipitated poorly or negligibly with Ricinus communis (RCA1); Dolichos biflorus (DBA); Viscum album, ML-I; Arachis hypogaea (PNA), and Triticum vulgaris (WGA). The reactivity of ASG-A (sialyl-Tn) was as active as that of ASG-Tn with MPA and less or slightly less active than that of ASG-Tn with VVL-A+B, VVL-B4, HPA, WFA, and jacalin, as one-third of its Tn was sialylated. These findings indicate that ASG-A and its desialylated product (ASG-Tn) are highly useful reagents for the differentiation of Tn, T (Gal beta 1-->3GalNAc), A (GalNAc alpha 1-->3Gal) or Gal specific lectins and monoclonal antibodies against such epitopes.

  9. 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

  10. Persistent Seoul virus infection in Lewis rats.

    PubMed

    Compton, S R; Jacoby, R O; Paturzo, F X; Smith, A L

    2004-07-01

    Mechanistic studies of hantavirus persistence in rodent reservoirs have been limited by the lack of a versatile animal model. This report describes findings from experimental infection of inbred Lewis rats with Seoul virus strain 80-39. Rats inoculated with virus intraperitoneally at 6 days of age became persistently infected without clinical signs. Tissues from Seoul virus-inoculated 6-day-old rats were assessed at 6, 9, and 12 weeks post-inoculation for viral RNA by RT-PCR and in situ hybridization (ISH) and for infectious virus by inoculation of Vero E6 cells. Virus was isolated from lung and kidney of infected rats at 6 weeks and viral RNA was detected in lung, kidney, pancreas, salivary gland, brain, spleen, liver and skin at 6, 9 and 12 weeks. Rats inoculated with Seoul virus intraperitoneally at 10 or 21 days of age became infected without clinical signs but had low to undetectable levels of viral RNA in tissues at 6 weeks post-inoculation. ISH identified vascular smooth muscle and endothelial cells as common sites of persistent infection. Cultured rat smooth muscle cells and to a lesser extent cultured endothelial cells also were susceptible to Seoul virus infection. Pancreatic infection resulted in insulitis with associated hyperglycemia. These studies demonstrate that infant Lewis rats are uniformly susceptible to asymptomatic persistent Seoul virus infection. Additionally, they offer opportunities for correlative in vivo and in vitro study of Seoul virus interactions in host cell types that support persistent infection.

  11. Glial involvement in diffuse Lewy body disease.

    PubMed

    Terada, Seishi; Ishizu, Hideki; Yokota, Osamu; Tsuchiya, Kuniaki; Nakashima, Hanae; Ishihara, Takeshi; Fujita, Daisuke; Uéda, Kenji; Ikeda, Kenji; Kuroda, Shigetoshi

    2003-02-01

    Diffuse Lewy body disease (DLBD) is characterized by the presence of Lewy bodies (LB) in the neurons and neurites of cortical, subcortical, and brain stem structures. Recently, alpha-synuclein (alphaS) has been found to be a central constituent of LB. In DLBD, abnormal accumulation of alphaS has been reported in both neurons and glia, but studies on glial lesions in DLBD have been limited. We examined in detail the constituents and distribution of glial lesions in eight patients with DLBD and report the pathogenesis of the glial lesions. alphaS-positive neuronal cytoplasmic inclusions (NI), neuropil threads (NT), and coiled bodies (CB) showed similar immunostaining profiles. Without pretreatment, NI, NT, and CB were detected by all antibodies against alphaS. The immunostaining profile of star-like astrocytes (SLA) was quite different from those of NI, NT, and CB. A few SLA were stained by an antibody against the non-Abeta component portion of alphaS without pretreatment, but formic acid pretreatment dramatically enhanced SLA immunoreactivity. SLA and CB were found in all eight brains with DLBD. SLA were scarce in the brain stem, but there were hundreds of SLA per visual field at x100 magnification in the temporal cortex of most cases, while CB were found diffusely in both the cerebral cortex and brain stem, similar to NI. This suggests that the pathogenesis of SLA is different from those of NI and CB.

  12. 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

  13. Small intestinal goblet cell proliferation induced by ingestion of soluble and insoluble dietary fiber is characterized by an increase in sialylated mucins in rats.

    PubMed

    Hino, Shingo; Takemura, Naoki; Sonoyama, Kei; Morita, Akio; Kawagishi, Hirokazu; Aoe, Seiichiro; Morita, Tatsuya

    2012-08-01

    The study aimed to examine the effects of insoluble and soluble fibers on mucin sialylation and sulfation in the small intestine. First, diets containing soluble [konjac mannan (KM), psyllium, or guar gum; 50 g/kg) or insoluble (polystyrene foam, wheat bran, or cornhusk; 80 g/kg) fiber were fed to rats for 13 d. The fiber-fed groups had more goblet cells in the ileum than the fiber-free control group. High-iron diamine/alcian blue staining showed more sialylated mucin-producing cells in the fiber-fed groups than in the control, whereas sulfated mucin-producing cells were fewer (insoluble fibers) or unchanged (soluble fibers). Second, feeding KM (50 g/kg) and beet fiber (BF) (80 g/kg) diets for 7 d yielded a higher ileum Siat4C expression than the control, but Gal3ST2 and Gal3ST4 expression was comparable. Luminal mucin content correlated with sialic acid (r = 0.96; P < 0.001) or sulfate (r = 0.62; P < 0.01), but the slope of the sialic acid-derived equation was greater than that of the sulfate-derived equation, indicating a preferred increase in sialylated mucins. Third, rats were fed the control diet for 10 d while receiving antibiotic treatment. Analysis of the luminal mucin showed that sialylated mucins were more vulnerable to bacterial degradation than sulfated mucins. Finally, a study of bromo-deoxyuridine incorporation in rats fed a BF diet indicated that goblet cell proliferation accompanied by increased sialylated mucin appeared to be related to accelerated ileal epithelial cell migration. We conclude that intestinal goblet cell responses to insoluble and soluble fibers are characterized by increases in sialylated mucin production.

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

    PubMed

    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

  15. 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…

  16. 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…

  17. 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…

  18. 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.

  19. 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

  20. 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

  1. 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.

  2. NASA Lewis Meshed VSAT Workshop meeting summary

    NASA Astrophysics Data System (ADS)

    Ivancic, William

    1993-11-01

    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.

  3. [Clinical Neuropsychology of Dementia with Lewy Bodies].

    PubMed

    Nagahama, Yasuhiro

    2016-02-01

    Dementia with Lewy bodies (DLB) shows lesser memory impairment and more severe visuospatial disability than Alzheimer disease (AD). Although deficits in both consolidation and retrieval underlie the memory impairment, retrieval deficit is predominant in DLB. Visuospatial dysfunctions in DLB are related to the impairments in both ventral and dorsal streams of higher visual information processing, and lower visual processing in V1/V2 may also be impaired. Attention and executive functions are more widely disturbed in DLB than in AD. Imitation of finger gestures is impaired more frequently in DLB than in other mild dementia, and provides additional information for diagnosis of mild dementia, especially for DLB. Pareidolia, which lies between hallucination and visual misperception, is found frequently in DLB, but its mechanism is still under investigation.

  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. Lewis morris rutherfurd 1816-1892.

    PubMed

    Devons, S

    1976-07-01

    Lewis M. Rutherfurd (1816-1892) was a wealthy amateur practitioner of science, making notable contributions to the optics of astronomy and spectroscopy. He graduated from Williams College at the age of 18 and soon began a career in law. Not long thereafter he was fortunate enough to acquire sufficient wealth through marriage to permit him to pursue scientific activity, for which he had gained interest. He soon became interested in photographing the heavens to obtain quantitative data regarding star motions. A few years later he developed a spectrometer with which he obtained some of the best attainable stellar spectra of the time. Rutherfurd is not widely known because he did not fully report his work; but through correspondence and instrument development he had a profound influence on his contemporaries. He was made a trustee of Columbia College in 1858, and in 1881 he helped to found a department of Geodesy and Practical Astronomy there.

  6. 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.

  7. 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

  8. 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.

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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

  14. New hypersonic facility capability at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Haas, Jeffrey E.; Chamberlin, Roger; Dicus, John H.

    1989-01-01

    Four facility activities are underway at NASA Lewis Research Center to develop new hypersonic propulsion test capability. Two of these efforts consist of upgrades to existing operational facilities. The other two activities will reactivate facilities that have been in a standby condition for over 15 years. These four activities are discussed and the new test facilities NASA Lewis will have in place to support evolving high speed research programs are described.

  15. 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.

  16. 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.

  17. 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

  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. 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.

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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.

  6. Lewis inverse design code (LINDES): Users manual

    NASA Technical Reports Server (NTRS)

    Sanz, Jose M.

    1987-01-01

    The method of complex characteristics and hodograph transformation for the design of shockless airfoils was introduced by Bauer, Garabedian, and Korn and has been extended by the author to design subcritical and supercritical cascades with high solidities and large inlet angles. This new capability was achieved by introducing a new conformal mapping of the hodograph domain onto an ellipse and expanding the solution in terms of Chebyshev polynomials. A new computer code, the NASA Lewis inverse design code, was developed based on this idea. This new design code is an efficient method for the design of airfoils in cascade. In particular, the design of subcritical cascades of airfoils is a very fast, robust, and versatile process. The inverse design code can be made to interact with a turbulent boundary layer calculation to obtain airfoils with no separated flows at the design condition. This report is intended to serve as a users manual for this design code. Material previously reported by the author is included here for completeness and quick access to the user. The manual contains a description of the method followed by a discussion of the design procedure and examples. The input parameters necessary to run the code are then described and their default values given. Output listings corresponding to six different blade shapes designed with the code are given, as well as the necessary input data to reproduce the computer runs. The examples have been chosen to show that a wide range of applications can be covered with the code, ranging from supercritical propeller sections to wind tunnel turning vanes that can operate with a large inlet flow angle range.

  7. 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

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

    PubMed Central

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

    2012-01-01

    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

  9. 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

  10. 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.

  11. 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

  12. 360-MHz 1H nuclear-magnetic-resonance spectroscopy of sialyl-oligosaccharides from patients with sialidosis (mucolipidosis I and II).

    PubMed

    Dorland, L; Haverkamp, J; Viliegenthart, J F; Strecker, G; Michalski, J C; Fournet, B; Spik, G; Montreuil, J

    1978-06-15

    360-MHz proton nuclear magnetic resonance spectra were recorded of 10 sialyl-oligosaccharides isolated from urine of sialidosis patients. Their structures are related to the complex asparagine-linked glycan chains of glycoproteins. By correlation of these spectra and comparison with spectra of reference glycopeptides and sialyl-lactose isomers it was possible to assign all signals belonging to anomeric, mannose H-2, sialic acid H-3 and N-acetyl protons. The number of the consituting monosaccharide residues of the oligomers can be obtained by integration of the above-mentioned signals. The chemical shifts of the anomeric and mannose H-2 protons give information about the type of glycan structure (mono-, bi-, triantennary) and the presence of terminal sialic acid at each of the antennas. The chemical shifts of sialic acid H-3 protons are typical for sialic acid residues in 2 leads to 3 or 2 leads to 6 linkage to galactose.

  13. Common Textbook and Teaching Misrepresentations of Lewis Structures

    NASA Astrophysics Data System (ADS)

    Suidan, Laila; Badenhoop, Jay K.; Glendening, Eric D.; Weinhold, Frank

    1995-07-01

    Current freshman chemistry textbooks commonly advise the drawing of Lewis structures with much emphasis on the reduction of formal charge and little on the preservation of the octet rule. This currently accepted method produces structures different from the original Lewis structures, which rarely had expanded valence shells on central atoms. Computational results from Gaussian 92 have shown us that the leading resonance structures cited in freshman chemistry textbooks are often not the most accurate to represent the molecules and are, at best, minor resonance structures, whose presentation is not worth the confusion that it causes for many first-year students. Instead, the Lewis structures that most accurately represent these molecules are the original Lewis structures, which generally abide by the octet rule. If the octet rule is more strongly stressed in the teaching of Lewis structures-thus avoiding the many complications and sources of confusion related to valence-shell expansion and reduction of formal charge-freshman chemistry students will be able to rest a little easier at night.

  14. The spectrum of cognitive impairment in Lewy body diseases.

    PubMed

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

    2014-04-15

    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. It is now recognized that cognitive dysfunction occurs 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 rapid eye movement 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. This has led to much research regarding the diagnosis, prognosis, and underlying neurobiology of mild cognitive impairment in Parkinson's disease, but 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. Although these disorders overlap in many aspects of their presentations and pathophysiology, they differ in other elements, 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.

  15. Habitat Selection and Reproductive Success of Lewis's Woodpecker (Melanerpes lewis) at Its Northern Limit

    PubMed Central

    Zhu, Xiang; Srivastava, Diane S.; Martin, Kathy

    2012-01-01

    Lewis's Woodpecker (Melanerpes lewis) has experienced population declines in both Canada and the United States and in 2010 was assigned a national listing of threatened in Canada. We conducted a two-year study (2004–2005) of this species at its northern range limit, the South Okanagan Valley in British Columbia, Canada. Our main objective was to determine whether the habitat features that influenced nest-site selection also predicted nest success, or whether other factors (e.g. cavity dimensions, clutch initiation date or time of season) were more important. Nest tree decay class, density of suitable cavities and total basal area of large trees were the best predictors of nest-site selection, but these factors were unrelated to nesting success. Estimates of demographic parameters (mean ± SE) included daily nest survival rate (0.988±0.003, years combined), nest success (0.52±0.08), clutch size (5.00±0.14 eggs), female fledglings per successful nest (1.31±0.11), and annual productivity (0.68±0.12 female fledglings per nest per year). Although higher nest survival was associated with both early and late initiated clutches, early-initiated clutches allowed birds to gain the highest annual productivity as early clutches were larger. Nests in deep cavities with small entrances experienced lower predation risk especially during the peak period of nest predation. We concluded that nest-site selection can be predicted by a number of easily measured habitat variables, whereas nest success depended on complicated ecological interactions among nest predators, breeding behaviors, and cavity features. Thus, habitat-based conservation strategies should also consider ecological factors that may not be well predicted by habitat. PMID:23028525

  16. A Lewis basicity scale in dichloromethane for amines and common nonprotogenic solvents using a zinc(II) Schiff-base complex as reference Lewis acid.

    PubMed

    Oliveri, Ivan Pietro; Maccarrone, Giuseppe; Di Bella, Santo

    2011-11-01

    A consistent, reliable scale of Lewis basicity in dichloromethane for 26 bases, involving amines and nonprotogenic solvents, is presented. A Lewis acidic Zn(II) Schiff-base complex, involving formation of stable 1:1 adducts is used as reference acid. Evaluation of binding constants is achieved from spectrophotometric titrations, by the least-squares nonlinear regression of multiwavelength spectrophotometric data. This Lewis basicity scale represents a unique set of data reflecting the actual Lewis basicity with respect this "real world" Lewis acidic species. The comparison of present Lewis basicity scale with data reported in the literature indicates that while for the involved solvents their relative basicity is scarcely affected by the reference Lewis acid, in contrast for sterically encumbered amines the Lewis basicity seems to be dependent from the reference species. Thus, Lewis basicity is governed by the steric hindrance at the donor atom and involves very different relative basicities than those predicted considering typical reference Lewis acids. This is expected to have a major involvement in the organic synthesis and catalysis, given the sterically encumbered nature of commonly involved Lewis acidic organometallic complexes.

  17. 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

  18. Hydrogen activation by frustrated lewis pairs: insights from computational studies.

    PubMed

    Rokob, Tibor András; Pápai, Imre

    2013-01-01

    Sterically encumbered Lewis acid-base pairs, the so-called frustrated Lewis pairs, can split dihydrogen heterolytically and act as transition metal free catalysts for the hydrogenation of unsaturated compounds. Here we review the results from our quantum chemical calculations aimed at the understanding of this remarkable class of reactions and we put them into the context of related works from other research groups. The thermodynamics of the H2 splitting reaction is discussed first; the role of acid-base properties, intramolecular cooperativity, and other factors is assessed, employing an energy partitioning scheme and also in the light of the latest experimental findings. The mechanism of hydrogen cleavage is then examined, and an overview about the applicability of our reactivity model involving synergistic electron transfers between H2 and preorganized Lewis acid/base centers is given. Finally, insights about catalytic cycles in FLP-mediated hydrogenations are summarized, pinpointing the diversity of the involved elementary steps and their possible sequences.

  19. 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.

  20. Hydrogen cleavage by solid-phase frustrated Lewis pairs.

    PubMed

    Xing, Jun-Yi; Buffet, Jean-Charles; Rees, Nicholas H; Nørby, Peter; O'Hare, Dermot

    2016-08-18

    We report the direct synthesis of a solid-phase frustrated Lewis pair (s-FLP) by combining a silica-supported Lewis acid ([triple bond, length as m-dash]SiOB(C6F5)2, s-BCF) with a Lewis base (tri-tert-butylphosphine, (t)Bu3P) to give [[triple bond, length as m-dash]SiOB(C6F5)2][(t)Bu3P]. Reaction of this s-FLP with H2 under mild conditions led to heterolytic H-H bond cleavage and the formation of [[triple bond, length as m-dash]SiOB(H)(C6F5)2][(t)Bu3PH].

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. Different binding properties of three monoclonal antibodies to sialyl Le(x) glycolipids in a gastric cancer cell line and normal stomach tissue.

    PubMed

    Dohi, T; Nemoto, T; Ohta, S; Shitara, K; Hanai, N; Nudelman, E; Hakomori, S; Oshima, M

    1993-01-01

    We established a mouse monoclonal antibody (Mab) KM93 which recognized sialyl Le(x)-carbohydrate epitope determined by solid phase radioimmunoassay using a panel of authentic glycolipids. The specificity of KM93 was similar to another anti-sialyl Le(x) Mab CSLEX-1 established previously, and different from that of Mab FH6 which recognized sialyl Le(x)-i (sialyl dimeric Le(x)). In a further study, however, we found that KM93 reacted with some glycolipids much more strongly than CSLEX-1 did on thin-layer chromatography (TLC) plates. We purified two gangliosides named K-1 and K-2 from gastric cancer cell line KATOIII, and three gangliosides named H-1, H-2, and H-3 from human stomach. KM93 reacted with all of these glycolipids. CSLEX-1 reacted with K-1 and K-2 with less intensity than KM93 did, and faintly reacted with H-1, but not at all with H-2 or H-3. FH6 did not react with K-1, K-2 or H-1, while it stained H-2 and H-3. In spite of this different reactivity with Mabs, analysis by proton nuclear magnetic resonance (1H NMR) proved that carbohydrate structure of K-1 and H-2 were the same: NeuAc alpha 2-->3Ga1 beta 1-->4 [Fuc alpha 1-->3] G1cNAc beta 1-->3 Ga1 beta 1-->4G1c beta 1-->1Cer. The H1 NMR spectrum of H-3 also indicated that H-3 consisted of the same sugars as K-1. These results indicated that KM93 had wider reactivity than CSLEX-1, and that the distinct reactivity of KM93 from CSLEX-1 was not caused by sugar moiety. It was also shown that the interaction of sialyl Le(x) sugar determinant with MAb depended on the tissue origin of molecules carrying carbohydrate. PMID:8239497

  13. 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

  14. 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

  15. Sialylation of Streptococcus suis serotype 2 is essential for capsule expression but is not responsible for the main capsular epitope.

    PubMed

    Lecours, Marie-Pier; Fittipaldi, Nahuel; Takamatsu, Daisuke; Okura, Masatoshi; Segura, Mariela; Goyette-Desjardins, Guillaume; Van Calsteren, Marie-Rose; Gottschalk, Marcelo

    2012-09-01

    The capsular polysaccharide is a critical virulence factor of the swine and zoonotic pathogen Streptococcus suis serotype 2. The capsule of this bacterium is composed of five different sugars, including terminal sialic acid. To evaluate the role of sialic acid in the pathogenesis of the infection, the neuC gene, encoding for an enzyme essential for sialic acid biosynthesis, was inactivated in a highly virulent S. suis serotype 2 strain. Using transmission electron microscopy, it was shown that inactivation of neuC resulted in loss of expression of the whole capsule. Compared to the parent strain, the ΔneuC mutant strain was more phagocytosed by macrophages and was also severely impaired in virulence in a mouse infection model. Both native and desialylated S. suis serotype 2 purified capsular polysaccharides were recognized by a polyclonal anti-whole cell S. suis serotype 2 serum and a monospecific polyclonal anti-capsule serotype 2 serum. In contrast, only the native capsular polysaccharide was recognized by a monoclonal antibody specific for the sialic acid moiety of the serotype 2 capsule. Together, our results infer that sialylation of S. suis serotype 2 may be essential for capsule expression, but that this sugar is not the main epitope of this serotype.

  16. An Improved Protocol for N-Glycosylation Analysis of Gel-Separated Sialylated Glycoproteins by MALDI-TOF/TOF

    PubMed Central

    Hao, Piliang; Ren, Yan; Xie, Yongming

    2010-01-01

    Different glycoforms of some proteins have been identified as differential spots for certain diseases in 2-DE, indicating disease-related glycosylation changes. It is routine to determine the site-specific glycosylation of nonsialylated N-glycoproteins from a single gel spot, but some obstacles still exist in analyzing sialylated glycoproteins due to the lability and higher detection limit of acid glycans in MALDI-TOF/TOF analysis. Thus, we present an improved protocol here. Tryptic glycopeptides were separated and subjected to MALDI-TOF/TOF analysis, resulting in the identification of site-specific glycosylation of high-intensity glycopeptides. Sequential deglycosylation and desialylation were used to improve the identification of glycosylation sites and desialylated glycans. The site-specific glycosylation of large glycopeptides and low-intensity glycopeptides was deduced based on the masses of glycopeptides, deglycosylated peptides and desialylated glycans. By applying it to 2-DE separated human serum, the difference of N-glycosylation was successfully determined for α1-antitrypsin between different gel spots. PMID:21124746

  17. 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

  18. Lewis base mediated β-elimination and Lewis acid mediated insertion reactions of disilazido zirconium compounds.

    PubMed

    Yan, KaKing; Duchimaza Heredia, Juan J; Ellern, Arkady; Gordon, Mark S; Sadow, Aaron D

    2013-10-01

    The reactivity of a series of disilazido zirconocene complexes is dominated by the migration of anionic groups (hydrogen, alkyl, halide, OTf) between the zirconium and silicon centers. The direction of these migrations is controlled by the addition of two-electron donors (Lewis bases) or two-electron acceptors (Lewis acids). The cationic nonclassical [Cp2ZrN(SiHMe2)2](+) ([2](+)) is prepared from Cp2Zr{N(SiHMe2)2}H (1) and B(C6F5)3 or [Ph3C][B(C6F5)4], while reactions of B(C6F5)3 and Cp2Zr{N(SiHMe2)2}R (R = Me (3), Et (5), n-C3H7 (7), CH═CHSiMe3 (9)) provide a mixture of [2](+) and [Cp2ZrN(SiHMe2)(SiRMe2)](+). The latter products are formed through B(C6F5)3 abstraction of a β-H and R group migration from Zr to the β-Si center. Related β-hydrogen abstraction and X group migration reactions are observed for Cp2Zr{N(SiHMe2)2}X (X = OTf (11), Cl (13), OMe (15), O-i-C3H7 (16)). Alternatively, addition of DMAP (DMAP = 4-(dimethylamino)pyridine) to [2](+) results in coordination to a Si center and hydrogen migration to zirconium, giving the cationic complex [Cp2Zr{N(SiHMe2)(SiMe2DMAP)}H](+) ([19](+)). Related hydrogen migration occurs from [Cp2ZrN(SiHMe2)(SiMe2OCHMe2)](+) ([18](+)) to give [Cp2Zr{N(SiMe2DMAP)(SiMe2OCHMe2)}H](+) ([22](+)), whereas X group migration is observed upon addition of DMAP to [Cp2ZrN(SiHMe2)(SiMe2X)](+) (X = OTf ([12](+)), Cl ([14](+))) to give [Cp2Zr{N(SiHMe2)(SiMe2DMAP)}X](+) (X = OTf ([26](+)), Cl ([20](+))). The species involved in these transformations are described by resonance structures that suggest β-elimination. Notably, such pathways are previously unknown in early metal amide chemistry. Finally, these migrations facilitate direct Si-H addition to carbonyls, which is proposed to occur through a pathway that previously had been reserved for later transition metal compounds.

  19. 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

  20. 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%.

  1. Lewis Latimer: African American Inventor, Poet and Activist.

    ERIC Educational Resources Information Center

    Judd, Michael

    1998-01-01

    Details a lesson plan that examines the life and career of Lewis Latimer. Latimer, the self-taught son of fugitive slaves, rose to a prominent position in Thomas Edison's Electric Company and pioneered many innovations in the early electric industry. Includes a biographical sketch of Latimer, photographs, and illustrations. (MJP)

  2. A neurobiological nonalternative: rejoinder to Lewis, Baumeister, and Mailman.

    PubMed

    Newsom, C; Lovaas, O I

    1987-01-01

    Certain misrepresentations of our theory of self-stimulatory behavior by Lewis, Baumeister, and Mailman (1987) are corrected and several questions raised by the commentators are answered. Their proposed neurobiological alternative is considered briefly and judged to be insufficiently detailed, inadequate in scope, and therefore premature.

  3. 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…

  4. 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.

  5. 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.

  6. Common Textbook and Teaching Misrepresentations of Lewis Structures.

    ERIC Educational Resources Information Center

    Suidan, Laila; Badenhoop, K.; Glendening, Eric D.; Weinhold, Frank

    1995-01-01

    The leading resonance structures cited in freshman chemistry textbooks are often not the most accurate to represent the molecules and are minor resonance structures at best. Suggests instead stressing more strongly the octet rule in the teaching of Lewis structures. Includes textbook examples to demonstrate problems with currently accepted methods…

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

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

    165. Photocopy of Photograph (original in Roger Lewis' private collection). Photographer and date unknown. MILNER DAM, TWIN FALLS COUNTY, MILNER IDAHO; CRANES USED TO PLACE ROCK ON DAM; NOTE ELECTRIC RAILROAD CAR AT LEFT. - 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

  9. 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…

  10. 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.

  11. 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…

  12. "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.…

  13. 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.…

  14. 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…

  15. 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…

  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. 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

  18. 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…

  19. 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…

  20. 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 §...

  1. 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 §...

  2. 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

  3. 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.…

  4. 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.

  5. 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.

  6. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM Range....” Business hours vary dependent on personnel fill, and are available by calling the above numbers. (c... been coordinated and approved, Area Access will determine when called for entry whether the...

  7. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM Range....” Business hours vary dependent on personnel fill, and are available by calling the above numbers. (c... been coordinated and approved, Area Access will determine when called for entry whether the...

  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. 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.

  10. 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.

  11. A Blend of Marcus Garvey and the 92nd Street Y: An Interview with Elma Lewis.

    ERIC Educational Resources Information Center

    Korzenik, Diana

    1982-01-01

    Presents an interview with Black educator, Elma Lewis, founder of the National Center for Afro-American Arts. The interview covers Lewis' early childhood education, family background, and Black cultural background. Lewis describes her vision for the Afro-American Center, its current financial problems, and her perception of the role of art in…

  12. 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...

  13. 33 CFR 117.899 - Youngs Bay and Lewis and Clark River.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Youngs Bay and Lewis and Clark... Lewis and Clark River. (a) The draw of the US101 (New Youngs Bay) highway bridge, mile 0.7, across... notice is given to the drawtender at the Lewis and Clark River Bridge by marine radio, telephone,...

  14. 77 FR 47282 - Drawbridge Operation Regulation; Lewis and Clark River, Astoria, OR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-08

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Lewis and Clark River, Astoria, OR... Guard has issued a temporary deviation from the operating schedule that governs the Lewis and Clark Bridge which crosses the Lewis and Clark River, mile 1.0, at Astoria, OR. This deviation is necessary...

  15. 78 FR 48315 - Drawbridge Operation Regulation; Lewis and Clark River, Astoria, OR

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-08

    ... SECURITY Coast Guard 33 CFR Part 117 Drawbridge Operation Regulation; Lewis and Clark River, Astoria, OR... Guard has issued a temporary deviation from the operating schedule that governs the Lewis and Clark Bridge which crosses the Lewis and Clark River, mile 1.0, at Astoria, OR. The deviation is necessary...

  16. 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)

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. Lewis Acids as Activators in CBS-Catalysed Diels-Alder Reactions: Distortion Induced Lewis Acidity Enhancement of SnCl4.

    PubMed

    Nödling, Alexander R; Möckel, Robert; Tonner, Ralf; Hilt, Gerhard

    2016-09-01

    The effect of several Lewis acids on the CBS catalyst (named after Corey, Bakshi and Shibata) was investigated in this study. While (2) H NMR spectroscopic measurements served as gauge for the activation capability of the Lewis acids, in situ FT-IR spectroscopy was employed to assess the catalytic activity of the Lewis acid oxazaborolidine complexes. A correlation was found between the Δδ((2) H) values and rate constants kDA , which indicates a direct translation of Lewis acidity into reactivity of the Lewis acid-CBS complexes. Unexpectedly, a significant deviation was found for SnCl4 as Lewis acid. The SnCl4 -CBS adduct was much more reactive than the Δδ((2) H) values predicted and gave similar reaction rates to those observed for the prominent AlBr3 -CBS adduct. To rationalize these results, quantum mechanical calculations were performed. The frontier molecular orbital approach was applied and a good correlation between the LUMO energies of the Lewis acid-CBS-naphthoquinone adducts and kDA could be found. For the SnCl4 -CBS-naphthoquinone adduct an unusual distortion was observed leading to an enhanced Lewis acidity. Energy decomposition analysis with natural orbitals for chemical valence (EDA-NOCV) calculations revealed the relevant interactions and activation mode of SnCl4 as Lewis acid in Diels-Alder reactions. PMID:27492791

  2. Biochemical and biophysical characterization of the sialyl-/hexosyltransferase synthesizing the meningococcal serogroup W135 heteropolysaccharide capsule.

    PubMed

    Romanow, Angela; Haselhorst, Thomas; Stummeyer, Katharina; Claus, Heike; Bethe, Andrea; Mühlenhoff, Martina; Vogel, Ulrich; von Itzstein, Mark; Gerardy-Schahn, Rita

    2013-04-26

    Neisseria meningitidis (Nm) is a leading cause of bacterial meningitis and sepsis. Crucial virulence determinants of pathogenic Nm strains are the polysaccharide capsules that support invasion by hindering complement attack. In NmW-135 and NmY the capsules are built from the repeating units (→ 6)-α-D-Gal-(1 → 4)-α-Neu5Ac-(2 →)n and (→ 6)-α-D-Glc-(1 → 4)-α-Neu5Ac-(2 →)n, respectively. These unusual heteropolymers represent unique examples of a conjugation between sialic acid and hexosyl-sugars in a polymer chain. Moreover, despite the various catalytic strategies needed for sialic acid and hexose transfer, single enzymes (SiaDW-135/Y) have been identified to form these heteropolymers. Here we used SiaDW-135 as a model system to delineate structure-function relationships. In size exclusion chromatography active SiaDW-135 migrated as a monomer. Fold recognition programs suggested two separate glycosyltransferase domains, both containing a GT-B-fold. Based on conserved motifs predicted folds could be classified as a hexosyl- and sialyltransferase. To analyze enzyme properties and interplay of the two identified glycosyltransferase domains, saturation transfer difference NMR and mutational studies were carried out. Simultaneous and independent binding of UDP-Gal and CMP-Sia was seen in the absence of an acceptor as well as when the catalytic cycle was allowed to proceed. Enzyme variants with only one functionality were generated by site-directed mutagenesis and shown to complement each other in trans when combined in an in vitro test system. Together the data strongly suggests that SiaDW-135 has evolved by fusion of two independent ancestral genes encoding sialyl- and galactosyltransferase activity.

  3. 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

  4. 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

    2015-08-12

    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.

  5. 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

  6. 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.

  7. 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

  8. Interaction of hamster submaxillary sialyl-Tn and Tn glycoproteins with Gal, GalNAc and GlcNAc specific lectins.

    PubMed

    Wu, A M; Shen, F; Herp, A; Wu, J H

    1994-04-01

    Hamster submaxillary glycoprotein (HSM), one of the simplest glycoproteins among mammalian salivary mucins, is composed of approximately equivalent amounts of protein, hexosamine and sialic acid. The Thr and Ser residues in the protein core account for more than half of all of the amino acid residues, while Lys, Glu, Pro and Ala are the major components of the remaining portion of amino acids. The carbohydrate side chains of this mucous glycoprotein have mainly the NeuAc-GalNAc-(sialyl-Tn) sequence (HSM), and those of the desialylated product (HSM-Tn) are almost exclusively unsubstituted GalNAc residues (Tn determinants). The binding properties of sialyl-Tn (HSM) and asialo-HSM (HSM-Tn) glycoproteins were tested by precipitin assay with Gal, GalNAc and GlcNAc specific lectins. The HSM-Tn completely precipitated Vicia villosa (VVL both B4 and mixture of A and B), Maclura pomifera (MPL), and Artocarpus integrifolia (Jacalin) lectins; less than 2 micrograms of HSM-Tn were required for precipitating 50% of 5.0-6.3 micrograms lectin nitrogen added. HSM-Tn also reacted well with Helix pomatia lectin (HPL), Wistaria floribunda lectin (WFL) and Abrus precatorius agglutinin (APA) and precipitated in each case over 81% of the lectin nitrogen added. The reactivity of HSM-Tn with other lectins (Ricinus communis, RCA1; Dolichol biflorus, DBL; Viscum album, ML-I; Arachis hypogaea, PNA, and Triticum vulgaris, WGA) was weak or negligible. The activity of sialyl-Tn (HSM) was more restricted; HSM reacted well with Jacalin, moderately with MPL and VVL-B4, but was inactive or only weakly with the other lectins used. These findings indicate that HSM and its desialylated product (HSM-Tn) are highly useful reagents for the differentiation of Tn and T/Gal specific lectins and for anti-T, Tn and Af monoclonal antibodies.

  9. 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.

  10. 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.

  11. Parkinson's disease dementia: what's in a Lewy body?

    PubMed

    Burn, D J

    2006-01-01

    This brief review deals with pathological aspects of dementia associated with Parkinson's disease (PDD). PDD has been variably linked with cortical Lewy body topography and density. alpha-Synuclein and Alzheimer-type pathology frequently co-exist, suggesting that a combination of pathology related to protein dysmetabolism, possibly with synergistic protein-protein interaction, underpins the cognitive impairment in PDD. Dementia may therefore ensue when a "toxic threshold" is reached, irrespective of the combination of pathologies involved in reaching that threshold. The nature of this putative protein-protein interaction needs to be further elucidated, and also whether there are specific clinical correlates of the pathological substrate. Serum and cerebrospinal fluid proteins or imaging techniques may be useful in future as biomarkers to identify the relative contribution of Lewy-related and Alzheimer-type pathology in a given case of PDD and to inform the rational use of drugs that can reduce alpha-synuclein aggregation and beta-amyloid production.

  12. 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.

  13. Lewis base catalysis of bromo- and iodolactonization, and cycloetherification

    PubMed Central

    Denmark, Scott E.; Burk, Matthew T.

    2010-01-01

    Lewis base catalyzed bromo- and iodolactonization reactions have been developed and the effects of catalyst structure on rate and cyclization selectivity have been systematically explored. The effects of substrate structure on halolactonization reactions and the interaction of those effects with the effects of catalyst structure have been investigated, leading to synthetically useful improvements in cyclization selectivity. The knowledge acquired was applied to the development of Lewis base catalyzed bromo- and iodocycloetherification reactions. The ability of some of the surveyed catalysts to influence the cyclization selectivity of halolactonization reactions demonstrates their presence in the transition structure of the product-determining cyclization step. This observation implies that chiral derivatives of these catalysts have the potential to provide enantioenriched products regardless of the rates or mechanisms of halonium ion racemization. PMID:20705900

  14. 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.}

  15. 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).

  16. 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.

  17. Imidazolinium and amidinium salts as Lewis acid organocatalysts

    PubMed Central

    Sereda, Oksana; Clemens, Nicole; Heckel, Tatjana

    2012-01-01

    Summary The application of imidazolinium and amidinium salts as soft Lewis acid organocatalysts is described. These salts were suitable catalysts for the activation of unsaturated thioesters in a Diels–Alder reaction and in the ring opening of thiiranes and epoxides. The products were isolated in good yields. The mild catalysts did not cause desulfurization of the products containing a thiol or thiocarbonyl group. PMID:23209514

  18. 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.

  19. 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.

  20. Otolaryngologic aspects of the Lewis & Clark Expedition, 1803-1806.

    PubMed

    Eisen, Marc D; Lustig, Lawrence R

    2002-06-01

    Medical difficulties related to otolaryngology that occurred during the Lewis & Clark Expedition (1803-1806) are highlighted. These difficulties included ear and face frostbite, upper respiratory infections, temporal vessel laceration from an air gun accident, neck scrofula, and a pediatric neck mass. The custom of Clatsop Indian head flattening is also described. These descriptions also aim to illustrate the state of otolaryngology during the early 19th century in America. PMID:12160275

  1. 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.

  2. 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.

  3. 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.

  4. Teaching Astronomy at Lewis and Clark Community College

    NASA Astrophysics Data System (ADS)

    Cornell, David A.

    2006-12-01

    Lewis and Clark Community College (LCCC) is a two-year college with "Tech Prep" programs in automotive technology, child development, drafting, office technology, and health occupations. LCCC invited me to teach astronomy as a temporary faculty member during fall semester 2006. As professor emeritus in physics with 40 years' teaching experience, I happily accepted the invitation. This talk describes the experience, emphasizing the way it served as an outreach to the community.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Otolaryngologic aspects of the Lewis & Clark Expedition, 1803-1806.

    PubMed

    Eisen, Marc D; Lustig, Lawrence R

    2002-06-01

    Medical difficulties related to otolaryngology that occurred during the Lewis & Clark Expedition (1803-1806) are highlighted. These difficulties included ear and face frostbite, upper respiratory infections, temporal vessel laceration from an air gun accident, neck scrofula, and a pediatric neck mass. The custom of Clatsop Indian head flattening is also described. These descriptions also aim to illustrate the state of otolaryngology during the early 19th century in America.

  15. 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.

  16. Selected results from combustion research at the Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Jones, R. E.

    1981-01-01

    Combustion research at Lewis is organized to provide a balanced program responsive to national needs and the gas turbine industry. The results of this research is a technology base that assists the gas turbine engine manufacturers in developing new and improved combustion systems for advanced civil and military engines with significant improvements in performance, durability, fuel flexibility and control of exhaust emissions. Research efforts consist of fundamentals and modeling, and applied component and combustor research.

  17. 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.

  18. 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.

  19. Living memories of Myrna Lewis: her personal and international dimensions.

    PubMed

    Resnick, Rosa Perla

    2009-01-01

    Dr. Myrna Lewis was an outstanding social worker, researcher, author and lecturer in the field of Aging, who was definitely recognized as an international expert. Above all her professional achievements the quality of her reach and warm personality will remain as a lively memory for her colleagues and friends. She will be remembered as an authentic source of inspiration to all who knew her and to future generations.

  20. 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

  1. 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.

  2. 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.

  3. 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.

  4. Three-layered structure shared between Lewy bodies and lewy neurites-three-dimensional reconstruction of triple-labeled sections.

    PubMed

    Kanazawa, Toshiro; Uchihara, Toshiki; Takahashi, Atsushi; Nakamura, Ayako; Orimo, Satoshi; Mizusawa, Hidehiro

    2008-07-01

    Lewy bodies (LBs) and Lewy neurites (LNs) are the hallmarks of Parkinson's disease (PD). Although LBs and LNs, frequently coexistent, share some histological properties, their appearances are quite different under conventional two-dimensional observation. In order to clarify how these apparently different structures (LBs and LNs) are related during their formation, we performed three-dimensional observation on post-mortem brainstem tissues with PD. Sixty-microm thick floating sections were multi-immunofluorolabeled for alpha-synuclein (alphaS), ubiquitin (Ub) and neurofilament (NF). Serial confocal images were reconstructed with software. External three-dimensional configuration of LBs, double-labeled for alphaS and NF, exhibited frequent continuity with LNs (70%). Internally, alphaS and Ub formed the three-dimensional concentric inner layers and NF rimmed these inner layers. This layered structure was shared among spherical LBs, rod-shaped LNs and even convoluted forms of LBs/LNs. Furthermore, each layer exhibited continuity without interruption even in the convoluted form and around its junction to spherical LBs. This three-layered structure shared among various Lewy pathologies and their layered continuity on three-dimensional basis favor the hypothesis that LNs evolve into LBs. Besides progression from pale bodies to LBs, structural evolution from LNs into LBs may provide an alternative explanation for the variability of alphaS deposits and their interrelation.

  5. Aberrant sialylation of serum IgA1 was associated with prognosis of patients with IgA nephropathy.

    PubMed

    Ding, Jia-Xiang; Xu, Li-Xia; Lv, Ji-Cheng; Zhao, Ming-Hui; Zhang, Hong; Wang, Hai-Yan

    2007-12-01

    Aberrant glycosylation of serum IgA1 was considered as an initial event and involvement in the pathogenesis of IgAN. We previously demonstrated that aberrant glycosylation of serum IgA1 was associated with pathologic phenotype of IgAN. The present study is to investigate if abnormal sialylation of IgA1 affects renal survival of IgAN. 127 patients with biopsy-proven IgAN were enrolled and followed up to 8 years. Seventy-nine healthy and 75 patients with non-IgAN renal diseases were selected as controls. Alpha 2, 6 sialic acid (SA) of serum IgA1 was measured by sandwich-ELISA. Renal survival rate was estimated by Kaplan-Meier method. Alpha 2, 6 SA level in patients with IgAN was lower than that in healthy controls (0.92+/-0.14 vs. 0.98+/-0.12, P=0.001) and non-IgAN glomerulonephritis (0.92+/-0.14 vs. 1.00+/-0.18, n=53, P=0.001). Patients with IgAN in Low SA Group were no significant differences compared with patients in Normal SA Group in age, gender, hypertension, serum creatinine, and excretion of proteinuria. Renal cumulative survival rate was 53.3% in patients in Low SA Group and 83.5% in Normal SA Group (P=0.0008). The lower the alpha 2, 6 SA level of serum IgA1 in patients with IgAN was, the worse their renal survival rate was. Although patients in Low SA Group had worse renal function evaluated by eGFR, there was no significant difference in various CKD stages in non-IgAN renal function controls (n=42, P=0.352). Alpha 2, 6 SA level of serum IgA1 was associated with the prognosis of patients with IgAN and could serve as a predictor of poor prognosis in IgAN.

  6. 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.

  7. The limits and robustness of reinforcement learning in Lewis signalling games

    NASA Astrophysics Data System (ADS)

    Catteeuw, David; Manderick, Bernard

    2014-04-01

    Lewis signalling games are a standard model to study the emergence of language. We introduce win-stay/lose-inaction, a random process that only updates behaviour on success and never deviates from what was once successful, prove that it always ends up in a state of optimal communication in all Lewis signalling games, and predict the number of interactions it needs to do so: N3 interactions for Lewis signalling games with N equiprobable types. We show three reinforcement learning algorithms (Roth-Erev learning, Q-learning, and Learning Automata) that can imitate win-stay/lose-inaction and can even cope with errors in Lewis signalling games.

  8. 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

  9. 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

  10. 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.

  11. 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.

  12. 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.

  13. Serotonin syndrome following levodopa treatment in diffuse Lewy body disease

    PubMed Central

    Kushwaha, Suman; Panda, Akhila Kumar; Malhotra, Hardeep Singh; Kaur, Manmeet

    2014-01-01

    Serotonin syndrome results from an acute hyperserotonergic state. It is a rare and potentially fatal complication of drugs that affect the central nervous system serotonin levels. It is characterised by a triad of clinical features comprising altered sensorium, autonomic instability and neuromuscular hyperexcitability, in different combinations. We present an atypical case of serotonin syndrome related to levodopa use in a patient of probable Lewy body dementia. This case highlights the difficulty in diagnosis and management of cases with serotonin syndrome in the absence of history of a known serotonergic drug and the fact that levodopa can contribute to its occurrence. PMID:25246451

  14. 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.

  15. 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.

  16. An explanation of flocculation using Lewis acid-base theory

    SciTech Connect

    Brown, P.M.; Stanley, D.A.; Scheiner, B.J.

    1988-01-01

    This paper describes a Bureau of Mines-devleoped method of dewatering clay slurries based on flocculation by high-molecular-weight polymers and water removal from the formed flocs using a trommel or hydrosieve. The exchange ion on the clays affects their dewaterability. Metal ions in solution and on the exchange sites of smectite clays are known to act as Lewis acids. Recent work has determined that these ions can be titrated with high-molecular-weight polymers. The relative acidity of the exchange ion and the basicity of the polymer determined by the new method give insight into the dewatering mechanism.

  17. 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

  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. 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.

  20. 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.

  1. 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

  2. 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

  3. Lewis base activation of Lewis acids: catalytic, enantioselective addition of glycolate-derived silyl ketene acetals to aldehydes.

    PubMed

    Denmark, Scott E; Chung, Won-Jin

    2008-06-20

    A catalytic system involving silicon tetrachloride and a chiral, Lewis basic bisphosphoramide catalyst is effective for the addition of glycolate-derived silyl ketene acetals to aldehydes. It was found that the sense of diastereoselectivity could be modulated by changing the size of the substituents on the silyl ketene acetals. In general, the trimethylsilyl ketene acetals derived from methyl glycolates with a large protecting group on the alpha-oxygen provide enantiomerically enriched alpha,beta-dihydroxy esters with high syn-diastereoselectivity, whereas the tert-butyldimethylsilyl ketene acetals derived from bulky esters of alpha-methoxyacetic acid provide enantiomerically enriched alpha,beta-dihydroxy esters with high anti-diastereoselecitvity.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. Parkinson's disease dementia: a diminished role for the Lewy body.

    PubMed

    Libow, Leslie S; Frisina, Pasquale G; Haroutunian, Vahram; Perl, Daniel P; Purohit, Dushyant P

    2009-09-01

    The literature currently views Lewy bodies as central in the pathogenesis of Parkinson's disease dementia (PDD) when Alzheimer's disease (AD) or vascular pathology is not present. Because the neuropathology of PDD is not well understood, the pathological features of PDD were characterized in eighteen PD brain specimens using published criteria for AD, Diffuse Lewy Body Disease (DLBD), and Vascular Disease as a framework. Among the PD dementia (n=16) subjects, 3 (19%) did not have LBs outside of the brain stem, nor AD or vascular pathology. In two additional cases, one did have rare LBs in the neocortex and cingulate gyrus. However, these two cases did not meet the diagnostic criteria for DLBD. Beyond these 5 cases, the remaining PD dementia subjects fitted a classical pathological profile consistent with AD (38%), vascular disease (12.5%), DLBD (6%), or a combination of these pathologies (12.5%). The findings from this study do not support the hypothesis that LBs are the main substrate for dementia in PD. More research with a larger sample size is needed to determine whether the LB may be a secondary phenomenon and/or an "innocent-bystander". The entire role of the LB in PD dementia is again brought into question.

  9. 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…

  10. Historical Contributions of Lewis, Willis, and Ogbu to American Ethnographic Research

    ERIC Educational Resources Information Center

    Watras, Joseph

    2014-01-01

    This article describes the work of Oscar Lewis, Paul Willis, and John U. Ogbu, who used the concept of culture to explain the difficulties some children had in schools. Although Lewis, Willis, and Ogbu were well trained as ethnographers and their work influenced educators, critics complained that their explanations did not fit their evidence. The…

  11. 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…

  12. 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...

  13. 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…

  14. 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…

  15. 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…

  16. 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.

  17. 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…

  18. 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…

  19. Elimination vs substitution reaction. A dichotomy between Brønsted-Lowry and Lewis basicity.

    PubMed

    Méndez, Francisco; Richaud, Arlette; Alonso, Julio A

    2015-02-20

    The Brønsted-Lowry and Lewis basicity dichotomy in the elimination vs substitution reaction competition is analyzed in terms of a novel Brønsted-Lowry-Lewis basicity ωp/e. This new index unifies the dichotomy and explains the competition between elimination and substitution mechanisms of alkyl centers with para-substituted phenols.

  20. Studies on Lewis acid-mediated intramolecular cyclization reactions of allene-ene systems.

    PubMed

    Hiroi, K; Watanabe, T; Tsukui, A

    2000-03-01

    The Lewis acid-mediated reactions of allene-ene compounds, derived from 3-methylcitronellal or dimethyl malonate, were carried out using various Lewis acids such as ethylaluminum dichloride, diethylaluminum chloride, titanium chloride, zinc chloride etherate, or boron trifluoride etherate, affording unexpectedly intramolecular [2+2]cycloaddition products under some particular reaction conditions without any formation of intramolecular ene reaction products.

  1. 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…

  2. Integrin VLA-4 enhances sialyl-Lewisx/a-negative melanoma adhesion to and extravasation through the endothelium under low flow conditions

    PubMed Central

    Liang, Shile; Dong, Cheng

    2008-01-01

    During their passage through the circulatory system, tumor cells undergo extensive interactions with various host cells including endothelial cells. The capacity of tumor cells to form metastasis is related to their ability to interact with and extravasate through endothelial cell layers, which involves multiple adhesive interactions between tumor cells and endothelium (EC). Thus it is essential to identify the adhesive receptors on the endothelial and melanoma surface that mediate those specific adhesive interactions. P-selectin and E-selectin have been reported as adhesion molecules that mediate the cell-cell interaction of endothelial cells and melanoma cells. However, not all melanoma cells express ligands for selectins. In this study, we elucidated the molecular constituents involved in the endothelial adhesion and extravasation of sialyl-Lewisx/a-negative melanoma cell lines under flow in the presence and absence of polymorphonuclear neutrophils (PMNs). Results show the interactions of α4β1 (VLA-4) on sialyl-Lewisx/a-negative melanoma cells and vascular adhesion molecule (VCAM-1) on inflamed EC supported melanoma adhesion to and subsequent extravasation through the EC in low shear flow. These findings provide clear evidence for a direct role of the VLA-4/VCAM-1 pathway in melanoma cell adhesion to and extravasation through the vascular endothelium in a shear flow. PMNs facilitated melanoma cell extravasation under both low and high shear conditions via the involvement of distinct molecular mechanisms. In the low shear regime, β2-integrins were sufficient to enhance melanoma cell extravasation, whereas in the high shear regime, selectin ligands and β2-integrins on PMNs were necessary for facilitating the melanoma extravasation process. PMID:18632734

  3. 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

  4. Carbocations as Lewis acid catalysts in Diels-Alder and Michael addition reactions.

    PubMed

    Bah, Juho; Franzén, Johan

    2014-01-20

    In general, Lewis acid catalysts are metal-based compounds that owe their reactivity to a low-lying empty orbital. However, one potential Lewis acid that has received negligible attention as a catalyst is the carbocation. We have demonstrated the potential of the carbocation as a highly powerful Lewis acid catalyst for organic reactions. The stable and easily available triphenylmethyl (trityl) cation was found to be a highly efficient catalyst for the Diels-Alder reaction for a range of substrates. Catalyst loadings as low as 500 ppm, excellent yields, and good endo/exo selectivities were achieved. Furthermore, by changing the electronic properties of the substituents on the tritylium ion, the Lewis acidity of the catalyst could be tuned to control the outcome of the reaction. The ability of this carbocation as a Lewis acid catalyst was also further extended to the Michael reaction.

  5. 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

  6. Altered thyroid axis function in Lewis rats with genetically defective hypothalamic CRH/VP neurosecretory cells.

    PubMed

    Whitnall, M H; Smallridge, R C

    1997-11-01

    Lewis rats display hyporesponsive hypothalamo-pituitary-adrenocortical (HPA) axes, overproduction of cytokines, and susceptibility to inflammatory disease. The Lewis corticotropin-releasing hormone (CRH) neurosecretory system contains normal numbers of vasopressin (VP)-deficient axon varicosities, but abnormally sparse VP-containing varicosities in the external zone of the median eminence, compared to the normoresponsive Sprague Dawley (SD), Wistar and Fischer 344 strains. Since VP may act as a thyrotropin-releasing factor, we hypothesized that thyroid axis responsivity may be altered in Lewis rats. T3, T4 and TSH were measured by radioimmunoassay, and free T4 by equilibrium dialysis, in adult male Lewis and SD rats. One h cold (5 degrees C) induced significant increases in T3, T4 and TSH levels in Lewis rats but not in SD rats. Ninety min insulin-induced hypoglycemia (1 IU/kg, i.p.) induced a significant T3 increase in Lewis rats and a significant T4 increase in SD rats. Two h after ip LPS (0.25 or 0.75 mg/kg), T4 levels fell significantly in Lewis rats but not in SD rats. TSH decreases were significant in Lewis rats after 0.75 mg/kg and in SD rats after 0.25 mg/kg. Baseline hormone levels were generally higher in Lewis rats; the differences were significant for T3 and T4 in the insulin experiments and for T3, T4 and free T4 in the LPS experiments. The data suggest that reduced inhibition from the adrenocortical axis in Lewis rats leads to hyperresponsivity of the thyroid axis to cold, and greater LPS-induced decreases in T4 levels, probably due to an exaggerated inhibitory cytokine response.

  7. 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.

  8. 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.

  9. 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.

  10. 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

  11. Liner cooling research at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Acosta, Waldo A.

    1987-01-01

    Described are recently completed and current advanced liner research applicable to advanced small gas turbine engines. Research relating to the evolution of fuel efficient small gas turbine engines capable of meeting future commercial and military aviation needs is currently under way at NASA Lewis Research Center. As part of this research, a reverse-flow combustor geometry was maintained while different advanced liner wall cooling techniques were investigated and compared to a baseline combustor. The performance of the combustors featuring counterflow film-cooled (CFFC) panels, transpiration cooled liner walls (TRANS), and compliant metal/ceramic (CMC) walls was obtained over a range of simulated flight conditions of a 16:1 pressure ratio gas turbine engine and fuel/air ratios up to 0.034. All the combustors featured an identical fuel injection system, identical geometric configuration outline, and similar designed internal aerothermodynamics.

  12. 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.

  13. 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.

  14. Lewis acid-assisted detection of nerve agents in water.

    PubMed

    Butala, Rahul R; Creasy, William R; Fry, Roderick A; McKee, Michael L; Atwood, David A

    2015-06-01

    The five-coordinate compound, Salen((t)Bu)Al(Ac), prepared in situ from Salen((t)Bu)AlBr and NH4Ac, forms Lewis acid-base adducts in aqueous solution with the G-type nerve agents, Sarin and Soman, and the VX hydrolysis product, ethylmethylphosphonate (EMPA). The resulting compounds, [Salen((t)Bu)Al(NA)](+)[Ac] (-) (with NA = Sarin, Soman, and EMPA) are sufficiently stable to be identified by ESI-MS. Molecular ion peaks were detected for every compound with little or no fragmentation. The distinctive MS signatures for the [Salen((t)Bu)Al(NA)](+) compounds provide a new technique for identifying nerve agents from aqueous solution. The energetics of the displacement of Ac(-) by the nerve agents to form [Salen((t)Bu)Al(NA)](+)[Ac](-) were determined computationally.

  15. 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

  16. Microfluidic Separation of Ethylene and Ethane Using Frustrated Lewis Pairs.

    PubMed

    Voicu, Dan; Stephan, Douglas W; Kumacheva, Eugenia

    2015-12-21

    Separation of gaseous olefins and paraffins is one of the most important separation processes in the industry. Development of new cost-effective technologies aims at reducing the high energy consumption during the separation process. Here, we took advantage of the reaction of frustrated Lewis pairs (FLPs) with ethylene to achieve reactive extraction of ethylene from ethylene-ethane mixtures. The extraction was studied using a microfluidic platform, which enabled a rapid, high-throughput assessment of reaction conditions to optimize gas separation efficiency. A separation factor of 7.3 was achieved for ethylene from a 1:1 volume ratio mixture of ethylene and ethane, which corresponded to an extracted ethylene purity of 88 %. The results obtained in the microfluidic studies were validated using infrared spectroscopy. This work paves the way for further development of the FLPs and optimization of reaction conditions, thereby maximizing the separation efficiency of olefins from their mixtures with paraffins.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  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.

  5. 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

  6. 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

  7. 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

  8. Biosynthesis and distribution of Lewis X- and Lewis Y-containing glycoproteins in the murine male reproductive system.

    PubMed

    Wang, Chunmei; Huang, Chengyang; Gu, Yihua; Zhou, Yuchuan; Zhu, Zhengmei; Zhang, Yonglian

    2011-02-01

    Although Lewis X (LeX) and Lewis Y (LeY) antigens were thought to play important roles in fertility, fucosyltransferase (Fut)-deficient (Fut1, Fut2 and Fut4) mice which lack LeX or LeY antigen are still fertile. In the present study, the Fut-deficient and wild-type mice were used to measure the expression of Fut mRNA along the mouse male reproductive tract and determine the role of each Fut in the biosynthesis of LeX/LeY antigens, which are conjugated to glycoproteins in the male reproductive system. LeX/LeY-containing glycoproteins were detected in the epididymis, vas deferens, seminal vesicle and coagulating gland, but not in the testis. We demonstrate that the synthesis of LeY-containing glycoproteins in the epididymis and vas deferens is catalyzed by Fut1 and Fut4. In the seminal vesicle and the coagulating gland, they are mainly synthesized by Fut2 and an α-(1,3)-Fut, but not Fut4. The synthesis of LeX-containing glycoproteins in the middle caput epididymis is catalyzed by Fut4 and by Fut4 and Fut2 in the seminal vesicle. We provide evidence that LeX is synthesized in the coagulating gland by Fut9. We found that the lack of activity by one Fut does not completely inhibit LeX/LeY antigen expression in the male reproductive tract. This redundancy may help to explain why in vivo studies with Fut-deficient mice do not support the presumption that LeX/LeY antigens play important roles in male fertility. We provide details regarding the phenotypes of established Fut-deficient mice and lay the foundation for elucidating the functions of LeX/LeY antigens in other aspects of the male reproductive system.

  9. 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

  10. Correlation between spontaneous metastatic potential, platelet-aggregating activity of cell surface extracts, and cell surface sialylation in 10 metastatic-variant derivatives of a rat renal sarcoma cell line.

    PubMed Central

    Pearlstein, E; Salk, P L; Yogeeswaran, G; Karpatkin, S

    1980-01-01

    Several properties of 10 cell lines derived from the polyoma-induced PW20 Wistar-Furth rat renal sarcoma have been examined, including the ability of the tumor cells to metastasize spontaneously from subcutaneous sites in syngeneic hosts, the platelet-aggregating activity of material extracted by urea from the surface of cultured cells, the sialic acid content of the platelet-aggregating material, and the degree of sialylation of cell surface glycoconjugates in cultured cells. A correlation has been observed among all of these parameters. The results suggest a possible link between the degree of cell surface sialylation of tumor cells, their ability to aggregate platelets, and their ability to metastasize. PMID:6933486

  11. Emerging pathways in genetic Parkinson's disease: Potential role of ceramide metabolism in Lewy body disease.

    PubMed

    Bras, Jose; Singleton, Andrew; Cookson, Mark R; Hardy, John

    2008-12-01

    Heterozygous loss-of-function mutations at the glucosecerebrosidase locus have recently been shown to be a potent risk factor for Lewy body disease. Based on this observation, we have re-evaluated the likelihood that the different PARK loci (defined using clinical criteria for disease) may be misleading attempts to find common pathways to pathogenesis. Rather, we suggest, grouping the different loci which lead to different Lewy body disease may be more revealing. Doing this, we suggest that several of the genes involved in disparate Lewy body diseases impinge on ceramide metabolism and we suggest that this may be a common theme for pathogenesis. PMID:19021754

  12. 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.

  13. 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.

  14. 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

  15. 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

  16. Co-Expression of NEU2 and GBA3 Causes a Drastic Reduction in Cytosolic Sialyl Free N-glycans in Human MKN45 Stomach Cancer Cells-Evidence for the Physical Interaction of NEU2 and GBA3.

    PubMed

    Wang, Li; Seino, Junichi; Tomotake, Haruna; Funakoshi, Yoko; Hirayama, Hiroto; Suzuki, Tadashi

    2015-01-01

    It is well known that the "free" form of glycans that are structurally related to asparagine (N)-linked glycans ("free N-glycans") are found in a wide variety of organisms. The mechanisms responsible for the formation/degradation of high mannose-type free N-glycans have been extensively studied in mammalian cells. Recent evidence, however, also suggests that sialylated, complex-type free N-glycans are also present in the cytosol of various mammalian-derived cultured cells/tissues. We report herein on an investigation of the mechanism responsible for the degradation of such sialyl free N-glycans. The findings show that the amount of glycans is dramatically reduced upon the co-expression of cytosolic sialidase NEU2 with cytosolic β-glycosidase GBA3 in human stomach cancer-derived MKN45 cells. The physical interaction between NEU2 and GBA3 was confirmed by co-precipitation analyses as well as gel filtration assays. The NEU2 protein was found to be stabilized in the presence of GBA3 both in cellulo and in vitro. Our results thus indicate that cytosolic GBA3 is likely involved in the catabolism of cytosolic sialyl free N-glycans, possibly by stabilizing the activity of the NEU2 protein. PMID:26193330

  17. A comparison of two instructional methods for drawing Lewis Structures

    NASA Astrophysics Data System (ADS)

    Terhune, Kari

    Two instructional methods for teaching Lewis structures were compared -- the Direct Octet Rule Method (DORM) and the Commonly Accepted Method (CAM). The DORM gives the number of bonds and the number of nonbonding electrons immediately, while the CAM involves moving electron pairs from nonbonding to bonding electrons, if necessary. The research question was as follows: Will high school chemistry students draw more accurate Lewis structures using the DORM or the CAM? Students in Regular Chemistry 1 (N = 23), Honors Chemistry 1 (N = 51) and Chemistry 2 (N = 15) at an urban high school were the study participants. An identical pretest and posttest was given before and after instruction. Students were given instruction with either the DORM (N = 45), the treatment method, or the CAM (N = 44), the control for two days. After the posttest, 15 students were interviewed, using a semistructured interview process. The pretest/posttest consisted of 23 numerical response questions and 2 to 6 free response questions that were graded using a rubric. A two-way ANOVA showed a significant interaction effect between the groups and the methods, F (1, 70) = 10.960, p = 0.001. Post hoc comparisons using the Bonferroni pairwise comparison showed that Reg Chem 1 students demonstrated larger gain scores when they had been taught the CAM (Mean difference = 3.275, SE = 1.324, p < 0.05), while Hon Chem 1 students demonstrated larger gain scores after learning the DORM (Mean difference = 1.931, SE = 0.848, p < 0.05). The DORM requires five mathematical operations, while the CAM only requires one. Honors Chemistry 1 students performed better with the DORM, perhaps due to better math skills, enhanced working memory, and better metacognitive skills. Regular Chemistry 1 students performed better with the CAM, perhaps because it is more visual. Teachers may want to use the CAM or a direct-pairing method to introduce the topic and use the DORM in advanced classes when a correct structure is needed

  18. A bidentate Lewis acid with a telluronium ion as an anion-binding site

    NASA Astrophysics Data System (ADS)

    Zhao, Haiyan; Gabbaï, François P.

    2010-11-01

    The search for receptors that can selectively capture small and potentially toxic anions in protic media has sparked a renewed interest in the synthesis and anion-binding properties of polydentate Lewis acids. Seeking new paradigms to enhance the anion affinities of such systems, we synthesized a bidentate Lewis acid that contains a boryl and a telluronium moiety as Lewis acidic sites. Anion-complexation studies indicate that this telluronium borane displays a high affinity for fluoride in methanol. Structural and computational studies show that the unusual fluoride affinity of this bidentate telluronium borane can be correlated with the formation of a B-F --> Te chelate motif supported by a strong lone-pair(F) --> σ*(Te-C) donor-acceptor interaction. These results, which illustrate the viability of heavier chalcogenium centres as anion-binding sites, allow us to introduce a novel strategy for the design of polydentate Lewis acids with enhanced anion affinities.

  19. 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.

  20. 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

  1. Lewis Acid-Catalyzed Indole Synthesis via Intramolecular Nucleophilic Attack of Phenyldiazoacetates to Iminium Ions

    PubMed Central

    Zhou, Lei; Doyle, Michael P.

    2009-01-01

    Lewis acids catalyze the cyclization of methyl phenyldiazoacetates with an ortho-imino group, prepared from o-aminophenylacetic acid, to give 2,3-substituted indoles in quantitative yields. PMID:19904905

  2. Highlighting High Performance: Adam Joseph Lewis Center for Environmental Studies, Oberlin College, Oberlin, Ohio

    SciTech Connect

    2002-11-01

    Oberlin College’s Adam Joseph Lewis Center for Environmental Studies is a high-performance building featuring an expansive photovoltaic system and a closed-loop groundwater heat pump system. Designers incorporated energy-efficient components and materials

  3. [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.

  4. 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.

  5. 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.

  6. A remote Lewis acid trigger dramatically accelerates biaryl reductive elimination from a platinum complex.

    PubMed

    Liberman-Martin, Allegra L; Bergman, Robert G; Tilley, T Don

    2013-07-01

    A strategy for the control of electron density at a metal center is reported, which uses a remote chemical switch involving second-sphere Lewis acid binding that modulates electron density in the first coordination sphere. Binding of the Lewis acid B(C6F5)3 at remote nitrogen positions of a bipyrazine-diarylplatinum(II) complex accelerates biaryl reductive elimination by a factor of 64,000. PMID:23789917

  7. 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.

  8. Epidemiology of alpha-synucleinopathies: from Parkinson disease to dementia with Lewy bodies.

    PubMed

    Savica, R; Boeve, B F; Logroscino, G

    2016-01-01

    The epidemiology of the diagnosis of Parkinson's disease and dementia with Lewy bodies is still based on clinical criteria and the definition of the different diseases is still a challenge for clinician and researcher. The epidemiologic estimates of prevalence and incidence are highly affected by differences in diagnostic criteria, geographic location, and methodologic limitations. Studies of prevalence and incidence show increases with advancing age and a higher rate of Parkinson's disease and dementia with Lewy bodies in men compared to women. PMID:27637957

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Cognitive impairment in Parkinson's disease and dementia with Lewy bodies.

    PubMed

    Aarsland, Dag

    2016-01-01

    Parkinson's disease (PD) and dementia with Lewy bodies (DLB) share clinical and pathological similarities. The defining features are motor parkinsonism and cognitive impairment, often accompanied by visual hallucinations, fluctuating consciousness, autonomic and sleep disturbances, and a number of other non-motor symptoms. Mild cognitive impairment (MCI) can be identified in 15% of PD patients at time of diagnosis, and may even precede motor symptoms. MCI usually progresses further, and dementia is a common endpoint. Cognitive impairment is usually the initial symptom of DLB, and the disease course is severe. A variety of biomarkers can assist in the diagnosis and prognosis of PD and DLB, including structural and functional imaging, cerebrospinal fluid, and EEG. Compared to the many treatments available for motor symptoms, relatively few systematic studies exist to guide the treatment of cognitive impairment in PD, and even less in DLB. However, there is good evidence for cholinesterase inhibitors in both DLB and PD with dementia, and some indications that memantine is helpful. Emerging evidence suggest that physical exercise and cognitive training are also effective, as are some reports of various brain stimulation techniques. Disease-modifying agents that delay the rate of cognitive decline in PD and DLB are urgently needed.

  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. 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

  17. 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.

  18. Streamline segment statistics of premixed flames with nonunity Lewis numbers

    NASA Astrophysics Data System (ADS)

    Chakraborty, Nilanjan; Wang, Lipo; Klein, Markus

    2014-03-01

    The interaction of flame and surrounding fluid motion is of central importance in the fundamental understanding of turbulent combustion. It is demonstrated here that this interaction can be represented using streamline segment analysis, which was previously applied in nonreactive turbulence. The present work focuses on the effects of the global Lewis number (Le) on streamline segment statistics in premixed flames in the thin-reaction-zones regime. A direct numerical simulation database of freely propagating thin-reaction-zones regime flames with Le ranging from 0.34 to 1.2 is used to demonstrate that Le has significant influences on the characteristic features of the streamline segment, such as the curve length, the difference in the velocity magnitude at two extremal points, and their correlations with the local flame curvature. The strengthenings of the dilatation rate, flame normal acceleration, and flame-generated turbulence with decreasing Le are principally responsible for these observed effects. An expression for the probability density function (pdf) of the streamline segment length, originally developed for nonreacting turbulent flows, captures the qualitative behavior for turbulent premixed flames in the thin-reaction-zones regime for a wide range of Le values. The joint pdfs between the streamline length and the difference in the velocity magnitude at two extremal points for both unweighted and density-weighted velocity vectors are analyzed and compared. Detailed explanations are provided for the observed differences in the topological behaviors of the streamline segment in response to the global Le.

  19. 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.

  20. 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.

  1. 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.

  2. A seasonal Bartlett-Lewis Rectangular Pulse model

    NASA Astrophysics Data System (ADS)

    Ritschel, Christoph; Agbéko Kpogo-Nuwoklo, Komlan; Rust, Henning; Ulbrich, Uwe; Névir, Peter

    2016-04-01

    Precipitation time series with a high temporal resolution are needed as input for several hydrological applications, e.g. river runoff or sewer system models. As adequate observational data sets are often not available, simulated precipitation series come to use. Poisson-cluster models are commonly applied to generate these series. It has been shown that this class of stochastic precipitation models is able to well reproduce important characteristics of observed rainfall. For the gauge based case study presented here, the Bartlett-Lewis rectangular pulse model (BLRPM) has been chosen. As it has been shown that certain model parameters vary with season in a midlatitude moderate climate due to different rainfall mechanisms dominating in winter and summer, model parameters are typically estimated separately for individual seasons or individual months. Here, we suggest a simultaneous parameter estimation for the whole year under the assumption that seasonal variation of parameters can be described with harmonic functions. We use an observational precipitation series from Berlin with a high temporal resolution to exemplify the approach. We estimate BLRPM parameters with and without this seasonal extention and compare the results in terms of model performance and robustness of the estimation.

  3. 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).

  4. 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.

  5. Liquid-Phase Catalytic Transfer Hydrogenation of Furfural over Homogeneous Lewis Acid-Ru/C Catalysts.

    PubMed

    Panagiotopoulou, Paraskevi; Martin, Nickolas; Vlachos, Dionisios G

    2015-06-22

    The catalytic performance of homogeneous Lewis acid catalysts and their interaction with Ru/C catalyst are studied in the catalytic transfer hydrogenation of furfural by using 2-propanol as a solvent and hydrogen donor. We find that Lewis acid catalysts hydrogenate the furfural to furfuryl alcohol, which is then etherified with 2-propanol. The catalytic activity is correlated with an empirical scale of Lewis acid strength and exhibits a volcano behavior. Lanthanides are the most active, with DyCl3 giving complete furfural conversion and a 97 % yield of furfuryl alcohol at 180 °C after 3 h. The combination of Lewis acid and Ru/C catalysts results in synergy for the stronger Lewis acid catalysts, with a significant increase in the furfural conversion and methyl furan yield. Optimum results are obtained by using Ru/C combined with VCl3 , AlCl3 , SnCl4 , YbCl3 , and RuCl3 . Our results indicate that the combination of Lewis acid/metal catalysts is a general strategy for performing tandem reactions in the upgrade of furans.

  6. 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.

  7. 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.

  8. [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

  9. [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.

  10. 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

  11. Supercharging Reagent for Enhanced Liquid Chromatographic Separation and Charging of Sialylated and High-Molecular-Weight Glycopeptides for NanoHPLC-ESI-MS/MS Analysis.

    PubMed

    Lin, Chia-Wei; Haeuptle, Micha A; Aebi, Markus

    2016-09-01

    Recent developments in proteomic techniques have led to the development of mass spectrometry (MS)-based methods to characterize site-specific glycosylation of proteins. However, appropriate analytical tools to characterize acidic and high-molecular-weight (hMW) glycopeptides are still lacking. In this study, we demonstrate that the addition of supercharging reagent, m-nitrobenzyl alcohol (m-NBA), into mobile phases greatly facilitates the analysis of acidic and hMW glycopeptides. Using commercial glycoproteins, we demonstrated that in the presence of m-NBA the charge state of sialylated glycopeptides increased and the chromatographic separation of neutral and acidic glycopeptides revealed a remarkable improvement. Next, we applied this system to the characterization of a glycoconjugate vaccine candidate consisting of a genetically detoxified exotoxin A of Pseudomonas aeruginosa covalently linked to Shigella flexneri type 2a O-antigen (Sf2E) produced by engineered Escherichia coli. The addition of m-NBA, allowed us to identify peptides with glycan chains of unprecedented size, up to 20 repeat units (98 monosaccharides). Our results indicated that incorporation of m-NBA into reversed-phase liquid chromatography (LC) solvents improves sensitivity, charging, and chromatographic resolution for acidic and hMW glycopeptides. PMID:27487254

  12. Supercharging Reagent for Enhanced Liquid Chromatographic Separation and Charging of Sialylated and High-Molecular-Weight Glycopeptides for NanoHPLC-ESI-MS/MS Analysis.

    PubMed

    Lin, Chia-Wei; Haeuptle, Micha A; Aebi, Markus

    2016-09-01

    Recent developments in proteomic techniques have led to the development of mass spectrometry (MS)-based methods to characterize site-specific glycosylation of proteins. However, appropriate analytical tools to characterize acidic and high-molecular-weight (hMW) glycopeptides are still lacking. In this study, we demonstrate that the addition of supercharging reagent, m-nitrobenzyl alcohol (m-NBA), into mobile phases greatly facilitates the analysis of acidic and hMW glycopeptides. Using commercial glycoproteins, we demonstrated that in the presence of m-NBA the charge state of sialylated glycopeptides increased and the chromatographic separation of neutral and acidic glycopeptides revealed a remarkable improvement. Next, we applied this system to the characterization of a glycoconjugate vaccine candidate consisting of a genetically detoxified exotoxin A of Pseudomonas aeruginosa covalently linked to Shigella flexneri type 2a O-antigen (Sf2E) produced by engineered Escherichia coli. The addition of m-NBA, allowed us to identify peptides with glycan chains of unprecedented size, up to 20 repeat units (98 monosaccharides). Our results indicated that incorporation of m-NBA into reversed-phase liquid chromatography (LC) solvents improves sensitivity, charging, and chromatographic resolution for acidic and hMW glycopeptides.

  13. 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

  14. Helicobacter pylori does not require Lewis X or Lewis Y expression to colonize C3H/HeJ mice.

    PubMed

    Takata, Tohru; El-Omar, Emad; Camorlinga, Margarita; Thompson, Stuart A; Minohara, Yutaka; Ernst, Peter B; Blaser, Martin J

    2002-06-01

    Helicobacter pylori strains frequently express Lewis X (Le(x)) and/or Le(y) on their cell surfaces as constituents of the O antigens of their lipopolysaccharide molecules. To assess the effect of Le(x) and Le(y) 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 Le(x) and Le(y) 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

  15. 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

  16. 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.

  17. Properties of lewis lung carcinoma cells surviving curcumin toxicity.

    PubMed

    Yan, Dejun; Geusz, Michael E; Jamasbi, Roudabeh J

    2012-01-01

    The anti-inflammatory agent curcumin can selectively eliminate malignant rather than normal cells. The present study examined the effects of curcumin on the Lewis lung carcinoma (LLC) cell line and characterized a subpopulation surviving curcumin treatments. Cell density was measured after curcumin was applied at concentrations between 10 and 60 μM for 30 hours. Because of the high cell loss at 60 μM, this dose was chosen to select for surviving cells that were then used to establish a new cell line. The resulting line had approximately 20% slower growth than the original LLC cell line and based on ELISA contained less of two markers, NF-κB and ALDH1A, used to identify more aggressive cancer cells. We also injected cells from the original and surviving lines subcutaneously into syngeneic C57BL/6 mice and monitored tumor development over three weeks and found that the curcumin surviving-line remained tumorigenic. Because curcumin has been reported to kill cancer cells more effectively when administered with light, we examined this as a possible way of enhancing the efficacy of curcumin against LLC cells. When LLC cells were exposed to curcumin and light from a fluorescent lamp source, cell loss caused by 20 μM curcumin was enhanced by about 50%, supporting a therapeutic use of curcumin in combination with white light. This study is the first to characterize a curcumin-surviving subpopulation among lung cancer cells. It shows that curcumin at a high concentration either selects for an intrinsically less aggressive cell subpopulation or generates these cells. The findings further support a role for curcumin as an adjunct to traditional chemical or radiation therapy of lung and other cancers.

  18. Visual search in Dementia with Lewy Bodies and Alzheimer's disease.

    PubMed

    Landy, Kelly M; Salmon, David P; Filoteo, J Vincent; Heindel, William C; Galasko, Douglas; Hamilton, Joanne M

    2015-12-01

    Visual search is an aspect of visual cognition that may be more impaired in Dementia with Lewy Bodies (DLB) than Alzheimer's disease (AD). To assess this possibility, the present study compared patients with DLB (n = 17), AD (n = 30), or Parkinson's disease with dementia (PDD; n = 10) to non-demented patients with PD (n = 18) and normal control (NC) participants (n = 13) on single-feature and feature-conjunction visual search tasks. In the single-feature task participants had to determine if a target stimulus (i.e., a black dot) was present among 3, 6, or 12 distractor stimuli (i.e., white dots) that differed in one salient feature. In the feature-conjunction task participants had to determine if a target stimulus (i.e., a black circle) was present among 3, 6, or 12 distractor stimuli (i.e., white dots and black squares) that shared either of the target's salient features. Results showed that target detection time in the single-feature task was not influenced by the number of distractors (i.e., "pop-out" effect) for any of the groups. In contrast, target detection time increased as the number of distractors increased in the feature-conjunction task for all groups, but more so for patients with AD or DLB than for any of the other groups. These results suggest that the single-feature search "pop-out" effect is preserved in DLB and AD patients, whereas ability to perform the feature-conjunction search is impaired. This pattern of preserved single-feature search with impaired feature-conjunction search is consistent with a deficit in feature binding that may be mediated by abnormalities in networks involving the dorsal occipito-parietal cortex.

  19. Defining the Recognition Elements of Lewis Y-Reactive Antibodies

    PubMed Central

    Saha, Somdutta; Pashov, Anastas; Siegel, Eric R.; Murali, Ramachandran; Kieber-Emmons, Thomas

    2014-01-01

    Antibody response to carbohydrate antigens is often independent of T cells and the process of affinity/specificity improvement is considered strictly dependent on the germinal centers. Antibodies induced during a T cell-independent type 2 (TI-2) response are less variable and less functionally versatile than those induced with T cell help. The antigen specificity consequences of accumulation of somatic mutations in antibodies during TI-2 responses of Marginal Zone (MZ) B cells is a fact that still needs explanation. Germline genes that define carbohydrate-reactive antibodies are known to sculpt antibody-combining sites containing innate, key side-chain contacts that define the antigen recognition step. However, substitutions associated with MZ B cell derived antibodies might affect the mobility and polyspecificity of the antibody. To examine this hypothesis, we analyzed antibodies reactive with the neolactoseries antigen Lewis Y (LeY) to define the residue subset required for the reactive repertoire for the LeY antigen. Our molecular simulation studies of crystallographically determined and modeled antibody-LeY complexes suggests that the heavy-chain germline gene VH7183.a13.20 and the light-chain Vκ cr1 germline gene are sufficient to account for the recognition of the trisaccharide-H determinant Types 1–4, while the specificity for LeY is driven by the CDR3 backbone conformation of the heavy chain and not the side chain interactions. These results confirm that these monoclonals use germline-encoded amino acids to recognize simple carbohydrate determinants like trisaccharide-H but relies on somatic mutations in the periphery of the combining site to modify affinity for LeY through electrostatic interactions that leads to their optimized binding. These observations bring further attention to the role of mutations in T-cell independent antibodies to distinguish self from non-self carbohydrate antigens. PMID:25117628

  20. 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.

  1. Luteolin attenuates endotoxin-induced uveitis in Lewis rats

    PubMed Central

    KANAI, Kazutaka; HATTA, Takuya; NAGATA, Sho; SUGIURA, Yuichi; SATO, Kazuaki; YAMASHITA, Yohei; KIMURA, Yuya; ITOH, Naoyuki

    2016-01-01

    The aim of the present study was to investigate the efficacy of luteolin on endotoxin-induced uveitis (EIU) in rats. EIU was induced in Lewis rats by subcutaneous injections of lipopolysaccharide (LPS). One hr before the LPS injection, 0.1, 1 or 10 mg/kg luteolin or 1 mg/kg prednisolone was intraperitoneally injected. We investigated its effect upon clinical scores, cellular infiltration and protein leakage, as well as on the level of tumor necrosis factor (TNF)-α, nitric oxide (NO) and prostaglandin (PG) E2 in the aqueous humor (AqH). Histologic examination and immunohistochemical analysis in the iris-ciliary body (ICB) were performed to determine the expressions of cyclooxygenase (COX)-2 and inducible NO synthase (iNOS), and then the activated nuclear factor (NF)-κB p65, I kappa B (IκB)-α degradation, phosphorylated (p)-IκB kinase (IKK) α/β and activator protein (AP)-1 c-Jun. Luteolin suppressed, in a dose-dependent manner, the clinical scores, number of inflammatory cells, the protein concentration, and the TNF-α, NO and PGE2 levels in the AqH and improved the histiologic status of the ocular tissue. Luteolin suppressed the expression of iNOS and COX-2 and the activated NF-κB p65, IκB-α degradation, p-IKKα/β and AP-1 p-c-Jun in the ICB. The anti-inflammatory potency of 10 mg/kg luteolin was as strong as that observed with 1 mg/kg prednisolone. These results demonstrate that luteolin attenuates ocular inflammation by inhibiting expression and release of inflammatory markers, along with the inhibition of the activated NF-κB pathway and at least partly AP-1 activity in the ICB. PMID:27098110

  2. 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.

  3. 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.

  4. Potential role of molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity.

    PubMed

    Appelmelk, B J; Simoons-Smit, I; Negrini, R; Moran, A P; Aspinall, G O; Forte, J G; De Vries, T; Quan, H; Verboom, T; Maaskant, J J; Ghiara, P; Kuipers, E J; Bloemena, E; Tadema, T M; Townsend, R R; Tyagarajan, K; Crothers, J M; Monteiro, M A; Savio, A; De Graaff, J

    1996-06-01

    Helicobacter pylori is involved in gastritis, gastric and duodenal ulcers, gastric adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma. Earlier studies already suggested a role for autoimmune phenomena in H. pylori-linked disease. We now report that lipopolysaccharides (LPS) of H. pylori express Lewis y, Lewis x, and H type I blood group structures similar to those commonly occurring in gastric mucosa. Immunization of mice and rabbits with H. pylori cells or purified LPS induced an anti-Lewis x or y or anti-H type I response, yielding antibodies that bound human and murine gastric glandular tissue, granulocytes, adenocarcinoma, and mucosa-associated lymphoid tissue lymphoma cells. Experimental oral infections in mice or natural infection in humans yielded anti-Lewis antibodies also. The beta chain of gastric (H+,K+)-ATPase, the parietal cell proton pump involved in acid secretion, contained Lewis y epitopes; gastric mucin contained Lewis x and y antigenic determinants. Growth in mice of a hybridoma that secretes H. pylori-induced anti-Lewis y monoclonal antibodies resulted in histopathological evidence of gastritis, which indicates a direct pathogenic role for anti-Lewis antibodies. In conclusion, our observations demonstrate that molecular mimicry between H. pylori LPS and the host, based on Lewis antigens, and provide understanding of an autoimmune mechanism for H. pylori-associated type B gastritis.

  5. Assessment of the constant non-unity Lewis number assumption in chemically-reacting flows

    NASA Astrophysics Data System (ADS)

    Burali, Nicholas; Lapointe, Simon; Bobbitt, Brock; Blanquart, Guillaume; Xuan, Yuan

    2016-07-01

    Accurate computation of molecular diffusion coefficients in chemically reacting flows can be an expensive procedure, and the use of constant non-unity Lewis numbers has been adopted often as a cheaper alternative. The goal of the current work is to explore the validity and the limitations of the constant non-unity Lewis number approach in the description of molecular mixing in laminar and turbulent flames. To carry out this analysis, three test cases have been selected, including a lean, highly unstable, premixed hydrogen/air flame, a lean turbulent premixed n-heptane/air flame, and a laminar ethylene/air coflow diffusion flame. For the hydrogen flame, both a laminar and a turbulent configuration have been considered. The three flames are characterised by Lewis numbers which are less than unity, greater than unity, and close to unity, respectively. For each flame, mixture-averaged transport simulations are carried out and used as reference data. The current analysis suggests that, for numerous combustion configurations, the constant non-unity Lewis number approximation leads to small errors when the set of Lewis numbers is chosen properly. For the selected test cases and our numerical framework, the reduction of computational cost is found to be minimal.

  6. Race and laboratory norms. The critical insights of Julian Herman Lewis (1891-1989).

    PubMed

    Crenner, Christopher

    2014-09-01

    The work of Julian Herman Lewis helps to expose the underlying racial organization of laboratory normality in early twentieth-century medicine. In the 1920s and 1930s, Lewis launched a critique of prevailing racial theory, as he established an academic career in pathology at the University of Chicago. As one of the small number of black research physicians at the time, Lewis met barriers to his work that eventually derailed his career. Although his research fell short of its goals, his work continues to provide a key insight into medical laboratory standards as they became institutionalized in Lewis's field of clinical pathology. By avoiding attributions of race and following prevailing practices of racial exclusion, medical laboratories quietly reasserted social norms in the formation of laboratory normality. An examination of Lewis's critiques and his research sharpens questions about the development of the concept of "normal" in the human sciences and a related tendency in twentieth-century medicine to conflate difference with pathology.

  7. 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)

  8. 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

  9. Formation, structural characterization, and reactions of a unique cyclotrimeric vicinal Lewis pair containing (C6F5)2P-Lewis base and (C6F5)BH-Lewis acid components.

    PubMed

    Erdmann, Markus; Wiegand, Thomas; Blumenberg, Jonas; Eckert, Hellmut; Ren, Jinjun; Daniliuc, Constantin G; Kehr, Gerald; Erker, Gerhard

    2014-10-28

    The synthesis of the new vicinal frustrated Lewis pair 5 containing (C6F5)2P-Lewis base and (C6F5)BH-Lewis acid functionality is described. It forms a unique cyclotrimer (5)3 which was structurally characterized by X-ray crystallography and high-resolution solid-state NMR spectroscopy. The relevant NMR Hamiltonian parameters ((11)B and (31)P chemical shielding tensors, (11)B quadrupolar coupling tensors, and (31)P-(11)B spin-spin coupling constants) indicate significant intramolecular covalent BP interactions, consistent with results from density functional theory (DFT) calculations. In addition, the (11)B/(31)P and (31)P/(31)P three-spin geometries are accurately reproduced by suitable high-resolution hetero- and homonuclear dipolar NMR experiments. As predicted from the bonding character portrayed by the solid-state NMR results, the cyclotrimer (5)3 possesses only moderate catalytic activity. However, it undergoes an addition reaction with pyridine and hydroboration reactions with benzaldehyde and tert-butylacetylene. The products of the hydroboration reactions form stable adducts with pyridine.

  10. The decrease of β-synuclein in cortical brain areas defines a molecular subgroup of dementia with Lewy bodies.

    PubMed

    Beyer, Katrin; Domingo-Sàbat, Montserrat; Santos, Cristina; Tolosa, Eduardo; Ferrer, Isidro; Ariza, Aurelio

    2010-12-01

    Lewy body diseases include dementia with Lewy bodies and Parkinson's disease. Whereas dementia with Lewy bodies and Parkinson's disease can be distinguished as separate clinical entities, the pathological picture is very often identical. α-synuclein aggregation is a key event in the pathogenesis of Lewy body diseases and β-synuclein inhibits α-synuclein aggregation in vitro and in vivo. Recently, β-synuclein has been shown to interact directly with α-synuclein, regulating its functionality and preventing its oligomerization. In this study, we analysed the expression of two β-synuclein transcript variants and the main α-synuclein transcript SNCA140, in frozen samples of three areas from brains of patients with (i) pure diffuse Lewy body pathology; (ii) pure Alzheimer's disease pathology; (iii) diffuse Lewy body pathology and concomitant Alzheimer's disease pathology and (iv) controls. Relative messenger RNA expression was determined by real-time polymerase chain reaction, expression changes were evaluated by the ΔΔC(t) method and messenger RNA expression data were confirmed at the protein level. A drastic diminution of β-synuclein expression was observed in cortical areas of all samples that presented neuropathological features corresponding to pure diffuse Lewy body pathology and the clinical phenotype of dementia with Lewy bodies, but not in those with neuropathological features corresponding to diffuse Lewy body pathology and concomitant Alzheimer's disease pathology or the clinical phenotype of Parkinson's disease with dementia. The correlation of expression data with the clinical phenotype and neuropathological diagnosis of the patients suggested the existence of a specific molecular subtype of dementia with Lewy bodies, characterized by a strong decrease of β-synuclein in the frontal and temporal cortices. Furthermore, our findings provide new insights into the pathogenesis of Lewy body diseases that may be important for the understanding of

  11. Stereo- and Temporally Controlled Coordination Polymerization Triggered by Alternating Addition of a Lewis Acid and Base.

    PubMed

    Liu, Bo; Cui, Dongmei; Tang, Tao

    2016-09-19

    Significant progress has been made with regard to temporally controlled radical and ring-opening polymerizations, for example, by means of chemical reagents, light, and voltage, whereas quantitative switch coordination polymerization is still challenging. Herein, we report the temporally and stereocontrolled 3,4-polymerization of isoprene through allosterically regulating the active metal center by alternating addition of Lewis basic pyridine to "poison" the Lewis acidic active metal species through acid-base interactions and Lewis acidic Al(i) Bu3 to release the original active species through pyridine abstraction. This process is quick, quantitative, and can be repeated multiple times while maintaining high 3,4-selectivity. Moreover, this strategy is also effective for the switch copolymerization of isoprene and styrene with dual 3,4- and syndiotactic selectivity. Tuning the switch cycles and intervals enables the isolation of various copolymers with different distributions of 3,4-polyisoprene and syndiotactic polystyrene sequences. PMID:27539866

  12. The possible involvement of mitochondrial dysfunctions in Lewy body dementia: a systematic review

    PubMed Central

    Spano, Mariangela; Signorelli, Maria; Vitaliani, Roberta; Aguglia, Eugenio; Giometto, Bruno

    2015-01-01

    Summary The hallmark of dementia with Lewy bodies (DLB) is the “Lewy body”, an abnormal aggregation of alpha-synuclein found in some areas of the brain. The brain is the organ/system that is most vulnerable to this oxidative damage, and reactive oxygen species can cause neurodegenerative diseases. Different models of mitochondrial deregulation have been compared in DLB. The results are consistent with the hypothesis that alpha-synuclein affects the mitochondria themselves, increasing their sensitivity or leading to cell death through protective (neurosin) and accelerating (cytochrome c) factors. This systematic review suggests that mitochondria play an important role in neurodegeneration and a crucial role in the formation of Lewy bodies. DLB is a disease characterized by abnormal accumulation of alpha-synuclein that could result in the release of cytochrome c and subsequent activation of the apoptotic cascade. PMID:26346695

  13. Lewis Basicity of Nitrogen-Doped Graphite Observed by CO2 Chemisorption

    NASA Astrophysics Data System (ADS)

    Kiuchi, Hisao; Shibuya, Riku; Kondo, Takahiro; Nakamura, Junji; Niwa, Hideharu; Miyawaki, Jun; Kawai, Maki; Oshima, Masaharu; Harada, Yoshihisa

    2016-03-01

    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.

  14. 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.

  15. 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

  16. Lewis Acidity/Basicity Changes in Imidazolium Based Ionic Liquids Brought About by Impurities.

    PubMed

    Gazitúa, Marcela; Fuentealba, Patricio; Contreras, Renato; Ormazábal-Toledo, Rodrigo

    2015-10-15

    We herein report on the effect that water molecules, present as impurities, in the vicinity of an ionic liquid model structure, may induce on the Lewis acidity/basicity patterns normally observed in these materials. Depending on the position and orientation of water, the Lewis acidity/basicity pattern changes from "normal distribution" (i.e., the basicity located at the anion moiety and the acidity located at the cation fragment) to "bifunctional distribution" (i.e., the acidity and basicity located at the cation moiety). In some specific cases, there appears a third Lewis acidity/basicity distribution, where water may bind both the cation and the anion of the ion pair; a response we tentatively call "amphoteric". These effects are clearly traced to the hydrogen bond formation ability of water to coordinate different regions of pure ionic liquids taken as references.

  17. 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.

  18. PPD and hsp65 induced monoarthritis initiates spontaneous recurrent flares in Lewis rats.

    PubMed Central

    Ragno, S; Morris, C J; Coumbe, A; Mapp, P I; Colston, M J; Blake, D R; Winrow, V R

    1995-01-01

    OBJECTIVES--To investigate the time course of a monoarthritis induced with the purified protein derivative of tuberculin (PPD) or a recombinant 65 kDa heat shock protein (rhsp65) in two different strains of sensitised rats. METHODS--Wistar and Lewis rats, sensitised with heat killed Mycobacterium tuberculosis in oil, were challenged intraarticularly with PPD or rhsp65 and monitored for six weeks. Inflammation was assessed by joint swelling, histology, and radiographic studies. RESULTS--Sensitised Lewis rats injected with PPD or rhsp65 showed a chronic response with recurrent spontaneous flares, while Wistar rats showed one inflammatory episode. CONCLUSIONS--The Wistar strain response to PPD resembles a transient reactive arthritis, while the response of the Lewis strain mimics the relapsing nature of rheumatoid synovitis, providing an interesting model to determine dominant immunopathogenic mechanisms. Images PMID:7880124

  19. 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

  20. NASA Lewis Helps Develop Advanced Saw Blades for the Lumber Industry

    NASA Technical Reports Server (NTRS)

    1998-01-01

    NASA Lewis Research Center's Structures and Material Divisions are centers of excellence in high-temperature alloys for aerospace applications such as advanced aircraft and rocket engines. Lewis' expertise in these fields was enlisted in the development of a new generation of circular sawblades for the lumber industry to use in cutting logs into boards. The U.S. Department of Agriculture's (USDA) Forest Products Laboratory and their supplier had succeeded in developing a thinner sawblade by using a nickel-based alloy, but they needed to reduce excessive warping due to residual stresses. They requested assistance from Lewis' experts, who successfully eliminated the residual stress problem and increased blade strength by over 12 percent. They achieved this by developing an innovative heat treatment based on their knowledge of nickel-based superalloys used in aeropropulsion applications.

  1. Neuronal RNA oxidation is a prominent feature of dementia with Lewy bodies.

    PubMed

    Nunomura, Akihiko; Chiba, Shigeru; Kosaka, Kenji; Takeda, Atsushi; Castellani, Rudy J; Smith, Mark A; Perry, George

    2002-11-15

    An approach was used to identify the oxidized nucleoside, 8-hydroxyguanosine in brains of dementia with Lewy bodies. Neurons with marked immunoreaction of 8-hydroxyguanosine in the cytoplasm were widely distributed in the hippocampal region and temporal neocortex. Relative intensity measurements of neuronal 8-hydroxyguanosine immunoreactivity showed that there was a significant increase in nucleic acid oxidation in dementia with Lewy bodies compared with controls. Treatment with nuclease (DNase or RNase) before the immunostaining demonstrated that RNA was a major site of nucleic acid oxidation. Together with the previously reported RNA oxidation in vulnerable neurons in Alzheimer and Parkinson diseases, neuronal RNA oxidation in dementia with Lewy bodies might represent one of the fundamental abnormalities in age-associated neurodegenerative diseases.

  2. 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.

  3. 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

  4. Adventures in Ichthyology: Pacific Northwest Fishes of the Lewis and Clark Expedition

    SciTech Connect

    Dauble, Dennis D.

    2005-09-01

    Captains Meriwether Lewis and William Clark and other members of their expedition collected and identified nearly 400 species of plants and animals during the Voyage of Discovery. Of this total, 31 species of fish were included in Burrough’s summary of the natural history of the Expedition, including 12 fishes considered unknown to science at that time. While there is little doubt of the identity of fish for which Lewis and Clark provided detailed descriptions in their daily logs, other species designations were largely conjecture based on later scholars interpretation of the Lewis and Clarks account. Unlike other biological specimens encountered during the Expedition, no fishes were brought back for study. As a result, the identity of some fishes was never resolved. Many other fishes were reclassified during the past century based on updated scientific methods.

  5. 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.

  6. Formation of Frustrated Lewis Pairs in Ptx -Loaded Zeolite NaY.

    PubMed

    Lee, Heeju; Choi, Yong Nam; Lim, Dae-Woon; Rahman, Md Mahbubur; Kim, Yong-Il; Cho, In Hwa; Kang, Hyun Wook; Seo, Jung-Hye; Jeon, Cheolho; Yoon, Kyung Byung

    2015-10-26

    The formation of a frustrated Lewis pair consisting of sodium hydride (Na(+) H(-) ) and a framework-bound hydroxy proton O(H(+) ) is reported upon H2 treatment of zeolite NaY loaded with Pt nanoparticles (Ptx /NaY). Frustrated Lewis pair formation was confirmed using in situ neutron diffraction and spectroscopic measurements. The activity of the intrazeolite NaH as a size-selective catalyst was verified by the efficient esterification of acetaldehyde (a small aldehyde) to form the corresponding ester ethyl acetate, whereas esterification of the larger molecule benzaldehyde was unsuccessful. The frustrated Lewis pair (consisting of Na(+) H(-) and O(H(+) )) generated within zeolite NaY may be a useful catalyst for various catalytic reactions which require both H(-) and H(+) ions, such as catalytic hydrogenation or dehydrogenation of organic compounds and activation of small molecules. PMID:26480339

  7. Anatomy of an organizational change effort at the Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Hawker, James R.; Dali, Richard S.

    1988-01-01

    By 1979, after a long decline following the end of the Apollo program, the Lewis Research Center found its very existence endangered because it was not doing the kind of research that could attract funding at the time. New management under Andrew J. Stofan applied a program of strategic planning, participative management, and consensus decision making. A corporate-cultural change was effected which enabled Lewis to commit itself to four fundable research and development projects. Morale-building and training programs which were essential to this change are described.

  8. Metalloenzyme-Like Zeolites as Lewis Acid Catalysts for C-C Bond Formation.

    PubMed

    Van de Vyver, Stijn; Román-Leshkov, Yuriy

    2015-10-19

    The use of metalloenzyme-like zeolites as Lewis acid catalysts for C-C bond formation reactions has received increasing attention over the past few years. In particular, the observation of direct aldol condensation reactions enabled by hydrophobic zeolites with isolated framework metal sites has encouraged the development of catalytic approaches for producing chemicals from biomass-derived compounds. The discovery of new Diels-Alder cycloaddition/dehydration routes and experimental and computational studies of Lewis acid catalyzed carbonyl-ene reactions have given a further boost to this rapidly evolving field. PMID:26465652

  9. Solar photovoltaics: Stand alone applications. [NASA Lewis Research Center research and development

    NASA Technical Reports Server (NTRS)

    Deyo, J. N.

    1980-01-01

    The Lewis Research Center involvement in space photovoltaic research and development and in using photovoltaics for terrestrial applications is described with emphasis on applications in which the normal source of power may be a diesel generator, batteries, or other types of power not connected to a utility grid. Once an application is processed, technology is developed and demonstrated with a user who participates in the cost and furnishes the site. Projects completed related to instruments, communication, refrigeration, and highways, are described as well as warning systems, weather stations, fire lookouts, and village power systems. A commercially available photovoltaic powered electric fence charger is the result of Lewis research and development.

  10. Evaluation of a Stirling engine heater bypass with the NASA Lewis nodal-analysis performance code

    SciTech Connect

    Sullivan, T.J.

    1986-05-01

    In support of the US Department of Energy's Stirling Engine Highway Vehicle Systems program, the NASA Lewis Research Center investigated whether bypassing the P-40 Stirling engine heater during regenerative cooling would improve the engine thermal efficiency. The investigation was accomplished by using the Lewis nodal-analysis Stirling engine computer model. Bypassing the P-40 Stirling engine heater at full power resulted in a rise in the indicated thermal efficiency from 40.6 to 41.0 percent. For the idealized (some losses not included) heater bypass that was analyzed, this benefit is not considered significant.

  11. Initial results from the Solar Dynamic (SD) Ground Test Demonstration (GTD) project at NASA Lewis

    NASA Technical Reports Server (NTRS)

    Shaltens, Richard K.; Boyle, Robert V.

    1995-01-01

    A government/industry team designed, built, and tested a 2 kWe solar dynamic space power system in a large thermal/vacuum facility with a simulated sun at the NASA Lewis Research Center. The Lewis facility provides an accurate simulation of temperatures, high vacuum, and solar flux as encountered in low earth orbit. This paper reviews the goals and status of the Solar Dynamic (SD) Ground Test Demonstration (GTD) program and describes the initial testing, including both operational and performance data. This SD technology has the potential as a future power source for the International Space Station Alpha.

  12. Lewis Acid Triggered Regioselective Magnesiation and Zincation of Uracils, Uridines, and Cytidines.

    PubMed

    Klier, Lydia; Aranzamendi, Eider; Ziegler, Dorothée; Nickel, Johannes; Karaghiosoff, Konstantin; Carell, Thomas; Knochel, Paul

    2016-03-01

    The Lewis acid MgCl2 allows control of the metalation regioselectivity of uracils and uridines. In the absence of the Lewis acid, metalation of uracil and uridine derivatives with TMPMgCl·LiCl occurs at the position C(5). In the presence of MgCl2, zincation using TMP2Zn·2LiCl·2MgCl2 occurs at the position C(6). This metalation method provides easy access to functionalized uracils and uridines. Using TMP2Zn·2LiCl·2MgCl2 also allows to functionalize cytidine derivatives at the position C(6).

  13. Life prediction of turbine components: On-going studies at the NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Spera, D. A.; Grisaffe, S. J.

    1973-01-01

    An overview is presented of the many studies at NASA-Lewis that form the turbine component life prediction program. This program has three phases: (1) development of life prediction methods for major failure modes through materials studies, (2) evaluation and improvement of these methods through a variety of burner rig studies on simulated components in research engines and advanced rigs. These three phases form a cooperative, interdisciplinary program. A bibliography of Lewis publications on fatigue, oxidation and coatings, and turbine engine alloys is included.

  14. Oberlin College Lewis Center for Environmental Studies: A Low-Energy Academic Building: Preprint

    SciTech Connect

    Pless, S.; Torcellini, P.; Petersen, J.

    2004-07-01

    The Adam Joseph Lewis Center for Environmental Studies at Oberlin College in Ohio is a building that houses classrooms and offices. The building was designed to be an energy-efficient model for commercial design and serve as a teaching aid to students. The long-term vision for the building was to export more energy than it consumes, sometimes referred to as a zero-energy building. To accomplish this, the Lewis Center was designed to minimize site energy use while producing electricity on-site.

  15. 76 FR 10889 - Record of Decision (ROD) for Grow the Army (GTA) Actions at Fort Lewis and the Yakima Training...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-28

    ... Training Center (YTC), Washington AGENCY: Department of the Army, DoD. ACTION: Notice of Availability (NOA). SUMMARY: The Executive Director of the Army's Installation Management Command (IMCOM) has reviewed the... at Fort Lewis as part of this decision would train at Fort Lewis and YTC. This alternative...

  16. An Alternative Proposition to Lewis' Views on the "Constructions of Professional Identity in a Dynamic Higher Education Sector"

    ERIC Educational Resources Information Center

    Feather, Denis

    2015-01-01

    This paper offers an alternative proposition to that of Lewis on identity and professional identity in higher education (HE). The proposition is provided from the narratives of 26 individual interviewees who deliver HE in college-based higher education, a viewpoint not considered by Lewis, who tends to adopt a more generalist view. Where Lewis…

  17. "OrganicPad": An Interactive Freehand Drawing Application for Drawing Lewis Structures and the Development of Skills in Organic Chemistry

    ERIC Educational Resources Information Center

    Cooper, Melanie M.; Grove, Nathaniel P.; Pargas, Roy; Bryfczynski, Sam P.; Gatlin, Todd

    2009-01-01

    Lewis structures are important for learning chemistry as they serve as an essential link between the structure of chemical compounds and their function. Unfortunately, the creation of valid Lewis structures remains an elusive goal for many students. In recent years, several web-based programs have been created that allow students to receive…

  18. A systematic revision of Baconia Lewis (Coleoptera, Histeridae, Exosternini)

    PubMed Central

    Caterino, Michael S.; Tishechkin, Alexey K.

    2013-01-01

    Abstract Here we present a complete revision of the species of Baconia. Up until now there have been 27 species assigned to the genus (Mazur, 2011), in two subgenera (Binhister Cooman and Baconia s. str.), with species in the Neotropical, Nearctic, Palaearctic, and Oriental regions. We recognize all these species as valid and correctly assigned to the genus, and redescribe all of them. We synonymize Binhister, previously used for a polyphyletic assemblage of species with varied relationships in the genus. We move four species into Baconia from other genera, and describe 85 species as new, bringing the total for the genus to 116 species. We divide these into 12 informal species groups, leaving 13 species unplaced to group. We present keys and diagnoses for all species, as well as habitus photos and illustrations of male genitalia for nearly all. The genus now contains the following species and species groups: Baconia loricata group [Baconia loricata Lewis, 1885, B. patula Lewis, 1885, Baconia gounellei (Marseul, 1887a), Baconia jubaris (Lewis, 1901), Baconia festiva (Lewis, 1891), Baconia foliosoma sp. n., Baconia sapphirina sp. n., Baconia furtiva sp. n., Baconia pernix sp. n., Baconia applanatis sp. n., Baconia disciformis sp. n., Baconia nebulosa sp. n., Baconia brunnea sp. n.], Baconia godmani group [Baconia godmani (Lewis, 1888), Baconia venusta (J. E. LeConte, 1845), Baconia riehli (Marseul, 1862), comb. n., Baconia scintillans sp. n., Baconia isthmia sp. n., Baconia rossi sp. n., Baconia navarretei sp. n., Baconia maculata sp. n., Baconia deliberata sp. n., Baconia excelsa sp. n., Baconia violacea (Marseul, 1853), Baconia varicolor (Marseul, 1887b), Baconia dives (Marseul, 1862), Baconia eximia (Lewis, 1888), Baconia splendida sp. n., Baconia jacinta sp. n., Baconia prasina sp. n., Baconia opulenta sp. n., Baconia illustris (Lewis, 1900), Baconia choaspites (Lewis, 1901), Baconia lewisi Mazur, 1984], Baconia salobrus group [Baconia salobrus (Marseul, 1887b

  19. The Photographer as Educator: The Child Labor Photo-Stories of Lewis Hine.

    ERIC Educational Resources Information Center

    Provenzo, Eugene F., Jr.

    1982-01-01

    From 1908 to 1918, Lewis Hine, educator and photographer, gave new meaning to the camera as an educational tool for social change. Published by the National Child Labor Committee, Hine's photo essays of exploited urban and rural children were intended to instigate reform. This essay with photographs describes Hine's crusade. (SG)

  20. 32 CFR Appendix D to Part 552 - Unauthorized Activities in Fort Lewis Maneuver Areas

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Areas D Appendix D to Part 552 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY RESERVATIONS AND NATIONAL CEMETERIES REGULATIONS AFFECTING MILITARY RESERVATIONS Pt. 552, App. D Appendix D to Part 552—Unauthorized Activities in Fort Lewis Maneuver Areas Civilian...