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Sample records for 6-sulfo sialyl lewis

  1. Selectin ligands and tumor-associated carbohydrate structures: specificities of alpha 2,3-sialyltransferases in the assembly of 3'-sialyl-6-sialyl/sulfo Lewis a and x, 3'-sialyl-6'-sulfo Lewis x, and 3'-sialyl-6-sialyl/sulfo blood group T-hapten.

    PubMed

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

    1995-03-07

    The sequence in the assembly of the functional unit of selectin ligands containing sulfate, sialic acid, and fucose and also tumor-associated O-glycan structures was studied by examining the specificities of alpha 2,3-sialyltransferases (ST). The first enzyme, porcine liver ST, was 57, 37, and 79% active (Km: 0.105, 0.420, and 0.200 mM), respectively, toward 6-sulfo, 6-sialyl, or 6-O-methyl derivatives of the Gal beta 1,3GalNAc alpha- unit; C-3 or C-6 substitution on Gal abolished sialylation. An acrylamide copolymer (MW approximately 40,000) containing approximately 40 T-haptens and asialo Cowper's gland mucin (MW approximately 200,000) containing approximately 48 T-haptens was 5-fold more active as an acceptor as compared to Gal beta 1, 3GalNAc alpha-O-Al on a molecular weight basis. The second enzyme, a cloned alpha-2,3-ST specific for lactose-based structure, was 70, 102, and 108% active (Km: 0.500, 0.210, and 0.330 mM), respectively, toward 6-sialyl, 6-sulfo, or 6-O-methyl derivatives of the Gal beta 1,3GlcNAc beta- unit; C-3 and C-6 substitution on Gal abolished sialylation. Gal beta 1,4GlcNAc beta- and its 6-sulfo derivative were approximately 20% active; the Lewis a structure, Gal beta 1,3- (Fuc alpha 1,4)GlcNAc beta-, was not an acceptor. The acrylamide copolymers containing approximately 40 units of Gal beta 1,3GlcNAc beta-, Gal beta 1,3(6-sulfo)GlcNAc beta-, or fetuin triantennary asialo or bovine IgG diantennary glycopeptides were respectively 5.9-, 5.4-, 0.7-, and 0.1-fold as active. A transfer of 7-9 mol of NeuAc per mole of the above copolymers was catalyzed by this ST, the sialyl linkage being susceptible to alpha 2,3-specific sialidase. A partially purified Colo 205 Lewis type (alpha 1, 3/4) fucosyltransferase catalyzed the formation of 3'-sialyl-6-sulfo Lewis a from [9-3H]NeuAc alpha 2, 3Gal beta 1, 3(6-sulfo)GlcNAc beta-O-Allyl and copolymer containing [9-3H]NeuAc alpha 2, 3Gal beta 1, 3(6-sulfo)GlcNAc beta- units, using GDP[14C]Fuc as fucosyl

  2. Human noroviruses recognize sialyl Lewis x neoglycoprotein.

    PubMed

    Rydell, Gustaf E; Nilsson, Jonas; Rodriguez-Diaz, Jesus; Ruvoën-Clouet, Nathalie; Svensson, Lennart; Le Pendu, Jacques; Larson, Göran

    2009-03-01

    The carbohydrate binding characteristics of a norovirus GII.3 (Chron1) and a GII.4 (Dijon) strain were investigated using virus-like particles (VLPs) and saliva samples from 81 individuals genotyped for FUT2 (secretor) and FUT3 (Lewis) and phenotyped for ABO and Lewis blood groups. The two VLPs showed a typical secretor-gene-dependent binding and bound significantly stronger to saliva from A, B, and AB than from O individuals (P < 0.0001 and P < 0.001) but did not bind to any samples from secretor-negative individuals. The GII.3 strain showed larger interindividual variation and bound stronger to saliva from B than from A(2) secretors (P < 0.01). When assaying for binding to neoglycoproteins, the GII.3 and GII.4 strains were compared with the Norwalk GI.1 prototype strain. Although all three strains bound to Lewis b (and H type 1 chain) glycoconjugates, only the two GII strains showed an additional binding to sialyl Lewis x. This novel binding was specific since the VLPs did not bind to structural analogs, e.g., Lewis x or sialyl Lewis a, but only to sialyl Lewis x, sialyl diLewis x and sialylated type 2 chain conjugates. In inhibition experiments, the sialyl Lewis x conjugate was the most potent inhibitor. The minimal requirement for this potential receptor structure is Neu5Ac alpha 3Gal beta 4(Fuc alpha 3)GlcNAc beta 3Gal beta- where Fuc is not absolutely necessary for binding. Our study shows that some human norovirus GII strains have at least two binding specificities: one secretor-gene-dependent related to alpha1,2-fucosylated carbohydrates and another related to alpha2,3-sialylated carbohydrates of the type 2 chain, e.g., sialyl Lewis x.

  3. Selectin Ligands Sialyl-Lewis a and Sialyl-Lewis x in Gastrointestinal Cancers

    PubMed Central

    Trinchera, Marco; Aronica, Adele; Dall’Olio, Fabio

    2017-01-01

    The tetrasaccharide structures Siaα2,3Galβ1,3(Fucα1,4)GlcNAc and Siaα2,3Galβ1,4(Fucα1,3)GlcNAc constitute the epitopes of the carbohydrate antigens sialyl-Lewis a (sLea) and sialyl-Lewis x (sLex), respectively, and are the minimal requirement for selectin binding to their counter-receptors. Interaction of sLex expressed on the cell surface of leucocytes with E-selectin on endothelial cells allows their arrest and promotes their extravasation. Similarly, the rolling of cancer cells ectopically expressing the selectin ligands on endothelial cells is potentially a crucial step favoring the metastatic process. In this review, we focus on the biosynthetic steps giving rise to selectin ligand expression in cell lines and native tissues of gastrointestinal origin, trying to understand whether and how they are deregulated in cancer. We also discuss the use of such molecules in the diagnosis of gastrointestinal cancers, particularly in light of recent data questioning the ability of colon cancers to express sLea and the possible use of circulating sLex in the early detection of pancreatic cancer. Finally, we reviewed the data dealing with the mechanisms that link selectin ligand expression in gastrointestinal cells to cancer malignancy. This promising research field seems to require additional data on native patient tissues to reach more definitive conclusions. PMID:28241499

  4. Sialyl Lewis x expression in cervical scrapes of premalignant lesions.

    PubMed

    Velázquez-Márquez, Noé; Santos-López, Gerardo; Jiménez-Aranda, Lucio; Reyes-Leyva, Julio; Vallejo-Ruiz, Verónica

    2012-12-01

    Sialylated oligosaccharides of glycoproteins and glycolipids have been implicated in tumour progression and metastases. Altered expression of glycosidic antigens has been reported in cervical cancer. In cervix premalignant lesions, an increased expression of sialic acid has been reported. In the present study we determined the expression profiles of the glycosidic antigens Tn, sialyl Tn (sTn), Lewis a (Lea), sialyl Lewis a (sLea), Lewis x (Lex) and sialyl Lewis x (sLex) in cervical scrapes with cytological diagnoses of normal, low-grade squamous intraepithelial lesions (LGSIL) and highgrade squamous intraepithelial lesions (HGSIL). Cervical scrapings were collected to detect tumour antigens expressions by flow cytometry using monoclonal antibodies. Cytometry analysis of Tn, sTn, Lea and Lex did not reveal differences at the expression level among groups. The number of positive cells to sLea antigen increased in the HGSIL group with respect to the normal group (p=0.0495). The number of positive cells to sLex antigen in the samples increased with respect to the grade of squamous intraepithelial lesion (SIL) (p less than 0.001, Mann-Whitney U test). The intensity of expression of this antigen increased in the HGSIL samples with respect to normal samples (p less than 0.0068). sLex antigen could be a candidate to be used as biomarker for the early diagnosis of cervical cancer.

  5. Carbohydrate antigen sialyl Lewis a--its pathophysiological significance and induction mechanism in cancer progression.

    PubMed

    Kannagi, Reiji

    2007-01-01

    Carbohydrate antigen sialyl Lewis a (CA19-9) is the most frequently applied serum tumor marker for diagnosis of cancers in the digestive organs. Recent progress disclosed the presence of a normal counterpart of the determinant, namely disialyl Lewis a, which is predominantly expressed in non-malignant epithelial cells of the digestive organs, while sialyl Lewis a is preferentially expressed in cancers. The disialyl Lewis a determinant carries one extra sialic residue attached through a 2 --> 6 linkage to the GlcNAc moiety compared to cancer-associated sialyl Lewis a, which carries only one 2 --> 3 linked sialic acid residue (monosialyl Lewis a). Disialyl Lewis a in normal epithelial cells serves as a ligand for immunosuppressive receptors such as sialic acid binding immunoglobulin (Ig)-like lectins (siglec-7) and -9 expressed on resident monocytes/macrophages and maintains immunological homeostasis of mucosal membranes in digestive organs. Epigenetic silencing of a gene for a 2 --> 6 sialyl-transferase in the early stages of carcinogenesis results in an impairment of 2 --> 6 sialylation, leading to incomplete synthesis and accumulation of sialyl Lewis a, which lacks the 2 --> 6 linked sialic acid residue, in cancer cells. Simultaneous determination of serum levels of sialyl- and disialyl Lewis a, and calculation of the monosialyl/disialyl Lewis a ratio provide information useful for excluding a false-positive serum diagnosis, and also for averting the undesired influence of the Lewis blood group of patients on serum antigen levels. During the course of cancer progression in locally advanced cancers, tumor hypoxia induces transcription of several glycogenes involved in sialyl Lewis a synthesis. Expression of the determinant, consequently, is further accelerated in more malignant hypoxia-resistant cancer cell clones, which become predominant clones in advanced stage cancers and frequently develop hematogenous metastasis. Sialyl Lewis a, as well as its positional

  6. Sialyl Lewis(x)/E-selectin-mediated rolling in a cell-free system.

    PubMed Central

    Brunk, D K; Goetz, D J; Hammer, D A

    1996-01-01

    Selections mediate transient adhesion of neutrophils to stimulated endothelial cells at sites of inflammation by binding counter-receptors that present carbohydrates such as sialyl Lewis(x). We have developed a cell-free adhesion assay using sialyl Lewis(x)-coated microspheres and E-selection-IgG chimera-coated substrates to investigate the premise that rolling primarily results from functional properties of selection-carbohydrate bonds, whereas cellular morphology and signaling act as secondary effects. Sialyl Lewis(x)-coated microspheres attach to and roll over E-selectin-IgG chimera-coated substrates between the physiological wall shear stresses of 0.7 and 2 dynes/cm2. Rolling velocities vary with time and depend on E-selectin-IgG chimera site density and wall shear stress. Our results show that sialyl Lewis(x) is a minimal functional recognition element required for rolling on E-selectin under flow. Images FIGURE 2 PMID:8913627

  7. Chemoenzymatic Synthesis of Functional Sialyl LewisX Mimetics with a Heteroaromatic Core

    PubMed Central

    Schlemmer, Claudine; Wiebe, Christine; Ferenc, Dorota; Kowalczyk, Danuta; Wedepohl, Stefanie; Ziegelmüller, Patrick; Dernedde, Jens; Opatz, Till

    2014-01-01

    Functional mimetics of the sialyl LewisX tetrasaccharide were prepared by the enzymatic sialylation of a 1,3-diglycosylated indole and a glycosyl azide, which was subsequently transformed into a 1,4-diglycosylated 1,2,3-triazole, by using the trans-sialidase of Trypanosoma cruzi. These compounds inhibited the binding of E-, L-, and P-selectin-coated nanoparticles to polyacrylamide-bound sialyl-LewisX-containing neighboring sulfated tyrosine residues (sTyr/sLeX-PAA) at low or sub-millimolar concentrations. Except for E-selectin, the mimetics showed higher activities than the natural tetrasaccharide. PMID:24888318

  8. The three members of the selectin receptor family recognize a common carbohydrate epitope, the sialyl Lewis(x) oligosaccharide

    PubMed Central

    1992-01-01

    The selectins (lectin-EGF-complement binding-cell adhesion molecules [LEC-CAMs]) are a family of mammalian receptors implicated in the initial interactions between leukocytes and vascular endothelia, leading to lymphocyte homing, platelet binding, and neutrophil extravasation. The three known selectins, L-selectin (leukocyte adhesion molecule-1 [LECAM-1]), E-selectin (endothelial-leukocyte adhesion molecule-1 [ELAM-1]), and P-selectin (GMP-140) share structural features that include a calcium-dependent lectin domain. The sialyl Lewis(x) carbohydrate epitope has been reported as a ligand for both E- and P-selectins. Although L-selectin has been demonstrated to bind to carbohydrates, structural features of potential mammalian carbohydrate ligand(s) have not been well defined. Using an ELISA developed with a sialyl Lewis(x)-containing glycolipid and an E- selectin-IgG chimera, we have demonstrated the direct binding of the L- selectin-IgG chimera to sialyl Lewis(x). This recognition was calcium dependent, and could be blocked by Mel-14 antibody but not by other antibodies. Recognition was confirmed by the ability of cells expressing the native L-selectin to adhere to immobilized sialyl Lewis(x). These data suggest that the sialyl Lewis(x) oligosaccharide may form the basis of a recognition domain common to all three selectins. PMID:1374413

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

    NASA Astrophysics Data System (ADS)

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

    1997-01-01

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

  10. Sialyl Lewis(x) hybridized complement receptor type 1 moderates acid aspiration injury.

    PubMed

    Kyriakides, C; Wang, Y; Austen, W G; Favuzza, J; Kobzik, L; Moore, F D; Hechtman, H B

    2001-12-01

    The potentially enhanced anti-inflammatory effects of the sialyl Lewis(x) (sLe(x))-decorated version of soluble complement receptor type 1 (sCR1) in moderating acid aspiration injury are examined. HCl was instilled in tracheostomy tubes placed in mice, and extravasation of (125)I-labeled albumin in bronchoalveolar lavage (BAL) fluid was used to calculate the vascular permeability index (PI). Neutrophil counts in BAL fluid and immunohistochemistry were performed. PI was moderated by 82% after treatment with sCR1sLe(x) compared with 54% in sCR1-untreated mice (P < 0.05). Respective reductions in PI in mice treated 0.5 and 1 h after acid aspiration with sCR1sLe(x) of 70 and 57% were greater than the decreases in PI of 45 and 38% observed in respective sCR1-treated groups (P < 0.05). BAL fluid neutrophil counts in sCR1sLe(x)-treated mice were significantly less than those in sCR1-treated animals, which were similar to those in untreated mice. Immunohistochemistry stained for sCR1 only on the pulmonary vascular endothelium of sCR1sLe(x)- but not sCR1-treated mice. In conclusion, sCR1sLe(x) moderates permeability by antagonizing complement activation and neutrophil adhesion. Delayed complement and neutrophil antagonism significantly reduces injury.

  11. In vitro evaluation of Sialyl Lewis X relationship with head and neck cancer stem cells

    PubMed Central

    Czerwinski, Michael J.; Desiderio, Vincenzo; Shkeir, Omar; Papagerakis, Petros; Lapadatescu, Martian C.; Owen, John H.; Athanassiou-Papaeftymiou, Maria; Zheng, Li; Papaccio, Gianpaolo; Prince, Mark E.; Papagerakis, Silvana

    2014-01-01

    Objective To evaluate in vitro the potential links between sialyl Lewis X (sLeX) and cancer stem cells (CSC) in head and neck squamous cell carcinoma (HNSCC). HNSCC is an aggressive malignancy with high mortality mainly due to metastasis. CSC have emerged as important players in HNSCC metastasis. sLeX is a tetrasaccharide carbohydrate known to play a key-role in metastatic dissemination by promoting binding of the tumor cells to the endothelium. Study Design Experimental, in vitro. Setting Laboratory of Head and Neck Cancer Metastasis, University of Michigan. Subjects and Methods A panel of stage- and anatomic-site specific primary and metastatic HNSCC cell lines was assessed by flow cytometry to quantify sLeX relative expression levels. Serum-free conditioned media from the same HNSCC lines was collected over a time-course of 72 hours and assessed by Western-blot for secreted sLeX expression. Representative HNSCC cell lines were cultured as floating orospheres (condition that enhance CSC growth) or under normal adherent conditions and characterized by flow cytometry for CSC markers (CD44, aldehyde dehydrogenase [ALDH]) comparatively with sLeX expression. Results sLeX is predominantly expressed in carcinomas originating from the oral cavity. Secreted sLeX is also found to be high in oral carcinomas and increased over the analyzed time course. Floating orospheres were strongly positive for CD44 and ALDH confirming CSC enrichment of the orospheres. Tumor cells grown as orospheres are 95-100% positive for sLeX compared to 10-40% of adherent counterpart. Conclusion These studies provide the first evidence of sLeX relationship with CSC in HNSCC. PMID:23558285

  12. Effects of carbocisteine on sialyl-Lewis x expression in an airway carcinoma cell line stimulated with tumor necrosis factor-alpha.

    PubMed

    Ishibashi, Yuji; Imai, Shigeru; Inouye, Yoshio; Okano, Teruo; Taniguchi, Akiyoshi

    2006-01-20

    Carbocisteine is a mucoregulatory drug normalizing sialic acid and fucose contents in mucins through the regulation of glycosyltransferase activities. Tumor necrosis factor (TNF)-alpha-induced overexpression of sialyl-Lewis x epitopes, containing sialic acid and fucose, in mucins were previously reported to be regulated by glycosyltransferase mRNAs expression through phosphatidyl inositol-specific phospholipase C (PI-PLC) signaling pathways [Ishibashi, Y., Inouye, Y., Okano, T., Taniguchi, A., 2005. Regulation of sialyl-Lewis x epitope expression by TNF-alpha and EGF in an airway carcinoma cell line. Glycoconj. J. 22, 53-62]. To investigate the mechanism behind the mucoregulatory action of carbocisteine, the present study evaluated the effects of carbocisteine on TNF-alpha-induced overexpression of sialyl-Lewis x epitopes in NCI-H292 cells. 100 mug/ml of carbocisteine was able to inhibit the TNF-alpha-induced expression of hST3GallV mRNA, FUT3 mRNA, C2/4GnT mRNA and sialyl-Lewis x epitopes as well as the TNF-alpha-induced activity of PI-PLC in NCI-H292 cells. These findings suggest that carbocisteine may normalize the sialyl-Lewis x epitopes expression in mucins through the inhibition of cellular PI-PLC activity in vivo.

  13. Production of a complement inhibitor possessing sialyl Lewis X moieties by in vitro glycosylation technology.

    PubMed

    Thomas, Lawrence J; Panneerselvam, Krishnasamy; Beattie, David T; Picard, Michele D; Xu, Bi; Rittershaus, Charles W; Marsh, Henry C; Hammond, Russell A; Qian, Jun; Stevenson, Tom; Zopf, David; Bayer, Robert J

    2004-10-01

    Recombinant soluble human complement receptor type 1 (sCR1) is a highly glycosylated glycoprotein intended for use as a drug to treat ischemia-reperfusion injury and other complement-mediated diseases and injuries. sCR1-sLe(x) produced in the FT-VI-expressing mutant CHO cell line LEC11 exists as a heterogeneous mixture of glycoforms, a fraction of which include structures with one or more antennae terminated by the sialyl Lewis X (sLe(x)) [Neu5Acalpha2-3Galbeta1-4(Fucalpha1-3)GlcNAc]) epitope. Such multivalent presentation of sLe(x) was shown previously to effectively target sCR1 to activated endothelial cells expressing E-selectin. Here, we describe the use of the soluble, recombinant alpha2-3 sialyltransferase ST3Gal-III and the alpha1-3 fucosyltransferase FT-VI in vitro to introduce sLe(x) moieties onto the N-glycan chains of sCR1 overexpressed in standard CHO cell lines. The product (sCR1-S/F) of these in vitro enzymatic glycan remodeling reactions performed at the 10-g scale has approximately 14 N-glycan chains per sCR1 molecule, comprised of biantennary (90%), triantennary (8.5%), and tetraantennary (1.5%) structures, nearly all of whose antennae terminate with sLe(x) moieties. sCR1-S/F retained complement inhibitory activity and, in comparison with sCR1-sLe(x) produced in the LEC11 cell line, contained twice the number of sLe(x) moieties per mole glycoprotein, exhibited a twofold increase in area under the intravenous clearance curve in a rat pharmacokinetic model, and exhibited a 10-fold increase in affinity for E-selectin in an in vitro binding assay. These results demonstrate that in vitro glycosylation of the sCR1 drug product reduces heterogeneity of the glycan profile, improves pharmacokinetics, and enhances carbohydrate-mediated binding to E-selectin.

  14. Anaplasma marginale Outer Membrane Protein A Is an Adhesin That Recognizes Sialylated and Fucosylated Glycans and Functionally Depends on an Essential Binding Domain.

    PubMed

    Hebert, Kathryn S; Seidman, David; Oki, Aminat T; Izac, Jerilyn; Emani, Sarvani; Oliver, Lee D; Miller, Daniel P; Tegels, Brittney K; Kannagi, Reiji; Marconi, Richard T; Carlyon, Jason A

    2017-03-01

    Anaplasma marginale causes bovine anaplasmosis, a debilitating and potentially fatal tick-borne infection of cattle. Because A. marginale is an obligate intracellular organism, its adhesins that mediate entry into host cells are essential for survival. Here, we demonstrate that A. marginale outer membrane protein A (AmOmpA; AM854) contributes to the invasion of mammalian and tick host cells. AmOmpA exhibits predicted structural homology to OmpA of A. phagocytophilum (ApOmpA), an adhesin that uses key lysine and glycine residues to interact with α2,3-sialylated and α1,3-fucosylated glycan receptors, including 6-sulfo-sialyl Lewis x (6-sulfo-sLe(x)). Antisera against AmOmpA or its predicted binding domain inhibits A. marginale infection of host cells. Residues G55 and K58 are contributory, and K59 is essential for recombinant AmOmpA to bind to host cells. Enzymatic removal of α2,3-sialic acid and α1,3-fucose residues from host cell surfaces makes them less supportive of AmOmpA binding. AmOmpA is both an adhesin and an invasin, as coating inert beads with it confers adhesiveness and invasiveness. Recombinant forms of AmOmpA and ApOmpA competitively antagonize A. marginale infection of host cells, but a monoclonal antibody against 6-sulfo-sLe(x) fails to inhibit AmOmpA adhesion and A. marginale infection. Thus, the two OmpA proteins bind related but structurally distinct receptors. This study provides a detailed understanding of AmOmpA function, identifies its essential residues that can be targeted by blocking antibody to reduce infection, and determines that it binds to one or more α2,3-sialylated and α1,3-fucosylated glycan receptors that are unique from those targeted by ApOmpA.

  15. 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

  16. Cimetidine inhibits the adhesion of gastric cancer cells expressing high levels of sialyl Lewis x in human vascular endothelial cells by blocking E-selectin expression.

    PubMed

    Liu, Fu-Rong; Jiang, Cheng-Gang; Li, Yan-Shu; Li, Jia-Bin; Li, Feng

    2011-04-01

    Cimetidine has been shown to have anti-metastatic activity and improves the survival of patients with colorectal cancer. One hypothesis is its modulation of the expression of the cell adhesion molecule by target organ endothelial cells. Because of the inconclusive results in clinical trials of gastric cancer, we investigated the effects of cimetidine on the adhesion of gastric cancer cells to activated endothelial cells and on the expression of some cell adhesion molecules. Human endothelial cells were pre-incubated with cimetidine for 6 h, incubated with the cytokine tumor necrosis factor for 4 h, and the endothelial surface expression of E-selectin was evaluated by flow cytometry, immunostaining and ELISA. Further, we investigated E-selectin mRNA expression by RT-PCR. Three gastric cancer cell lines (SGC-7901, MGC-803, BGC-823) and a normal gastric epithelial cell line, GES-1, were studied for the surface expression of sialyl Lewis x by flow cytometry and immunostaining. Adherence of CFSE-labeled gastric cancer cells and GES-1 cells to endothelial cell monolayers was determined. Cimetidine significantly reduced E-selectin expression of activated endothelial cells, but did not influence E-selectin expression at the mRNA level. Three gastric cancer cell lines expressed high levels of sialyl Lewis x, whereas GES-1 did not. Cimetidine also significantly decreased gastric cancer cell adherence to stimulated endothelial cells. The inhibition of E-selectin expression corresponded to the reduction of tumor cell adherence. The effects of cimetidine on tumor adhesion were almost nullified by pre-incubation with E-selectin and sialyl Lewis x antibody. Furthermore, there was no significant change of GES-1 adherence to endothelial cells by TNF-α, cimetidine, E-selectin and sialyl Lewis x antibody. The inhibiton of gastric cancer cell adherence to cytokine-stimulated endothelial cells treated with cimetidine appears to result from blocking endothelial E-selectin expression

  17. 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.

  18. 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

  19. Adhesive dynamics simulations of sialyl-Lewis(x)/E-selectin-mediated rolling in a cell-free system.

    PubMed

    Chang, K C; Hammer, D A

    2000-10-01

    Selectin-mediated leukocyte rolling is crucial for the proper function of the immune response. Recently, selectin-mediated rolling was recreated in a cell-free system (Biophysical Journal 71:2902-2907 (1996)); it was shown that sialyl Lewis(x) (sLe(x))-coated microspheres roll over E-selectin-coated surfaces under hydrodynamic flow. The cell-free system removes many confounding cellular features, such as cell deformability and signaling, allowing us to focus on the role of carbohydrate/selectin physical chemistry in mediating rolling. In this paper, we use adhesive dynamics, a computational method that allows us to simulate adhesion, to analyze the experimental data produced in the cell-free system. We simulate the effects of shear rate, ligand density, and number of receptors per particle on rolling velocity and compare them with experimental results obtained with the cell-free system. If we assume the population of particles is homogeneous in receptor density, we predict that particle rolling velocity calculated in simulations is more sensitive to shear rate than found in experiments. Also, the calculated rolling velocity is more sensitive to the number of receptors on the microspheres than to the ligand density on the surface, again in contrast to experiment. We argue that heterogeneity in the distribution of receptors throughout the particle population causes these discrepancies. We improve the agreement between experiment and simulation by calculating the average rolling velocity of a population whose receptors follow a normal distribution, suggesting heterogeneity among particles significantly affects the experimental results. Further comparison between theory and experiment yields an estimate of the reactive compliance of sLe(x)/E-selectin interactions of 0.25 A, close to that reported in the literature for E-selectin and its natural ligand (0.3 A). We also provide an estimate of the value of the intrinsic association rate (between 10(4) and 10(5) s(-1)) for

  20. Inflammation-induced expression of sialyl Lewis X-containing glycan structures on alpha 1-acid glycoprotein (orosomucoid) in human sera

    PubMed Central

    1993-01-01

    The glycosylation of the acute phase glycoprotein alpha 1-acid glycoprotein (AGP) in human sera is subject to marked changes during acute inflammation as a result of the cytokine-induced hepatic acute phase reaction. The changes described thus far comprise alterations in the type of branching of the carbohydrate structures as revealed by increased reactivity of AGP with concanavalin A. We now report on acute inflammation-induced increases in alpha 1-->3-fucosylated AGP molecules, as detected by the reactivity of AGP towards the fucose- binding Aleuria aurantia lectin (AAL) in crossed affino- immunoelectrophoresis of human sera. Laparotomy of women, for the removal of benign tumors of the uterus, was used as a model for the development of the hepatic acute phase response. Hugh increases were detected in the amounts of strongly AAL-reactive fractions of AGP, presumably containing three or more fucosylated N-acetyllactosamine units. At least part of these Lewis X-type glycans (Gal beta 1-->[Fuc alpha 1-->3]GlcNAc-R) appeared to be substituted also with an alpha 2-- >3-linked sialic acid residue. This was revealed by the laparotomy- induced abundant staining of AGP with an antisialyl Lewis X monoclonal antibody (CSLEX-1) on blots of sodium dodecyl sulfate-polyacrylamide gels containing AGP isolated from the sera of a patient at various days after operation. It is concluded that acute inflammation induces a strong increase in sialyl Lewis X-substituted AGP molecules that persists at a high level throughout the inflammatory period. We postulate that these changes represent a physiological feedback response on the interaction between leukocytes and inflamed endothelium, which is mediated via sialylated Lewis X structures and the selectin endothelial-leukocyte adhesion molecule 1. PMID:7679706

  1. TNF-alpha increases the carbohydrate sulfation of CD44: induction of 6-sulfo N-acetyl lactosamine on N- and O-linked glycans.

    PubMed

    Delcommenne, Marc; Kannagi, Reiji; Johnson, Pauline

    2002-10-01

    CD44 and sulfation have both been implicated in leukocyte adhesion. In monocytes, the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) stimulates CD44 sulfation, and this correlates with the induction of CD44-mediated adhesion events. However, little is known about the sulfation of CD44 or its induction by inflammatory cytokines. We determined that TNF-alpha induces the carbohydrate sulfation of CD44. CD44 was established as a major sulfated cell surface protein on myeloid cells. In the SR91 myeloid cell line, the majority of CD44 sulfation was attributed to the glycosaminoglycan chondroitin sulfate. However, TNF-alpha stimulation increased CD44 sulfation two- to threefold, largely attributed to the increased sulfation of N- and O-linked glycans on CD44. Therefore, TNF-alpha induced a decrease in the percentage of CD44 sulfation due to chondroitin sulfate and an increase due to N- and O-linked sulfation. Furthermore, TNF-alpha induced the expression of 6-sulfo N-acetyl lactosamine (LacNAc)/Lewis x on these cells, which was detected by a monoclonal antibody after neuraminidase treatment. This 6-sulfo LacNAc/Lewis x epitope was induced on N-linked and (to a lesser extent) on O-linked glycans present on CD44. This demonstrates that CD44 is modified by sulfated carbohydrates in myeloid cells and that TNF-alpha modifies both the type and amount of carbohydrate sulfation occurring on CD44. In addition, it demonstrates that TNF-alpha can induce the expression of 6-sulfo N-acetyl glucosamine on both N- and O-linked glycans of CD44 in myeloid cells.

  2. Characterization of N-linked oligosaccharides bearing sialyl lewis x moieties on an alternatively glycosylated form of soluble complement receptor type 1 (sCR1).

    PubMed

    Picard, M D; Pettey, C L; Marsh, H C; Thomas, L J

    2000-02-01

    We sought to produce a complement inhibitory protein possessing oligosaccharides specifically modified to contain the sialyl Lewis x (sLe(x)) moiety. This modified glycoprotein could combine anti-complement activity with the ability to inhibit selectin-mediated interactions and concentrate this activity to sites of activated endothelium where selectins are upregulated. Soluble complement receptor type 1 (sCR1), previously shown to be effective in inhibiting the complement cascade, was produced in a cell line capable of adding fucose to N-linked oligosaccharides in the alpha1-3 linkage, which is necessary for sLe(x) glycosylation. The glycoprotein purified from these cells was designated sCR1sLe(x), and may prove to be more effective than sCR1 in some clinical applications. Detailed analysis and characterization of sCR1sLe(x) was performed to confirm that the N-linked oligosaccharides possessed sLe(x) moieties and also to determine the extent of sLe(x) glycosylation. The glycoproteins were characterized by oligosaccharide profiling, sequencing, linkage analysis and quantified by differential enzymic digestion, using fluorophore-assisted carbohydrate electrophoresis. The major glycans were identified as biantennary oligosaccharides (including sialylated and non-core fucosylated glycans). The linkages of sialic acid and the branched fucose were analysed by digestion with linkage-specific enzymes and subsequent separation by electrophoresis. All data were consistent with the presence of sLe(x) moieties on the N-linked oligosaccharides of sCR1sLe(x). sCR1sLe(x) is a prime example of a recombinant protein expressed with oligosaccharides engineered for a specific biological function, and produced using a commercially viable method.

  3. 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.

  4. Synthesis and Functional Characterization of Novel Sialyl LewisX Mimic-Decorated Liposomes for E-selectin-Mediated Targeting to Inflamed Endothelial Cells.

    PubMed

    Chantarasrivong, Chanikarn; Ueki, Akiharu; Ohyama, Ryutaro; Unga, Johan; Nakamura, Shinya; Nakanishi, Isao; Higuchi, Yuriko; Kawakami, Shigeru; Ando, Hiromune; Imamura, Akihiro; Ishida, Hideharu; Yamashita, Fumiyoshi; Kiso, Makoto; Hashida, Mitsuru

    2017-02-24

    Sialyl LewisX (sLeX) is a natural ligand of E-selectin that is overexpressed by inflamed and tumor endothelium. Although sLeX is a potential ligand for drug targeting, synthesis of the tetrasaccharide is complicated with many reaction steps. In this study, structurally simplified novel sLeX analogues were designed and linked with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-polyethylene glycol-2000 (DSPE-PEG) for E-selectin-mediated liposomal delivery. The sLeX structural simplification strategies include (1) replacement of the Gal-GlcNAc disaccharide unit with lactose to reduce many initial steps and (2) substitution of neuraminic acid with a negatively charged group, i.e., 3'-sulfo, 3'-carboxymethyl (3'-CM), or 3'-(1-carboxy)ethyl (3'-CE). While all the liposomes developed were similar in particle size and charge, the 3'-CE sLeX mimic liposome demonstrated the highest uptake in inflammatory cytokine-treated human umbilical vein endothelial cells (HUVECs), being even more potent than native sLeX-decorated liposomes. Inhibition studies using antiselectin antibodies revealed that their uptake was mediated primarily by overexpressed E-selectin on inflamed HUVECs. Molecular dynamics simulations were performed to gain mechanistic insight into the E-selectin binding differences among native and mimic sLeX. The terminally branched methyl group of the 3'-CE sLeX mimic oriented and faced the bulk hydrophilic solution during E-selectin binding. Since this state is entropically unfavorable, the 3'-CE sLeX mimic molecule might be pushed toward the binding pocket of E-selectin by a hydrophobic effect, leading to a higher probability of hydrogen-bond formation than native sLeX and the 3'-CM sLeX mimic. This corresponded with the fact that the 3'-CE sLeX mimic liposome exhibited much greater uptake than the 3'-CM sLeX mimic liposome.

  5. α3/4 Fucosyltransferase 3-dependent synthesis of Sialyl Lewis A on CD44 variant containing exon 6 mediates polymorphonuclear leukocyte detachment from intestinal epithelium during transepithelial migration.

    PubMed

    Brazil, Jennifer C; Liu, Renpeng; Sumagin, Ronen; Kolegraff, Keli N; Nusrat, Asma; Cummings, Richard D; Parkos, Charles A; Louis, Nancy A

    2013-11-01

    Polymorphonuclear leukocyte (PMN) migration across the intestinal epithelium closely parallels disease symptoms in patients with inflammatory bowel disease. PMN transepithelial migration (TEM) is a multistep process that terminates with PMN detachment from the apical epithelium into the lumen. Using a unique mAb (GM35), we have previously demonstrated that engagement of the CD44 variant containing exon 6 (CD44v6) blocks both PMN detachment and cleavage of CD44v6. In this article, we report that PMN binding to CD44v6 is mediated by protein-specific O-glycosylation with sialyl Lewis A (sLe(a)). Analyses of glycosyltransferase expression identified fucosyltransferase 3 (Fut3) as the key enzyme driving sLe(a) biosynthesis in human intestinal epithelial cells (IECs). Fut3 transfection of sLe(a)-deficient IECs resulted in robust expression of sLe(a). However, this glycan was not expressed on CD44v6 in these transfected IECs; therefore, engagement of sLe(a) had no effect on PMN TEM across these cells. Analyses of sLe(a) in human colonic mucosa revealed minimal expression in noninflamed areas, with striking upregulation under colitic conditions that correlated with increased expression of CD44v6. Importantly, intraluminal administration of mAb GM35 blocked PMN TEM and attenuated associated increases in intestinal permeability in a murine intestinal model of inflammation. These findings identify a unique role for protein-specific O-glycosylation in regulating PMN-epithelial interactions at the luminal surface of the intestine.

  6. 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.

  7. 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.

    PubMed

    Baker, Heather M; Basu, Indira; Chung, Matthew C; Caradoc-Davies, Tom; Fraser, John D; Baker, Edward N

    2007-12-14

    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.

  8. Selective α-Sialylation

    NASA Astrophysics Data System (ADS)

    Ando, Hiromune; Kiso, Makoto

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

  9. Porcine Sperm Bind to Specific 6-Sialylated Biantennary Glycans to Form the Oviduct Reservoir1

    PubMed Central

    Kadirvel, Govindasamy; Machado, Sergio A.; Korneli, Claudia; Collins, Emily; Miller, Paul; Bess, Kelsey N.; Aoki, Kazuhiro; Tiemeyer, Michael; Bovin, Nicolai; Miller, David J.

    2012-01-01

    ABSTRACT After mating, many female mammals store a subpopulation of sperm in the lower portion of the oviduct, forming a reservoir. The reservoir lengthens sperm lifespan, regulates sperm capacitation, controls polyspermy, and selects normal sperm. It is believed that sperm bind to glycans on the oviduct epithelium to form the reservoir, but the specific adhesion molecules that retain sperm are unclear. Herein, using a glycan array to test 377 glycans for their ability to bind porcine sperm, we found two glycan motifs in common among all glycans with sperm-binding ability: the Lewis X trisaccharide and biantennary structures containing a mannose core with 6-sialylated lactosamine at one or more termini. Binding to both motifs was specific; isomers of each motif did not bind sperm. Further work focused on sialylated lactosamine. Sialylated lactosamine was found abundantly on the apical side of epithelial cells collected from the oviduct isthmus, among N-linked and O-linked glycans. Sialylated lactosamine bound to the head of sperm, the region that interacts with the oviduct epithelium. After capacitation, sperm lost affinity for sialylated lactosamine. Receptor modification may contribute to release from the reservoir so that sperm can move to the site of fertilization. Sialylated lactosamine was required for sperm to bind oviduct cells. Simbucus nigra agglutinin or an antibody specific to sialylated lactosamine with a preference for Neu5Acalpha2-6Gal rather than Neu5Acalpha2-3Gal reduced sperm binding to oviduct isthmic cells, as did occupying putative receptors on sperm with sialylated biantennary glycans. These results demonstrate that sperm binding to oviduct 6-sialylated biantennary glycans is necessary for normal adhesion to the oviduct. PMID:23115267

  10. 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

  11. Sialylation of Helicobacter bizzozeronii lipopolysaccharides modulates Toll-like receptor (TLR) 2 mediated response.

    PubMed

    Kondadi, Pradeep Kumar; Revez, Joana; Hänninen, Marja-Liisa; Rossi, Mirko

    2015-01-21

    Sialic acid in lipopolysaccharides (LPS) of mucosal pathogens is known to be an important virulence factor. Few strains of Helicobacter pylori express sialyl-Lewis-X and we have reported that human and canine Helicobacter bizzozeronii strains express sialyl-lactoseamine in their LPS. However, the role of sialyation of Helicobacter LPS in the interaction with the host cells is still unknown. In this study H. bizzozeronii LPS is shown to activate the TLR2 in a dose and strain dependent manner in the in vitro HEK-293 cells model expressing TLR2, but not the cells expressing TLR4. These results indicate that TLR2 is the specific receptor for H. bizzozzeronii LPS, as previously described for H. pylori. To further explore the role of sialylation of H. bizzozeronii LPS on TLR2 response, H. bizzozeronii Δhbs2 mutant strains deficient in sialyltransferase activity were constructed by homologous recombination. LPS from H. bizzozeronii Δhbs2 strains enhanced the NF-ĸB induction via TLR2 compared to the respective wild types, leading to the conclusion that the sialylation of H. bizzozeronii LPS in wild-type strains may modulate host immune response.

  12. Deficits in Sialylation Impair Podocyte Maturation

    PubMed Central

    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

    2012-01-01

    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 Cmasnls 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 Cmasnls 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. PMID:22745475

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

    PubMed

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

    2012-09-01

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

  14. Engineering of complex protein sialylation in plants

    PubMed Central

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

    2016-01-01

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

  15. Novel O-linked glycans containing 6'-sulfo-Gal/GalNAc of MUC1 secreted from human breast cancer YMB-S cells: possible carbohydrate epitopes of KL-6(MUC1) monoclonal antibody.

    PubMed

    Seko, Akira; Ohkura, Takashi; Ideo, Hiroko; Yamashita, Katsuko

    2012-02-01

    Human serum Krebs von den Lugen-6 (KL-6) antigen is a MUC1 glycoprotein (KL-6/MUC1) recognized by anti-KL-6 monoclonal antibody (KL-6/mAb) and has been utilized as a diagnostic marker for interstitial pneumonia. KL-6/mAb is thought to recognize the specific glycopeptides sequence of MUC1, but the precise glycan structure of the epitope is unclear. In this study, we determined the carbohydrate structures of KL-6/MUC1 to search the carbohydrate epitopes for KL-6/mAb. KL-6/MUC1 was purified from the culture medium of human breast cancer YMB-S cells by KL-6/mAb-affinity chromatography; the O-linked glycan structures were determined in combination with paper electrophoresis, several lectin column chromatographies, sialidase digestion and methanolysis. KL-6/MUC1 contained core 1 and extended core 1 glycans modified with one or two sialic acid/sulfate residues. Based on these structures, several synthetic glycans binding to anti-KL-6/mAb were compared with one another by surface plasmon resonance. Sequentially, related radiolabeled oligosaccharides were enzymatically synthesized and analyzed for binding to a KL-6/mAb-conjugated affinity column. 3'-sialylated, 6'-sulfated LNnT [Neu5Acα2-3(SO(3)(-)-6)Galβ1-4GlcNAcβ1-3Galβ1-4Glc], 3'-sialylated, 6-sulfated core 1 [Neu5Acα2-3Galβ1-3(SO(3)(-)-6)GalNAc] and disulfated core 1 SO(3)(-)-3Galβ1-3(SO(3)(-)-6)GalNAc exhibited substantial affinity for KL-6/mAb, and 3'-sulfated core 1 derivatives [SO(3)(-)-3Galβ1-3(±Neu5Acα2-6)GalNAc] and 3'-sialylated core 1 weakly interacted with KL-6/mAb. These results indicated that the possible carbohydrate epitopes of KL-6/mAb involve not only 3'-sialylated core 1 but also novel core 1 and extended core 1 with sulfate and sialic acid residues. Epitope expressing changes with suppression or over-expression of the Gal6ST (Gal 6-O-sulfotransferase) gene, suggesting that Gal6ST is involved in the biosynthesis of the unique epitopes of KL-6/mAb.

  16. Carbocisteine normalizes the viscous property of mucus through regulation of fucosylated and sialylated sugar chain on airway mucins.

    PubMed

    Ishibashi, Yuji; Takayama, Goh; Inouye, Yoshio; Taniguchi, Akiyoshi

    2010-09-01

    Almost all of fucose and sialic acid in mucus are found on the mucus glycoproteins (mucins), and these sugar components on mucins are known to be associated with the viscous property of mucus. We have reported some aspects of carbocisteine, a mucoregulatory drug, correcting fucose and sialic acid contents in mucus. At present, carbocisteine's expectorant action of airway mucus is postulated to involve - the regulation of fucose and sialic acid contents on mucins. However little information is available about the relationship between the viscosity and sugar contents on mucins when treated with carbocisteine. To investigate further the mechanism behind the action of carbocisteine, the present study prepared MUC5AC fusion protein which has tandem repeat regions associated with MUC5AC, and evaluated the effects of carbocisteine on tumor necrosis factor (TNF)-alpha-induced increases of mucus viscosity and sialyl-Lewis x-epitopes antigen, an antigen which consists of fucosylated and sialylated sugar chains on the MUC5AC fusion proteins. Carbocisteine inhibited the TNF-alpha-induced increases of the viscosity and sialyl-Lewis x-epitopes on MUC5AC fusion protein. These findings suggest that carbocisteine may normalize the viscosity of mucus through "balancing" of fucose and sialic acid contents on airway mucins.

  17. 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 ...

  18. 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

  19. 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

  20. Enzymatic Basis for N-Glycan Sialylation

    PubMed Central

    Meng, Lu; Forouhar, Farhad; Thieker, David; Gao, Zhongwei; Ramiah, Annapoorani; Moniz, Heather; Xiang, Yong; Seetharaman, Jayaraman; Milaninia, Sahand; Su, Min; Bridger, Robert; Veillon, Lucas; Azadi, Parastoo; Kornhaber, Gregory; Wells, Lance; Montelione, Gaetano T.; Woods, Robert J.; Tong, Liang; Moremen, Kelley W.

    2013-01-01

    Glycan structures on glycoproteins and glycolipids play critical roles in biological recognition, targeting, and modulation of functions in animal systems. Many classes of glycan structures are capped with terminal sialic acid residues, which contribute to biological functions by either forming or masking glycan recognition sites on the cell surface or secreted glycoconjugates. Sialylated glycans are synthesized in mammals by a single conserved family of sialyltransferases that have diverse linkage and acceptor specificities. We examined the enzymatic basis for glycan sialylation in animal systems by determining the crystal structures of rat ST6GAL1, an enzyme that creates terminal α2,6-sialic acid linkages on complex-type N-glycans, at 2.4 Å resolution. Crystals were obtained from enzyme preparations generated in mammalian cells. The resulting structure revealed an overall protein fold broadly resembling the previously determined structure of pig ST3GAL1, including a CMP-sialic acid-binding site assembled from conserved sialylmotif sequence elements. Significant differences in structure and disulfide bonding patterns were found outside the sialylmotif sequences, including differences in residues predicted to interact with the glycan acceptor. Computational substrate docking and molecular dynamics simulations were performed to predict and evaluate the CMP-sialic acid donor and glycan acceptor interactions, and the results were compared with kinetic analysis of active site mutants. Comparisons of the structure with pig ST3GAL1 and a bacterial sialyltransferase revealed a similar positioning of donor, acceptor, and catalytic residues that provide a common structural framework for catalysis by the mammalian and bacterial sialyltransferases. PMID:24155237

  1. Role of Receptor Sialylation in the Ovarian Tumor Cell Phenotype

    DTIC Science & Technology

    2012-06-01

    blocks apoptosis induced by the mammalian lectin, galectin - 3 , which our studies show is expressed in human ovarian tumor tissues and in ascitic fluid...omental cultures. • Optimized immunoblotting protocol for galectin - 3 in ascites • Determination that sialylation of Fas and TNFR1 blocks apoptotic...REPORT DATE 2. REPORT TYPE Annual report 3 . DATES COVERED 4. TITLE AND SUBTITLE Role of receptor sialylation in the ovarian tumor cell

  2. 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

  3. Bernard Lewis: An Appreciation.

    ERIC Educational Resources Information Center

    Humphreys, R. Stephen

    1990-01-01

    Discusses the career and publications of Bernard Lewis, a noted scholar in the field of Middle-Eastern studies and Islamic history. Traces the history of Western-based Islamic historiography. Examines Lewis' interpretation of Islamic history, outlining his political and social views. (RW)

  4. 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…

  5. 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

  6. Quantitative enzymatic production of sialylated galactooligosaccharides with an engineered sialidase from Trypanosoma rangeli.

    PubMed

    Zeuner, Birgitte; Holck, Jesper; Perna, Valentina; Mikkelsen, Jørn Dalgaard; Meyer, Anne S

    2016-01-01

    Sialylated galactooligosaccharides (GOS) represent a potential infant formula ingredient, which is believed to contribute with a combination of the beneficial properties of the prebiotic GOS as well as of sialylated human milk oligosaccharides. Sialylated GOS do not exist in natural milk, but can be produced from κ(kappa)-casein glycomacropeptide (CGMP), a sialylated side stream component from cheese-making, by sialidase-catalyzed transsialylation. Using a rationally designed mutant of the sialidase from Trypanosoma rangeli, Tr13, with enhanced transsialylation activity, six different GOS preparations with a varying degree of polymerization (DP) were effectively sialylated with molar yields of 20-30% on the CGMP sialyl in batch reactions. The rate of sialylation of the individual DPs was largely dependent on the DP distribution in each GOS preparation, and Tr13 catalysis did not discriminate against large GOS molecules, providing the novelty point that GOS molecules are sialylated independently of their size by Tr13. Using CGMP, GOS, and Tr13, the production of gram-scale quantities of sialyl-GOS was achieved in 20L volume reactions. Compared to the benchmark transsialidase from pathogenic Trypanosoma cruzi, the Tr13 was significantly more thermostable. By employing an enzymatic membrane reactor, Tr13 could be recycled and after seven consecutive 1-h reaction cycles, the biocatalytic productivity of the enzyme was increased 7-fold compared to the batch reaction. Assuming that the enzyme may be specific for α-2,3-bound sialyl moieties only, and that only 50% of sialyl linkages in CGMP are α-2,3-linked, the molar yield of sialyl-GOS on the available α-2,3-bound sialyl moieties in CGMP reached 80% in the enzymatic membrane reactor system.

  7. Efficient chemoenzymatic synthesis of sialyl Tn-antigen and derivatives†

    PubMed Central

    Ding, Li; Yu, Hai; Lau, Kam; Li, Yanhong; Muthana, Saddam; Wang, Junru; Chen, Xi

    2011-01-01

    An N-terminal and C-terminal truncated recombinant α2–6-sialyltransferase cloned from Photobacterium sp. JH-ISH-224, Psp2,6ST(15–501)-His6, was shown to be an efficient catalyst for one-pot three-enzyme synthesis of sialyl Tn (STn) antigens and derivatives containing natural and non-natural sialic acid forms. PMID:21725542

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

    PubMed Central

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

    2016-01-01

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

  9. Lewy Body Dementia Diagnosis

    MedlinePlus

    ... as part of their protocols. Participating in research studies is a good way to benefit others with Lewy body dementia. Medications Medications are one of the most controversial subjects in dealing with LBD. A medication that doesn't work for one person may work for another person. ...

  10. 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.

  11. 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.

  12. 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

  13. 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.

  14. Dementia with Lewy bodies.

    PubMed

    McKeith, Ian G; Burn, David J; Ballard, Clive G; Collerton, Daniel; Jaros, Evelyn; Morris, Chris M; McLaren, Andrew; Perry, Elaine K; Perry, Robert; Piggott, Margaret A; O'Brien, John T

    2003-01-01

    The objective was to summarize recent findings about the clinical features, diagnosis and investigation of dementia with Lewy (DLB) bodies, together with its neuropathology, neurochemistry and genetics. Dementia with Lewy bodies (DLB) is a primary, neurodegenerative dementia sharing clinical and pathological characteristics with both Parkinson's disease (PD) and Alzheimer's disease (AD). Antiubiquitin immunocytochemical staining, developed in the early 1990s, allowed the frequency and distribution of cortical LBs to be defined. More recently, alpha-synuclein antibodies have revealed extensive neuritic pathology in DLB demonstrating a neurobiological link with other "synucleinopathies" including PD and multiple system atrophy (MSA). The most significant correlates of cognitive failure in DLB appear to be with cortical LB and Lewy neurites (LNs) rather than Alzheimer type pathology. Clinical diagnostic criteria for DLB, published in 1996, have been subjected to several validation studies against autopsy findings. These conclude that although diagnostic specificity is high (range 79- 100%, mean 92%), sensitivity is lower (range 0- 83 %, mean, 49%). Improved methods of case detection are therefore required. Fluctuating impairments in attention, visual recognition and construction are more indicative of DLB than AD. Relative preservation of medial temporal lobe volume on structural MRI and the use of SPECT tracers for regional blood flow and the dopamine transporter are the most reliable current biomarkers for DLB. There are no genetic or CSF tests recommended for the diagnosis of DLB at present. Between 15 and 20% of all elderly demented cases reaching autopsy have DLB, making it the most common cause of degenerative dementia after AD. Exquisite, not infrequently fatal, sensitivity to neuroleptic drugs and encouraging reports of the effects of cholinesterase inhibitors on cognitive, psychiatric and neurological features, mean that an accurate diagnosis of DLB is more

  15. Sialidase specificity determined by chemoselective modification of complex sialylated glycans.

    PubMed

    Parker, Randy B; McCombs, Janet E; Kohler, Jennifer J

    2012-09-21

    Sialidases hydrolytically remove sialic acids from sialylated glycoproteins and glycolipids. Sialidases are widely distributed in nature and sialidase-mediated desialylation is implicated in normal and pathological processes. However, mechanisms by which sialidases exert their biological effects remain obscure, in part because sialidase substrate preferences are poorly defined. Here we report the design and implementation of a sialidase substrate specificity assay based on chemoselective labeling of sialosides. We show that this assay identifies components of glycosylated substrates that contribute to sialidase specificity. We demonstrate that specificity of sialidases can depend on structure of the underlying glycan, a characteristic difficult to discern using typical sialidase assays. Moreover, we discovered that Streptococcus pneumoniae sialidase NanC strongly prefers sialosides containing the Neu5Ac form of sialic acid versus those that contain Neu5Gc. We propose using this approach to evaluate sialidase preferences for diverse potential substrates.

  16. 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.

  17. 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.

  18. Production of sialylated O-linked glycans in Pichia pastoris.

    PubMed

    Hamilton, Stephen R; Cook, W James; Gomathinayagam, Sujatha; Burnina, Irina; Bukowski, John; Hopkins, Daniel; Schwartz, Shaina; Du, Min; Sharkey, Nathan J; Bobrowicz, Piotr; Wildt, Stefan; Li, Huijuan; Stadheim, Terrance A; Nett, Juergen H

    2013-10-01

    The methylotrophic yeast, Pichia pastoris, is an important organism used for the production of therapeutic proteins. Previously, we have reported the glycoengineering of this organism to produce human-like N-linked glycans but up to now no one has addressed engineering the O-linked glycosylation pathway. Typically, O-linked glycans produced by wild-type P. pastoris are linear chains of four to five α-linked mannose residues, which may be capped with β- or phospho-mannose. Previous genetic engineering of the N-linked glycosylation pathway of P. pastoris has eliminated both of these two latter modifications, resulting in O-linked glycans which are linear α-linked mannose structures. Here, we describe a method for the co-expression of an α-1,2-mannosidase, which reduces these glycans to primarily a single O-linked mannose residue. In doing so, we have reduced the potential of these glycans to interact with carbohydrate-binding proteins, such as dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin. Furthermore, the introduction of the enzyme protein-O-linked-mannose β-1,2-N-acetylglucosaminyltransferase 1, resulted in the capping of the single O-linked mannose residues with N-acetylglucosamine. Subsequently, this glycoform was extended into human-like sialylated glycans, similar in structure to α-dystroglycan-type glycoforms. As such, this represents the first example of sialylated O-linked glycans being produced in yeast and extends the utility of the P. pastoris production platform beyond N-linked glycosylated biotherapeutics to include molecules possessing O-linked glycans.

  19. 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.

  20. 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…

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

    PubMed Central

    2012-01-01

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

  2. Enzyme catalysed production of sialylated human milk oligosaccharides and galactooligosaccharides by Trypanosoma cruzi trans-sialidase.

    PubMed

    Holck, Jesper; Larsen, Dorte M; Michalak, Malwina; Li, Haiying; Kjærulff, Louise; Kirpekar, Finn; Gotfredsen, Charlotte H; Forssten, Sofia; Ouwehand, Arthur C; Mikkelsen, Jørn D; Meyer, Anne S

    2014-03-25

    A Trypanosoma cruzi trans-sialidase (E.C. 3.2.1.18) was cloned into Pichia pastoris and expressed. The pH and temperature optimum of the enzyme was determined as pH 5.7 and 30°C. Using casein glycomacropeptide (CGMP) and lactose as sialyl-donor and acceptor respectively, the optimal donor/acceptor ratio for the trans-sialidase catalysed 3'-sialyllactose production was found to be 1:4. Quantitative amounts of 3'-sialyllactose were produced from CGMP and lactose at a yield of 40mg/g CGMP. The 3'-sialyllactose obtained exerted a stimulatory effect on selected probiotic strains, including different Bifidobacterium strains in single culture fermentations. The trans-sialidase also catalysed the transfer of sialic acid from CGMP to galacto-oligosaccharides (GOS) and to the human milk oligosaccharide (HMO) backbone lacto-N-tetraose (LNT) to produce 3'-sialyl-GOS, including doubly sialylated GOS products, and 3'-sialyl-LNT, respectively. This work thus provides proof of the concept of producing 3'-sialyllactose and potentially other sialylated HMOs as well as sialylated GOS enzymatically by trans-sialidase activity, while at the same time providing valorisation of CGMP, a co-processing product from cheese manufacture.

  3. Expression of N-Acetylglucosaminyltransferase III Suppresses α2,3-Sialylation, and Its Distinctive Functions in Cell Migration Are Attributed to α2,6-Sialylation Levels*

    PubMed Central

    Lu, Jishun; Isaji, Tomoya; Im, Sanghun; Fukuda, Tomohiko; Kameyama, Akihiko; Gu, Jianguo

    2016-01-01

    N-Acetylglucosaminyltransferase III (GnT-III), which catalyzes the addition of the bisecting GlcNAc branch on N-glycans, is usually described as a metastasis suppressor. Overexpression of GnT-III inhibited migration in multiple types of tumor cells. However, these results seem controversial to the clinical observations for the increased expression of GnT-III in human hepatomas, glioma, and ovarian cancers. Here, we present evidence that these inconsistencies are mainly attributed to the different expression pattern of cell sialylation. In detail, we show that overexpression of GnT-III significantly inhibits α2,3-sialylation but not α2,6-sialylation. The migratory ability of cells without or with a low level of α2,6-sialylation is consistently suppressed after GnT-III overexpression. In contrast, the effects of GnT-III overexpression are variable in tumor cells that are highly α2,6-sialylated. Overexpression of GnT-III promotes the cell migration in glioma cells U-251 and hepatoma cells HepG2, although it has little influence in human breast cancer cell MDA-MB-231 and gastric cancer cell MKN-45. Interestingly, up-regulation of α2,6-sialylation by overexpressing β-galactoside α2,6-sialyltranferase 1 in the α2,6-hyposialylated HeLa-S3 cells abolishes the anti-migratory effects of GnT-III. Conversely, depletion of α2,6-sialylation by knock-out of β-galactoside α2,6-sialyltranferase 1 in α2,6-hypersialylated HepG2 cells endows GnT-III with the anti-migratory ability. Taken together, our data clearly demonstrate that high expression of α2,6-sialylation on the cell surface could affect the anti-migratory role of GnT-III, which provides an insight into the mechanistic roles of GnT-III in tumor metastasis. PMID:26801611

  4. Enhanced sialylation of recombinant erythropoietin in genetically engineered Chinese-hamster ovary cells.

    PubMed

    Jeong, Yeon Tae; Choi, One; Son, Young Dok; Park, Seung Yeol; Kim, Jung Hoe

    2009-04-01

    Sialic acid, the terminal sugar in N-linked complex glycans, is usually found in glycoproteins and plays a major role in determining the circulatory lifespan of glycoproteins. In the present study we attempted to enhance the sialylation of recombinant EPO (erythropoietin) in CHO (Chinese-hamster ovary) cells. To enhance EPO sialylation, we introduced human alpha2,3-ST (alpha2,3-sialyltransferase) and CMP-SAS (CMP-sialic acid synthase) into recombinant human EPO-producing CHO cells. The sialylation of EPO was increased by the expression of alpha2,3-ST alone. Although the co-expression of alpha2,3-ST and CMP-SAS did not further increase sialylation, an increase in the intracellular pool of CMP-sialic acid was noted. On the basis of these observations, it was postulated that the transport capacity of CMP-sialic acid into the Golgi lumen was limited, thereby causing the reduced availability of CMP-sialic acid substrate for sialylation. Therefore, we co-expressed human alpha2,3-ST and CMP-SAS, as well as overexpress Chinese hamster CMP-sialic acid transporter (CMP-SAT) in CHO cells, which produced recombinant human EPO. When alpha2,3-ST, CMP-SAS, and CMP-SAT were overexpressed in CHO cells, there was a corresponding increase in sialylation compared with the co-expression of alpha2,3-ST and CMP-SAS. The present study provides a useful strategy for enhancing the sialylation of therapeutic glycoproteins produced in CHO cells.

  5. 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.

  6. Sialoadhesin Promotes Rapid Proinflammatory and Type I IFN Responses to a Sialylated Pathogen, Campylobacter jejuni

    PubMed Central

    Klaas, Mariliis; Oetke, Cornelia; Lewis, Leanne E.; Erwig, Lars P.; Heikema, Astrid P.; Easton, Alistair; Willison, Hugh J.

    2012-01-01

    Sialoadhesin (Sn) is a macrophage (Mϕ)-restricted receptor that recognizes sialylated ligands on host cells and pathogens. Although Sn is thought to be important in cellular interactions of Mϕs with cells of the immune system, the functional consequences of pathogen engagement by Sn are unclear. As a model system, we have investigated the role of Sn in Mϕ interactions with heat-killed Campylobacter jejuni expressing a GD1a-like, sialylated glycan. Compared to Sn-expressing bone marrow-derived macrophages (BMDM) from wild-type mice, BMDM from mice either deficient in Sn or expressing a non-glycan–binding form of Sn showed greatly reduced phagocytosis of sialylated C. jejuni. This was accompanied by a strong reduction in MyD88-dependent secretion of TNF-α, IL-6, IL-12, and IL-10. In vivo studies demonstrated that functional Sn was required for rapid TNF-α and IFN-β responses to i.v.-injected sialylated C. jejuni. Bacteria were captured within minutes after i.v. injection and were associated with Mϕs in both liver and spleen. In the spleen, IFN-β–reactive cells were localized to Sn+ Mϕs and other cells in the red pulp and marginal zone. Together, these studies demonstrate that Sn plays a key role in capturing sialylated pathogens and promoting rapid proinflammatory cytokine and type I IFN responses. PMID:22851711

  7. 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.

  8. Histochemical identification of sialylated glycans in Xenopus laevis testis

    PubMed Central

    Valbuena, Galder; Alonso, Edurne; Ubago, María Martínez; Madrid, Juan Francisco; Díaz-Flores, Lucio; Sáez, Francisco José

    2012-01-01

    Carbohydrate chains of glycoprotein and glycosphingolipids are highly diverse molecules involved in many cell functions, including cell recognition, adhesion and signalling. Sialylated glycans are of special interest because the terminal position of sialic acid (NeuAc) in glycans linked by different ways to subterminal monosaccharides has been shown to be involved in several biological processes, as occurs with gangliosides, which have been reported as being essential in spermatogenesis in mammals. Some glycan-binding proteins, the lectins, which specifically recognize glycan sequences, have been extensively used to characterize tissue and cell carbohydrates by means of cytochemical techniques. The aim of the present work was to determine the presence of NeuAc by means of histochemical techniques in the testis of Xenopus laevis, an animal model widely used in cell and molecular biology research. However, considering that some NeuAc-binding lectins are capable of binding to N-acetylglucosamine (GlcNAc), other GlcNAc-binding lectins were also assayed. The results showed that NeuAc is mainly expressed in the interstitium, and only a weak labelling in the male germ cells was observed. Most NeuAc was located in O-linked oligosaccharides, but some masked NeuAc in N-glycans were identified in primary and secondary spermatogonia and spermatocytes. By contrast, GlcNAc was widely expressed in all germ cell types. Deglycosylative pre-treatments suggest that both N- and O-glycans and/or glycolipids could be responsible for this labelling. In addition, GlcNAc in O-linked oligosaccharides has been identified in spermatogonial cells. The acrosome of spermatids was always negative. Variations of glycan expression have been found in different cell types, suggesting that glycosylation is modified during spermatogenetic development. PMID:22881213

  9. 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

  10. 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.

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

    PubMed

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

    2015-12-01

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

  12. Enhanced sialylation of recombinant erythropoietin in CHO cells by human glycosyltransferase expression.

    PubMed

    Jeong, Yeon Tae; Choi, One; Lim, Hye Rim; Son, Young Dok; Kim, Hong Jin; Kim, Jung Hoe

    2008-12-01

    Sialylation, the attachment of sialic acid residues to a protein, can affect the biological activity and in vivo circulatory half-life of glycoproteins. Human alpha2,3- sialyltransferase (alpha2,3-ST) and beta1,4-galactosyltransferase (beta1,4-GT) are responsible for terminal sialylation and galactosylation, respectively. Enhanced sialylation of human erythropoietin (EPO) by the expression of alpha2,3-ST and beta1,4-GT was achieved using recombinant Chinese hamster ovary (CHO) cells (EC1). The sialic acid content and sialylation of N-glycans were evaluated by HPLC. When alpha2,3-ST was expressed in CHO cells (EC1-ST2), the sialic acid content (moles of sialic acid/mole of EPO) increased from 6.7 to 7.5. In addition, the amount of trisialylated glycans increased from 17.3% to 26.1%. When alpha2,3-ST and beta1,4-GT were coexpressed in CHO cells (EC1-GTST15), the degree of sialylation was greater than that in EC1-ST2 cells. In the case of EC1-GTST15 cells, the sialic acid content increased to 8.2 and the proportion of trisialylated glycans was markedly increased from 17.3% to 35.5%. Interestingly, the amount of asialoglycans decreased only in the case of GTST15 cells (21.4% to 14.2%). These results show that coexpression of alpha2,3- ST and beta1,4-GT is more effective than the expression of alpha2,3-ST alone. Coexpression of alpha2,3-ST and beta1,4-GT did not affect CHO cell growth and metabolism or EPO production. Thus, coexpression of alpha2,3-ST and beta1,4-GT may be beneficial for producing therapeutic glycoproteins with enhanced sialylation in CHO cells.

  13. ST6Gal-I Regulates Macrophage Apoptosis via α2-6 Sialylation of the TNFR1 Death Receptor*

    PubMed Central

    Liu, Zhongyu; Swindall, Amanda F.; Kesterson, Robert A.; Schoeb, Trenton R.; Bullard, Daniel C.; Bellis, Susan L.

    2011-01-01

    Macrophages play a central role in innate immunity, however mechanisms regulating macrophage survival are not fully understood. Herein we describe a novel apoptotic pathway involving α2-6 sialylation of the TNFR1 death receptor by the ST6Gal-I sialyltransferase. Variant glycosylation of TNFR1 has not previously been implicated in TNFR1 function, and little is known regarding the TNFR1 glycan composition. To study sialylation in macrophages, we treated U937 monocytic cells with PMA, which stimulates both macrophage differentiation and apoptosis. Interestingly, macrophage differentiation induces ST6Gal-I down-regulation, leading to reduced α2-6 sialylation of selected receptors. To prevent loss of α2-6 sialylation, we forced constitutive expression of ST6Gal-I, and found that this strongly inhibited PMA-induced apoptosis. Given that PMA-mediated apoptosis is thought to result from up-regulation of TNFα, which then activates TNFR1, we next evaluated the α2-6 sialylation of TNFR1. U937 cells with forced ST6Gal-I displayed TNFR1 with elevated α2-6 sialylation, and this was associated with diminished TNFα-stimulated apoptosis. Correspondingly, removal of α2-6 sialylation from TNFR1 through either neuraminidase treatment or expression of ST6Gal-I shRNA markedly enhanced TNFα-mediated apoptosis. To confirm the physiologic importance of TNFR1 sialylation, we generated overexpressing ST6Gal-I transgenic mice. Peritoneal macrophages from transgenic lines displayed TNFR1 with elevated α2-6 sialylation, and these cells were significantly protected against TNFα-stimulated apoptosis. Moreover, greater numbers of thioglycollate-induced peritoneal cells were observed in transgenic mice. These collective results highlight a new mechanism of TNFR1 regulation, and further intimate that loss of α2-6 sialylation during macrophage differentiation may limit macrophage lifespan by sensitizing cells to TNFα-stimulated apoptosis. PMID:21930713

  14. 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,…

  15. 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…

  16. Action Learning in John Lewis

    ERIC Educational Resources Information Center

    Spencer, Chris

    2005-01-01

    A small group of training professionals within the John Lewis Partnership set up an action learning group about 2 years ago. The main aim was to explore the technique for our own learning and development. The timing and lifespan of the group reflected the generally strategic and long-term nature of our projects. One of these was to introduce…

  17. 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.

  18. Role of binding in Mycoplasma mobile and Mycoplasma pneumoniae gliding analyzed through inhibition by synthesized sialylated compounds.

    PubMed

    Kasai, Taishi; Nakane, Daisuke; Ishida, Hideharu; Ando, Hiromune; Kiso, Makoto; Miyata, Makoto

    2013-02-01

    Mycoplasmas, which have been shown to be the causative pathogens in recent human pneumonia epidemics, bind to solid surfaces and glide in the direction of the membrane protrusion at a pole. During gliding, the legs of the mycoplasma catch, pull, and release sialylated oligosaccharides fixed on a solid surface. Sialylated oligosaccharides are major structures on animal cell surfaces and are sometimes targeted by pathogens, such as influenza virus. In the present study, we analyzed the inhibitory effects of 16 chemically synthesized sialylated compounds on the gliding and binding of Mycoplasma mobile and Mycoplasma pneumoniae and concluded the following. (i) The recognition of sialylated oligosaccharide by mycoplasma legs proceeds in a "lock-and-key" fashion, with the binding affinity dependent on structural differences among the sialylated compounds examined. (ii) The binding of the leg and the sialylated oligosaccharide is cooperative, with Hill constants ranging from 2 to 3. (iii) Mycoplasma legs may generate a drag force after a stroke, because the gliding speed decreased and pivoting motion occurred more frequently when the number of working legs was reduced by the addition of free sialylated compounds.

  19. 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

  20. Rational design of a new Trypanosoma rangeli trans-sialidase for efficient sialylation of glycans.

    PubMed

    Jers, Carsten; Michalak, Malwina; Larsen, Dorte M; Kepp, Kasper P; Li, Haiying; Guo, Yao; Kirpekar, Finn; Meyer, Anne S; Mikkelsen, Jørn D

    2014-01-01

    This paper reports rational engineering of Trypanosoma rangeli sialidase to develop an effective enzyme for a potentially important type of reactivity: production of sialylated prebiotic glycans. The Trypanosoma cruzi trans-sialidase and the homologous T. rangeli sialidase has previously been used to investigate the structural requirements for trans-sialidase activity. We observed that the T. cruzi trans-sialidase has a seven-amino-acid motif (197-203) at the border of the substrate binding cleft. The motif differs substantially in chemical properties and substitution probability from the homologous sialidase, and we hypothesised that this motif is important for trans-sialidase activity. The 197-203 motif is strongly positively charged with a marked change in hydrogen bond donor capacity as compared to the sialidase. To investigate the role of this motif, we expressed and characterised a T. rangeli sialidase mutant, Tr13. Conditions for efficient trans-sialylation were determined, and Tr13's acceptor specificity demonstrated promiscuity with respect to the acceptor molecule enabling sialylation of glycans containing terminal galactose and glucose and even monomers of glucose and fucose. Sialic acid is important in association with human milk oligosaccharides, and Tr13 was shown to sialylate a number of established and potential prebiotics. Initial evaluation of prebiotic potential using pure cultures demonstrated, albeit not selectively, growth of Bifidobacteria. Since the 197-203 motif stands out in the native trans-sialidase, is markedly different from the wild-type sialidase compared to previous mutants, and is shown here to confer efficient and broad trans-sialidase activity, we suggest that this motif can serve as a framework for future optimization of trans-sialylation towards prebiotic production.

  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. Rational Design of a New Trypanosoma rangeli Trans-Sialidase for Efficient Sialylation of Glycans

    PubMed Central

    Jers, Carsten; Michalak, Malwina; Larsen, Dorte M.; Kepp, Kasper P.; Li, Haiying; Guo, Yao; Kirpekar, Finn; Meyer, Anne S.; Mikkelsen, Jørn D.

    2014-01-01

    This paper reports rational engineering of Trypanosoma rangeli sialidase to develop an effective enzyme for a potentially important type of reactivity: production of sialylated prebiotic glycans. The Trypanosoma cruzi trans-sialidase and the homologous T. rangeli sialidase has previously been used to investigate the structural requirements for trans-sialidase activity. We observed that the T. cruzi trans-sialidase has a seven-amino-acid motif (197–203) at the border of the substrate binding cleft. The motif differs substantially in chemical properties and substitution probability from the homologous sialidase, and we hypothesised that this motif is important for trans-sialidase activity. The 197–203 motif is strongly positively charged with a marked change in hydrogen bond donor capacity as compared to the sialidase. To investigate the role of this motif, we expressed and characterised a T. rangeli sialidase mutant, Tr13. Conditions for efficient trans-sialylation were determined, and Tr13's acceptor specificity demonstrated promiscuity with respect to the acceptor molecule enabling sialylation of glycans containing terminal galactose and glucose and even monomers of glucose and fucose. Sialic acid is important in association with human milk oligosaccharides, and Tr13 was shown to sialylate a number of established and potential prebiotics. Initial evaluation of prebiotic potential using pure cultures demonstrated, albeit not selectively, growth of Bifidobacteria. Since the 197–203 motif stands out in the native trans-sialidase, is markedly different from the wild-type sialidase compared to previous mutants, and is shown here to confer efficient and broad trans-sialidase activity, we suggest that this motif can serve as a framework for future optimization of trans-sialylation towards prebiotic production. PMID:24404142

  3. 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

    1996-07-09

    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

  4. New sialyl Lewisx mimic containing an α-substituted β3-amino acid spacer

    PubMed Central

    Pedatella, Silvana; De Nisco, Mauro; Ernst, Beat; Guaragna, Annalisa; Wagner, Beatrice; Woods, Robert J.; Palumbo, Giovanni

    2014-01-01

    A highly convergent and efficient synthesis of a new sialyl Lewisx (sLex) mimic, which was predicted by computational studies to fulfil the spacial requirements for a selectin antagonist, has been developed. With a β2,3-amino acid residue L-galactose (bioisostere of the L-fucose moiety present in the natural sLex) and succinate are linked, leading to a mimic of sLex that contains all the required pharmacophores, namely the 3- and 4-hydroxy group of L-fucose, the 4- and 6-hydroxy group of D-galactose and the carboxylic acid of N-acetylneuraminic acid. The key step of the synthesis involves a tandem reaction consisting of a N-deprotection and a suitable O→N intramolecular acyl migration reaction which is promoted by cerium ammonium nitrate (CAN). Finally, the new sialyl Lewisx mimic was biologically evaluated in a competitive binding assay. PMID:17980866

  5. Sialylation of lipooligosaccharides is dispensable for the virulence of Haemophilus ducreyi in humans.

    PubMed

    Spinola, Stanley M; Li, Wei; Fortney, Kate R; Janowicz, Diane M; Zwickl, Beth; Katz, Barry P; Munson, Robert S

    2012-02-01

    Sialylated glycoconjugates on the surfaces of mammalian cells play important roles in intercellular communication and self-recognition. The sialic acid preferentially expressed in human tissues is N-acetylneuraminic acid (Neu5Ac). In a process called molecular mimicry, many bacterial pathogens decorate their cell surface glycolipids with Neu5Ac. Incorporation of Neu5Ac into bacterial glycolipids promotes bacterial interactions with host cell receptors called Siglecs. These interactions affect bacterial adherence, resistance to serum killing and phagocytosis, and innate immune responses. Haemophilus ducreyi, the etiologic agent of chancroid, expresses lipooligosaccharides (LOS) that are highly sialylated. However, an H. ducreyi sialyltransferase (lst) mutant, whose LOS contain reduced levels of Neu5Ac, is fully virulent in human volunteers. Recently, a second sialyltransferase gene (Hd0053) was discovered in H. ducreyi, raising the possibility that Hd0053 compensated for the loss of lst during human infection. CMP-Neu5Ac is the obligate nucleotide sugar donor for all bacterial sialyltransferases; LOS derived from an H. ducreyi CMP-Neu5Ac synthetase (neuA) mutant has no detectable Neu5Ac. Here, we compared an H. ducreyi neuA mutant to its wild-type parent in several models of pathogenesis. In human inoculation experiments, the neuA mutant formed papules and pustules at rates that were no different than those of its parent. When grown in media with and without Neu5Ac supplementation, the neuA mutant and its parent had similar phenotypes in bactericidal, macrophage uptake, and dendritic cell activation assays. Although we cannot preclude a contribution of LOS sialylation to ulcerative disease, these data strongly suggest that sialylation of LOS is dispensable for H. ducreyi pathogenesis in humans.

  6. Physiologic and pathophysiologic consequences of altered sialylation and glycosylation on ion channel function.

    PubMed

    Baycin-Hizal, Deniz; Gottschalk, Allan; Jacobson, Elena; Mai, Sunny; Wolozny, Daniel; Zhang, Hui; Krag, Sharon S; Betenbaugh, Michael J

    2014-10-17

    Voltage-gated ion channels are transmembrane proteins that regulate electrical excitability in cells and are essential components of the electrically active tissues of nerves, muscle and the heart. Potassium channels are one of the largest subfamilies of voltage sensitive channels and are among the most-studied of the voltage-gated ion channels. Voltage-gated channels can be glycosylated and changes in the glycosylation pattern can affect ion channel function, leading to neurological and neuromuscular disorders and congenital disorders of glycosylation (CDG). Alterations in glycosylation can also be acquired and appear to play a role in development and aging. Recent studies have focused on the impact of glycosylation and sialylation on ion channels, particularly for voltage-gated potassium and sodium channels. The terminal step of sialylation often affects channel activation and inactivation kinetics. The presence of sialic acids on O or N-glycans can alter the gating mechanism and cause conformational changes in the voltage-sensing domains due to sialic acid's negative charges. This manuscript will provide an overview of sialic acids, potassium and sodium channel function, and the impact of sialylation on channel activation and deactivation.

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

    PubMed Central

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

    2015-01-01

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

  8. Modifications to Ivor Lewis esophagectomy.

    PubMed

    David, Elizabeth A; Marshall, M Blair

    2010-11-01

    The surgical approach to esophagectomy is variable. A number of factors are considered when determining the optimal approach to esophagectomy: location and extent of disease, fibrosis, additional patient factors and surgeon preference. One of the disadvantages to some approaches is the need for a change in position, which increases operative time. Also, because typically the abdomen is initially explored, patients may later be deemed unresectable at thoracotomy. We describe time saving modifications to the standard Ivor Lewis esophagectomy that eliminate the need for repositioning and facilitate a stapled end-to-end anastomosis.

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

    SciTech Connect

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

    1988-01-05

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

  10. 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

  11. 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…

  12. 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)

  13. A functional analysis of N-glycosylation-related genes on sialylation of recombinant erythropoietin in six commonly used mammalian cell lines.

    PubMed

    Zhang, Peiqing; Tan, Diana Lifen; Heng, Desmond; Wang, Tianhua; Mariati; Yang, Yuansheng; Song, Zhiwei

    2010-11-01

    Significant efforts have been made to improve the sialylation of recombinant glycoproteins with the aim of extending their in vivo circulation time. Here, we report a systematic functional analysis of 31 N-glycosylation-related genes on sialylation of recombinant EPO in six cell lines. BHK and CHO cells were found to sialylate recombinant EPO most effectively. None of the 31 genes, individually or in combination, was able to improve EPO sialylation in these cells. HEK293, Cos-7 and 3T3 cells showed intermediate sialylation capabilities, whereas NS0 cells sialylated recombinant EPO poorly. Overexpression of ST6GalI, ST3GalIII or ST3GalIV, but not ST3GalVI, was able to improve EPO sialylation in these four cell lines. qRT-PCR experiments revealed that ST3GalIII and ST3GalIV are indeed under expressed in HEK293, 3T3 and NS0 cells. Co-expression of upstream glycogenes failed to synergize with these sialyltransferases to further enhance sialylation, suggesting that the upstream glycogenes are all expressed at sufficient levels.

  14. Cell surface alpha 2,6 sialylation affects adhesion of breast carcinoma cells.

    PubMed

    Lin, Shaoqiang; Kemmner, Wolfgang; Grigull, Sabine; Schlag, Peter M

    2002-05-15

    Tumor-associated alterations of cell surface glycosylation play a crucial role in the adhesion and metastasis of carcinoma cells. The aim of this study was to examine the effect of alpha 2,6-sialylation on the adhesion properties of breast carcinoma cells. To this end mammary carcinoma cells, MDA-MB-435, were sense-transfected with sialyltransferase ST6Gal-I cDNA or antisense-transfected with a part of the ST6Gal-I sequence. Sense transfectants showed an enhanced ST6Gal-I mRNA expression and enzyme activity and an increased binding of the lectin Sambucus nigra agglutinin (SNA), specific for alpha 2,6-linked sialic acid. Transfection with ST6Gal-I in the antisense direction resulted in less enzyme activity and SNA reactivity. A sense-transfected clone carrying increased amounts of alpha 2,6-linked sialic acid adhered preferentially to collagen IV and showed reduced cell-cell adhesion and enhanced invasion capacity. In contrast, antisense transfection led to less collagen IV adhesion but enhanced homotypic cell-cell adhesion. In another approach, inhibition of ST6Gal-I enzyme activity by application of soluble antisense-oligodeoxynucleotides was studied. Antisense treatment resulted in reduced ST6 mRNA expression and cell surface 2,6-sialylation and significantly decreased collagen IV adhesion. Our results suggest that cell surface alpha 2,6-sialylation contributes to cell-cell and cell-extracellular matrix adhesion of tumor cells. Inhibition of sialytransferase ST6Gal-I by antisense-oligodeoxynucleotides might be a way to reduce the metastatic capacity of carcinoma cells.

  15. 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.

  16. Glycoengineering of Chinese hamster ovary cells for enhanced erythropoietin N-glycan branching and sialylation.

    PubMed

    Yin, Bojiao; Gao, Yuan; Chung, Cheng-Yu; Yang, Shuang; Blake, Emily; Stuczynski, Mark C; Tang, Juechun; Kildegaard, Helene F; Andersen, Mikael R; Zhang, Hui; Betenbaugh, Michael J

    2015-11-01

    Sialic acid, a terminal residue on complex N-glycans, and branching or antennarity can play key roles in both the biological activity and circulatory lifetime of recombinant glycoproteins of therapeutic interest. In order to examine the impact of glycosyltransferase expression on the N-glycosylation of recombinant erythropoietin (rEPO), a human α2,6-sialyltransferase (ST6Gal1) was expressed in Chinese hamster ovary (CHO-K1) cells. Sialylation increased on both EPO and CHO cellular proteins as observed by SNA lectin analysis, and HPLC profiling revealed that the sialic acid content of total glycans on EPO increased by 26%. The increase in sialic acid content was further verified by detailed profiling of the N-glycan structures using mass spectra (MS) analysis. In order to enhance antennarity/branching, UDP-N-acetylglucosamine: α-1,3-D-mannoside β1,4-N-acetylglucosaminyltransferase (GnTIV/Mgat4) and UDP-N-acetylglucosamine:α-1,6-D-mannoside β1,6-N-acetylglucosaminyltransferase (GnTV/Mgat5), was incorporated into CHO-K1 together with ST6Gal1. Tri- and tetraantennary N-glycans represented approximately 92% of the total N-glycans on the resulting EPO as measured using MS analysis. Furthermore, sialic acid content of rEPO from these engineered cells was increased ∼45% higher with tetra-sialylation accounting for ∼10% of total sugar chains compared to ∼3% for the wild-type parental CHO-K1. In this way, coordinated overexpression of these three glycosyltransferases for the first time in model CHO-K1 cell lines provides a mean for enhancing both N-glycan branching complexity and sialylation with opportunities to generate tailored complex N-glycan structures on therapeutic glycoproteins in the future.

  17. Reduced Sialylation Impacts Ventricular Repolarization by Modulating Specific K+ Channel Isoforms Distinctly*

    PubMed Central

    Ednie, Andrew R.; Bennett, Eric S.

    2015-01-01

    Voltage-gated K+ channels (Kv) are responsible for repolarizing excitable cells and can be heavily glycosylated. Cardiac Kv activity is indispensable where even minimal reductions in function can extend action potential duration, prolong QT intervals, and ultimately contribute to life-threatening arrhythmias. Diseases such as congenital disorders of glycosylation often cause significant cardiac phenotypes that can include arrhythmias. Here we investigated the impact of reduced sialylation on ventricular repolarization through gene deletion of the sialyltransferase ST3Gal4. ST3Gal4-deficient mice (ST3Gal4−/−) had prolonged QT intervals with a concomitant increase in ventricular action potential duration. Ventricular apex myocytes isolated from ST3Gal4−/− mice demonstrated depolarizing shifts in activation gating of the transient outward (Ito) and delayed rectifier (IKslow) components of K+ current with no change in maximum current densities. Consistently, similar protein expression levels of the three Kv isoforms responsible for Ito and IKslow were measured for ST3Gal4−/− versus controls. However, novel non-enzymatic sialic acid labeling indicated a reduction in sialylation of ST3Gal4−/− ventricular Kv4.2 and Kv1.5, which contribute to Ito and IKslow, respectively. Thus, we describe here a novel form of regulating cardiac function through the activities of a specific glycogene product. Namely, reduced ST3Gal4 activity leads to a loss of isoform-specific Kv sialylation and function, thereby limiting Kv activity during the action potential and decreasing repolarization rate, which likely contributes to prolonged ventricular repolarization. These studies elucidate a novel role for individual glycogene products in contributing to a complex network of cardiac regulation under normal and pathologic conditions. PMID:25525262

  18. Cation affinity numbers of Lewis bases.

    PubMed

    Lindner, Christoph; Tandon, Raman; Maryasin, Boris; Larionov, Evgeny; Zipse, Hendrik

    2012-01-01

    Using selected theoretical methods the affinity of a large range of Lewis bases towards model cations has been quantified. The range of model cations includes the methyl cation as the smallest carbon-centered electrophile, the benzhydryl and trityl cations as models for electrophilic substrates encountered in Lewis base-catalyzed synthetic procedures, and the acetyl cation as a substrate model for acyl-transfer reactions. Affinities towards these cationic electrophiles are complemented by data for Lewis-base addition to Michael acceptors as prototypical neutral electrophiles.

  19. Frustrated Lewis pair chemistry: development and perspectives.

    PubMed

    Stephan, Douglas W; Erker, Gerhard

    2015-05-26

    Frustrated Lewis pairs (FLPs) are combinations of Lewis acids and Lewis bases in solution that are deterred from strong adduct formation by steric and/or electronic factors. This opens pathways to novel cooperative reactions with added substrates. Small-molecule binding and activation by FLPs has led to the discovery of a variety of new reactions through unprecedented pathways. Hydrogen activation and subsequent manipulation in metal-free catalytic hydrogenations is a frequently observed feature of many FLPs. The current state of this young but rapidly expanding field is outlined in this Review and the future directions for its broadening sphere of impact are considered.

  20. Stable expression of sialyl-Tn antigen in T47-D cells induces a decrease of cell adhesion and an increase of cell migration.

    PubMed

    Julien, Sylvain; Lagadec, Chann; Krzewinski-Recchi, Marie-Ange; Courtand, Gilles; Le Bourhis, Xuefen; Delannoy, Philippe

    2005-03-01

    Sialyl-Tn is a carbohydrate antigen overexpressed in several epithelial cancers including breast cancer, and usually associated with poor prognosis. Sialyl-Tn is synthesized by a CMP-Neu5Ac: GalNAc alpha2,6-sialyltransferase: ST6GalNAc I, which catalyzes the transfer of a sialic acid residue in alpha2,6-linkage to the GalNAcalpha1-O-Ser/Thr structure. The resulting disaccharide (Neu5Acalpha2-6GalNAcalpha1-O-Ser/Thr) cannot be further elongated and sialyl-Tn expression results therefore in a shortening of the O-glycan chains. However, usual breast cancer cell lines express neither ST6GalNAc I nor sialyl-Tn antigen. We have previously shown that stable transfection of MDA-MB-231 cells with the hST6GalNAc I cDNA induces the sialyl-Tn antigen expression at the cell surface and leads to a decreased cell growth and an increased cell migration. We describe herein the generation of new T47-D clones expressing sialyl-Tn antigen after hST6GalNAc I cDNA stable transfection. sialyl-Tn antigen is carried by several high molecular weight membrane bound O-glycoproteins, including MUC1. We show that sialyl-Tn expression induces a decrease of cell growth and adhesion, and an increase of cell migration in sialyl-Tn positive clones compared to mock transfected cells. These observations show that the alteration of the O-glycans pattern is sufficient to modify the biological features of cancer cells. These T47-D sialyl-Tn expressing clones might allow further in vivo investigation to determine precisely the impact of such O-glycosylation modifications on breast cancer development.

  1. 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,…

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

    ERIC Educational Resources Information Center

    Keefe, Carolyn

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

  3. 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)

  4. 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)

  5. 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.

  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. 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.

  9. Investigation of Lewis acid versus Lewis base catalysis in asymmetric cyanohydrin synthesis.

    PubMed

    North, Michael; Omedes-Pujol, Marta; Williamson, Courtney

    2010-10-04

    The asymmetric addition of trimethylsilyl cyanide to aldehydes can be catalysed by Lewis acids and/or Lewis bases, which activate the aldehyde and trimethylsilyl cyanide, respectively. It is not always apparent from the structure of the catalyst whether Lewis acid or Lewis base catalysis predominates. To investigate this in the context of using salen complexes of titanium, vanadium and aluminium as catalysts, a Hammett analysis of asymmetric cyanohydrin synthesis was undertaken. When Lewis acid catalysis is dominant, a significantly positive reaction constant is observed, whereas reactions dominated by Lewis base catalysis give much smaller reaction constants. [{Ti(salen)O}(2)] was found to show the highest degree of Lewis acid catalysis, whereas two [VO(salen)X] (X=EtOSO(3) or NCS) complexes both displayed lower degrees of Lewis acid catalysis. In the case of reactions catalysed by [{Al(salen)}(2)O] and triphenylphosphine oxide, a non-linear Hammett plot was observed, which is indicative of a change in mechanism with increasing Lewis base catalysis as the carbonyl compound becomes more electron-deficient. These results suggested that the aluminium complex/triphenylphosphine oxide catalyst system should also catalyse the asymmetric addition of trimethylsilyl cyanide to ketones and this was found to be the case.

  10. Cell surface sialylation affects binding of enterovirus 71 to rhabdomyosarcoma and neuroblastoma cells

    PubMed Central

    2012-01-01

    Background Enterovirus 71 (EV71) is a major causative agent of hand-foot-and-mouth disease (HFMD), and infection of EV71 to central nerve system (CNS) may result in a high mortality in children less than 2 years old. Although there are two highly glycosylated membrane proteins, SCARB2 and PSGL-1, which have been identified as the cellular and functional receptors of EV71, the role of glycosylation in EV71 infection is still unclear. Results We demonstrated that the attachment of EV71 to RD and SK-N-SH cells was diminished after the removal of cell surface sialic acids by neuraminidase. Sialic acid specific lectins, Maackia amurensis (MAA) and Sambucus Nigra (SNA), could compete with EV71 and restrained the binding of EV71 significantly. Preincubation of RD cells with fetuin also reduced the binding of EV71. In addition, we found that SCARB2 was a sialylated glycoprotein and interaction between SCARB2 and EV71 was retarded after desialylation. Conclusions In this study, we demonstrated that cell surface sialic acids assist in the attachment of EV71 to host cells. Cell surface sialylation should be a key regulator that facilitates the binding and infection of EV71 to RD and SK-N-SH cells. PMID:22853823

  11. Novel Kv3 glycoforms differentially expressed in adult mammalian brain contain sialylated N-glycans.

    PubMed

    Schwalbe, Ruth A; Corey, Melissa J; Cartwright, Tara A

    2008-02-01

    The N-glycan pool of mammalian brain contains remarkably high levels of sialylated N-glycans. This study provides the first evidence that voltage-gated K+ channels Kv3.1, Kv3.3, and Kv3.4, possess distinct sialylated N-glycan structures throughout the central nervous system of the adult rat. Electrophoretic migration patterns of Kv3.1, Kv3.3, and Kv3.4 glycoproteins from spinal cord, hypothalamus, thalamus, cerebral cortex, hippocampus, and cerebellum membranes digested with glycosidases were used to identify the various glycoforms. Differences in the migration of Kv3 proteins were attributed to the desialylated N-glycans. Expression levels of the Kv3 proteins were highest in cerebellum, whereas those of Kv3.1 and Kv3.3 were much lower in the other 5 regions. The lowest level of Kv3.1 was expressed in the hypothalamus, whereas the lowest levels of Kv3.3 were expressed in both thalamus and hypothalamus. The other regions expressed intermediate levels of Kv3.3, with spinal cord expressing the highest. The expression level of Kv3.4 in the hippocampus was slightly lower than that in cerebellum, and was closely followed by the other 4 regions, with spinal cord expressing the lowest level. We suggest that novel Kv3 glycoforms may endow differences in channel function and expression among regions throughout the central nervous system.

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

    PubMed

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

    2016-02-25

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

  13. Producing recombinant therapeutic glycoproteins with enhanced sialylation using CHO-gmt4 glycosylation mutant cells

    PubMed Central

    Goh, John SY; Liu, Yingwei; Chan, Kah Fai; Wan, Corrine; Teo, Gavin; Zhang, Peiqing; Zhang, Yuanxing; Song, Zhiwei

    2014-01-01

    Recombinant glycoprotein drugs require proper glycosylation for optimal therapeutic efficacy. Glycoprotein therapeutics are rapidly removed from circulation and have reduced efficacy if they are poorly sialylated. Ricinus communis agglutinin-I (RCA-I) was found highly toxic to wild-type CHO-K1 cells and all the mutants that survived RCA-I treatment contained a dysfunctional N-acetylglucosaminyltransferase I (GnT I) gene. These mutants are named CHO-gmt4 cells. Interestingly, upon restoration of GnT I, the sialylation of a model glycoprotein, erythropoietin, produced in CHO-gmt4 cells was shown to be superior to that produced in wild-type CHO-K1 cells. This addendum summarizes the applicability of this cell line, from transient to stable expression of the recombinant protein, and from a lab scale to an industrial scale perfusion bioreactor. In addition, CHO-gmt4 cells can be used to produce glycoproteins with mannose-terminated N-glycans. Recombinant glucocerebrosidase produced by CHO-gmt4 cells will not require glycan remodeling and may be directly used to treat patients with Gaucher disease. CHO-gmt4 cells can also be used to produce other glycoprotein therapeutics which target cells expressing mannose receptors. PMID:24911584

  14. Producing recombinant therapeutic glycoproteins with enhanced sialylation using CHO-gmt4 glycosylation mutant cells.

    PubMed

    Goh, John S Y; Liu, Yingwei; Chan, Kah Fai; Wan, Corrine; Teo, Gavin; Zhang, Peiqing; Zhang, Yuanxing; Song, Zhiwei

    2014-01-01

    Recombinant glycoprotein drugs require proper glycosylation for optimal therapeutic efficacy. Glycoprotein therapeutics are rapidly removed from circulation and have reduced efficacy if they are poorly sialylated. Ricinus communis agglutinin-I (RCA-I) was found highly toxic to wild-type CHO-K1 cells and all the mutants that survived RCA-I treatment contained a dysfunctional N-acetylglucosaminyltransferase I (GnT I) gene. These mutants are named CHO-gmt4 cells. Interestingly, upon restoration of GnT I, the sialylation of a model glycoprotein, erythropoietin, produced in CHO-gmt4 cells was shown to be superior to that produced in wild-type CHO-K1 cells. This addendum summarizes the applicability of this cell line, from transient to stable expression of the recombinant protein, and from a lab scale to an industrial scale perfusion bioreactor. In addition, CHO-gmt4 cells can be used to produce glycoproteins with mannose-terminated N-glycans. Recombinant glucocerebrosidase produced by CHO-gmt4 cells will not require glycan remodeling and may be directly used to treat patients with Gaucher disease. CHO-gmt4 cells can also be used to produce other glycoprotein therapeutics which target cells expressing mannose receptors.

  15. Sialylated milk oligosaccharides promote microbiota-dependent growth in models of infant undernutrition

    PubMed Central

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

    2016-01-01

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

  16. 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.

  17. A Novel Method for the Simultaneous Enrichment, Identification, and Quantification of Phosphopeptides and Sialylated Glycopeptides Applied to a Temporal Profile of Mouse Brain Development*

    PubMed Central

    Palmisano, Giuseppe; Parker, Benjamin L.; Engholm-Keller, Kasper; Lendal, Sara Eun; Kulej, Katarzyna; Schulz, Melanie; Schwämmle, Veit; Graham, Mark E.; Saxtorph, Henrik; Cordwell, Stuart J.; Larsen, Martin R.

    2012-01-01

    We describe a method that combines an optimized titanium dioxide protocol and hydrophilic interaction liquid chromatography to simultaneously enrich, identify and quantify phosphopeptides and formerly N-linked sialylated glycopeptides to monitor changes associated with cell signaling during mouse brain development. We initially applied the method to enriched membrane fractions from HeLa cells, which allowed the identification of 4468 unique phosphopeptides and 1809 formerly N-linked sialylated glycopeptides. We subsequently combined the method with isobaric tagging for relative quantification to compare changes in phosphopeptide and formerly N-linked sialylated glycopeptide abundance in the developing mouse brain. A total of 7682 unique phosphopeptide sequences and 3246 unique formerly sialylated glycopeptides were identified. Moreover 669 phosphopeptides and 300 formerly N-sialylated glycopeptides differentially regulated during mouse brain development were detected. This strategy allowed us to reveal extensive changes in post-translational modifications from postnatal mice from day 0 until maturity at day 80. The results of this study confirm the role of sialylation in organ development and provide the first extensive global view of dynamic changes between N-linked sialylation and phosphorylation. PMID:22843994

  18. A novel method for the simultaneous enrichment, identification, and quantification of phosphopeptides and sialylated glycopeptides applied to a temporal profile of mouse brain development.

    PubMed

    Palmisano, Giuseppe; Parker, Benjamin L; Engholm-Keller, Kasper; Lendal, Sara Eun; Kulej, Katarzyna; Schulz, Melanie; Schwämmle, Veit; Graham, Mark E; Saxtorph, Henrik; Cordwell, Stuart J; Larsen, Martin R

    2012-11-01

    We describe a method that combines an optimized titanium dioxide protocol and hydrophilic interaction liquid chromatography to simultaneously enrich, identify and quantify phosphopeptides and formerly N-linked sialylated glycopeptides to monitor changes associated with cell signaling during mouse brain development. We initially applied the method to enriched membrane fractions from HeLa cells, which allowed the identification of 4468 unique phosphopeptides and 1809 formerly N-linked sialylated glycopeptides. We subsequently combined the method with isobaric tagging for relative quantification to compare changes in phosphopeptide and formerly N-linked sialylated glycopeptide abundance in the developing mouse brain. A total of 7682 unique phosphopeptide sequences and 3246 unique formerly sialylated glycopeptides were identified. Moreover 669 phosphopeptides and 300 formerly N-sialylated glycopeptides differentially regulated during mouse brain development were detected. This strategy allowed us to reveal extensive changes in post-translational modifications from postnatal mice from day 0 until maturity at day 80. The results of this study confirm the role of sialylation in organ development and provide the first extensive global view of dynamic changes between N-linked sialylation and phosphorylation.

  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. Sialylated β1, 6 branched N-glycans modulate the adhesion, invasion and metastasis of hepatocarcinoma cells.

    PubMed

    Yu, Xiao; Zhao, Yujie; Wang, Liping; Chen, Xixi; Su, Zhen; Zhang, Han; Yuan, Qingmin; Wang, Shujing

    2016-12-01

    The mouse hepatocarcinoma cell lines Hca-F and Hca-P have been derived from hepatocarcinoma in mice and metastasize only to the lymph node. Hca-F cells displayed greater lymphatic metastasis ability than Hca-P cells. When the two cell lines were compared for cell surface sialylated β1,6 branched N-glycans by flow cytometry using L-PHA and SNA, Hca-F cells were found to express significantly higher levels. To explore the effect of increased sialylated β1,6 branched N-glycans on hepatocarcinoma progression, we inhibit their expression in Hca-F cells by using swainsonine treatment and RNA interference. We found that swainsonine treatment or GnT-V-shRNA transfection significantly inhibited the formation of β1,6 branched N-glycans, and partially inhibited the expression of α2,6 sialic acids. Knockdown of sialylated β1,6 branched N-glycans significantly attenuated the invasive and metastatic capability both in vitro and in vivo. Blockade of α2,6 sialic acid expression on Hca-F cell surface by the treatment with neuraminidase caused reduction in cellular adherence to lymph node. In addition, knockdown of sialylated β1,6 branched N-glycans could decrease the expression of Notch1, NICD1, NICD2 and HES1 in Hca-F cells. Collectively, these findings suggest that increased sialylated β1,6 branched N-glycans may contribute to hepatocarcinoma progression by altering the adhesive, invasive and metastatic ability to lymph node via Notch signaling pathway.

  1. Scales of Lewis basicities toward C-centered Lewis acids (carbocations).

    PubMed

    Mayr, Herbert; Ammer, Johannes; Baidya, Mahiuddin; Maji, Biplab; Nigst, Tobias A; Ofial, Armin R; Singer, Thomas

    2015-02-25

    Equilibria for the reactions of benzhydryl cations (Ar2CH(+)) with phosphines, tert-amines, pyridines, and related Lewis bases were determined photometrically in CH2Cl2 and CH3CN solution at 20 °C. The measured equilibrium constants can be expressed by the sum of two parameters, defined as the Lewis Acidity (LA) of the benzhydrylium ions and the Lewis basicity (LB) of the phosphines, pyridines, etc. Least-squares minimization of log K = LA + LB with the definition LA = 0 for (4-MeOC6H4)2CH(+) gave a Lewis acidity scale for 18 benzhydrylium ions covering 18 orders of magnitude in CH2Cl2 as well as Lewis basicities (with respect to C-centered Lewis acids) for 56 bases. The Lewis acidities correlated linearly with the quantum chemically calculated (B3LYP/6-311++G(3df,2pd)//B3LYP/6-31G(d,p) level) methyl anion affinities of the corresponding benzhydrylium ions, which can be used as reference compounds for characterizing a wide variety of Lewis bases. The equilibrium measurements were complemented by isothermal titration calorimetry studies. Rates of SN1 solvolyses of benzhydryl chlorides, bromides, and tosylates derived from E(13-33)(+), i.e., from highly reactive carbocations, correlate excellently with the corresponding Lewis acidities and the quantum chemically calculated methyl anion affinities. This correlation does not hold for solvolyses of derivatives of the better stabilized amino-substituted benzhydrylium ions E(1-12)(+). In contrast, the correlation between electrophilic reactivities and Lewis acidities (or methyl anion affinities) is linear for all donor-substituted benzhydrylium ions E(1-21)(+), while the acceptor-substituted benzhydrylium ions E(26-33)(+) react more slowly than expected from their thermodynamic stabilities. The boundaries of linear rate-equilibrium relationships were thus defined.

  2. Quinic acid derivatives as sialyl Lewis(x)-mimicking selectin inhibitors: design, synthesis, and crystal structure in complex with E-selectin.

    PubMed

    Kaila, Neelu; Somers, William S; Thomas, Bert E; Thakker, Paresh; Janz, Kristin; DeBernardo, Silvano; Tam, Steve; Moore, William J; Yang, Ruiyang; Wrona, Wojciech; Bedard, Patricia W; Crommie, Deidre; Keith, James C; Tsao, Desiree H H; Alvarez, Juan C; Ni, Heyu; Marchese, Erik; Patton, John T; Magnani, John L; Camphausen, Raymond T

    2005-06-30

    A search for noncarbohydrate sLe(x) mimics led to the development of quinic acid derivatives as selectin inhibitors. At Wyeth we solved the first cocrystal structure of a small molecule, quinic acid, with E-selectin. In the cocomplex two hydroxyls of quinic acid mimic the calcium-bound fucose of the tetrasaccharide sLe(x). The X-ray structure, together with structure based computational methods, was used to design quinic acid based libraries that were synthesized and evaluated for their ability to block the interaction of sLex with P-selectin. A large number of analogues were prepared using solution-phase parallel synthesis. Selected compounds showed decrease in leukocyte rolling in the IVM mouse model. Compound 2 inhibited neutrophil influx in the murine TIP model and demonstrated good plasma exposure.

  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. 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.

  6. Gene expression of fucosyl- and sialyl-transferases which synthesize sialyl Lewisx, the carbohydrate ligands for E-selectin, in human breast cancer.

    PubMed

    Matsuura, N; Narita, T; Hiraiwa, N; Hiraiwa, M; Murai, H; Iwase, T; Funahashi, H; Imai, T; Takagi, H; Kannagi, R

    1998-05-01

    The adhesion of circulating cancer cells to vascular endothelium is an important step in the hematogenous metastasis of cancer. Until recently, it has been believed that carbohydrate antigens are expressed on cancer cells, and E-selectin is expressed on endothelial cells to effect this adhesion. We investigated the gene expression of fucosyl-transferase (Fuc-T) and sialyltransferase (ST), which are involved in the synthesis of sialyl Lewisx (s-Lex) in breast cancer by using Northern blot analysis. The concentration of s-Lex in the cancerous portion was increased, compared to that in the adjacent non-cancerous portion. A correlation was found between the concentration of s-Lex and the amount of Fuc-T VI message in 9 cases of breast cancer tissue. Expression of the Fuc-T III message was found in only one case who expressed s-Lea. No expression of the Fuc-T V or VII message was observed. There was no relationship between the concentration of s-Lex and the amount of ST3N and ST4 transcripts. Similar findings were obtained from an analysis using cell lines derived from human breast cancer. When Fuc-T VI gene was transfected to MCF-7 cells, the expression of s-Lex was markedly induced on MCF-7 cells, and the attachment of cancer cells to endothelial cells was enhanced. These findings suggest that Fuc-T VI is chiefly involved in the synthesis of s-Lex on breast cancer cells.

  7. 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…

  8. 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…

  9. Lewis Mumford and the Ecology of Technics.

    ERIC Educational Resources Information Center

    Strate, Lance; Lum, Casey Man Kong

    2000-01-01

    Examines Lewis Mumford's scholarship and his contribution to the emergence of media ecology as both an intellectual tradition and a theoretical perspective on the study of technology, media, and culture. Focuses on Mumford's epochal historiography of technology, the techno-organicism in his thinking about technology and human development, and his…

  10. 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…

  11. 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…

  12. 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.

  13. 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)

  14. 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…

  15. 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…

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

    PubMed

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

    2016-05-19

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

  17. 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

  18. Altered (neo-) lacto series glycolipid biosynthesis impairs α2-6 sialylation on N-glycoproteins in ovarian cancer cells

    PubMed Central

    Alam, Shahidul; Anugraham, Merrina; Huang, Yen-Lin; Kohler, Reto S.; Hettich, Timm; Winkelbach, Katharina; Grether, Yasmin; López, Mónica Núñez; Khasbiullina, Nailia; Bovin, Nicolai V.; Schlotterbeck, Götz; Jacob, Francis

    2017-01-01

    The (neo-) lacto series glycosphingolipids (nsGSLs) comprise of glycan epitopes that are present as blood group antigens, act as primary receptors for human pathogens and are also increasingly associated with malignant diseases. Beta-1, 3-N-acetyl-glucosaminyl-transferase 5 (B3GNT5) is suggested as the key glycosyltransferase for the biosynthesis of nsGSLs. In this study, we investigated the impact of CRISPR-Cas9 -mediated gene disruption of B3GNT5 (∆B3GNT5) on the expression of glycosphingolipids and N-glycoproteins by utilizing immunostaining and glycomics-based PGC-UHPLC-ESI-QTOF-MS/MS profiling. ∆B3GNT5 cells lost nsGSL expression coinciding with reduction of α2-6 sialylation on N-glycoproteins. In contrast, disruption of B4GALNT1, a glycosyltransferase for ganglio series GSLs did not affect α2-6 sialylation on N-glycoproteins. We further profiled all known α2-6 sialyltransferase-encoding genes and showed that the loss of α2-6 sialylation is due to silencing of ST6GAL1 expression in ∆B3GNT5 cells. These results demonstrate that nsGSLs are part of a complex network affecting N-glycosylation in ovarian cancer cells. PMID:28358117

  19. 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.

  20. Sialylated glycans and mucins in the lacrimal gland and eyelid of man and pig. Potential receptors for pathogenic microorganisms.

    PubMed

    Kirkeby, Svend; Mikkelsen, Hanne B; Vorum, Henrik

    2011-12-20

    The conjunctiva of the eyelid is coated by secretion products from the lacrimal and eyelid glands, and by mucins produced by conjunctival goblet cells, which together form a glycoprotein-rich layer that lubricates and protects the surface of the eye. However, these ocular carbohydrates may also act as adhesives for viruses and bacteria and thereby facilitate their colonization. This paper provides histochemical demonstration of the in situ localization of such carbohydrate receptors in the form of sialylated glycans and mucins in the lacrimal and eyelid glands and conjunctiva from both humans and pigs. The pig is included in this study because viruses of swine origin may be capable of transmission to humans. We found that the human and pig ocular surfaces contain receptors for bacteria and viruses in the form of mucins (both membrane bound and secreted) and carbohydrates terminating in Sialylα2-6Gal epitopes and to a lesser degree in Sialylα2-3Gal. The glycosylation of the human soft palate could indicate a mucinous route for the spread of microorganisms from the eye via the nasolacrimal duct to the nasopharynx and thus to the upper part of the respiratory tract.

  1. Increased sialylation of oligosaccharides on IgG paraproteins--a potential new tumour marker in multiple myeloma.

    PubMed Central

    Fleming, S C; Smith, S; Knowles, D; Skillen, A; Self, C H

    1998-01-01

    AIMS: To investigate whether changes in carbohydrate structure of IgG are related to malignancy and stage of disease in myeloma and monoclonal gammopathy of uncertain significance (MGUS). METHODS: 61 patients were studied at diagnosis: 14 with MGUS, nine with stage I multiple myeloma, 11 with stage II, 21 with stage III, and five with solitary plasmacytoma. IgG was extracted from serum by protein G affinity chromatography. Oligosaccharides were cleaved from the protein backbone enzymatically by N-glycosidase F. Oligosaccharide analysis was performed by high pressure anion exchange chromatography with pulsed electrochemical detection (HPAE-PED). RESULTS: Up to 15 oligosaccharide peaks were identified in three major fractions: neutral, monosialylated, and disialylated. Patients with myeloma showed an increase in the proportion of sialylated oligosaccharides in comparison with patients with MGUS. The ratio of neutral to sialylated oligosaccharides (N:S) was reduced at all stages of myeloma compared with MGUS: MGUS, 11.35; myeloma stage I, 7.6 (p = 0.047); stage II, 5.20 (p = 0.035); stage III, 3.60 (p = 0.0002); plasmacytoma, 7.5 (p = 0.046). The N:S ratio was independent of paraprotein concentration (r = 0.05). CONCLUSIONS: The ratio of neutral to sialylated oligosaccharides may act as a new marker of malignancy in IgG paraproteinaemia and warrants further investigation. Images PMID:10193323

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

    PubMed Central

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

    2013-01-01

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

  3. Investigating the Lewis acidity of aluminium fluoride surfaces

    NASA Astrophysics Data System (ADS)

    Bailey, C. L.; Mukhopadhyay, S.; Wander, A.; Harrison, N. M.

    2008-03-01

    The current study employs state of the art hybrid-exchange density functional theory (DFT) to investigate the Lewis acidic sites on the β-AlF3 (100) surface. It is shown that the strong Lewis base, NH3, binds to the surface with a binding energy of up to 1.9 eV. This demonstrates that the material is strongly Lewis acidic. We also consider the binding of the weak Lewis base CO to the surface. We calculate the shift in its stretch frequency compared to the gas phase molecule. Shifts are compared to experimental data and are shown to be typical of strong Lewis acidity.

  4. The human H3N2 influenza viruses A/Victoria/3/75 and A/Hiroshima/52/2005 preferentially bind to α2-3-sialylated monosialogangliosides with fucosylated poly-N-acetyllactosaminyl chains.

    PubMed

    Meisen, Iris; Dzudzek, Tabea; Ehrhardt, Christina; Ludwig, Stephan; Mormann, Michael; Rosenbrück, Regina; Lümen, Regine; Kniep, Bernhard; Karch, Helge; Müthing, Johannes

    2012-08-01

    Among influenza A viruses, subtype H3N2 is the major cause of human influenza morbidity and is associated with seasonal epidemics causing annually half million deaths worldwide. Influenza A virus infection is initiated via hemagglutinin that binds to terminally sialylated glycoconjugates exposed on the surface of target cells. Gangliosides from human granulocytes were probed using thin-layer chromatography overlay assays for their binding potential to H3N2 virus strains A/Victoria/3/75 and A/Hiroshima/52/2005. Highly polar gangliosides with poly-N-acetyllactosaminyl chains showing low chromatographic mobility exhibited strong virus adhesion which was entirely abolished by sialidase treatment. Auxiliary overlay assays using anti-sialyl Lewis(x) (sLe(x)) monoclonal antibodies showed identical binding patterns compared with those performed with the viruses. A comprehensive structural analysis of fractionated gangliosides by electrospray ionization quadrupole time-of-flight mass spectrometry revealed sLe(x) gangliosides with terminal Neu5Acα2-3Galβ1-4(Fucα1-3)GlcNAc epitope and extended neolacto (nLc)-series core structures as the preferential virus binding gangliosides. More precisely, sLe(x) gangliosides with nLc8, nLc10 and nLc12Cer cores, carrying sphingosine (d18:1) and a fatty acid with variable chain length (mostly C24:0, C24:1 or C16:0) in the ceramide moiety and one or two additional internal fucose residues in the oligosaccharide portion, were identified as the preferred receptors recognized by H3N2 virus strains A/Victoria/3/75 and A/Hiroshima/52/2005. This study describes glycan-binding requirements of hemagglutinin beyond binding to glycans with a specific sialic acid linkage of as yet undefined neutrophil receptors acting as ligands for H3N2 viruses. In addition, our results pose new questions on the biological and clinical relevance of this unexpected specificity of a subtype of influenza A viruses.

  5. 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.

  6. 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

  7. 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

  8. O-glycan sialylation alters galectin-3 subcellular localization and decreases chemotherapy sensitivity in gastric cancer

    PubMed Central

    Santos, Sofia N.; Junqueira, Mara S.; Francisco, Guilherme; Vilanova, Manuel; Magalhães, Ana; Baruffi, Marcelo Dias; Chammas, Roger; Harris, Adrian L.; Reis, Celso A.; Bernardes, Emerson S.

    2016-01-01

    ST6GalNAc-I, the sialyltransferase responsible for sialyl-Tn (sTn) synthesis, has been previously reported to be positively associated with cancer aggressiveness. Here we describe a novel sTn-dependent mechanism for chemotherapeutic resistance. We show that sTn protects cancer cells against chemotherapeutic-induced cell death by decreasing the interaction of cell surface glycan receptors with galectin-3 and increasing its intracellular accumulation. Moreover, exogenously added galectin-3 potentiated the chemotherapeutics-induced cytotoxicity in sTn non-expressing cells, while sTn overexpressing cells were protected. We also found that the expression of sTn was associated with a reduction in galectin-3-binding sites in human gastric samples tumors. ST6GalNAc-I knockdown restored galectin-3-binding sites on the cell surface and chemotherapeutics sensibility. Our results clearly demonstrate that an interruption of O-glycans extension caused by ST6GalNAc-I enzymatic activity leads to tumor cells resistance to chemotherapeutic drugs, highlighting the need for the development of novel strategies to target galectin-3 and/or ST6GalNAc-I. PMID:27835877

  9. 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.

  10. High affinity antibodies against Lex and sialyl Lex from a phage display library.

    PubMed

    Dinh, Q; Weng, N P; Kiso, M; Ishida, H; Hasegawa, A; Marcus, D M

    1996-07-15

    Our previous studies of seven murine mAbs against the carbohydrate Lex Ag demonstrated that they were all encoded by VH441 and V kappa 24B. To obtain higher affinity Abs, and to ascertain whether their L chains could be encoded by other genes, we constructed a phage display library in a modified pComb 8 vector. The library contained random L chains, and Fd segments enriched in VH domains encoded by the VHX24 gene family. We selected phage with an Lex-BSA Ag, and obtained two Fab mAbs, clones 23 and 24, whose affinities were more than 100-fold higher than hybridoma mAb PM81. Both new mAbs were encoded by VH441, and their L chains were encoded by genes of the V kappa Ox1 and V kappa 9 families. In contrast to hybridoma mAb PM81, which binds only Lex, clones 23 and 24 bound sialyl Lex (SLex) as well as Lex, and clone 23 also binds the backbone carbohydrate structure nLacCer. Analysis of the binding of these three mAbs to synthetic glycolipids that contained structural modifications indicated that they recognize different aspects of the Lex structure, and suggested that they bind to limited regions of the oligosaccharide.

  11. Anionic Lewis Acids. A Chemical Oxymoron.

    DTIC Science & Technology

    1995-10-17

    NUMBER OF PAGES12 anionic lewis acid ab initio synthesis 1 2 methide FT NMR 16. PRICE CODE imide multi-nule r 17. SECURITY CLASSIFICATION 18...chemically robust, thermally stable, non-toxic, environmentally safe, and cost-effective. One of our current areas of interest involves the synthesis and...developing a predictive knowledge base that can be used to guide the synthesis of new locally electron-deficient anions. Additionally, we proposed to

  12. Calcium-based Lewis acid catalysts.

    PubMed

    Begouin, Jeanne-Marie; Niggemann, Meike

    2013-06-17

    Recently, Lewis acidic calcium salts bearing weakly coordinating anions such as Ca(NTf₂)₂, Ca(OTf)₂, CaF₂ and Ca[OCH(CF₃)₂]₂ have been discovered as catalysts for the transformation of alcohols, olefins and carbonyl compounds. High stability towards air and moisture, selectivity and high reactivity under mild reaction conditions render these catalysts a sustainable and mild alternative to transition metals, rare-earth metals or strong Brønsted acids.

  13. Polymerization by classical and frustrated Lewis pairs.

    PubMed

    Chen, Eugene Y-X

    2013-01-01

    Main-group classical and frustrated Lewis pairs (CLPs and FLPs) comprising strong Lewis acids (LAs) and strong Lewis bases (LBs) are highly active for polymerization of conjugated polar alkenes, affording typically high molecular weight polymers with relatively narrow molecular weight distributions. Especially effective systems are the Lewis pairs (LPs) consisting of the strong LA Al(C6F5)3 and strong LBs, such as achiral phosphines and chiral chelating diphosphines, N-heterocyclic carbenes, and phosphazene superbases, for polymerization of methacrylates and acrylamides as well as renewable α-methylene-γ-butyrolactones. Chain initiation involves cooperative addition of LPs to the monomer to generate zwitterionic active species, and chain propagation proceeds via a bimetallic, activated-monomer addition mechanism. Transition metal nucleophile/electrophile pairs comprising neutral metallocene bis(ester enolate)s and strong LAs E(C6F5)3 (E = Al, B) generate two drastically different polymerization systems, depending on the LA. With E = Al, catalyst activation and chain initiating events lead to dually active ion-pairs, thereby effecting ion-pairing polymerization that affords polymers with unique stereo-multiblock microstructures. With E = B, on the other hand, the FLP-induced catalyst activation generates metallacyclic cations paired with the hydridoborate anion [HB(C6F5)3](-); uniquely, such ion-pairs effect catalytic polymerization of conjugated polar alkenes by an H-shuttling mechanism, with the cation catalyzing chain growth and the anion promoting chain transfer by shuttling the hydride between the cation and anion centers through the neutral borane.

  14. 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.

  15. A Lewis acid-mediated conformational switch.

    PubMed

    Knipe, Peter C; Lingard, Hannah; Jones, Ian M; Thompson, Sam; Hamilton, Andrew D

    2014-10-28

    Molecules that change conformation in response to a stimulus have numerous uses, such as artificial chemoreceptors, novel drug delivery strategies and liquid crystal technology. Here we describe the design, synthesis and conformational behaviour of an isonicotinamide-substituted diphenylacetylene upon recognition of Lewis acids, including metalloporphyrins. Binding of these at a remote site - the pyridyl nitrogen - increases hydrogen-bond donor ability of the proximal amide NH, causing an increased preference for the alkyne rotamer in which this hydrogen bond is maintained.

  16. Maudlin's challenge refuted: A reply to Lewis

    NASA Astrophysics Data System (ADS)

    Kastner, Ruth E.

    2014-08-01

    Lewis has recently argued that Maudlin's contingent absorber experiment remains a significant problem for the Transactional Interpretation (TI). He argues that the only straightforward way to resolve the challenge is by describing the absorbers as offer waves, and asserts that this is a previously unnoticed aspect of the challenge for TI. This argument is refuted in two basic ways: (i) it is noted that the Maudlin experiment cannot be meaningfully recast with absorbers described by quantum states; instead the author replaces it with an ordinary which-way experiment; and (ii) the extant rebuttals to the Maudlin challenge in its original form are not in fact subject to the alleged flaws that Lewis ascribes to them. This paper further seeks to clarify the issues raised in Lewis' presentation concerning the distinction between quantum systems and macroscopic objects in TI. It is noted that the latest, possibilist version of TI (PTI) has no ambiguity concerning macroscopic absorbers. In particular, macroscopic objects are not subject to indeterminate trajectories, since they are continually undergoing collapse. It is concluded that the Maudlin challenge poses no significant problem for the transactional interpretation.

  17. 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.

  18. 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.

  19. Structure of an anti-Lewis X Fab fragment in complex with its Lewis X antigen.

    PubMed

    van Roon, Anne-Marie M; Pannu, Navraj S; de Vrind, Johannes P M; van der Marel, Gijs A; van Boom, Jacques H; Hokke, Cornelis H; Deelder, André M; Abrahams, Jan Pieter

    2004-07-01

    The Lewis X trisaccharide is pivotal in mediating specific cell-cell interactions. Monoclonal antibody 291-2G3-A, which was generated from mice infected with schistosomes, has been shown to recognize the Lewis X trisaccharide. Here we describe the structure of the Fab fragment of 291-2G3-A, with Lewis X, to 1.8 A resolution. The crystallographic analysis revealed that the antigen binding site is a rather shallow binding pocket, and residues from all six complementary determining regions of the antibody contact all sugar residues. The high specificity of the binding pocket does not result in high affinity; the K(D) determined by isothermal calorimetry is 11 microM. However, this affinity is in the same range as for other sugar-antibody complexes. The detailed understanding of the antibody-Lewis X interaction revealed by the crystal structure may be helpful in the design of better diagnostic tools for schistosomiasis and for studying Lewis X-mediated cell-cell interactions by antibody interference.

  20. 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

    2016-03-07

    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.

  1. Frustrated Lewis pairs: from concept to catalysis.

    PubMed

    Stephan, Douglas W

    2015-02-17

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

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

    PubMed

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

    2015-12-15

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

  3. Effect of mild-thiol reducing agents and alpha2,3-sialyltransferase expression on secretion and sialylation of recombinant EPO in CHO cells.

    PubMed

    Chang, Kern Hee; Jeong, Yeon Tae; Kwak, Chan Yeong; Choi, One; Kim, Jung Hoe

    2013-05-01

    We have previously reported that N-acetylcysteine (NAC) not only delayed apoptosis but also enhanced the production of recombinant erythropoietin (EPO) in Chinese hamster ovary (CHO) cell culture. To investigate the production enhancement mechanism, the effects of similar thiolreducing agents were studied. Intriguingly, all mild reducing agents examined including mercaptoethanesulfonic acid (MESNA), thiolactic acid (TLA), and thioglycolate (TG) were shown to block apoptosis and increase EPO production. A pulse-chase study of EPO secretion revealed that all four thiol-reducing agents increased the EPO secretion rate; among them TLA showed the highest rate. In terms of product quality, the sialic acid content of the glycoprotein is one of the most important factors. It was reported that a number of glycoproteins produced by CHO cells often have incomplete sialylation, particularly under high-producing conditions. Human alpha2,3-sialyltransferase (alpha2,3-ST) was introduced into EPO-producing CHO cells in order to compensate for the reduced sialylation during supplementation with NAC. When alpha2,3-ST was expressed in the presence of NAC, reduced sialylation was restored and an even more sialylated EPO was produced. Thus, our study is significant in that it offers increased EPO production while still allowing the prevention of decreased sialylation of EPO.

  4. In-Depth Analysis of Glycoprotein Sialylation in Serum Using a Dual-Functional Material with Superior Hydrophilicity and Switchable Surface Charge.

    PubMed

    Dong, Xuefang; Qin, Hongqiang; Mao, Jiawei; Yu, Dongping; Li, Xiuling; Shen, Aijin; Yan, Jingyu; Yu, Long; Guo, Zhimou; Ye, Mingliang; Zou, Hanfa; Liang, Xinmiao

    2017-03-16

    Sialylation typically occurs at the terminal of glycans, and its aberration often correlates with diseases including neurological diseases and cancer. However, the analysis of glycoprotein sialylation in complex biological samples is still challenging due to their low abundance. Herein, a histidine-bonded silica (HBS) material with a hydrophilic interaction and switchable surface charge was fabricated to enrich sialylated glycopeptides (SGPs) from the digest of proteomics samples. High selectivity toward SGPs was obtained by combining the superior hydrophilicity and switchable-charge characteristics. During the enrichment of sialylated glycopeptides from bovine fetuin digest, seven glycopeptides were detected even at the ratio of 1:5000 with the nonsialylated glycopeptides, demonstrating the high specificity of SGP enrichment by using HBS material. Then, HBS material was further utilized to selectively enrich SGPs from the protein digest of human serum, and 487 glycosites were identified from only 2 μL of human serum; 92.0% of the glycopeptides contained at least one sialic acid, indicating good performance for SGP enrichment by using HBS material. Furthermore, the prepared HBS material also has great potential applications in the analysis of glycoprotein sialylation from other complex biological samples.

  5. The role of sialyl glycan recognition in host tissue tropism of the avian parasite Eimeria tenella.

    PubMed

    Lai, Livia; Bumstead, Janene; Liu, Yan; 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

    2011-10-01

    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.

  6. Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes.

    PubMed

    Yu, Zhuo-Teng; Chen, Ceng; Newburg, David S

    2013-11-01

    Human milk oligosaccharides (HMOS) are not digested in the proximal intestine. In distal intestine, HMOS collectively modify the microbiota, but the response of individual bacteria to individual components of the HMOS is not well defined. Here, each of 25 major isolates of the human intestinal microbiota was fed individual major fucosylated and sialylated HMOS in anaerobic culture. This allowed for an assessment of the influence of specific HMOS on the growth and metabolic products of individual microbiota bacteria. Most Bifidobacteria spp. and Bacteroides spp. grew, induced α-L-fucosidase activity, and produced abundant lactate or short-chain fatty acids (SCFAs) when fed 2'-fucosyllactose (2'-FL), 3-FL, and lactodifucotetraose (LDFT). Lactobacillus delbrueckii ATCC7830, Enterococcus faecalis ATCC19433, and Streptococcus thermophilus ATCC19258 exhibited slight growth, pH reduction, and lactate production when supplemented with 2'-FL or 3-FL, but not LDFT. Supplementation with 3'-sialyllactose (3'-SL) and 6'-SL promoted moderate growth of Bifidobacterium longum JCM7007, 7009, 7010, 7011, 1272, 11347, ATCC15708, Bacteroides vulgatus ATCC8482, and B. thetaiotaomicron ATCC29148; accordingly, these bacteria exhibited greater neuraminidase activity and produced copious lactate, SCFA, or both. Lactobacillus delbrueckii ATCC7830 also consumed 6'-SL. In contrast, Clostridium spp., L. rhamnosus ATCC53103, E. faecalis ATCC29200, Staphylococcus spp., Enterobacter spp., and Escherichia coli K12 did not consume milk oligosaccharides nor produce appreciable acidic fermentation products. Specific Bifidobacteria and Bacteroides differentially digest specific individual HMOS, with the major fucosylated milk oligosaccharides most strongly stimulating key species of mutualist symbionts. This suggests strategies for treating dysbiosis of the microbiota and associated inflammatory disorders.

  7. Utilization of major fucosylated and sialylated human milk oligosaccharides by isolated human gut microbes

    PubMed Central

    Yu, Zhuo-Teng; Chen, Ceng; Newburg, David S

    2013-01-01

    Human milk oligosaccharides (HMOS) are not digested in the proximal intestine. In distal intestine, HMOS collectively modify the microbiota, but the response of individual bacteria to individual components of the HMOS is not well defined. Here, each of 25 major isolates of the human intestinal microbiota was fed individual major fucosylated and sialylated HMOS in anaerobic culture. This allowed for an assessment of the influence of specific HMOS on the growth and metabolic products of individual microbiota bacteria. Most Bifidobacteria spp. and Bacteroides spp. grew, induced α-l-fucosidase activity, and produced abundant lactate or short-chain fatty acids (SCFAs) when fed 2′-fucosyllactose (2′-FL), 3-FL, and lactodifucotetraose (LDFT). Lactobacillus delbrueckii ATCC7830, Enterococcus faecalis ATCC19433, and Streptococcus thermophilus ATCC19258 exhibited slight growth, pH reduction, and lactate production when supplemented with 2′-FL or 3-FL, but not LDFT. Supplementation with 3′-sialyllactose (3′-SL) and 6′-SL promoted moderate growth of Bifidobacterium longum JCM7007, 7009, 7010, 7011, 1272, 11347, ATCC15708, Bacteroides vulgatus ATCC8482, and B. thetaiotaomicron ATCC29148; accordingly, these bacteria exhibited greater neuraminidase activity and produced copious lactate, SCFA, or both. Lactobacillus delbrueckii ATCC7830 also consumed 6′-SL. In contrast, Clostridium spp., L. rhamnosus ATCC53103, E. faecalis ATCC29200, Staphylococcus spp., Enterobacter spp., and Escherichia coli K12 did not consume milk oligosaccharides nor produce appreciable acidic fermentation products. Specific Bifidobacteria and Bacteroides differentially digest specific individual HMOS, with the major fucosylated milk oligosaccharides most strongly stimulating key species of mutualist symbionts. This suggests strategies for treating dysbiosis of the microbiota and associated inflammatory disorders. PMID:24013960

  8. 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

  9. 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

  10. Dementia with Lewy bodies: early diagnostic challenges.

    PubMed

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

    2013-06-01

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

  11. 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.

  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. Targeted O-glycoproteomics explored increased sialylation and identified MUC16 as a poor prognosis biomarker in advanced stage bladder tumours.

    PubMed

    Cotton, Sofia; Azevedo, Rita; Gaiteiro, Cristiana; Ferreira, Dylan; Lima, Luís; Peixoto, Andreia; Fernandes, Elisabete; Neves, Manuel; Neves, Diogo; Amaro, Teresina; Cruz, Ricardo; Tavares, Ana; Rangel, Maria; Silva, André M N; Santos, Lúcio Lara; Ferreira, José Alexandre

    2017-02-03

    Bladder carcinogenesis and tumour progression is accompanied by profound alterations in protein glycosylation on the cell surface, which may be explored for improving disease management. In a search for prognosis biomarkers and novel therapeutic targets we have screened, using immunohistochemistry, a series of bladder tumours with differing clinicopathology for short-chain O-glycans commonly found in glycoproteins of human solid tumours. These included the Tn and T antigens and their sialylated counterparts sialyl-Tn(STn) and sialyl-T(ST), which are generally associated with poor prognosis. We have also explored the nature of T antigen sialylation, namely the sialyl-3-T(S3T) and sialyl-6-T(S6T) sialoforms, based on combinations of enzymatic treatments. We observed a predominance of sialoglycans over neutral glycoforms (Tn and T antigens) in bladder tumours. In particular, the STn antigen was associated with high-grade disease and muscle invasion, in accordance with our previous observations. The S3T and S6T antigens were detected for the first time in bladder tumours but not in healthy urothelia, highlighting their cancer-specific nature. These glycans were also overexpressed in advanced lesions, especially in cases showing muscle invasion. Glycoproteomic analyses of advanced bladder tumours based on enzymatic treatments, Vicia Villosa lectin-affinity chromatography enrichment and nanoLC-ESI-MS/MS analysis resulted in the identification of several key cancer-associated glycoproteins (MUC16, CD44, integrins) carrying altered glycosylation. Of particular interest were MUC16 STn(+) -glycoforms, characteristic of ovarian cancers, which were found in a subset of advanced-stage bladder tumours facing the worst prognosis. In summary, significant alterations in the O-glycome and O-glycoproteome of bladder tumors hold promise for the development of novel non-invasive diagnostic tools and targeted therapeutics. Furthermore, abnormal MUC16 glycoforms hold potential as

  15. A zwitterionic carbanion frustrated by boranes--dihydrogen cleavage with weak Lewis acids via an "inverse" frustrated Lewis pair approach.

    PubMed

    Li, Hui; Aquino, Adelia J A; Cordes, David B; Hung-Low, Fernando; Hase, William L; Krempner, Clemens

    2013-10-30

    The synthesis, structural characterization, and acid-base chemistry of [C(SiMe2OCH2CH2OMe)3]Na (2), a sterically encumbered zwitterionic organosodium compound, is reported. 2 is a strong Brønsted base that forms frustrated Lewis pairs (FLPs) with a number of boron-containing Lewis acids ranging from weakly Lewis acidic aryl and alkyl boranes to various alkyl borates. These intermolecular FLPs readily cleave H2, which confirms that even poor Lewis acids can engage in FLP-mediated H2 cleavage provided that the present bulky base is of sufficiently high Brønsted basicity.

  16. Neurophysiological biomarkers for Lewy body dementias

    PubMed Central

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

    2016-01-01

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

  17. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 3 2014-07-01 2014-07-01 false Fort Lewis Area Access Office. 552.168 Section 552.168 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY..., Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM...

  18. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 3 2010-07-01 2010-07-01 true Fort Lewis Area Access Office. 552.168 Section 552.168 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY..., Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM...

  19. 32 CFR 552.168 - Fort Lewis Area Access Office.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 3 2012-07-01 2009-07-01 true Fort Lewis Area Access Office. 552.168 Section 552.168 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY MILITARY..., Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM...

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

    NASA Technical Reports Server (NTRS)

    Lewis, Cathleen; Wright, Rebecca

    2012-01-01

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

  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, Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM Range Division operates the Area Access Section to issue permits and grant non-training access to the...

  2. 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, Yakima Training Center, and Camp Bonneville § 552.168 Fort Lewis Area Access Office. (a) DPTM Range Division operates the Area Access Section to issue permits and grant non-training access to the...

  3. 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…

  4. 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…

  5. 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…

  6. New entries to water-compatible Lewis acids.

    PubMed

    Kobayashi, Shu; Ogawa, Chikako

    2006-08-07

    Lewis acid catalysis has attracted much attention in organic synthesis as it often affords access to unique reactivity and selectivity under mild conditions. Although various kinds of Lewis acids have been developed and applied in industry, these Lewis acids must be generally used under strictly anhydrous conditions, as the presence of even a small amount of water interferes with the reactions due to preferential reaction of the Lewis acids with water rather than the substrates. In contrast to this, rare earth and other metal complexes have been found to be water-compatible. Furthermore, Bi(OTf)(3)- and Ga(OTf)(3)-basic ligand complexes have also been found to be stable in water, and have been used as water-compatible Lewis acids. This application is particularly significant, as Bi(OTf)(3) and Ga(OTf)(3) themselves are unstable in the presence of water, but are stabilized by the basic ligands. This observation has led to the development of a new approach to Lewis acid catalysis in which Lewis acids that are generally unstable in the presence of water are rendered amenable to aqueous systems when combined with basic ligands. In particular, the use of chiral basic ligands leading to new types of water-compatible chiral Lewis acids may enable a wide range of asymmetric catalysis in aqueous media.

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

    ERIC Educational Resources Information Center

    Starnes, Bobby Ann

    2004-01-01

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

  8. Tyrosine derivatization and preparative purification of the sialyl and asialy-N-linked oligosaccharides from porcine fibrinogen.

    PubMed

    Da Silva, M L; Tamura, T; McBroom, T; Rice, K G

    1994-07-01

    The N-linked oligosaccharides from porcine fibrinogen were purified following their release from glycopeptides using N-glycosidase F. In separate experiments, both sialyl and asialyl oligosaccharides were prepared from 5 g of fibrinogen. The reducing oligosaccharides were reacted with ammonium bicarbonate to form/oligosaccharide-glycosylamines and then derivatized with tert-butoxycarbonyl-L-tyrosine N-hydroxysuccinimidyl ester. Tyrosinamide--oligosaccharides were purified first by gel filtration chromatography and then by reverse-phase HPLC and the products were characterized by proton NMR and fast atom bombardment-MS. Porcine fibrinogen was found to have predominantly a single asialyl biantennary oligosaccharide containing a fucose linked alpha 1-6 to GlcNAc 1. The oligosaccharide possesses two sialylation patterns with a major form (70%) having a single N-acetyl neuraminic acid (NeuAc) residue linked alpha 2-6 to galactose on only one antenna and a minor form (30%) possessing two NeuAc residues linked alpha 2-6 to both terminal galactose residues. In addition to developing an isolation procedure and establishing the structures of porcine fibrinogen oligosaccharides, this study improves on the tyrosine derivatization technique as a general approach to isolate structurally diverse N-linked oligosaccharides from glycoproteins.

  9. Endothelial targeting and enhanced antiinflammatory effects of complement inhibitors possessing sialyl Lewisx moieties.

    PubMed

    Mulligan, M S; Warner, R L; Rittershaus, C W; Thomas, L J; Ryan, U S; Foreman, K E; Crouch, L D; Till, G O; Ward, P A

    1999-04-15

    The complement inhibitor soluble complement receptor type 1 (sCR1) and a truncated form of sCR1, sCR1[desLHR-A], have been generated with expression of the selectin-reactive oligosaccharide moiety, sialyl Lewisx (sLex), as N-linked oligosaccharide adducts. These modified proteins, sCR1sLex and sCR1[desLHR-A]sLex, were assessed in the L-selectin- and P-selectin-dependent rat model of lung injury following systemic activation of complement by cobra venom factor and in the L-selectin-, P-selectin-, and E-selectin-dependent model of lung injury following intrapulmonary deposition of IgG immune complexes. In the cobra venom factor model, sCR1sLex and sCR1[desLHR-A]sLex caused substantially greater reductions in neutrophil accumulation and in albumin extravasation in lung when compared with the non-sLex-decorated forms. In this model, increased lung vascular binding of sCR1sLex and sCR1[desLHR-A]sLex occurred in a P-selectin-dependent manner, in contrast to the absence of any increased binding of sCR1 or sCR1[desLHR-A]. In the IgG immune complex model, sCR1[desLHR-A]sLex possessed greater protective effects relative to sCR1[desLHR-A], based on albumin extravasation and neutrophil accumulation. Enhanced protective effects correlated with greater lung vascular binding of sCR1[desLHR-A]sLex as compared with the non-sLex-decorated form. In TNF-alpha-activated HUVEC, substantial in vitro binding occurred with sCR1[desLHR-A]sLex (but not with sCR1[desLHR-A]). This endothelial cell binding was blocked by anti-E-selectin but not by anti-P-selectin. These data suggest that sLex-decorated complement inhibitors have enhanced antiinflammatory effects and appear to have enhanced ability to localize to the activated vascular endothelium.

  10. 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.

  11. Aluminium Diphosphamethanides: Hidden Frustrated Lewis Pairs.

    PubMed

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

    2016-07-04

    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.

  12. Superconducting Microwave Electronics at Lewis Research Center

    NASA Technical Reports Server (NTRS)

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

    1991-01-01

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

  13. Dementia with Lewy bodies: current concepts.

    PubMed

    Buracchio, Teresa; Arvanitakis, Zoe; Gorbien, Martin

    2005-01-01

    As life expectancy continues to increase over time, dementia is becoming an increasingly more common problem and a major cause of disability in older persons. It is now more important than ever to identify and manage common causes of dementia given variations in disease course, treatments and the possibility for modification of risk factors. Dementia with Lewy bodies (DLB) is a dementia syndrome characterized by progressive cognitive decline, with fluctuating cognition, recurrent detailed and well-formed hallucinations, and parkinsonism. This article aims to provide an overview of current concepts of DLB, including a description of the key clinical features and neuropathology, neurochemistry, and genetics of DLB, then a discussion of the relationship of DLB with Alzheimer's disease and Parkinson's disease, and, finally, a summary of current management strategies available for this disorder.

  14. 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.

  15. Large Lewis No. Edge-Flame Instabilities

    NASA Technical Reports Server (NTRS)

    Buckmaster, J.

    2001-01-01

    Edge-flames play an important role in a number of microgravity investigations, and in the general study of flames. Examples include the candle-flame experiments carried out on board both the Space Shuttle and the Mir Space Station; the flame-spread-over-liquid work carried out by H. Ross and W. Sirignano amongst others and lifted turbulent diffusion flames. In all of these configurations a local two-dimensional flame structure can be identified which looks like a flame-sheet with an edge, and these structures exhibit dynamical behavior which characterizes them and distinguishes them from ad hoc 2D flame structures. Edge-flames can exist in both a non-premixed context (edges of diffusion flames) and in a premixed context (edges of deflagrations), but the work reported here deals with the edges of diffusion flames. It is particularly relevant, we believe, to oscillations that have been seen in both the candle-flame context, and the flame-spread-over-liquid context. These oscillations are periodic edge-oscillations (in an appropriate reference frame), sans oscillation of the trailing diffusion flame. It is shown that if the Lewis number of the fuel is sufficiently large (the Lewis number of the oxidizer is taken to be 1), and the Damkohler number is sufficiently small, oscillating-edge solutions can be found. Oscillations are encouraged by an on-edge convective flow and the insertion of a cold probe, discouraged by an off-edge convective flow. In the present work, the nature of these oscillations is examined in more depth, using a variety of numerical strategies.

  16. Chiral organoborane Lewis pairs derived from pyridylferrocene.

    PubMed

    Chen, Jiawei; Lalancette, Roger A; Jäkle, Frieder

    2014-07-14

    In an effort to develop a new class of redox-active chiral Lewis pairs, pyridine and borane moieties with different steric and electronic properties were introduced onto a planar chiral 1,2-disubstituted ferrocene framework. Metathesis of lithiated, stannylated, or mercuriated pyridylferrocenes with boron halides afforded (pR)-2-[bis(pentafluorophenyl)boryl]-1-(3,5-dimethylpyrid-2-yl)ferrocene (4-Pf), (pR)-2-[dimesitylboryl]-1-(3,5-dimethylpyrid-2-yl)ferrocene (4-Mes), (pS)-2-(bis(pentafluorophenyl)boryl)-1-(2-trimethylsilylpyrid-6-yl)ferrocene (5-Pf), or (pS)-2-[dimesitylboryl]-1-(2-trimethylsilylpyrid-6-yl)ferrocene (5-Mes). The borylated products were analyzed by multinuclear NMR spectroscopy, HRMS, and single-crystal X-ray diffraction. Chiral HPLC and optical-rotation measurements were employed to assess the stereoselectivity of the borylation process and to establish the correct stereochemical assignments. The strength of the B-N interactions were investigated in solution and in the solid state. Compounds 4-Pf and 4-Mes formed robust 'closed' B-N heterocyclic systems that proved to be perfectly stable to air and moisture, whereas 5-Pf established a dynamic equilibrium, in which the B-N heterocycle was observed exclusively at room temperature, but opened up at high temperature according to (19)F NMR exchange spectroscopy data. As a consequence, 5-Pf reacted readily with a molecule of water to generate a ring-opened pyridinium borate. The combination of bulky borane and bulky pyridyl groups in 5-Mes led to a completely 'open' frustrated Lewis pair system with uncomplexed pyridine and borane groups, even at room temperature. Electrochemical studies were performed and the effect of preparative ferrocene oxidation on the structural features was also explored.

  17. Parkinson disease and incidental Lewy body disease

    PubMed Central

    Geraci-Erck, Maria; Rabin, Marcie L.; Adler, Charles H.; Serrano, Geidy; Beach, Thomas G.; Kurlan, Roger

    2015-01-01

    Objective: To quantify the loss of pigmented neurons in the substantia nigra (SN) of autopsy-confirmed Parkinson disease (PD) and incidental Lewy body disease (ILBD) vs age-matched controls (C). Methods: Unbiased stereology methods were used to rigorously count number and measure volumes of nigral pigmented neurons in PD, ILBD, and C brains. The obtained stereologic results were correlated with Lewy body (LB), amyloid plaque (AP), neurofibrillary tangle (NFT), and vascular pathology loads assessed in nigral and extranigral regions of each PD, ILBD, and C brain. The stereologic measurements were also correlated to predeath motor and cognitive scores as available for each participant. Results: A marked nigral neuronal loss (NNL) in PD (−82%) and ILBD (−40%) compared to C (p < 0.0001) was found. While there was significant correlation between NNL and LB in some cortical areas of PD (i.e., olfactory bulb), there were no correlations between NNL and LB, AP, or NFT loads or cerebral infarct volumes in any other examined regions for PD and ILBD brains. Conclusions: Using unbiased stereology methods, we show that there is a significant loss and absence of hypertrophic changes in nigral pigmented neurons of ILBD in comparison to C brains. Intriguingly, no significant correlations were found between NNL and LB loads in the SN of both PD and ILBD brains. These autopsy-verified stereologically based findings are novel and support ILBD as a pathologic condition. These results suggest possible new and alternative pathophysiologic hypotheses on the actual relationship between NNL and LB pathology. PMID:26468408

  18. Incidental Lewy Body Disease: Electrophysiological Findings Suggesting Pre-clinical Lewy Body Disorders

    PubMed Central

    Caviness, John N.; Adler, Charles H.; Hentz, Joseph G.; Shill, Holly A.; Evidente, Virgilio G.H.; Driver-Dunckley, Erika D.; Sabbagh, Marwan N.; Sue, Lucia; Beach, Thomas G.

    2011-01-01

    Objective Evaluate electrophysiologic findings in incidental Lewy Body disease (ILBD). Methods ILBD, Control, and Parkinson's disease (PD) subjects had electrophysiological evaluation within two years prior to autopsy. Data analyzed included surface electromyography (EMG) of upper extremity muscles during rest and muscle activation, and electroencephalography (EEG) recording at rest. For EMG, gross tracings and spectral peaks were analyzed. EEG measures analyzed were background frequency and power in delta, theta, alpha, and beta bands. Results Three of ten ILBD subjects (30%) showed unilateral rhythmic EMG discharges at rest without a visually apparent rest tremor. The ILBD resting EMG frequency was lower than in the Control group with no overlap (P=0.03) and close to that of the PD group. The ILBD group had significantly lower background rhythm frequency than the Control group (P=0.001) but was greater than the PD group (P=0.01). Conclusions The electrophysiologic changes in ILBD cases are between those of Control and PD, suggesting that these findings may reflect changes correlating with ILBD as a possible precursor to PD. Significance Electrophysiologic changes in ILBD may assist with the identification of a preclinical stage for Lewy body disorders and help the development of a therapeutic agent for modifying Lewy body disease progression. PMID:21616709

  19. Biosynthesis of the carbohydrate antigenic determinants, Globo H, blood group H, and Lewis b: a role for prostate cancer cell alpha1,2-L-fucosyltransferase.

    PubMed

    Chandrasekaran, E V; Chawda, Ram; Locke, Robert D; Piskorz, Conrad F; Matta, Khushi L

    2002-03-01

    Prostate carcinoma LNCaP cells were unique among several human cancer cell lines which include two other prostate cancer cell lines, PC-3 and DU-145, in expressing alpha1,2-L-fucosyltransferase (FT) as an exclusive FT activity. Affinity gel-GDP and Sephacryl S100 HR columns were used for a partial purification of this enzyme from 3.9 x 10(9) LNCaP cells (approximately 200-fold; 40% yield). The K(m) value (2.7 mM) for the LacNAc type 2 acceptor was quite similar to the one reported for the cloned blood group H gene-specified alpha1,2-FT [Chandrasekaran et al. (1996) Biochemistry 35, 8914-8924]. N-Ethylmaleimide was a potent inhibitor (K(i ) 12.5 microM). The enzyme showed four-fold acceptor preference for the LacNAc type 2 unit in comparison to the T-hapten in mucin core 2 structure. Its main features were similar to those of the cloned enzyme: (1) C-6 sulfation of terminal Gal in the LacNAc unit increased the acceptor efficiency, whereas C-6 sialylation abolished acceptor ability; (2) C-6 sulfation of GlcNAc in LacNAc type 2 decreased by 80% the acceptor ability, whereas LacNAc type 1 was unaffected; (3) Lewis x did not serve as an acceptor; (4) the C-4 hydroxyl rather than the C-6 hydroxyl group of the GlcNAc moiety in LacNAc type1 was essential for activity; and (5) the acrylamide copolymer of Galbeta1,3GlcNAcbeta-O-Al was the best acceptor among the acrylamide copolymers. Additionally, highly significant biological features of alpha1,2FT were identified in the present study. The synthesis of Globo H and Lewis b determinants became evident from the fact that Galbeta1,3GalNAcbeta1,3Galalpha-O-Me and Galbeta1,3(Fucalpha1,4)Glc-NAcbeta1,3Galbeta-O-Me served as high-affinity acceptors for this enzyme. Further, D-Fucbeta1,3Gal-NAcbeta1,3Galalpha-O-Me was a very efficient acceptor, indicating that the C-6 hydroxyl group of the terminal Gal moiety in Globo H is not essential for the enzyme activity. Thus, the present study was able to demonstrate three different

  20. Differentiation of Sialyl Linkage Isomers by One-Pot Sialic Acid Derivatization for Mass Spectrometry-Based Glycan Profiling.

    PubMed

    Nishikaze, Takashi; Tsumoto, Hiroki; Sekiya, Sadanori; Iwamoto, Shinichi; Miura, Yuri; Tanaka, Koichi

    2017-02-21

    Matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) has been used for high-throughput glycan profiling analysis. In spite of the biological importance of sialic acids on nonreducing ends of glycans, it is still difficult to analyze glycans containing sialic acid residues due to their instability and the presence of linkage isomers. In this Article, we describe a one-pot glycan purification/derivatization method employing a newly developed linkage-specific sialic acid derivatization for MS-based glycan profiling with differentiation of sialyl linkage isomer. The derivatization, termed sialic acid linkage specific alkylamidation (SALSA), consists of sequential two-step alkylamidations. As a result of the reactions, α2,6- and α2,3-linked sialic acids are selectively amidated with different length of alkyl chains, allowing distinction of α2,3-/α2,6-linkage isomers from given mass spectra. Our studies using N-glycan standards with known sialyl linkages proved high suitability of SALSA for reliable relative quantification of α2,3-/α2,6-linked sialic acids compared with existing sialic acid derivatization approaches. SALSA fully stabilizes both α2,3- and α2,6-linked sialic acids by alkylamidation; thereby, it became possible to combine SALSA with existing glycan analysis/preparation methods as follows. The combination of SALSA and chemoselective glycan purification using hydrazide beads allows easy one-pot purification of glycans from complex biological samples, together with linkage-specific sialic acid stabilization. Moreover, SALSA-derivatized glycans can be labeled via reductive amination without causing byproducts such as amide decomposition. This solid-phase SALSA followed by glycan labeling has been successfully applied to human plasma N-glycome profiling.

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

    ERIC Educational Resources Information Center

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

    2004-01-01

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

  2. Is It Lewy Body Dementia or Something Else?

    MedlinePlus

    ... Options Join the fight against LBD! Donate Is It LBD or Something Else? Early and accurate diagnosis ... dementia with Lewy bodies’ (DLB). Symptoms that differentiate it from Alzheimer’s include unpredictable levels of cognitive ability, ...

  3. 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

  4. 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

  5. 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.

  6. 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

  7. Chemistry and Electrochemistry in Lewis Acid and Superacid Ionic Liquids

    DTIC Science & Technology

    1994-04-30

    LEWIS ACID AND SUPERACID IONIC LIQUIDS PRINCIPAL INVESTIGATOR: Dr. Robert A. Osteryoung Department of Chemistry North Carolina State University...Spectroscopic Study of Anthracene in a Mixed Lewis-Bronsted Acid Ambient Temperature Molten Salt System", Electrochim. Acta, 37, 2615-2628 (1992...investigated. In acidic melts, electrochemical oxidation of anthracene produces a cation radical which exhibits stability similar to that found in "Msuperdry

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

    NASA Technical Reports Server (NTRS)

    Birchenough, Arthur G.; Martin, Donald F.

    1988-01-01

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

  9. 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.

  10. False memories in Lewy-body disease.

    PubMed

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

    2015-12-01

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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. DatSCAN In Differential Diagnostics of Lewy Body Disease.

    PubMed

    Luzny, Jan; Ivanova, Katerina

    2016-06-01

    Differential diagnosis between Lewy body disease and Alzheimer´s disease might be difficult because of similarities of clinical symptoms in both neurodegenerative diseases. DatSCAN is a modern functional neuroimmaging method which differentiates between this similar diseases and helps in correct treatment strategy. We report our positive experience with DatSCAN in differentiating Lewy body disease from Alzheimer´s disease. This is a case report of a woman with Lewy body disease, initially diagnosed as Alzheimer´s disease. DatSCAN neuroimmaging method was used in differential diagnosis of dementia. Memory impairment, impaired activities of daily living, sleep and behavioral disturbances were present in our case. Donepezil was well tolerated, but haloperidol administration was followed by development of severe dystonia. DatSCAN showed deficient dopaminergic presynaptic transport in substantia nigra and striatum. This finding is typical for Lewy body disease not for Alzheimer´s disease. DatSCAN neuroimmaging is a suitable method for differentiating Lewy body disease from Alzheimer´s disease. Deficient dopaminergic presynaptic transport in substantia nigra and striatum is typical for Lewy body disease.

  16. Functional roles of sialylation in breast cancer progression through miR-26a/26b targeting ST8SIA4

    PubMed Central

    Ma, Xiaolu; Dong, Weijie; Su, Zhen; Zhao, Lifen; Miao, Yuan; Li, Nana; Zhou, Huimin; Jia, Li

    2016-01-01

    Sialylation is one of the altered glycosylation patterns associated with cancer progression. In this study, we investigated the N-glycan profiles of breast cancer patients and cell lines to reveal sialylation associated with breast cancer progression, and provided new evidences of miRNA-mediated sialylation. MALDI-TOF MS analysis revealed that N-glycans found in breast cancer tissues and breast cancer cell MDA-MB-231 featured increased levels of sialylation compared with adjacent tissues and normal breast epithelial cell MCF-10A. The expressional profiles of 20 sialyltransferase genes were then analyzed and found significantly different comparing breast cancer samples with adjacent tissues, and two breast cancer cell lines MDA-MB-231 and MCF-7 with different metastatic potential and MCF-10A cells. Tumor tissues and highly metastatic breast cancer cell line MDA-MB-231 exhibited higher levels of ST8SIA4. Knocking down ST8SIA4 in breast cancer cell lines significantly inhibited their malignant behaviors including cell proliferation and invasion in a sialyltransferase-dependent manner. By applying bioinformatic approaches for the prediction of miRNA targeting 3′-UTR of ST8SIA4, we identified ST8SIA4 as one of the miR-26a/26b-targeted genes. Further data analysis revealed the inversely related expression of ST8SIA4 and miR-26a/26b in breast cancer cells, tumor tissues and corresponding adjacent tissues. The ability of miR-26a/26b to interact specifically with and regulate the 3′-UTR of ST8SIA4 was demonstrated via a luciferase reporter assay. The forced expression of miR-26a/26b was able to induce a decrease of ST8SIA4 level and also to affect breast cancer cells progression, while altered expression of ST8SIA4 in breast cancer cells modulated progression upon transfection with miR-26a/26b mimics or inhibiter. Taken together, these results indicate that changes in the glycosylation patterns and sialylation levels may be useful markers of the progression of breast

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

    PubMed Central

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

    2014-01-01

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

  18. 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.

  19. Neuroimaging characteristics of dementia with Lewy bodies.

    PubMed

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

    2014-01-01

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

  20. Capgras syndrome in Dementia with Lewy Bodies

    PubMed Central

    Thaipisutikul, Papan; Lobach, Iryna; Zweig, Yael; Gurnani, Ashita; Galvin, James E.

    2014-01-01

    Background Capgras syndrome is characterized by the recurrent, transient belief that a person has been replaced by an identical imposter. We reviewed clinical characteristics of Dementia with Lewy Bodies (DLB) patients with Capgras syndrome compared to those without Capgras. Methods We identified 55 consecutive DLB patients (11 cases with Capgras syndrome (DLB-C) and 44 cases without evidence of Capgras (DLB). Semi-structured interviews with the patient and an informant, neurological exams, and neuropsychological testing were performed. Caregivers were assessed for caregiver burden and depression. Primary comparisons were made between DLB-C and DLB. Exploratory analyses using stepwise logistic regression and bootstrap analyses were performed to determine clinical features associated with Capgras. Results DLB-C patients experienced more visual hallucinations and self-reported anxiety, had higher scores on the Neuropsychiatric Inventory, and were less likely to be treated with cholinesterase inhibitors at time of initial evaluation. Extrapyramidal symptoms and depression were not associated with Capgras. Caregivers of DLB-C patients had higher caregiver burden. DLB-C was associated with self-reported anxiety (OR 10.9; 95% CI 2.6-47.6). In a bootstrap analysis, clinical findings that were predictors of Capgras included visual hallucinations (log(OR) 18.3; 95% CI 17.9-19.3) and anxiety (log(OR) 2.9; 95% CI (0.31-20.2). Conclusions Our study suggests that Capgras syndrome is common in DLB and usually occurs in the presence of anxiety and visual hallucinations, suggesting related etiopathogenesis. Early appreciation of Capgras syndrome may afford the opportunity to alleviate caregiver burden and improve patient and caregiver outcomes. PMID:23211760

  1. 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.

  2. 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

  3. Friedrich Heinrich Lewy (1885-1950) and his work.

    PubMed

    Holdorff, Bernd

    2002-03-01

    In 1912, Friedrich Heinrich Lewy first described the inclusion bodies named after him and seen in paralysis agitans (p.a.). Tretiakoff had found (1919) that the nucleus niger is most likely to be affected but in a subsequent large-scale series of post-mortem examinations (1923). Lewy was able to confirm this for a minority of cases only, with the exception of those that displayed postencephalitic Parkinsonism (and an unknown number of atypical Parkinson syndrome cases not identified until the 1960s). In a speculative paper (1932), he saw similarities between inclusion bodies in p.a. and viral diseases like lyssa and postulated a viral genesis of p.a. In a historical review of basal ganglia diseases (1942), he did not mention the putative significance of the inclusion bodies for the post-mortem diagnosis. It seems that their importance was seen only after Lewy's death, long after Tretiakoff's initial naming of the 'corps de Lewy'. Lewy, however, had already described their diffuse and cortical distribution (1923). An identification of diffuse Lewy body disease or dementia followed much later. Lewy's career in many diverse branches of neurology and internal medicine was strongly affected by World War I and the difficult situation faced by Jews in Germany. Shortly after the Neurological Institute was founded in Berlin in 1932 (as a clinic and research institute), he was forced, in 1933, to emigrate. His exile in England and the United States mirrors the fate of many German Jews and academics in the first half of the 20th century.

  4. Sialylation of the Fas Death Receptor by ST6Gal-I Provides Protection against Fas-mediated Apoptosis in Colon Carcinoma Cells*

    PubMed Central

    Swindall, Amanda F.; Bellis, Susan L.

    2011-01-01

    The glycosyltransferase, ST6Gal-I, adds sialic acid in an α2–6 linkage to the N-glycans of membrane and secreted glycoproteins. Up-regulation of ST6Gal-I occurs in many cancers, including colon carcinoma, and correlates with metastasis and poor prognosis. However, mechanisms by which ST6Gal-I facilitates tumor progression remain poorly understood due to limited knowledge of enzyme substrates. Herein we identify the death receptor, Fas (CD95), as an ST6Gal-I substrate, and show that α2–6 sialylation of Fas confers protection against Fas-mediated apoptosis. Intriguingly, differences in ST6Gal-I activity do not affect the function of DR4 or DR5 death receptors upon treatment with TRAIL, implicating a selective effect of ST6Gal-I on the Fas receptor. Using ST6Gal-I knockdown and forced overexpression colon carcinoma cell models, we find that α2–6 sialylation of Fas prevents apoptosis stimulated by FasL as well as the Fas-activating antibody, CH11, as evidenced by decreased activation of caspases 8 and 3. We also show that α2–6 sialylation of Fas does not alter the binding of CH11, but rather inhibits the capacity of Fas to induce apoptosis by blocking the association of FADD with Fas cytoplasmic tails, an event that initiates death-inducing signaling complex formation. Furthermore, α2–6 sialylation of Fas inhibits Fas internalization, which is required for apoptotic signaling. Although dysregulated Fas activity is a well known mechanism through which tumors evade apoptosis, the current study is the first to link Fas insensitivity to the actions of a specific sialyltransferase. This finding establishes a new paradigm by which death receptor function is impaired for the self-protection of tumors against apoptosis. PMID:21550977

  5. Metabolic flux-driven sialylation alters internalization, recycling, and drug sensitivity of the epidermal growth factor receptor (EGFR) in SW1990 pancreatic cancer cells

    PubMed Central

    Mathew, Mohit P.; Tan, Elaine; Saeui, Christopher T.; Bovonratwet, Patawut; Sklar, Samuel; Bhattacharya, Rahul; Yarema, Kevin J.

    2016-01-01

    In prior work we reported that advanced stage, drug-resistant pancreatic cancer cells (the SW1990 line) can be sensitized to the EGFR-targeting tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib by treatment with 1,3,4-O-Bu3ManNAc (Bioorg. Med. Chem. Lett. (2015) 25(6):1223-7). Here we provide mechanistic insights into how this compound inhibits EGFR activity and provides synergy with TKI drugs. First, we showed that the sialylation of the EGFR receptor was at most only modestly enhanced (by ∼20 to 30%) compared to overall ∼2-fold increase in cell surface levels of this sugar. Second, flux-driven sialylation did not alter EGFR dimerization as has been reported for cancer cell lines that experience increased sialylation due to spontaneous mutations. Instead, we present evidence that 1,3,4-O-Bu3ManNAc treatment weakens the galectin lattice, increases the internalization of EGFR, and shifts endosomal trafficking towards non-clathrin mediated (NCM) endocytosis. Finally, by evaluating downstream targets of EGFR signaling, we linked synergy between 1,3,4-O-Bu3ManNAc and existing TKI drugs to a shift from clathrin-coated endocytosis (which allows EGFR signaling to continue after internalization) towards NCM endocytosis, which targets internalized moieties for degradation and thereby rapidly diminishes signaling. PMID:27613843

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

    NASA Technical Reports Server (NTRS)

    Rutland, C. J.; Trouve, A.

    1993-01-01

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

  7. 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

  8. Chinese hamster ovary (CHO) host cell engineering to increase sialylation of recombinant therapeutic proteins by modulating sialyltransferase expression.

    PubMed

    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.

  9. 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

  10. Galactosyl-lactose sialylation using Trypanosoma cruzi trans-sialidase as the biocatalyst and bovine κ-casein-derived glycomacropeptide as the donor substrate.

    PubMed

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

    2014-10-01

    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.

  11. 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.

  12. 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.

  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. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. Chemoenzymatic Syntheses of Sialylated Oligosaccharides Containing C5-Modified Neuraminic Acids for Dual Inhibition of Hemagglutinins and Neuraminidases.

    PubMed

    Birikaki, Lémonia; Pradeau, Stéphanie; Armand, Sylvie; Priem, Bernard; Márquez-Domínguez, Luis; Reyes-Leyva, Julio; Santos-López, Gerardo; Samain, Eric; Driguez, Hugues; Fort, Sébastien

    2015-07-20

    A fast chemoenzymatic synthesis of sialylated oligosaccharides containing C5-modified neuraminic acids is reported. Analogues of GM3 and GM2 ganglioside saccharidic portions where the acetyl group of NeuNAc has been replaced by a phenylacetyl (PhAc) or a propanoyl (Prop) moiety have been efficiently prepared with metabolically engineered E. coli bacteria. GM3 analogues were either obtained by chemoselective modification of biosynthetic N-acetyl-sialyllactoside (GM3 NAc) or by direct bacterial synthesis using C5-modified neuraminic acid precursors. The latter strategy proved to be very versatile as it led to an efficient synthesis of GM2 analogues. These glycomimetics were assessed against hemagglutinins and sialidases. In particular, the GM3 NPhAc displayed a binding affinity for Maackia amurensis agglutinin (MAA) similar to that of GM3 NAc, while being resistant to hydrolysis by Vibrio cholerae (VC) neuraminidase. A preliminary study with influenza viruses also confirmed a selective inhibition of N1 neuraminidase by GM3 NPhAc, suggesting potential developments for the detection of flu viruses and for fighting them.

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

    PubMed

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

    2016-01-01

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

  1. Developmental expression of a sialyltransferase responsible for sialylation of cortical alveolus glycoprotein during oogenesis in rainbow trout (Oncorhynchus mykiss).

    PubMed

    Asahina, Shinji; Sato, Chihiro; Kitajima, Ken

    2004-08-01

    Polysialoglycoprotein (PSGP) is a major cortical alveolus glycoprotein of rainbow trout eggs that is characterized by the attachment of a polysialic acid structure to its O-glycan chains. It has been demonstrated that the polysialic acid structure is synthesized by at least three sialyltransferases mostly localized in cortical alveoli. Here we have cloned a cDNA encoding the sialyltransferase, designated rtST6GalNAc, responsible for the transfer of the first sialic acid residue onto the O-glycan chain of PSGP. This enzyme belongs to the vertebrate ST6GalNAc II family, and is strongly expressed in ovaries. Of those O-glycoproteins tested as substrates, asialo-PSGP is the best substrate. These results indicate that rtST6GalNAc is the enzyme responsible for the sialylation of PSGP during oogenesis. Furthermore, the rtST6GalNAc mRNA is expressed throughout oogenesis, is down-regulated at the late yolk vesicle stage (May), and then up-regulated during vitellogenesis (until August). This developmental profile is highly similar to that of STL2, a cortical alveolus lectin, while it is quite different from that of PSGP, which is extensively expressed at the yolk vesicle stage and down-regulated at later stages. Thus, not all cortical alveolus components are transcribed concomitantly. This is the first description of a developmental change in the transcription of a glycosyltransferase during oogenesis.

  2. RCA-I-resistant CHO mutant cells have dysfunctional GnT I and expression of normal GnT I in these mutants enhances sialylation of recombinant erythropoietin.

    PubMed

    Goh, John S Y; Zhang, Peiqing; Chan, Kah Fai; Lee, May May; Lim, Sing Fee; Song, Zhiwei

    2010-07-01

    A large number of CHO glycosylation mutants were isolated by Ricinus communis agglutinin-I (RCA-I). Complementation tests revealed that all these mutant lines possessed a dysfunctional N-acetylglucosaminyltransferase I (GnT I) gene. Sequencing analyses on the GnT I cDNAs isolated from 16 mutant lines led to the identification of nine different single base pair mutations. Some mutations result in a premature stop codon whereas others cause a single amino acid substitution in the GnT I protein. Interestingly, expression of the normal GnT I cDNA in mutant cells resulted in enhanced sialylation of N-glycans. The sialylation of recombinant erythropoietin (EPO) produced in mutant cells that were co-transfected with GnT I was enhanced compared to that of EPO produced in wild type CHO cells. The enhanced sialylation of EPO produced by JW152 cells in the presence of GnT I over CHO-K1 cells is a result of increased sialylated glycan structures with higher antennary branching. These findings represent a new strategy that may be utilized by the biotechnology industry to produce highly sialylated therapeutic glycoproteins.

  3. Lewis Y Antigen as a Target for Breast Cancer Therapy

    DTIC Science & Technology

    1998-09-01

    that peptide mimotopes of adenocarcinomac associated carbohydrate forms that include Lewis Y may function4as a breast cancer vaccine , 3.) established the...the feasibility of peptide mimotopes and design requirements for their use as potential vaccine surrogates for carbohydrate antigens in future vaccine ...understanding mechanisms associated with the utility of peptide mimotopes for vaccine efficacy, priming with mimicking peptides might establish beneficial

  4. 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…

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

    ERIC Educational Resources Information Center

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

    2011-01-01

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

  6. 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%.

  7. 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)

  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. 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. Metabolic connectomics targeting brain pathology in dementia with Lewy bodies.

    PubMed

    Caminiti, Silvia P; Tettamanti, Marco; Sala, Arianna; Presotto, Luca; Iannaccone, Sandro; Cappa, Stefano F; Magnani, Giuseppe; Perani, Daniela

    2017-04-01

    Dementia with Lewy bodies is characterized by α-synuclein accumulation and degeneration of dopaminergic and cholinergic pathways. To gain an overview of brain systems affected by neurodegeneration, we characterized the [18F]FDG-PET metabolic connectivity in 42 dementia with Lewy bodies patients, as compared to 42 healthy controls, using sparse inverse covariance estimation method and graph theory. We performed whole-brain and anatomically driven analyses, targeting cholinergic and dopaminergic pathways, and the α-synuclein spreading. The first revealed substantial alterations in connectivity indexes, brain modularity, and hubs configuration. Namely, decreases in local metabolic connectivity within occipital cortex, thalamus, and cerebellum, and increases within frontal, temporal, parietal, and basal ganglia regions. There were also long-range disconnections among these brain regions, all supporting a disruption of the functional hierarchy characterizing the normal brain. The anatomically driven analysis revealed alterations within brain structures early affected by α-synuclein pathology, supporting Braak's early pathological staging in dementia with Lewy bodies. The dopaminergic striato-cortical pathway was severely affected, as well as the cholinergic networks, with an extensive decrease in connectivity in Ch1-Ch2, Ch5-Ch6 networks, and the lateral Ch4 capsular network significantly towards the occipital cortex. These altered patterns of metabolic connectivity unveil a new in vivo scenario for dementia with Lewy bodies underlying pathology in terms of changes in whole-brain metabolic connectivity, spreading of α-synuclein, and neurotransmission impairment.

  11. 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.

  12. 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.…

  13. 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.

  14. 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.

  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…

  16. 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.

  17. 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.

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

    PubMed Central

    Yasue, Ichiro; Iwata, Nakao

    2016-01-01

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

  19. 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. 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.

  1. 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.

  2. 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…

  3. "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.…

  4. Californian Genius: Lewis Terman's Gifted Child in Regional Perspective

    ERIC Educational Resources Information Center

    Beauvais, Clémentine

    2016-01-01

    This article pays attention to the regional embeddedness of early research on giftedness, looking principally at the works of Lewis Terman and his peers, between the 1910s and 1930s. The rhetoric, ideology, and aesthetics of giftedness in those early works were, I argue, stamped by the context and imaginary of Progressive-Era California and shaped…

  5. 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.…

  6. 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…

  7. Impact of predatory threat on fear extinction in Lewis rats.

    PubMed

    Goswami, Sonal; Cascardi, Michele; Rodríguez-Sierra, Olga E; Duvarci, Sevil; Paré, Denis

    2010-10-01

    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. Lewis rats were subjected to classical auditory fear conditioning before or after exposure to a predatory threat that mimics a type of traumatic stress that leads to PTSD in humans. Exploratory behavior on the elevated plus maze 1 wk after predatory threat exposure was used to distinguish resilient vs. PTSD-like rats. Properties of extinction varied depending on whether fear conditioning and extinction occurred before or after predatory threat. When fear conditioning was carried out after predatory threat, PTSD-like rats showed a marked extinction deficit compared with resilient rats. In contrast, no differences were seen between resilient and PTSD-like rats when fear conditioning and extinction occurred prior to predatory threat. These findings in Lewis rats closely match the results seen in humans with PTSD, thereby suggesting that studies comparing neuronal interactions in resilient vs. at-risk Lewis rats might shed light on the causes and pathophysiology of human PTSD.

  8. 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…

  9. 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

  10. 76 FR 62835 - Notice of Inventory Completion: Fort Lewis College, Durango, CO

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-11

    ... National Park Service Notice of Inventory Completion: Fort Lewis College, Durango, CO AGENCY: National Park... Anthropology, Fort Lewis College, 1000 Rim Dr., Durango, CO 81301, telephone (970) 247-7500. SUPPLEMENTARY... funerary objects in the possession of Fort Lewis College, Durango, CO. The human remains and...

  11. 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.

  12. 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.

  13. Lewis acid-Lewis acid heterobimetallic cooperative catalysis: mechanistic studies and application in enantioselective aza-Michael reaction.

    PubMed

    Yamagiwa, Noriyuki; Qin, Hongbo; Matsunaga, Shigeki; Shibasaki, Masakatsu

    2005-09-28

    The full details of a catalytic asymmetric aza-Michael reaction of methoxylamine promoted by rare earth-alkali metal heterobimetallic complexes are described, demonstrating the effectiveness of Lewis acid-Lewis acid cooperative catalysis. First, enones were used as substrates, and the 1,4-adducts were obtained in good yield (57-98%) and high ee (81-96%). Catalyst loading was successfully reduced to 0.3-3 mol % with enones. To broaden the substrate scope of the reaction to carboxylic acid derivatives, alpha,beta-unsaturated N-acylpyrroles were used as monodentate, carboxylic acid derivatives. With beta-alkyl-substituted N-acylpyrroles, the reaction proceeded smoothly and the products were obtained in high yield and good ee. Transformation of the 1,4-adducts from enones and alpha,beta-unsaturated N-acylpyrroles afforded corresponding chiral aziridines and beta-amino acids. Detailed mechanistic studies, including kinetics, NMR analysis, nonlinear effects, and rare earth metal effects, are also described. The Lewis acid-Lewis acid cooperative mechanism, including the substrate coordination mode, is discussed in detail.

  14. Tuning the Lewis acidity of boranes in frustrated Lewis pair chemistry: implications for the hydrogenation of electron-poor alkenes.

    PubMed

    Nicasio, Juan A; Steinberg, Sebastian; Inés, Blanca; Alcarazo, Manuel

    2013-08-12

    An analysis of the metal-free reduction of electron deficient olefins by frustrated Lewis pairs indicates that the rate-determining step might be either the heterolytic cleavage of H2 to form an -onium borohydride salt, or the subsequent transfer of the hydride moiety to the substrate following a Michael-type addition reaction. While the use of strong Lewis acids such as B(C6F5)3 facilitates the first of these processes, hydride transfer to the olefin should be contrarily favoured by the use of weak Lewis acids which, for this very same reason, might be unable to promote the prior H2 split. After systematic testing of several boranes of different Lewis acidity (assessed by using the Childs' method) and steric demand, an optimal situation that employs tris(2,4,6-trifluorophenyl)borane was reached. Mixtures of this borane with 1,4-diazabicyclo[2.2.2]octane (DABCO) exhibited excellent catalytic activity for the hydrogenation of alkylidene malonates. In fact, this transformation could be achieved under milder conditions than those we reported previously. Moreover, the reaction scope could be expanded to other electron deficient olefins containing esters, sulfones or nitro functionalities as electron-withdrawing substituents.

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

    PubMed Central

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

    2016-01-01

    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

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

    PubMed

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

    2016-03-01

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

  17. Relationship of Sialyl-Lewisx/a Underexpression and E-Cadherin Overexpression in the Lymphovascular Embolus of Inflammatory Breast Carcinoma

    PubMed Central

    Alpaugh, Mary L.; Tomlinson, James S.; Ye, Yin; Barsky, Sanford H.

    2002-01-01

    Inflammatory breast carcinoma (IBC) is characterized by florid tumor emboli within lymphovascular spaces called lymphovascular invasion. These emboli have a unique microscopic appearance of compact clumps of tumor cells retracted away from the surrounding endothelial cell layer. Using a human SCID model of IBC (MARY-X), we, in previous studies, demonstrated that the tumor cell embolus (IBC spheroid) forms on the basis of an intact and overexpressed E-cadherin/α,β-catenin axis that mediates tumor cell-tumor cell adhesion. In the present study we examine the mechanism behind the apparent lack of binding of the tumor embolus to the surrounding endothelium. We find that this lack of tumor cell binding is because of markedly decreased sialyl-Lewisx/a (sLex/a) carbohydrate ligand-binding epitopes on its overexpressed MUC1 and other surface molecules that bind endothelial E-selectin. Decreased sLex/a is because of decreased α3/4-fucosyltransferase activity in MARY-X. The decreased sLex/a fail to confer electrostatic repulsions between tumor cells, which further contributes to the compactness of the MARY-X spheroid by allowing the E-cadherin homodimeric interactions to go unopposed. MARY-X spheroids were retrovirally transfected with FucT-III cDNA, significantly raising their levels of fucosyltransferase activity and surface sLex/a. In parallel experiments, enzymatic transfers with a milk α1,3-fucosyltransferase and an α2,3-sialyltransferase (ST3GalIV) were performed on the MARY-X spheroids and increased surface sLex/a. The addition of sLex/a by either manipulation caused disadherence of the MARY-X spheroids and the disruption of the E-cadherin homodimers mediating cell adhesion. Our findings support the cooperative relationship of sLex/a underexpression and E-cadherin overexpression in the genesis of the lymphovascular embolus of IBC. PMID:12163386

  18. Reduction of myocardial infarct size with sCR1sLe(x), an alternatively glycosylated form of human soluble complement receptor type 1 (sCR1), possessing sialyl Lewis x.

    PubMed

    Zacharowski, K; Otto, M; Hafner, G; Marsh, H C; Thiemermann, C

    1999-11-01

    1 This study investigated the effects of soluble complement receptor type 1 (sCR1) or sCR1sLex, agents which function as a complement inhibitor or as a combined complement inhibitor and selectin adhesion molecule antagonist, respectively, on the infarct size and cardiac troponin T (cTnT) release caused by regional myocardial ischaemia and reperfusion in the rat. 2 Eighty-two, male Wistar rats were subjected to 30 min occlusion of the left anterior descending coronary artery (LAD) followed by 2 h of reperfusion. Haemodynamic parameters were continuously recorded and at the end of the experiments infarct size (with p-nitro-blue tetrazolium) and cTnT release were determined. 3 Infusion of sCR1 (1, 5 or 15 mg kg-1, each n=7) or sCR1sLe(x) (1, 5 or 15 mg kg-1, n=7, 13 or 13, respectively) 5 min prior to LAD-reperfusion caused a reduction in infarct size from 59+/-2% (PBS - control, n=12) to 46+/-6%, 25+/-9% and 37+/-6% or 42+/-6%, 35+/-6% and 35+/-4%, respectively. 4 Infusion of sCR1 (15 mg kg-1, n=5) or sCR1sLe(x) (15 mg kg-1, n=5) also reduces the myocardial TnT release from 80+/-20 ng ml-1 (control) to 13+/-7 or 4+/-1 ng ml-1, respectively. 5 Thus, sCR1 or sCRsLe(x) significantly reduce infarct size and cardiac TnT release caused by 30 min of regional myocardial ischaemia and 2 h of reperfusion in the rat. The mechanisms of the cardioprotective effects of sCR1 or sCR1sLe(x) are not entirely clear, but may be due complement inhibition and/or prevention of the adhesion and activation of neutrophils.

  19. NEU1 sialidase regulates the sialylation state of CD31 and disrupts CD31-driven capillary-like tube formation in human lung microvascular endothelia.

    PubMed

    Lee, Chunsik; Liu, Anguo; Miranda-Ribera, Alba; Hyun, Sang Won; Lillehoj, Erik P; Cross, Alan S; Passaniti, Antonino; Grimm, P Richard; Kim, Bo-Young; Welling, Paul A; Madri, Joseph A; DeLisser, Horace M; Goldblum, Simeon E

    2014-03-28

    The highly sialylated vascular endothelial surface undergoes changes in sialylation upon adopting the migratory/angiogenic phenotype. We recently established endothelial cell (EC) expression of NEU1 sialidase (Cross, A. S., Hyun, S. W., Miranda-Ribera, A., Feng, C., Liu, A., Nguyen, C., Zhang, L., Luzina, I. G., Atamas, S. P., Twaddell, W. S., Guang, W., Lillehoj, E. P., Puché, A. C., Huang, W., Wang, L. X., Passaniti, A., and Goldblum, S. E. (2012) NEU1 and NEU3 sialidase activity expressed in human lung microvascular endothelia. NEU1 restrains endothelial cell migration whereas NEU3 does not. J. Biol. Chem. 287, 15966-15980). We asked whether NEU1 might regulate EC capillary-like tube formation on a Matrigel substrate. In human pulmonary microvascular ECs (HPMECs), prior silencing of NEU1 did not alter tube formation. Infection of HPMECs with increasing multiplicities of infection of an adenovirus encoding for catalytically active WT NEU1 dose-dependently impaired tube formation, whereas overexpression of either a catalytically dead NEU1 mutant, NEU1-G68V, or another human sialidase, NEU3, did not. NEU1 overexpression also diminished EC adhesion to the Matrigel substrate and restrained EC migration in a wounding assay. In HPMECs, the adhesion molecule, CD31, also known as platelet endothelial cell adhesion molecule-1, was sialylated via α2,6-linkages, as shown by Sambucus nigra agglutinin lectin blotting. NEU1 overexpression increased CD31 binding to Arachis hypogaea or peanut agglutinin lectin, indicating CD31 desialylation. In the postconfluent state, when CD31 ectodomains are homophilically engaged, NEU1 was recruited to and desialylated CD31. In postconfluent ECs, CD31 was desialylated compared with subconfluent cells, and prior NEU1 silencing completely protected against CD31 desialylation. Prior CD31 silencing and the use of CD31-null ECs each abrogated the NEU1 inhibitory effect on EC tube formation. Sialyltransferase 6 GAL-I overexpression increased α2

  20. NEU1 Sialidase Regulates the Sialylation State of CD31 and Disrupts CD31-driven Capillary-like Tube Formation in Human Lung Microvascular Endothelia*

    PubMed Central

    Lee, Chunsik; Liu, Anguo; Miranda-Ribera, Alba; Hyun, Sang Won; Lillehoj, Erik P.; Cross, Alan S.; Passaniti, Antonino; Grimm, P. Richard; Kim, Bo-Young; Welling, Paul A.; Madri, Joseph A.; DeLisser, Horace M.; Goldblum, Simeon E.

    2014-01-01

    The highly sialylated vascular endothelial surface undergoes changes in sialylation upon adopting the migratory/angiogenic phenotype. We recently established endothelial cell (EC) expression of NEU1 sialidase (Cross, A. S., Hyun, S. W., Miranda-Ribera, A., Feng, C., Liu, A., Nguyen, C., Zhang, L., Luzina, I. G., Atamas, S. P., Twaddell, W. S., Guang, W., Lillehoj, E. P., Puché, A. C., Huang, W., Wang, L. X., Passaniti, A., and Goldblum, S. E. (2012) NEU1 and NEU3 sialidase activity expressed in human lung microvascular endothelia. NEU1 restrains endothelial cell migration whereas NEU3 does not. J. Biol. Chem. 287, 15966–15980). We asked whether NEU1 might regulate EC capillary-like tube formation on a Matrigel substrate. In human pulmonary microvascular ECs (HPMECs), prior silencing of NEU1 did not alter tube formation. Infection of HPMECs with increasing multiplicities of infection of an adenovirus encoding for catalytically active WT NEU1 dose-dependently impaired tube formation, whereas overexpression of either a catalytically dead NEU1 mutant, NEU1-G68V, or another human sialidase, NEU3, did not. NEU1 overexpression also diminished EC adhesion to the Matrigel substrate and restrained EC migration in a wounding assay. In HPMECs, the adhesion molecule, CD31, also known as platelet endothelial cell adhesion molecule-1, was sialylated via α2,6-linkages, as shown by Sambucus nigra agglutinin lectin blotting. NEU1 overexpression increased CD31 binding to Arachis hypogaea or peanut agglutinin lectin, indicating CD31 desialylation. In the postconfluent state, when CD31 ectodomains are homophilically engaged, NEU1 was recruited to and desialylated CD31. In postconfluent ECs, CD31 was desialylated compared with subconfluent cells, and prior NEU1 silencing completely protected against CD31 desialylation. Prior CD31 silencing and the use of CD31-null ECs each abrogated the NEU1 inhibitory effect on EC tube formation. Sialyltransferase 6 GAL-I overexpression increased

  1. 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).

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

    PubMed

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

    2014-03-12

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

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Structure Of Flame Balls At Low Lewis-number (SOFBALL)

    NASA Technical Reports Server (NTRS)

    Ronney, Paul D.

    1995-01-01

    The work has encompassed several topics related to the experimental and theoretical study of combustion limits in premixed flames at microgravity. These topics include (1) flame structure and stability at low Lewis number (which is the basis for the SOFBALL space flight experiment), (2) flame propagation and extinction in cylindrical tubes, and (3) experimental simulation of combustion processes using autocatalytic chemical reactions. Progress on each of these topics is outlined.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

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

    NASA Technical Reports Server (NTRS)

    1988-01-01

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

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. Carbon-CArbon bond formation by Lewis superacid catalysis.

    PubMed

    Dunach, Elisabet

    2014-11-01

    Diverse intramolecular cyclizations involving the formation of CC bonds are described using catalytic methodologies based on Lewis superacids. Examples are presented on 1,6-diene cyclizations to gem-dimethylcyclohexane structures. Tandem cyclization of trienes are described to afford bicyclic structures in reactions involving rearrangements. Hydroarylation of olefins and of allenes is developed in catalytic FriedelCrafts-type coupling processes, which can give rise to tandem reactions. The olfactory evaluation of the series of prepared compounds is also presented.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. LEWY BODY DEMENTIA: CAREGIVER BURDEN AND UNMET NEEDS

    PubMed Central

    Galvin, James E.; Duda, John E.; Kaufer, Daniel I.; Lippa, Carol F.; Taylor, Angela; Zarit, Steven H.

    2010-01-01

    Lewy body dementia (LBD) is a common cause of dementia but to date, little is known about caregiver burden. The Lewy Body Dementia Association (www.LBDA.org) conducted a web-based survey of 962 caregivers (mean age 56y; 88% women). The most common initial symptoms were cognitive (48%), motor (39%), or both (13%). Caregivers expressed concerns about fear of future (77%), feeling stressed (54%), loss of social life (52%) and uncertainty about what to do next (50%). Caregivers reported moderate to severe burden; 80% felt the people around them did not understand their burden and 54% reported feelings of isolation with spousal caregivers reporting more burden than non-spousal caregivers. Only 29% hired in-home assistance while less than 40% used respite or adult day care, geriatric case managers or attended a support group meeting. Lack of service utilization occurred despite two-thirds of caregivers reporting medical crises requiring emergency services, psychiatric care or law enforcement. Caregivers reported preferences for web-based information, directories of LBD expert providers, information on LBD research and location of local support groups. These findings highlight significant unmet needs for LBD caregivers and provide targets for intervention to reduce caregiver burden. Community resources such as the Lewy Body Dementia Association may serve this end, while also providing practical information and support for caregivers. PMID:20505434

  10. Planar chiral organoborane Lewis acids derived from naphthylferrocene.

    PubMed

    Chen, Jiawei; Venkatasubbaiah, Krishnan; Pakkirisamy, Thilagar; Doshi, Ami; Yusupov, Andrej; Patel, Yesha; Lalancette, Roger A; Jäkle, Frieder

    2010-08-02

    Enantiomerically pure metalated 2-(1-naphthyl)ferrocene (NpFc) derivatives NpFcM (M=SnMe(3), HgCl) were prepared and characterized by multinuclear NMR and UV/Vis spectroscopy, cyclic voltammetry, and elemental analysis. Optical rotation measurements were performed and the absolute configuration of the new planar chiral ferrocene species was confirmed by single-crystal X-ray diffraction analysis. The mercuriated species NpFcHgCl proved suitable as a reagent for the preparation of the chiral organoborane Lewis acid NpFcBCl(2), which can in turn be converted to other ferrocenylboranes by replacement of Cl with nucleophiles. The highly Lewis acidic perfluoroarylborane derivatives NpFcB(C(6)F(5))Cl and NpFcB(C(6)F(5))(2) were successfully prepared by treatment with CuC(6)F(5). The structures were studied by single-crystal X-ray diffraction and variable-temperature (19)F NMR spectroscopy, which suggested that pi stacking of a C(6)F(5) group on boron with the adjacent naphthyl group is energetically favorable. UV/Vis absorption spectroscopy and cyclic voltammetry measurements were performed to examine the electronic properties of these novel redox-active chiral Lewis acids.

  11. Synthesis of the O-linked hexasaccharide containing β-D-Galp-(1→2)-D-Galf in Trypanosoma cruzi mucins. Differences on sialylation by trans-sialidase of the two constituent hexasaccharides.

    PubMed

    Agustí, Rosalía; Giorgi, M Eugenia; Mendoza, Verónica M; Kashiwagi, Gustavo A; de Lederkremer, Rosa M; Gallo-Rodriguez, Carola

    2015-03-15

    The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galp(1→2)-β-D-Galf(1→4)]-D-GlcNAc (10) and its β-D-Galf-(1→2)-β-D-Galf containing isomer (7) are the largest carbohydrates in mucins of some strains of Trypanosoma cruzi. The terminal β-D-Galp units are sites of sialylation by the parasite trans-sialidase. Hexasaccharide 10 was chemically synthesized for the first time by a [3+3] nitrilium based convergent approach, using the trichloroacetimidate method of glycosylation. The (1)H NMR spectrum of its alditol was identical to the spectrum of the product released by β-elimination from the parasite mucin. The trans-sialylation reaction studied on the benzyl glycoside of 10 showed two monosialylated products whose relative abundance changed with time. On the other hand, only one product was produced by sialylation of the benzyl glycoside of 7. A preparative synthesis of the latter and spectroscopic analysis of the product unequivocally established the sialylation site at the less hindered (1→3)-linked galactopyranose.

  12. The ST6GalNAc-I sialyltransferase localizes throughout the Golgi and is responsible for the synthesis of the tumor-associated sialyl-Tn O-glycan in human breast cancer.

    PubMed

    Sewell, Robert; Bäckström, Malin; Dalziel, Martin; Gschmeissner, Steven; Karlsson, Hasse; Noll, Thomas; Gätgens, Jochem; Clausen, Henrik; Hansson, Gunnar C; Burchell, Joy; Taylor-Papadimitriou, Joyce

    2006-02-10

    The functional properties of glycoproteins are strongly influenced by their profile of glycosylation, and changes in this profile are seen in malignancy. In mucin-type O-linked glycosylation these changes can result in the production of mucins such as MUC1, carrying shorter sialylated O-glycans, and with different site occupancy. Of the tumor-associated sialylated O-glycans, the disaccharide, sialyl-Tn (sialic acid alpha2,6GalNAc), is expressed by 30% of breast carcinomas and is the most tumor-specific. The ST6GalNAc-I glycosyltransferase, which can catalyze the transfer of sialic acid to GalNAc, shows a highly restricted pattern of expression in normal adult tissues, being largely limited to the gastrointestinal tract and absent in mammary gland. In breast carcinomas, however, a complete correlation between the expression of RNA-encoding ST6GalNAc-I and the expression of sialyl-Tn is evident, demonstrating that the expression of sialyl-Tn results from switching on expression of hST6GalNAc-I. Endogenous or exogenous expression of hST6GalNAc-I (but not ST6GalNAc-II) always results in the expression of sialyl-Tn. This ability to override core 1/core 2 pathways of O- linked glycosylation is explained by the localization of ST6GalNAc-I, which is found throughout the Golgi stacks. The development of a Chinese hamster ovary (CHO) cell line expressing MUC1 and ST6GalNAc-I allowed the large scale production of MUC1 carrying 83% sialyl-Tn O-glycans. The presence of ST6GalNAc-I in the CHO cells reduced the number of O-glycosylation sites occupied in MUC1, from an average of 4.3 to 3.8 per tandem repeat. The availability of large quantities of this MUC1 glycoform will allow the evaluation of its efficacy as an immunogen for immunotherapy of MUC1/STn-expressing tumors.

  13. 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.

  14. 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.

  15. The Lewis heat pipe code with application to SP-100 GES heat pipes

    NASA Technical Reports Server (NTRS)

    Baker, Karl W.; Tower, Leonard K.

    1988-01-01

    The NASA Lewis Research Center has a thermal management program supporting SP-100 goals, which includes heat pipe radiator development. As a part of the program Lewis has elected to prepare an in-house heat pipe code tailored to the needs of its SP-100 staff to supplement codes from other sources. The latter, designed to meet the needs of the originating organizations, were deemed not entirely appropriate for use at Lewis. However, a review of their features proved most beneficial in the design of the Lewis code.

  16. Sialylation of E-cadherin does not change the spontaneous or ET-18-OMe-mediated aggregation of MCF-7 human breast cancer cells.

    PubMed

    Steelant, W F; Recchi, M A; Noë, V T; Boilly-Marer, Y; Bruyneel, E A; Verbert, A; Mareel, M M; Delannoy, P

    1999-05-01

    We have investigated the role of sialylation on cell-cell adhesion mediated by E-cadherin. Two MCF-7 human breast cancer cell variants were studied: MCF-7/AZ cells showed a spontaneous cell-cell adhesion in the fast and slow aggregation assay. whereas the adhesion deficient MCF-7/6 cell variant failed to form larger aggregates, suggesting that E-cadherin was not functional under the conditions of both assays. We measured the sialyltransferase activities using Galbeta1-3GalNAcalpha-O-benzyl and Galbeta1-4GlcNAcalpha-O-benzyl as acceptor substrates as well as mRNA levels of four sialyltransferases, ST3Gal I, ST3Gal III, ST3Gal IV, ST6Gal I, using multiplex RT-PCR in MCF-7 cell variants. The alpha2-6 and alpha2-3 sialylation of E-cadherin was investigated by immuno-blot using Sambucus nigra agglutinin and Maackia amurensis agglutinin. Compared to the adhesion-proficient MCF-7/AZ cells, the adhesion-deficient MCF-7/6 cell line apparently lacks ST6Gal I mRNA, has a lower ST3Gal I mRNA, a lower ST3Gal I sialyltransferase activity, and no alpha2-3 linked sialic acid moieties on E-cadherin. The potential anti-cancer drug 1-O-octadecyl-2-O-methylglycero-3-phosphocholine (ET-18-OMe, 48 h, 25 microg/ml) belonging to the class of alkyllysophospholipids restored the E-cadherin function in the adhesion-deficient MCF-7/6 cells as evidenced by an increased aggregation. ET-18-OMe caused loss of ST6Gal I mRNA in MCF-7/AZ cells but no changes of sialyltransferase activities or sialic acid moieties on E-cadherin could be observed. We conclude that Ca2+-dependent, E-cadherin-specific homotypic adhesion of MCF-7/AZ or MCF-7/6 cells treated with ET-18-OMe was not affected by sialylation of E-cadherin.

  17. 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

  18. LEWY BODY DEMENTIA: THE CAREGIVER EXPERIENCE OF CLINICAL CARE

    PubMed Central

    Galvin, James E.; Duda, John E.; Kaufer, Daniel I.; Lippa, Carol F.; Taylor, Angela; Zarit, Steven H.

    2010-01-01

    BACKGROUND Lewy body dementia (LBD) is the second most common cause of dementia, however, little is known about how the clinical diagnosis of LBD is obtained in the community or the caregiver experience while seeking the diagnosis. METHODS The Lewy Body Dementia Association (www.LBDA.org) conducted a web-based survey of 962 caregivers over a 6-month period. RESULTS The mean age of respondents was 55.9y; 88% were female and 64% had daily contact with patients. The mean age of LBD patients was 75.4y; 62% were male and 46% lived with a caregiver. The most common presentation of symptoms as reported by LBD caregivers was cognitive (48%), motor (39%) or both (13%). The first diagnoses given to the patients were Parkinson disease or other movement disorder (39%), Alzheimer disease or other cognitive disorder (36%), or mental illness (24%). Fifty percent of patients saw >3 doctors for more than 10 visits over the course of 1 year before an LBD diagnosis was established. Neurologists diagnosed most cases (62%), while primary care-providers diagnosed only 6% of cases. No differences were found between the presentation of disease and the number of physicians, number of office visits, length of time to establish diagnosis, or type of doctor who finally made an LBD diagnosis. Caregivers viewed physicians as knowledgeable about disease manifestations and treatment options, but not about disease course/prognosis and available community resources and referrals. CONCLUSIONS These data highlight a need for increasing physician awareness and knowledge of LBD, which will facilitate accurate diagnosis and treatment. Community resources such as the Lewy Body Dementia Association may serve this end, while also providing practical information and support for caregivers. PMID:20434939

  19. 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

  20. 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.

  1. 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.

  2. Violence and mental illness: what Lewis Carroll had to say.

    PubMed

    Torrey, E Fuller; Miller, Judy

    2014-12-01

    In 1873 Skeffington Lutwidge, a Lunacy Commission inspector of asylums in England, was killed by an asylum patient. Lutwidge was the uncle and close friend of Charles Lutwidge Dodgson, also known as Lewis Carroll. One year later, Carroll began writing The Hunting of the Snark, a poem whose meaning has mystified Carroll enthusiasts. In fact, the poem is a description of the Lunacy Commission inspection team and reflects Carroll's personal understanding of, and reaction to, the killing of his uncle by an individual with a severe mental illness. Carroll's close relationship with his uncle also explains the prominence of psychotic thinking in Carroll's work, including the Mad Hatter's tea party.

  3. 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.

  4. Hypersonic engine seal development at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Steinetz, Bruce M.

    1994-01-01

    NASA Lewis Research Center is developing advanced seal concepts and sealing technology for advanced combined cycle ramjet/scramjet engines being designed for the National Aerospace Plane (NASP). Technologies are being developed for both the dynamic seals that seal the sliding interfaces between articulating engine panels and sidewalls, and for the static seals that seal the heat exchanger to back-up structure interfaces. This viewgraph presentation provides an overview of the candidate engine seal concepts, seal material assessments, and unique test facilities used to assess the leakage and thermal performance of the seal concepts.

  5. 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.

  6. Skewed Fc glycosylation profiles of anti-proteinase 3 immunoglobulin G1 autoantibodies from granulomatosis with polyangiitis patients show low levels of bisection, galactosylation, and sialylation.

    PubMed

    Wuhrer, Manfred; Stavenhagen, Kathrin; Koeleman, Carolien A M; Selman, Maurice H J; Harper, Lorraine; Jacobs, Bart C; Savage, Caroline O S; Jefferis, Roy; Deelder, André M; Morgan, Matthew

    2015-04-03

    Granulomatosis with polyangiitis (GPA) is associated with circulating immunoglobulin (Ig) G anti-proteinase 3 specific (anti-PR3) anti-neutrophil cytoplasm antibodies (ANCA), which activate cytokine primed neutrophils via Fcgamma receptors. ANCA are class switched IgG antibodies implying T cell help in their production. Glycosylation of IgG Fc, under the control of T cell cytokines, determines the interaction between IgG and its receptors. Previous studies have reported aberrant glycosylation of Ig Fc in GPA patients. We investigated whether aberrant Fc glycosylation was present on anti-PR3 ANCA as well as whole IgG subclass preparations compared to healthy controls and whether this correlated with Birmingham vasculitis activity scores (BVAS), serum cytokines, and time to remission. Here, IgG Fc glycosylation of GPA patients and controls and anti-PR3 ANCA Fc glycosylation were determined by mass spectrometry of glycopeptides. IgG1 and IgG2 subclasses from GPA patients showed reduced galactosylation, sialylation, and bisection compared to healthy controls. Anti-PR3 IgG1 ANCA Fc galactosylation, sialylation, and bisection were reduced compared to total IgG1 in GPA. Galactosylation of anti-PR3 ANCA Fc correlated with inflammatory cytokines and time to remission but not BVAS. Bisection of anti-PR3 ANCA Fc correlated with BVAS. Total IgG1 and anti-PR3 IgG1 Fc galactosylation were weakly correlated, while bisection of IgG1 and anti-PR3 showed no correlation. Our data indicate that aberrant ANCA galactosylation may be driven in an antigen-specific manner.

  7. 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.

  8. Metal-free pincer ligand chemistry polycationic phosphonium Lewis acids.

    PubMed

    Szkop, Kevin M; Stephan, Douglas W

    2017-03-07

    Oxidation of 2,6-bis(diphenylphosphine)methyl pyridine with MeO3SCF3, yields the dication [2,6-(CH2PMePh2)2C5H3N][CF3SO3]22, while subsequent treatment with two equivalents of [K(THF)n][B(C6F5)4] (n = 1.3-1.5) afforded [2,6-(CH2PMePh2)2C5H3N][B(C6F5)4]23. Analogous treatment using XeF2 afforded 2,6-(CH2PF2Ph2)2C5H3N 4, while subsequent fluoride abstractions afford the corresponding [BF4], [CF3SO3] and [B(C6F5)4] salts, 5-7, respectively. Compound 4 reacts with an excess of MeO3SCF3 to give [2,6-(CH2PF2Ph2)2C5H3N(CH3)][CF3SO3] 8 while subsequent reaction with [Et3Si·2C7H8][B(C6F5)4] gave the related tricationic species, 9. The Lewis acidity of these di- and triphosphonium cations 3, 7 and 9 was examined and their utility as Lewis acid catalysts was assessed in the dimerization of 1,1-diphenylethylene, the hydrodefluorination of 1-fluoroadamantane, and the dehydrocoupling of phenol and silane.

  9. Dementia with Lewy bodies: a comprehensive review for nurses.

    PubMed

    Ajon Gealogo, Gretchel

    2013-12-01

    Much of the current nursing literature on dementia focuses on Alzheimer disease (AD), the dementia subtype most commonly diagnosed in the older adults. There is a paucity of nursing literature on dementia with Lewy bodies (DLB), the second most common subtype of dementia, which is closely associated with Parkinson disease with dementia (PDD), considered the third most common dementia subtype. Both are aging-related disorders attributed to Lewy bodies, abnormal protein aggregates or "clumps" found to cause cumulative neurodegeneration over time. DLB is defined as dementia onset that is preceded by Parkinsonian symptoms for 1 year or less, whereas in PDD, 2 or more years of Parkinsonian symptoms precede dementia onset. Although basic science knowledge of DLB has increased exponentially, the lack of nursing research on DLB indicates that this knowledge excludes the nursing perspective and its implications for nursing practice. The purpose of this article is to provide nurses with a comprehensive overview of DLB as it compares with PDD and Alzheimer disease and to propose key nursing interventions for clinical practice.

  10. 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.

  11. Lewis acid assisted methyl/chlorine exchange in silylated hydrazinochlorophosphanes.

    PubMed

    Westenkirchner, Andrea; Villinger, Alexander; Karaghiosoff, Konstantin; Wustrack, Ronald; Michalik, Dirk; Schulz, Axel

    2011-03-21

    Differently substituted hydrazinophosphanes of the type (Me(3)Si)(2)N-N(SiMe(3))-PR(1)R(2) (R(1) = Cl with R(2) = Me, C(6)F(5) and R(1) = Me, R(2) = C(6)H(5)) have been studied in the reaction with Lewis acids such as ECl(3) (E = Al, Ga). For (Me(3)Si)(2)N-N(SiMe(3))-P(Cl)(Me) and (Me(3)Si)(2)N-N(SiMe(3))-P(Me)(C(6)H(5)), only adduct formation was found while a chlorine/methyl exchange reaction was observed for (Me(3)Si)(2)N-N(SiMe(3))-P(Cl)R (R = C(6)H(5) and C(6)F(5)) leading to the formation of (Me(2)ClSi)(Me(3)Si)N-N(SiMe(3))-P(Me)R, which crystallize as ECl(3) adducts. The free hydrazinophosphanes can be obtained by removal of the Lewis acid with the help of a strong base such as 4-(dimethylamino)pyridine (DMAP).

  12. Transmission diagnostic research at NASA Lewis Research Center

    NASA Astrophysics Data System (ADS)

    Zakrajsek, J. J.; Townsend, D. P.; Lewicki, D. G.; Decker, H. J.; Handschuh, R. F.

    1995-05-01

    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.

  13. The Triplet State: An Example of G. N. Lewis' Research Style.

    ERIC Educational Resources Information Center

    Kasha, Michael

    1984-01-01

    Examines background of ideas against which Lewis's last researches were done, reflecting on his conduct of scientific research. Also analyzes Lewis's unique habit of writing research previews and indicates, through his research memoranda to the author, his intensity of research interest and activity during the last years of his life. (JN)

  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. 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…

  16. 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…

  17. C.S. Lewis as a Forensic Figure in the Religious Agora.

    ERIC Educational Resources Information Center

    Keefe, Carolyn

    This paper considers the British thinker C.S. Lewis as a "forensic figure," defining "forensic" in the sense of public discussion and debate. The paper relates that, long before Lewis emerged as a public persuader, he learned to hold his own in private exchanges with William T. Kirkpatrick, his tutor from 1914-1917, and in…

  18. 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…

  19. Adele Parot: Beacon of the Dioclesian Lewis School of Gymnastic Expression in the American West.

    ERIC Educational Resources Information Center

    Barney, Robert Knight

    In the late 1800's, Dioclesian Lewis developed and introduced into the schools his new concept of physical education. Dr. Lewis thought in terms of preventing illness and maintaining bodily strength and health through physical fitness. His "new gymnastics" were based on programs of exercise movements. Employing light equipment suitable…

  20. 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…

  1. 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 Park Service, Interior. ACTION: Announcement of boundary revision. SUMMARY: Notice is hereby given that, pursuant to 16 U.S.C. 460l- (9)(c)(1), the boundary of Lewis and Clark National Historical Park is...

  2. 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…

  3. 32 CFR Appendix C to Part 552 - Authorized Activities for Fort Lewis Maneuver Area Access

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 3 2014-07-01 2014-07-01 false 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...

  4. 32 CFR Appendix C to Part 552 - Authorized Activities for Fort Lewis Maneuver Area Access

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 3 2012-07-01 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...

  5. 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…

  6. Transcriptional network analysis in frontal cortex in Lewy body diseases with focus on dementia with Lewy bodies.

    PubMed

    Santpere, Gabriel; Garcia-Esparcia, Paula; Andres-Benito, Pol; Lorente-Galdos, Belen; Navarro, Arcadi; Ferrer, Isidro

    2017-03-21

    The present study investigates global transcriptional changes in frontal cortex area 8 in incidental Lewy Body disease (iLBD), Parkinson disease (PD) and Dementia with Lewy bodies (DLB). We identified different co-expressed gene sets associated with disease stages, and gene ontology categories enriched in gene modules and differentially expressed genes including modules or gene clusters correlated to iLBD comprising upregulated dynein genes and taste receptors, and down-regulated innate inflammation. Focusing on DLB, we found modules with genes significantly enriched in functions related to RNA and DNA production, mitochondria and energy metabolism, purine metabolism, chaperone and protein folding system, and synapses and neurotransmission (particularly the GABAergic system). The expression of more than fifty selected genes was assessed with RT-qPCR. Our findings provide, for the first time, evidence of molecular cortical alterations in iLBD and involvement of several key metabolic pathways and gene hubs in DLB which may underlie cognitive impairment and dementia. This article is protected by copyright. All rights reserved.

  7. Streptococcal cell wall-induced arthritis and adjuvant arthritis in F344----Lewis and in Lewis----F344 bone marrow chimeras

    SciTech Connect

    van Bruggen, M.C.; van den Broek, M.F.; van den Berg, W.B. )

    1991-09-01

    Streptococcal cell wall (SCW)-induced arthritis and adjuvant arthritis (AA) are rat models for chronic, erosive polyarthritis. Both models can be induced in susceptible Lewis rats, whereas F344 rats are resistant. In AA as well as in SCW arthritis, antigen-specific T lymphocytes have been demonstrated to be crucial for chronic disease. In this communication the authors describe their studies to probe the cellular mechanism responsible for the difference in susceptibility of Lewis and F344, using bone marrow chimeras. By transplanting bone marrow cells from F344 into lethally irradiated Lewis recipients, Lewis rats were rendered resistant to SCW arthritis induction. F344 rats reconstituted with Lewis bone marrow, i.e., Lewis----F344 chimeras, develop an arthritis upon SCW injection. For AA comparable results were obtained. These data suggest that both resistance and susceptibility to bacterium-induced chronic arthritis are mediated by hemopoietic/immune cells and that the recipiental environment does not influence the susceptibility to chronic joint inflammation.

  8. 75 FR 55313 - Final Environmental Impact Statement (FEIS) for Grow the Army Actions at Fort Lewis and the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-10

    ... Lewis-McChord, WA 98433-9500. FOR FURTHER INFORMATION CONTACT: Mr. Bill Van Hoesen, Joint Base Lewis- McChord National Environmental Policy Act (NEPA) Coordinator, at (253) 966-1780 during normal...

  9. 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.

  10. 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

  11. 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

  12. [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.

  13. 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.

  14. 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.

  15. 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

  16. 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.

  17. Lewis Carroll and psychoanalysis: why nothing adds up in wonderland.

    PubMed

    Lane, Christopher

    2011-08-01

    Each generation of psychoanalyst has found different things to value and sometimes to censure in Lewis Carroll's remarkable fiction and flights of fancy. But what does Carroll's almost 'surrealist' perspective in the Alice stories tell us about the rituals and symbols that govern life beyond Wonderland and Looking-Glass World? Arguing that Carroll's strong interest in meaning and nonsense in these and later works helps make the world strange to readers, the better to show it off-kilter, this essay focuses on Jacques Lacan's Carroll - the writer-logician who stressed, as Lacan did, the difficulty and price of adapting to the symbolic order. By reconsidering Lacan's 1966 homage to the eccentric Victorian, I argue that Carroll's insight into meaning and interpretation remains of key interest to psychoanalysts intent on hearing all that he had to say about psychic life.

  18. 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

  19. 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.

  20. The NASA Lewis Strain Gauge Laboratory: An update

    NASA Technical Reports Server (NTRS)

    Hobart, H. F.

    1986-01-01

    Efforts continue in the development and evaluation of electrical resistance strain gauges of the thin film and small diameter wire type. Results obtained early in 1986 on some Chinese gauges and Kanthal A-1 gauges mounted on a Hastelloy-X substrate are presented. More recent efforts include: (1) the determination of the uncertainty in the ability to establish gauge factor, (2) the evaluation of sputtered gauges that were fabricated at Lewis, (3) an investigation of the efficacy of dual element temperature compensated gauges when using strain gauge alloys having large thermal coefficients of resistance, and (4) an evaluation of the practical methods of stabilizing gauges whose apparent strain is dependent on cooling rate (e.g., FeCrAl gauges).

  1. 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.

  2. NASA Lewis Research Center Workshop on Forced Response in Turbomachinery

    NASA Technical Reports Server (NTRS)

    Stefko, George L. (Compiler); Murthy, Durbha V. (Compiler); Morel, Michael (Compiler); Hoyniak, Dan (Compiler); Gauntner, Jim W. (Compiler)

    1994-01-01

    A summary of the NASA Lewis Research Center (LeRC) Workshop on Forced Response in Turbomachinery in August, 1993 is presented. It was sponsored by the following NASA organizations: Structures, Space Propulsion Technology, and Propulsion Systems Divisions of NASA LeRC and the Aeronautics and Advanced Concepts & Technology Offices of NASA Headquarters. In addition, the workshop was held in conjunction with the GUIde (Government/Industry/Universities) Consortium on Forced Response. The workshop was specifically designed to receive suggestions and comments from industry on current research at NASA LeRC in the area of forced vibratory response of turbomachinery blades which includes both computational and experimental approaches. There were eight presentations and a code demonstration. Major areas of research included aeroelastic response, steady and unsteady fluid dynamics, mistuning, and corresponding experimental work.

  3. Delayed blink reflex in dementia with Lewy bodies

    PubMed Central

    Bonanni, Laura; Anzellotti, Francesca; Varanese, Sara; Thomas, Astrid; Manzoli, Lamberto; Onofrj, Marco

    2007-01-01

    Blink reflexes (BR) to electric stimuli of the supraorbital nerve were recorded in 26 patients with dementia with Lewy bodies (DLB), 26 patients with multiple system atrophy, 26 patients with Parkinson's disease, with or without REM sleep behaviour disorder (RBD), and in 20 patients with Alzheimer's disease and 20 with progressive supranuclear palsy without RBD, and compared with recordings in 30 healthy controls. BR were significantly delayed (p<0.001) only in DLB patients in comparison with controls and with the other groups of patients; 14 (53.8%) patients had BR latency above 2 SD of the control mean, ranging from 36.1 to 46.3 ms. BR latency was not related to the presence of RBD, while a Spearman correlation rho of 0.68 was found for scores assessing the presence of cognitive fluctuations. R2 delay was prominently (71.5%) bilateral. PMID:17878193

  4. 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.

  5. 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.

  6. Lewy body dementia: the impact on patients and caregivers.

    PubMed

    Zweig, Yael R; Galvin, James E

    2014-01-01

    Lewy body dementia (LBD) is the second most common neurodegenerative dementia in older adults, yet there remains a delay in diagnosis that limits healthcare providers' ability to maximize therapeutic outcomes and enhance patient and caregiver quality of life. The impact of LBD on patients includes limiting the potential exposure to medications that may cause adverse outcomes, and addressing how the disease manifestations, such as autonomic features and behavior, affect quality of life. LBD impact on caregivers has been discussed to a greater degree in the literature, and there is clear evidence of caregiver burden and grief associated with disease manifestations. Other common caregiving concerns, such as access to care, prevention of hospitalization, managing behavior, and reviewing prognosis and nursing home placement, are important to comprehensively address the needs of patients with LBD and their caregivers.

  7. 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

    2015-06-07

    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.

  8. The NASA Lewis integrated propulsion and flight control simulator

    NASA Technical Reports Server (NTRS)

    Bright, Michelle M.; Simon, Donald L.

    1991-01-01

    A new flight simulation facility was developed at NASA-Lewis. The purpose of this flight simulator is to allow integrated propulsion control and flight control algorithm development and evaluation in real time. As a preliminary check of the simulator facility capabilities and correct integration of its components, the control design and physics models for a short take-off and vertical landing fighter aircraft model were shown, with their associated system integration and architecture, pilot vehicle interfaces, and display symbology. The initial testing and evaluation results show that this fixed based flight simulator can provide real time feedback and display of both airframe and propulsion variables for validation of integrated flight and propulsion control systems. Additionally, through the use of this flight simulator, various control design methodologies and cockpit mechanizations can be tested and evaluated in a real time environment.

  9. [Diagnosis and treatment of multifocal motor neuropathy (Lewis-Sumner)].

    PubMed

    Kaji, R

    1999-01-01

    We made a retrospective long-term follow-up study of 25 patients with multifocal motor neuropathy (Lewis-Sumner). The diagnosis was based upon criteria modified from those of AAEM (Sumner 1997). The electrophysiological findings indicating conduction block or focal demyelinative lesions were more diagnostic than anti-GM 1 antibody titers, which were elevated in only 40% of these patients. Demonstration of definite conduction block was not always possible in those patients who responded favorably to intravenous immunoglobulins (IVIg), whereas indirect pieces of evidence such as F-wave abnormalities or focal conduction delay or dispersion were equally helpful. IVIg had superior outcome to cyclophosphamide, which sometimes caused serious adverse effects. Three patients with severe axonal involvement showed elevated monospecific antibodies to GalNAc-GD1a.

  10. 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.

  11. Association of Glucocerebrosidase Mutations With Dementia With Lewy Bodies

    PubMed Central

    Clark, Lorraine N.; Kartsaklis, Lykourgos A.; Wolf Gilbert, Rebecca; Dorado, Beatriz; Ross, Barbara M.; Kisselev, Sergey; Verbitsky, Miguel; Mejia-Santana, Helen; Cote, Lucien J.; Andrews, Howard; Vonsattel, Jean-Paul; Fahn, Stanley; Mayeux, Richard; Honig, Lawrence S.; Marder, Karen

    2009-01-01

    Background Mutations in the glucocerebrosidase (GBA) gene are associated with Lewy body (LB) disorders. Objective To determine the relationship of GBA mutations and APOE4 genotype to LB and Alzheimer disease (AD) pathological findings. Design Case-control study. Setting Academic research. Participants The 187 subjects included patients with primary neuropathological diagnoses of LB disorders with or without AD changes (95 cases), randomly selected patients with AD (without significant LB pathological findings; 60 cases), and controls with neither LB nor AD pathological findings (32 cases). Main Outcome Measures GBA mutation status, APOE4 genotype, LB pathological findings (assessed according to the third report of the Dementia With Lewy Body Consortium), and Alzheimer plaque and tangle pathological findings (rated by criteria of Braak and Braak, the Consortium to Establish a Registry for Alzheimer Disease, and the National Institute on Aging–Reagan Institute). Results GBA mutations were found in 18% (34 of 187) of all subjects, including 28% (27 of 95) of those with primary LB pathological findings compared with 10% (6 of 60) of those with AD pathological findings and 3% (1 of 32) of those without AD or LB pathological findings (P=.001). GBA mutation status was significantly associated with the presence of cortical LBs (odds ratio, 6.48; 95% confidence interval, 2.45–17.16; P<.001), after adjusting for sex, age at death, and presence of APOE4. GBA mutation carriers were significantly less likely to meet AD pathological diagnostic (National Institute on Aging–Reagan Institute intermediate or high likelihood) criteria (odds ratio, 0.35; 95% confidence interval, 0.15–0.79; P=.01) after adjustment for sex, age at death, and APOE4. Conclusion GBA mutations may be associated with pathologically “purer” LB disorders, characterized by more extensive (cortical) LB, and less severe AD pathological findings and may be a useful marker for LB disorders. PMID

  12. 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.

  13. Experimental allergic encephalomyelitis in pituitary-grafted Lewis rats

    PubMed Central

    Esquifino, Ana I; Cano, Pilar; Zapata, Agustín; Cardinali, Daniel P

    2006-01-01

    Treatment of susceptible rats with dopaminergic agonists that reduce prolactin release decreases both severity and duration of clinical signs of experimental allergic encephalomyelitis (EAE). To assess to what extent the presence of an ectopic pituitary (that produces an increase in plasma prolactin levels mainly derived from the ectopic gland) affects EAE, 39 male Lewis rats were submitted to pituitary grafting from littermate donors. Another group of 38 rats was sham-operated by implanting a muscle fragment similar in size to the pituitary graft. All rats received subcutaneous (s.c.) injections of complete Freund's adjuvant (CFA) plus spinal cord homogenate (SCH) and were monitored daily for clinical signs of EAE. Animals were killed by decapitation on days 1, 4, 7, 11 or 15 after immunization and plasma was collected for prolactin RIA. In a second experiment, 48 rats were immunized by s.c. injection of a mixture of SCH and CFA, and then received daily s.c. injections of bromocriptine (1 mg/kg) or saline. Groups of 8 animals were killed on days 8, 11 or 15 after immunization and plasma prolactin was measured. Only sham-operated rats exhibited clinical signs of the disease when assessed on day 15 after immunization. A progressive decrease in plasma prolactin levels was observed in pituitary-grafted rats, attaining a minimum 15 days after immunization, whereas plasma prolactin levels were increased during the course of the disease in sham-operated rats. Plasma prolactin levels were higher in pituitary-grafted rats than in sham-operated rats 1 day after immunization, but lower on days 7, 11 and 15 after immunogen injection. Further supporting a correlation of suppressed prolactin levels with absence of clinical signs of EAE, rats that were administered the dopaminergic agonist bromocriptine showed very low plasma prolactin levels and did not exhibit any clinical sign of EAE. These results indicate that low circulating prolactin levels coincide with absence of

  14. 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.

  15. Mars Pathfinder Rover-Lewis Research Center Technology Experiments Program

    NASA Astrophysics Data System (ADS)

    Stevenson, Steven M.

    1997-07-01

    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.

  16. 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.

  17. Structural characterization of the DC-SIGN-Lewis(X) complex.

    PubMed

    Pederson, Kari; Mitchell, Daniel A; Prestegard, James H

    2014-09-09

    Dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is a C-type lectin highly expressed on the surface of antigen-presenting dendritic cells. DC-SIGN mediates interactions among dendritic cells, pathogens, and a variety of epithelia, myeloid cells, and endothelia by binding to high mannose residues on pathogenic invaders or fucosylated residues on the membranes of other immune cells. Although these interactions are normally beneficial, they can also contribute to disease. The structural characterization of binding geometries is therefore of interest as a basis for the construction of mimetics that can mediate the effects of abnormal immune response. Here, we report the structural characteristics of the interaction of the DC-SIGN carbohydrate recognition domain (CRD) with a common fucosylated entity, the Lewis(X) trisaccharide (Le(X)), using NMR methods. Titration of the monomeric DC-SIGN CRD with Le(X) monitored by 2D NMR revealed significant perturbations of DC-SIGN cross-peak positions in (1)H-(15)N heteronuclear single quantum coherence (HSQC) spectra and identified residues near the binding site. Additionally, saturation transfer difference (STD) and transferred nuclear Overhauser effect (trNOE) NMR experiments, using a tetrameric form of DC-SIGN, identified binding epitopes and bound conformations of the Le(X) ligand. The restraints derived from these multiple experiments were used to generate models for the binding of Le(X) to the DC-SIGN CRD. Ranking of the models based on the fit of model-based simulations of the trNOE data and STD buildup curves suggested conformations distinct from those seen in previous crystal structures. The new conformations offer insight into how differences between binding of Lewis(X) and mannose-terminated saccharides may be propagated.

  18. 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

  19. Surface properties of turbulent premixed propane/air flames at various Lewis numbers

    SciTech Connect

    Lee, T.W.; North, G.L.; Santavicca, D.A. )

    1993-06-01

    Surface properties of turbulent premixed flames including the wrinkled flame perimeter, fraction of the flame pocket perimeter, flame curvature, and orientation distributions have been measured for propane-air flames at Lewis numbers ranging from 0.98 to 1.86 and u[prime]/S[sub L] = 1.42-5.71. The wrinkled flame perimeter is found to be greater for the thermodiffusively unstable Lewis number (Le < 1) by up to 30% in comparison to the most stable condition (Le = 1.86) tested, while the fraction of the flame pocket perimeter shows a similar tendency to be greater for Le < 1. The flame curvature probability density functions are nearly symmetric with respect to the zero mean at all Lewis numbers throughout the range of u[prime]/S[sub L] tested, and show a much stronger dependence on the turbulence condition than on the Lewis number. Similarly, the flame orientation distributions show a trend from anisotropy toward a more uniform distribution with increasing u[prime]/S[sub L] at a similar rate for all Lewis numbers. Thus, for turbulent premixed propane/air flames for a practical range of Lewis number from 0.98 to 1.86, the effect of Lewis number is primarily to affect the flame structures and thereby flame surface areas and flame pocket areas, while the flame curvature and orientation statistics are essentially determined by the turbulence properties.

  20. 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.

  1. Conceptual quantum chemical analysis of bonding and noncovalent interactions in the formation of frustrated Lewis pairs.

    PubMed

    Skara, Gabriella; Pinter, Balazs; Top, Jens; Geerlings, Paul; De Proft, Frank; De Vleeschouwer, Freija

    2015-03-27

    The contributions of covalent and noncovalent interactions to the formation of classical adducts of bulky Lewis acids and bases and frustrated Lewis pairs (FLPs) were scrutinized by using various conceptual quantum chemical techniques. Significantly negative complexation energies were calculated for fourteen investigated Lewis pairs containing bases and acids with substituents of various sizes. A Ziegler-Rauk-type energy decomposition analysis confirmed that two types of Lewis pairs can be distinguished on the basis of the nature of the primary interactions between reactants; dative-bond formation and concomitant charge transfer from the Lewis base to the acid is the dominant and most stabilizing factor in the formation of Lewis acid-base adducts, whereas weak interactions are the main thermodynamic driving force (>50 %) for FLPs. Moreover, the ease and extent of structural deformation of the monomers appears to be a key component in the formation of the former type of Lewis pairs. A Natural Orbital for Chemical Valence (NOCV) analysis, which was used to visualize and quantify the charge transfer between the base and the acid, clearly showed the importance and lack of this type of interaction for adducts and FLPs, respectively. The Noncovalent Interaction (NCI) method revealed several kinds of weak interactions between the acid and base components, such as dispersion, π-π stacking, C-H⋅⋅⋅π interaction, weak hydrogen bonding, halogen bonding, and weak acid-base interactions, whereas the Quantum Theory of Atoms in Molecules (QTAIM) provided further conceptual insight into strong acid-base interactions.

  2. 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.

  3. Diagnostic value of minor salivary glands biopsy for the detection of Lewy pathology.

    PubMed

    Folgoas, Emmanuelle; Lebouvier, Thibaud; Leclair-Visonneau, Laurène; Cersosimo, Maria-Graciela; Barthelaix, Annick; Derkinderen, Pascal; Letournel, Franck

    2013-09-13

    The recent demonstration of the presence of Lewy pathology in the submandibular glands of Parkinson's disease (PD) patients prompted us to evaluate the diagnostic performance of minor salivary gland biopsy for PD. Minor salivary glands were examined for Lewy pathology using phosphorylated alpha-synuclein antibody in 16 patients with clinically diagnosed PD and 11 control subjects with other neurological disorders. Abnormal accumulation of alpha-synuclein was found in 3 out of 16 PD patients. Two control subjects exhibited weak phosphorylated alpha-synuclein immunoreactivity. Our results do not support the use of minor salivary glands biopsy for the detection of Lewy pathology in living subjects.

  4. 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.

  5. 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.

  6. Rapid Dihydrogen Cleavage by Persistent Nitroxide Radicals under Frustrated Lewis Pair Conditions.

    PubMed

    Tao, Xin; Kehr, Gerald; Wang, Xiaowu; Daniliuc, Constantin G; Grimme, Stefan; Erker, Gerhard

    2016-07-04

    Persistent radicals undergo hydrogen atom abstraction reactions with a great variety of substrates, but not with dihydrogen. It has now been found that the TEMPO radical splits dihydrogen under mild conditions in the presence of the strong bulky B(C6 F5 )3 boron Lewis acid. The reaction is thought to proceed by a typical frustrated Lewis pair mechanism with the TEMPO radical acting as the active Lewis base. The reaction was analyzed by DFT, which indicates that no significant spin density on the hydrogen atoms is accumulated along the H2 splitting reaction path.

  7. Understanding the Role of Dispersion in Frustrated Lewis Pairs and Classical Lewis Adducts: A Domain-Based Local Pair Natural Orbital Coupled Cluster Study.

    PubMed

    Bistoni, Giovanni; Auer, Alexander A; Neese, Frank

    2017-01-18

    The interaction of Lewis acids and bases in both classical Lewis adducts and frustrated Lewis pairs (FLPs) is investigated to elucidate the role that London dispersion plays in different situations. The analysis comprises 14 different adducts between tris(pentafluorophenyl)borane and a series of phosphines, carbenes, and amines with various substituents, differing in both steric and electronic properties. The domain-based local pair natural orbital coupled-cluster (DLPNO-CCSD(T)) method is used in conjunction with the recently introduced local energy decomposition (LED) analysis to obtain state-of-the-art dissociation energies and, at the same time, a clear-cut definition of the London dispersion component of the interaction, with the ultimate goal of aiding in the development of designing principles for acid/base pairs with well-defined bonding features and reactivity. In agreement with previous DFT investigations, it is found that the London dispersion dominates the interaction energy in FLPs, and is also remarkably strong in Lewis adducts. In these latter systems, its magnitude can be easily modulated by modifying the polarizability of the substituents on the basic center, which is consistent with the recently introduced concept of dispersion energy donors. By counteracting the destabilizing energy contribution associated with the deformation of the monomers, the London dispersion drives the stability of many Lewis adducts.

  8. 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

  9. 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

  10. Cascade dearomatization of N-substituted tryptophols via Lewis acid-catalyzed Michael reactions.

    PubMed

    Liu, Chuan; Zhang, Wei; Dai, Li-Xin; You, Shu-Li

    2012-09-21

    Lewis acid-catalyzed cascade dearomatization of N-substituted tryptophols via Michael addition reaction was developed. The generality of the method has been demonstrated by the synthesis of versatile furoindoline derivatives with a quaternary carbon center in good yields.

  11. 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.

  12. 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

  13. Redox and Lewis acid-base activities through an electronegativity-hardness landscape diagram.

    PubMed

    Das, Ranjita; Vigneresse, Jean-Louis; Chattaraj, Pratim Kumar

    2013-11-01

    Chemistry is the science of bond making and bond breaking which requires redistribution of electron density among the reactant partners. Accordingly acid-base and redox reactions form cardinal components in all branches of chemistry, e.g., inorganic, organic, physical or biochemistry. That is the reason it forms an integral part of the undergraduate curriculum all throughout the globe. In an electronegativity (χ)- hardness (η) landscape diagram the diagonal χ = η line separates reducing agents from oxidizing agents as well as Lewis acids from Lewis bases. While electronegativity is related to the degree of electron transfer between two reactants, hardness is related to the resistance to that process. Accordingly the electronegativities of oxidizing agents/Lewis acids are generally greater than the corresponding hardness values and the reverse is true for reducing agents/Lewis bases. Electrophiles and nucleophiles are also expected to follow similar trends.

  14. Facile synthesis of planar chiral N-oxides and their use in Lewis base catalysis.

    PubMed

    Fulton, J Robin; Glover, Jean E; Kamara, Lamin; Rowlands, Gareth J

    2011-01-07

    A rapid and versatile method for the preparation of planar chiral [2.2]paracyclophane-derived pyridines and pyridine N-oxides is reported. The potential utility of these compounds in Lewis base catalysis is briefly introduced.

  15. C{sub 2}-symmetric Copper(II) complexes as chiral Lewis acids

    SciTech Connect

    Evans, D.A.; Murry, J.A.; Matt, P. von

    1995-12-01

    Two new Cu(II)-derived Lewis acid catalysts 1 and 2 have been prepared and their utility as catalysts in the Diels-Alder reaction documented. While complex 1 is effective in catalyzing the cycloaddition of unsaturated aldehyde dienophiles with cyclopentadiene complex 2 is optimal for imide dienophiles. This study provides a rational basis for the design of Lewis acids based on the coordinating capacity of cationic Cu(II) complexes which possess sufficient Lewis acidity to catalyze a range of synthetically useful Diels-Alder reactions. In particular, documentation of the importance of counterion structure in the use of cationic metal centers as Lewis acids has been made for the first time.

  16. [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.

  17. Lewis Research Center studies of multiple large wind turbine generators on a utility network

    NASA Technical Reports Server (NTRS)

    Gilbert, L. J.; Triezenberg, D. M.

    1979-01-01

    A NASA-Lewis program to study the anticipated performance of a wind turbine generator farm on an electric utility network is surveyed. The paper describes the approach of the Lewis Wind Energy Project Office to developing analysis capabilities in the area of wind turbine generator-utility network computer simulations. Attention is given to areas such as, the Lewis Purdue hybrid simulation, an independent stability study, DOE multiunit plant study, and the WEST simulator. Also covered are the Lewis mod-2 simulation including analog simulation of a two wind turbine system and comparison with Boeing simulation results, and gust response of a two machine model. Finally future work to be done is noted and it is concluded that the study shows little interaction between the generators and between the generators and the bus.

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

    PubMed

    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.

  20. 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.

  1. Synergistic effects between Lewis and Brønsted acids: application to the Prins cyclization.

    PubMed

    Breugst, Martin; Grée, René; Houk, K N

    2013-10-04

    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.

  2. Human (α2→6) and Avian (α2→3) Sialylated Receptors of Influenza A Virus Show Distinct Conformations and Dynamics in Solution

    PubMed Central

    Macchi, Eleonora; Yates, Edwin A.; Naggi, Annamaria; Shriver, Zachary; Raman, Rahul; Sasisekharan, R.; Torri, Giangiacomo; Guerrini, Marco

    2013-01-01

    Differential interactions between influenza A virus protein hemagglutinin (HA) and α2→3 (avian) or α2→6 (human) sialylated glycan receptors play an important role in governing host specificity and adaptation of the virus. Previous analysis of HA–glycan interactions with trisaccharides showed that, in addition to the terminal sialic acid linkage, the conformation and topology of the glycans, while they are bound to HA, are key factors in regulating these interactions. Here, the solution conformation and dynamics of two representative avian and human glycan pentasaccharide receptors [LSTa, Neu5Ac-α(2→3)-Gal-β(1→3)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc; LSTc, (Neu5Ac-α(2→6)-Gal-β(1→4)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc] have been explored using nuclear magnetic resonance and molecular dynamics simulation. Analyses demonstrate that, in solution, human and avian receptors sample distinct conformations, topologies, and dynamics. These unique features of avian and human receptors in solution could represent distinct molecular characteristics for recognition by HA, thereby providing the HA–glycan interaction specificity in influenza. PMID:24015903

  3. Human (α2→6) and avian (α2→3) sialylated receptors of influenza A virus show distinct conformations and dynamics in solution.

    PubMed

    Sassaki, Guilherme L; Elli, Stefano; Rudd, Timothy R; Macchi, Eleonora; Yates, Edwin A; Naggi, Annamaria; Shriver, Zachary; Raman, Rahul; Sasisekharan, R; Torri, Giangiacomo; Guerrini, Marco

    2013-10-15

    Differential interactions between influenza A virus protein hemagglutinin (HA) and α2→3 (avian) or α2→6 (human) sialylated glycan receptors play an important role in governing host specificity and adaptation of the virus. Previous analysis of HA-glycan interactions with trisaccharides showed that, in addition to the terminal sialic acid linkage, the conformation and topology of the glycans, while they are bound to HA, are key factors in regulating these interactions. Here, the solution conformation and dynamics of two representative avian and human glycan pentasaccharide receptors [LSTa, Neu5Ac-α(2→3)-Gal-β(1→3)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc; LSTc, (Neu5Ac-α(2→6)-Gal-β(1→4)-GlcNAc-β(1→3)-Gal-β(1→4)-Glc] have been explored using nuclear magnetic resonance and molecular dynamics simulation. Analyses demonstrate that, in solution, human and avian receptors sample distinct conformations, topologies, and dynamics. These unique features of avian and human receptors in solution could represent distinct molecular characteristics for recognition by HA, thereby providing the HA-glycan interaction specificity in influenza.

  4. 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.

  5. 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.

  6. Lactadherin is a candidate oviduct Lewis X trisaccharide receptor on porcine spermatozoa.

    PubMed

    Silva, E; Frost, D; Li, L; Bovin, N; Miller, D J

    2017-03-15

    A recent study has demonstrated that porcine spermatozoa recognize with high affinity carbohydrate structures containing Lewis X motifs. Sperm adhesion to Lewis X is proposed to mediate sperm binding to the oviduct epithelium to form a reservoir. The objective of this study was to identify Lewis X-binding proteins from porcine spermatozoa as candidate receptors for oviduct glycans. To identify low-abundance proteins typically masked by proteins originating from seminal fluid, Lewis X candidate receptors were enriched from cauda epididymal boar spermatozoa. Plasma membrane preparations from cauda epididymal spermatozoa were subjected to RP-HPLC and glycan blotting assays to isolate and detect proteins that bind Lewis X. Following bottom-up LC-MS/MS analysis, among the two bands that bound sulfated Lewis X, ADAM5, which spermatozoa, was confidently identified. ADAM family members have been established as contributors to sperm entry into the oviduct. A second sulfated Lewis X-binding protein identified was the peripheral membrane protein lactadherin (also known as P47, SED1 and MFG-E8 in different species). The interaction between Lewis X and lactadherin was functionally important because competitive inhibition by soluble recombinant lactadherin reduced sperm binding to the oviduct epithelium. Furthermore, far-western blotting demonstrated that purified lactadherin could bind oviduct cells. In summary, these findings reveal that, in addition to the previously reported glycan affinity of accessory gland proteins that adhere to spermatozoa, multiple proteins intrinsic to spermatozoa have affinity for a specific oviduct glycan. Further, in addition to binding to the zona pellucida, lactadherin is now implicated in binding to oviduct glycans to promote formation of the sperm reservoir.

  7. Prospective study of relations between cortical Lewy bodies, poor eyesight, and hallucinations in Alzheimer's disease.

    PubMed

    McShane, R; Gedling, K; Reading, M; McDonald, B; Esiri, M M; Hope, T

    1995-08-01

    The presence of hallucinations is included in some, but not all, of the sets of clinical diagnostic criteria that have been proposed for dementia associated with cortical Lewy bodies. These criteria were developed from retrospective casenote analyses. This prospective, longitudinal study suggests that, in patients with Alzheimer's disease, cortical Lewy bodies are associated with more persistent and severe hallucinations, independently of any association with severity of cognitive decline. Poor eyesight contributes to the severity but not the persistence of the hallucinations.

  8. A dual Lewis base activation strategy for enantioselective carbene-catalyzed annulations.

    PubMed

    Izquierdo, Javier; Orue, Ane; Scheidt, Karl A

    2013-07-24

    A dual activation strategy integrating N-heterocyclic carbene (NHC) catalysis and a second Lewis base has been developed. NHC-bound homoenolate equivalents derived from α,β-unsaturated aldehydes combine with transient reactive o-quinone methides in an enantioselective formal [4 + 3] fashion to access 2-benzoxopinones. The overall approach provides a general blueprint for the integration of carbene catalysis with additional Lewis base activation modes.

  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. Bifunctional ruthenium(II) hydride complexes with pendant strong Lewis acid moieties: structure, dynamics, and cooperativity.

    PubMed

    Ostapowicz, Thomas G; Merkens, Carina; Hölscher, Markus; Klankermayer, Jürgen; Leitner, Walter

    2013-02-13

    The synthesis of a novel class of bifunctional ruthenium hydride complexes incorporating Lewis acidic BR(2) moieties is reported. Determination of the molecular structures in the solid state and in solution provided evidence for tunable interaction between the two functionalities. Cooperative effects on the reactivity of the complexes were demonstrated including the activation of small Lewis basic molecules by reversible anchoring at the boron center.

  11. Synthesis and Lewis acid properties of a ferrocene-based planar-chiral borenium cation.

    PubMed

    Chen, Jiawei; Lalancette, Roger A; Jäkle, Frieder

    2013-05-28

    The first planar chiral ferrocenylborenium species (pR)-3(+) is obtained in the enantiopure form by halide abstraction from the corresponding chloroborane adduct (pR)-2 using Krossing's salt. Competition experiments suggest that the Lewis acidity of (pR)-3(+) is higher than that of B(C6F5)3 towards anions and slightly lower towards neutral Lewis bases. The ferrocenylborenium species (pR)-3(+) is examined as a catalyst for the stereoselective hydrosilylation of ketones.

  12. 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

  13. Frustrated Lewis Pair Chemistry: Searching for New Reactions.

    PubMed

    Kehr, Gerald; Erker, Gerhard

    2017-04-12

    Frustrated Lewis pair chemistry has taken a steep development in the recent years. It offers possibilities of developing new variants of known reactions and of finding new chemical transformations. This is demonstrated and described by the recently developed FLP-formylborane chemistry, which has led to the formation of the unique (η(2) -formylborane)FLP adducts and opened a way of preparing a genuine formylborane compound, which shows an interesting follow-up chemistry. FLPs have helped finding phosphorus analogues of the enamine Stork reaction and the Claisen reaction. These reactions lead to new organophosphorus compounds and they make new phosphane/borane systems available. P/B FLPs add to a variety of small main group element oxides. They undergo 1,2-addition reactions to CO2 , SO2 and other heterocumulenes and they feature unique 1,1-addition reactions to carbon monoxide, to isonitriles and even to nitric oxide (NO), the latter yielding examples of a new class of persistent nitroxide radicals, the FLPNO nitroxyls. Eventually, some remarkable radical reactions of FLPs and related compounds are briefly mentioned.

  14. 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.

  15. 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).

  16. Cyclosporin a. Inhibition of experimental autoimmune uveitis in Lewis rats.

    PubMed Central

    Nussenblatt, R B; Rodrigues, M M; Wacker, W B; Cevario, S J; Salinas-Carmona, M C; Gery, I

    1981-01-01

    Cyclosporin A (CS-A), a selective inhibitor of T lymphocytes, is reported here to prevent S antigen (S-Ag) induced uveitis in Lewis rats. The S-Ag, found in all mammalian retinas, is uveitogenic under experimental conditions and patients with certain uveitic entities demonstrate cell mediated responses to this antigen. Daily treatment with CS-A (10 mg/kg) begun on the same day as S-Ag immunization totally inhibited the development of the uveitis in this experimental autoimmune model. Moreover a greater CS-A dose (40 mg/kg) efficiently prevented the disease process when therapy was started 7 d after S-Ag immunization. Anti-S-Ag antibody titers were observed to be similar in rats either protected or not protected with CS-A. Our data support strongly the need for T cell participation in this disease model. Since ocular inflammatory disease is an important cause of visual impairment, the data further suggest that CS-A may be useful in the treatment of patients with intractable uveitis. Images PMID:7204576

  17. 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.

  18. 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.

  19. Clinical and neuroimaging characteristics of Chinese dementia with Lewy bodies

    PubMed Central

    Wang, Ying; Shi, Zhihong; Cai, Li; Liu, Shuling; Han, Tong; Zhou, Yuying; Wang, Xinping; Gao, Shuo; Ji, Yong

    2017-01-01

    Dementia with Lewy bodies (DLB) is the second most common subtype of degenerative dementia. To our knowledge, available information about the clinical features of DLB in China remains limited. Our study therefore aimed to address this issue. Thirty-seven Chinese patients with probable DLB were recruited for this study. All subjects underwent neuropsychological assessment by trained neurologists, as well as undergoing MRI, 11C-PIB PET scans for Aβ deposition and 18F-FDG PET scans for regional cerebral glucose metabolism. Our results showed that the gender ratio of patients was 16:21 (F:M). The mean age of onset was 69.5 ± 9.0 years and the mean age at diagnosis was 71.8 ± 9.1 years. At diagnosis, the prevalence of three core clinical features of DLB was: 64.9% for fluctuating cognition, 73.0% for visual hallucinations and 62.2% for parkinsonism. The result from 11C-PiB PET and 18F-FDG PET scans confirmed Aβ deposition in the cortex and demonstrated hypometabolism in the bilateral temporoparietooccipital region, the frontal lobe, the insular lobe, and the posterior cingulate, precuneus and caudate nuclei. Our study elucidated the clinical features of Chinese DLB patients, and will improve the understanding and the early diagnosis of DLB in Chinese patients. PMID:28253276

  20. Biomarkers of Parkinson's disease and Dementia with Lewy bodies.

    PubMed

    Henchcliffe, Claire; Dodel, Richard; Beal, M Flint

    2011-12-01

    Parkinson's disease (PD) and Dementia with Lewy bodies (DLB) are progressive and disabling neurodegenerative disorders, in which signs and symptoms overlap with each other and with other neurodegenerative conditions. Currently, diagnosis, measurement of progression, and response to therapeutic intervention rely upon clinical observation. However, there remains a critical need for validated biomarkers in each of these areas. A definitive diagnostic test would improve clinical management and enrollment into clinical trials. An objective measure of progression is vitally important in identifying neuroprotective interventions. Biomarkers may also provide insight into pathogenesis, and might therefore suggest possible novel targets for therapeutic intervention. In addition, certain biomarkers might be of use in monitoring the biochemical and physiological effects of therapeutic interventions. Development of diagnostic biomarkers has focused until recently upon imaging techniques based upon measuring loss of dopamine neurons. Additionally, advances in understanding the genetic contribution to neurodegenerative disorders, in particular in PD, have identified multiple causative genes and risk factors that in some cases may help estimate PD risk. However, recent availability of increasingly sophisticated bioinformatics technology has rendered development of fluid biomarkers feasible, opening the possibility of generally accessible blood or cerebrospinal fluid (CSF) tests that could impact upon diagnosis, management, and research in PD, PDD, and DLB.

  1. 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.

  2. 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.

  3. Naphthylaminoborane: from structural switches to frustrated Lewis pair reactivity.

    PubMed

    Pla, Daniel; Sadek, Omar; Cadet, Sarah; Mestre-Voegtlé, Béatrice; Gras, Emmanuel

    2015-11-14

    A series of naphthyl-bridged amino-borane derivatives, namely 1-(dimethylamino)-8-naphthylboranes (1, 3, 5, 7) and 5-(dimethylamino)-6-acenaphthylboranes (2, 4, 6, 8, 10, 11), differing in the steric and electronic properties of the boryl moiety, have been synthesized and fully characterized by spectroscopic and crystallographic means. Structural X-ray analysis of the peri-atom displacement and ring torsion angles served to experimentally assess the presence and magnitude of the B-N interactions. The reversible quaternarization of nitrogen has been explored and was found to provide an efficient switch corresponding to different molecular organizations. The electronic characteristics of the nature of B-N interactions were further studied by Natural Bonding Orbital analysis derived from the theoretically calculated electron densities. This real-space bonding indicator discriminates the bonding B-N contact in 5 from the nonbonding in 8, which correlates with the flexibility of the naphthyl scaffold to respond to the Lewis acidity of boron allowing shorter peri interactions. Whereas, the steric shielding imposed by the two mesityl groups, and/or the rigidity of the acenaphthene framework disrupt B-N interaction. Thus, this communication reports on the modulation of the B-N bonding continuum by means of structural tuning leading to a molecular switch, as well as its implications towards revealing FLP reactivities through the isolation of intermediates of a stepwise mechanism.

  4. Lewis-Sumner syndrome and multifocal motor neuropathy.

    PubMed

    Verschueren, Annie; Azulay, Jean Philippe; Attarian, Shahram; Boucraut, José; Pellissier, Jean François; Pouget, Jean

    2005-01-01

    We compared the clinical, electrophysiological, laboratory, and pathological features of 13 patients with Lewis-Sumner syndrome (LSS) with those of 20 patients with multifocal motor neuropathy (MMN). LSS and MMN patients have several common clinical features: age at onset, weakness in the distribution of individual peripheral nerves, mild wasting, cramps and fasciculations, partial areflexia, and frequent stepwise disease course. Cerebrospinal fluid protein level was normal or slightly elevated, but always less than 100 mg/dl. Conduction blocks are the electrophysiological hallmarks of these two neuropathies, and no differences in distribution and number of blocks were found. Contrary to MMN, lower-limb involvement at onset was frequent in LSS but extension to the upper limbs was a frequent later feature of the disease. Cranial nerve involvement was noted in 4 LSS patients during relapses and absent in all MMN patients. The major distinguishing features were the clinical and electrophysiological sensory involvement in LSS, and the lack of anti-GM1 antibodies in LSS, whereas IgM anti-GM1 were found in 40% of MMN patients. Some LSS patients responded to steroid therapy, whereas this was ineffective in MMN. From these features, LSS can be considered an entity distinct from MMN, with its own clinical, laboratory, and electrophysiological characteristics, and as an intermediate link between chronic inflammatory demyelinating polyneuropathy and MMN.

  5. Dissociation between the aversive and pharmacokinetic effects of ethanol in female Fischer and Lewis rats.

    PubMed

    Roma, Peter G; Chen, Scott A; Barr, Christina S; Riley, Anthony L

    2007-08-22

    In humans and laboratory animal models, vulnerability to alcohol abuse is influenced by endogenous factors such as genotype. Using the inbred Fischer and Lewis rat strains, we previously reported stronger conditioned taste aversions (CTA) in male Fischer rats that could not be predicted by genotypic differences in alcohol absorption [Roma PG, Flint WW, Higley JD, Riley AL. Assessment of the aversive and rewarding effects of alcohol in Fischer and Lewis rats. Psychopharmacology (Berl) 2006;189:187-99]. The present study made similar assessments in Fischer and Lewis females via four-trial CTA induced by 1 or 1.5 g/kg intraperitoneal (IP) ethanol (n=10-12/strain/dose) as well as measures of blood alcohol concentrations (BAC) at 15, 60 and 180 min post-injection with 1.5 g/kg IP ethanol or saline (n=7-8/strain/dose). Dose-dependent CTAs were produced, but the strains did not differ from each other in these measures; however, BACs in the Lewis females were significantly higher than Fischer at all three time points. As with males of the Fischer and Lewis genotypes, a dissociation between BACs and the aversive effects of alcohol was observed. These data are the first assessments of these particular phenotypes in Fischer and Lewis females, and when considered with the historical data, suggest a Genotype x Sex interaction in the centrally mediated sensitivity to alcohol's aversive effects.

  6. Rapid eye movement sleep behavior disorder and subtypes in autopsy-confirmed dementia with Lewy bodies.

    PubMed

    Dugger, Brittany N; Boeve, Bradley F; Murray, Melissa E; Parisi, Joseph E; Fujishiro, Hiroshige; Dickson, Dennis W; Ferman, Tanis J

    2012-01-01

    The purpose of this study was to determine whether dementia with Lewy bodies with and without probable rapid eye movement sleep behavior disorder differ clinically or pathologically. Patients with dementia with Lewy bodies (DLB) with probable rapid eye movement sleep behavior sleep disorder (n = 71) were compared with those without it (n = 19) on demographics, clinical variables (core features of dementia with Lewy bodies, dementia duration, rate of cognitive/motor changes), and pathologic indices (Lewy body distribution, neuritic plaque score, Braak neurofibrillary tangle stage). Individuals with probable rapid eye movement sleep behavior disorder were predominantly male (82% vs 47%) and had a shorter duration of dementia (mean, 8 vs 10 years), earlier onset of parkinsonism (mean, 2 vs 5 years), and earlier onset of visual hallucinations (mean, 3 vs 6 years). These patients also had a lower Braak neurofibrillary tangle stage (stage IV vs stage VI) and lower neuritic plaque scores (18% vs 85% frequency), but no difference in Lewy body distribution. When probable rapid eye movement sleep behavior disorder developed early (at or before dementia onset), the onset of parkinsonism and hallucinations was earlier and Braak neurofibrillary tangle stage was lower compared with those who developed the sleep disorder after dementia onset. Women with autopsy-confirmed DLB without a history of dream enactment behavior during sleep had a later onset of hallucinations and parkinsonism and a higher Braak NFT stage. Probable rapid eye movement sleep behavior disorder is associated with distinct clinical and pathologic characteristics of dementia with Lewy bodies.

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. Comparative Proteomic Analysis of Two Uveitis Models in Lewis Rats

    PubMed Central

    Pepple, Kathryn L.; Rotkis, Lauren; Wilson, Leslie; Sandt, Angela; Van Gelder, Russell N.

    2015-01-01

    Purpose Inflammation generates changes in the protein constituents of the aqueous humor. Proteins that change in multiple models of uveitis may be good biomarkers of disease or targets for therapeutic intervention. The present study was conducted to identify differentially-expressed proteins in the inflamed aqueous humor. Methods Two models of uveitis were induced in Lewis rats: experimental autoimmune uveitis (EAU) and primed mycobacterial uveitis (PMU). Differential gel electrophoresis was used to compare naïve and inflamed aqueous humor. Differentially-expressed proteins were separated by using 2-D gel electrophoresis and excised for identification with matrix-assisted laser desorption/ionization–time of flight (MALDI-TOF). Expression of select proteins was verified by Western blot analysis in both the aqueous and vitreous. Results The inflamed aqueous from both models demonstrated an increase in total protein concentration when compared to naïve aqueous. Calprotectin, a heterodimer of S100A8 and S100A9, was increased in the aqueous in both PMU and EAU. In the vitreous, S100A8 and S100A9 were preferentially elevated in PMU. Apolipoprotein E was elevated in the aqueous of both uveitis models but was preferentially elevated in EAU. Beta-B2–crystallin levels decreased in the aqueous and vitreous of EAU but not PMU. Conclusions The proinflammatory molecules S100A8 and S100A9 were elevated in both models of uveitis but may play a more significant role in PMU than EAU. The neuroprotective protein β-B2–crystallin was found to decline in EAU. Therapies to modulate these proteins in vivo may be good targets in the treatment of ocular inflammation. PMID:26747776

  12. 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.

  13. 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.

  14. Brain amyloid and cognition in Lewy body diseases.

    PubMed

    Gomperts, Stephen N; Locascio, Joseph J; Marquie, Marta; Santarlasci, Andrea L; Rentz, Dorene M; Maye, Jacqueline; Johnson, Keith A; Growdon, John H

    2012-07-01

    Many patients with PD develop PD with dementia (PDD), a syndrome that overlaps clinically and pathologically with dementia with Lewy bodies (DLB); PDD and DLB differ chiefly in the relative timing of dementia and parkinsonism. Brain amyloid deposition is an early feature of DLB and may account, in part, for its early dementia. We sought to confirm this hypothesis and also to determine whether amyloid accumulation contributes to cognitive impairment and dementia in the broad range of parkinsonian diseases. Twenty-nine cognitively healthy PD, 14 PD subjects with mild cognitive impairment (PD-MCI), 18 with DLB, 12 with PDD, and 85 healthy control subjects (HCS) underwent standardized neurologic and neuropsychological examinations and Pittsburgh compound B (PiB) imaging with PET. Apolipoprotein E (ApoE) genotypes were obtained in many patients. PiB retention was expressed as the distribution volume ratio using a cerebellar tissue reference. PiB retention was significantly higher in DLB than in any of the other diagnostic groups. PiB retention did not differ across PDD, PD-MCI, PD, and HCS. Amyloid burden increased with age and with the presence of the ApoE ε4 allele in all patient groups. Only in the DLB group was amyloid deposition associated with impaired cognition. DLB subjects have higher amyloid burden than subjects with PDD, PD-MCI, PD, or HCS; amyloid deposits are linked to cognitive impairment only in DLB. Early amyloid deposits in DLB relative to PDD may account for their difference in the timing of dementia and parkinsonism.

  15. 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

  16. 1,2-Diphosphonium dication: a strong P-based Lewis acid in frustrated lewis pair (FLP)-activations of B-H, Si-H, C-H, and H-H bonds.

    PubMed

    Holthausen, Michael H; Bayne, Julia M; Mallov, Ian; Dobrovetsky, Roman; Stephan, Douglas W

    2015-06-17

    A highly Lewis acidic diphosphonium dication [(C10H6)(Ph2P)2](2+) (1), in combination with a Lewis basic phosphine, acts as a purely phosphorus-based frustrated Lewis pair (FLP) and abstracts hydride from [HB(C6F5)3](-) and Et3SiH demonstrating the remarkable hydridophilicity of 1. The P-based FLP is also shown to activate H2 and C-H bonds.

  17. 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.

  18. 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.

  19. The interaction between Siglec-15 and tumor-associated sialyl-Tn antigen enhances TGF-β secretion from monocytes/macrophages through the DAP12-Syk pathway.

    PubMed

    Takamiya, Rina; Ohtsubo, Kazuaki; Takamatsu, Shinji; Taniguchi, Naoyuki; Angata, Takashi

    2013-02-01

    We previously demonstrated that Siglec-15, a member of the Siglec family of glycan-recognition proteins, is expressed on a subset of macrophages and preferentially recognizes the sialyl-Tn (sTn) antigen, a tumor-associated glycan structure. In this study, we report on the biological significance of the Siglec-15-mediated interaction between monocytes/macrophages and cancer cells. Siglec-15 is expressed on tumor-associated macrophages (TAMs) in various human tumor tissues. We further demonstrated that its expression is substantially elevated in macrophage colony-stimulating factor-induced M2-like macrophages, which produced more transforming growth factor-β (TGF-β) in response to sTn-positive cells than to negative cells. We designed a co-culture model of THP-1 (human monocytic leukemia) cells and H157 (human lung carcinoma) cells mimicking the interaction between monocytes/macrophages and cancer cells that recapitulated the enhanced TGF-β production in Siglec-15 expressing THP-1 cells by the cellular interaction with sTn expressing H157 cells. The enhanced TGF-β production required a direct interaction between the two cell lines through sialic acids. Siglec-15 associates with adaptor protein DNAX activation protein of 12 kDa (DAP12) at the binding determinant Lys(274) in the transmembrane domain and transduces a signal to spleen tyrosine kinase (Syk). The enhanced TGF-β secretion was significantly attenuated by Syk inhibitor treatment of THP-1 cells or by substitution of the Siglec-15 Lys(274) to Ala, which disrupts the molecular interaction between Siglec15 and DAP12. These findings indicate that Siglec-15 recognizes the tumoral sTn antigen and transduces a signal for enhanced TGF-β secretion in TAMs and further suggest that Siglec-15 on macrophages may contribute to tumor progression by the TGF-β-mediated modulation of intratumoral microenvironments.

  20. A new method for detection of tumor driver-dependent changes of protein sialylation in a colon cancer cell line reveals nectin-3 as TGFBR2 target

    PubMed Central

    Lee, Jennifer; Warnken, Uwe; Schnölzer, Martina; Gebert, Johannes; Kopitz, Jürgen

    2015-01-01

    Protein-linked glycans play key roles in cell differentiation, cell–cell interactions, cell growth, adhesion and immune response. Aberrant glycosylation is a characteristic feature of tumor cells and is involved in tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. It can serve as cancer biomarker and treatment target. To enable comprehensive screening for the impact of tumor driving mutations in colorectal cancer cells we present a method for specific analysis of tumor driver-induced glycome changes. The strategy is based on a combination of three technologies, that is recombinase-mediated cassette exchange (RMCE), Click-It chemistry and mass spectrometry. The new method is exemplified by the analysis of the impact of inactivating mutations of the TGF-ß-receptor type II (TGFBR2) on sialic acid incorporation into protein-linked glycans of the colon cancer cell line HCT116. Overall, 70 proteins were found to show de novo sialic acid incorporation exclusively upon TGFBR2 expression whereas 7 proteins lost sialylation upon TGFBR2 reconstitution. Validation of detected candidate glycoproteins is demonstrated with the cell surface glycoprotein nectin-3 known to be involved in metastasis, invasion and prognosis of various cancers. Altogether, our new approach can help to systematically puzzle out the influence of tumor-specific mutations in a major signaling pathway, as exemplified by the TGFBR2 tumor suppressor, on the tumor glycome. It facilitates the identification of glycan-based tumor markers that could be used for diagnostic and therapeutic applications. In principle the outlined strategy can be adapted to any cancer cell line, tumor driver mutation and several glycan-building blocks. PMID:26177744

  1. A new method for detection of tumor driver-dependent changes of protein sialylation in a colon cancer cell line reveals nectin-3 as TGFBR2 target.

    PubMed

    Lee, Jennifer; Warnken, Uwe; Schnölzer, Martina; Gebert, Johannes; Kopitz, Jürgen

    2015-10-01

    Protein-linked glycans play key roles in cell differentiation, cell-cell interactions, cell growth, adhesion and immune response. Aberrant glycosylation is a characteristic feature of tumor cells and is involved in tumor growth, escape from apoptosis, metastasis formation, and resistance to therapy. It can serve as cancer biomarker and treatment target. To enable comprehensive screening for the impact of tumor driving mutations in colorectal cancer cells we present a method for specific analysis of tumor driver-induced glycome changes. The strategy is based on a combination of three technologies, that is recombinase-mediated cassette exchange (RMCE), Click-It chemistry and mass spectrometry. The new method is exemplified by the analysis of the impact of inactivating mutations of the TGF-ß-receptor type II (TGFBR2) on sialic acid incorporation into protein-linked glycans of the colon cancer cell line HCT116. Overall, 70 proteins were found to show de novo sialic acid incorporation exclusively upon TGFBR2 expression whereas 7 proteins lost sialylation upon TGFBR2 reconstitution. Validation of detected candidate glycoproteins is demonstrated with the cell surface glycoprotein nectin-3 known to be involved in metastasis, invasion and prognosis of various cancers. Altogether, our new approach can help to systematically puzzle out the influence of tumor-specific mutations in a major signaling pathway, as exemplified by the TGFBR2 tumor suppressor, on the tumor glycome. It facilitates the identification of glycan-based tumor markers that could be used for diagnostic and therapeutic applications. In principle the outlined strategy can be adapted to any cancer cell line, tumor driver mutation and several glycan-building blocks.

  2. Effectiveness of low-dose pregabalin in three patients with Lewy body disease and central neuropathic pain.

    PubMed

    Ukai, Katsuyuki; Fujishiro, Hiroshige; Ozaki, Norio

    2017-03-01

    Many patients with Lewy body disease complain of pain, and their pain may be associated with this disease. Recently, pain has become a focus of attention in Parkinson's disease, but there is little information regarding pain in patients who have dementia with Lewy bodies. We used pregabalin to treat three Lewy body disease patients with chronic pain that may have been related to degeneration of central neurons. All three patients responded well to pregabalin at 25-50 mg/day. To our knowledge, there have been no previous reports of pregabalin showing efficacy for central neuropathic pain in Parkinson's disease or Lewy body disease.

  3. Adaptive numerical simulation of pulsating planar flames for large Lewis and Zeldovich ranges

    NASA Astrophysics Data System (ADS)

    Roussel, Olivier; Schneider, Kai

    2006-06-01

    We study numerically the behaviour of pulsating planar flames in the thermo-diffusive approximation. The numerical scheme is based on a finite volume discretization with an adaptive multi-resolution technique for automatic grid adaption. This allows an accurate and efficient computation of pulsating flames even for very large activation energies. Depending on the Lewis number and the Zeldovich number, we observe different behaviours, like stable or pulsating flames, the latter being either damped, periodic, or a-periodic. A bifurcation diagram in the Lewis-Zeldovich plane is computed and our results are compared with previous computations [Rogg B. The effect of Lewis number greater than unity on an unsteady propagating flame with one-step chemistry. In: Peters N, Warnatz J, editors, Numerical methods in laminar flame propagation, Notes on numerical fluid mechanics, vol. 6. Vieweg; 1982. p. 38-48.] and theoretical predictions [Joulin G, Clavin P. Linear stability analysis of nonadiabatic flames: diffusional-thermal model. Combust Flame 1979;35:139-53]. For Lewis numbers larger than 6 we find that the stability limit is again increasing towards larger Zeldovich numbers and not monotonically decreasing as predicted by the asymptotic theory. A study of the flame velocities for different Zeldovich numbers shows that the amplitude of the pulsations strongly varies with the Lewis number. A Fourier analysis yields information on their frequency.

  4. 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.

  5. 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

  6. The effects of isoflurane on airway smooth muscle crossbridge kinetics in Fisher and Lewis rats.

    PubMed

    Duracher, Caroline; Blanc, François-Xavier; Gueugniaud, Pierre-Yves; David, Jean Stéphane; Riou, Bruno; Lecarpentier, Yves; Coirault, Catherine

    2005-07-01

    Our aim was to determine how isoflurane modified crossbridge (CB) number and kinetics in airway smooth muscle (ASM) and to compare its effects in Fisher and Lewis rats, two strains with differences in airway responsiveness. The effects of isoflurane (2 MAC) on isotonic and isometric contractility in tracheal ASM strips were investigated after methacholine (10(-6) M)-induced contraction. CB mechanics and kinetics were analyzed using the formalism of Huxley's equations adapted to ASM. After isoflurane, maximum velocity did not differ from baseline in Lewis rats, whereas it was significantly less than baseline in Fisher rats ( approximately 25%), the most reactive strain. Isoflurane totally reversed methacholine-induced increase in active CB number in Lewis rats (2.4 +/- 0.5 versus 1.8 +/- 0.4 10(9)/mm(2) after methacholine and isoflurane, respectively) whereas reversal was only partial in Fisher rats (2.7 +/- 0.4 versus 2.1 +/- 0.3 10(9)/mm(2) after methacholine and isoflurane, respectively). Isoflurane induced a 40% increase in attachment step duration in both strains and an almost twofold increase in the CB cycle duration compared with baseline in Lewis rats. The isoflurane-induced increase in detachment step duration was less in Lewis than in Fisher rats (P < 0.05). We concluded that isoflurane modulated CB number and CB cycling rates of isolated rat ASM differently depending on the level of airway responsiveness.

  7. Deubiquitinase Usp8 regulates α-synuclein clearance and modifies its toxicity in Lewy body disease.

    PubMed

    Alexopoulou, Zoi; Lang, Johannes; Perrett, Rebecca M; Elschami, Myriam; Hurry, Madeleine E D; Kim, Hyoung Tae; Mazaraki, Dimitra; Szabo, Aron; Kessler, Benedikt M; Goldberg, Alfred Lewis; Ansorge, Olaf; Fulga, Tudor A; Tofaris, George K

    2016-08-09

    In Parkinson's disease, misfolded α-synuclein accumulates, often in a ubiquitinated form, in neuronal inclusions termed Lewy bodies. An important outstanding question is whether ubiquitination in Lewy bodies is directly relevant to α-synuclein trafficking or turnover and Parkinson's pathogenesis. By comparative analysis in human postmortem brains, we found that ubiquitin immunoreactivity in Lewy bodies is largely due to K63-linked ubiquitin chains and markedly reduced in the substantia nigra compared with the neocortex. The ubiquitin staining in cells with Lewy bodies inversely correlated with the content and pathological localization of the deubiquitinase Usp8. Usp8 interacted and partly colocalized with α-synuclein in endosomal membranes and, both in cells and after purification, it deubiquitinated K63-linked chains on α-synuclein. Knockdown of Usp8 in the Drosophila eye reduced α-synuclein levels and α-synuclein-induced eye toxicity. Accordingly, in human cells, Usp8 knockdown increased the lysosomal degradation of α-synuclein. In the dopaminergic neurons of the Drosophila model, unlike knockdown of other deubiquitinases, Usp8 protected from α-synuclein-induced locomotor deficits and cell loss. These findings strongly suggest that removal of K63-linked ubiquitin chains on α-synuclein by Usp8 is a critical mechanism that reduces its lysosomal degradation in dopaminergic neurons and may contribute to α-synuclein accumulation in Lewy body disease.

  8. Deubiquitinase Usp8 regulates α-synuclein clearance and modifies its toxicity in Lewy body disease

    PubMed Central

    Alexopoulou, Zoi; Lang, Johannes; Perrett, Rebecca M.; Elschami, Myriam; Hurry, Madeleine E. D.; Kim, Hyoung Tae; Mazaraki, Dimitra; Szabo, Aron; Kessler, Benedikt M.; Goldberg, Alfred Lewis; Ansorge, Olaf; Fulga, Tudor A.; Tofaris, George K.

    2016-01-01

    In Parkinson’s disease, misfolded α-synuclein accumulates, often in a ubiquitinated form, in neuronal inclusions termed Lewy bodies. An important outstanding question is whether ubiquitination in Lewy bodies is directly relevant to α-synuclein trafficking or turnover and Parkinson’s pathogenesis. By comparative analysis in human postmortem brains, we found that ubiquitin immunoreactivity in Lewy bodies is largely due to K63-linked ubiquitin chains and markedly reduced in the substantia nigra compared with the neocortex. The ubiquitin staining in cells with Lewy bodies inversely correlated with the content and pathological localization of the deubiquitinase Usp8. Usp8 interacted and partly colocalized with α-synuclein in endosomal membranes and, both in cells and after purification, it deubiquitinated K63-linked chains on α-synuclein. Knockdown of Usp8 in the Drosophila eye reduced α-synuclein levels and α-synuclein–induced eye toxicity. Accordingly, in human cells, Usp8 knockdown increased the lysosomal degradation of α-synuclein. In the dopaminergic neurons of the Drosophila model, unlike knockdown of other deubiquitinases, Usp8 protected from α-synuclein–induced locomotor deficits and cell loss. These findings strongly suggest that removal of K63-linked ubiquitin chains on α-synuclein by Usp8 is a critical mechanism that reduces its lysosomal degradation in dopaminergic neurons and may contribute to α-synuclein accumulation in Lewy body disease. PMID:27444016

  9. Slow reactant-water exchange and high catalytic performance of water-tolerant Lewis acids.

    PubMed

    Koito, Yusuke; Nakajima, Kiyotaka; Kobayashi, Hisayoshi; Hasegawa, Ryota; Kitano, Masaaki; Hara, Michikazu

    2014-06-23

    (31)P nuclear magnetic resonance (NMR) spectroscopic measurement with trimethylphosphine oxide (TMPO) was applied to evaluate the Lewis acid catalysis of various metal triflates in water. The original (31)P NMR chemical shift and line width of TMPO is changed by the direct interaction of TMPO molecules with the Lewis acid sites of metal triflates. [Sc(OTf)3] and [In(OTf)3] had larger changes in (31)P chemical shift and line width by formation of the Lewis acid-TMPO complex than other metal triflates. It originates from the strong interaction between the Lewis acid and TMPO, which results in higher stability of [Sc(OTf)3TMPO] and [In(OTf)3TMPO] complexes than other metal triflate-TMPO complexes. The catalytic activities of [Sc(OTf)3] and [In(OTf)3] for Lewis acid-catalyzed reactions with carbonyl compounds in water were far superior to the other metal triflates, which indicates that the high stability of metal triflate-carbonyl compound complexes cause high catalytic performance for these reactions. Density functional theory (DFT) calculation suggests that low LUMO levels of [Sc(OTf)3] and [In(OTf)3] would be responsible for the formation of stable coordination intermediate with nucleophilic reactant in water.

  10. Neural correlates of attention-executive dysfunction in lewy body dementia and Alzheimer's disease.

    PubMed

    Firbank, Michael; Kobeleva, Xenia; Cherry, George; Killen, Alison; Gallagher, Peter; Burn, David J; Thomas, Alan J; O'Brien, John T; Taylor, John-Paul

    2016-03-01

    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.

  11. Understanding of decreased sialylation of Fc-fusion protein in hyperosmotic recombinant Chinese hamster ovary cell culture: N-glycosylation gene expression and N-linked glycan antennary profile.

    PubMed

    Lee, Jong Hyun; Jeong, Yeong Ran; Kim, Yeon-Gu; Lee, Gyun Min

    2017-03-07

    To understand the effects of hyperosmolality on protein glycosylation, recombinant Chinese hamster ovary (rCHO) cells producing the Fc-fusion protein were cultivated in hyperosmolar medium resulting from adding NaCl (415 mOsm/kg). The hyperosmotic culture showed increased specific Fc-fusion protein productivity (qFc ) but a decreased proportion of acidic isoforms and sialic acid content of the Fc-fusion protein. The intracellular and extracellular sialidase activities in the hyperosmotic cultures were similar to those in the control culture (314 mOsm/kg), indicating that reduced sialylation of Fc-fusion protein at hyperosmolality was not due to elevated sialidase activity. Expression of 52 N-glycosylation-related genes was assessed by the NanoString nCounter system, which provides a direct digital readout using custom-designed color-coded probes. After three days of hyperosmotic culture, nine genes (ugp, slc35a3, slc35d2, gcs1, manea, mgat2, mgat5b, b4galt3, and b4galt4) were differentially expressed over 1.5-fold of the control, and all these genes were down-regulated. N-linked glycan analysis by anion exchange and hydrophilic interaction HPLC showed that the proportion of highly sialylated (di-, tri-, tetra-) and tetra-antennary N-linked glycans was significantly decreased upon hyperosmotic culture. Addition of betaine, an osmoprotectant, to the hyperosmotic culture significantly increased the proportion of highly sialylated and tetra-antennary N-linked glycans (P ≤ 0.05), while it increased the expression of the N-glycan branching/antennary genes (mgat2 and mgat4b). Thus, decreased expression of the genes with roles in the N-glycan biosynthesis pathway correlated with reduced sialic acid content of Fc-fusion protein caused by hyperosmolar conditions. Taken together, the results obtained in this study provide a better understanding of the detrimental effects of hyperosmolality on N-glycosylation, especially sialylation, in rCHO cells. This article is protected

  12. Lewis-Acid/Base Effects on Gallium Volatility in Molten Chlorides

    SciTech Connect

    Williams, D.F.

    2001-02-26

    It has been proposed that GaCl{sub 3} can be removed by direct volatilization from a Pu-Ga alloy that is dissolved in a molten chloride salt. Although pure GaCl{sub 3} is quite volatile (boiling point, 201 C), the behavior of GaCl{sub 3} dissolved in chloride salts is different due to solution effects and is critically dependent on the composition of the solvent salt (i.e., its Lewis-acid/base character). In this report, the behavior of gallium in prototypical Lewis-acid and Lewis-base salts is compared. It was found that gallium volatility is suppressed in basic melts and enhanced in acidic melts. The implications of these results on the potential for simple gallium removal in molten salt systems are significant.

  13. On the behaviour of biradicaloid [P(μ-NTer)]2 towards Lewis acids and bases.

    PubMed

    Hinz, Alexander; Schulz, Axel; Villinger, Alexander

    2016-05-07

    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.

  14. In between worlds: G.N. Lewis, the shared pair bond and its multifarious contexts.

    PubMed

    Simões, Ana

    2007-01-15

    In this paper, I will look at the rather convoluted discovery process which gave birth to the concept of the shared electron pair bond as developed by G.N. Lewis, to be subsequently appropriated by the American founders of quantum chemistry, and highlight the complex relations between conceptual development and the different contexts in which ideas are created and presented. I will show how the successive installments of Lewis's model of the chemical bond were supported by and gained credence from an epistemological background in which Lewis explored the relations of chemistry to physics. Furthermore, they were shaped by the changing public contexts in which the successive metamorphoses of the ideas took place and their epistemological background was outlined and explored. The complexities which are always associated with a discovery process can therefore be illuminated if one pays attention to different interactive realms-the conceptual, epistemological, and the presentational one.

  15. NASA-ASEE Summer Faculty Fellowship Program at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Prahl, Joseph M.; Keith, Theo G., Jr.; Montegani, Francis J.

    1996-01-01

    During the summer of 1996, a ten-week Summer Faculty Fellowship Program was conducted at the NASA Lewis Research Center (LeRC) in collaboration with Case Western Reserve University (CWRU), and the Ohio Aerospace Institute (OAI). This is the thirty-third summer of this program at Lewis. It was one of nine summer programs sponsored by NASA in 1996, at various field centers under the auspices of the American Society for Engineering Education (ASEE). The objectives of the program are: (1) to further the professional knowledge of qualified engineering and science educators, (2) to stimulate an exchange of ideas between participants and NASA, (3) to enrich and refresh the research activities of participants' institutions. (4) to contribute to the research objectives of LeRC. This report is intended to recapitulate the activities comprising the 1996 Lewis Summer Faculty Fellowship Program, to summarize evaluations by the participants, and to make recommendations regarding future programs.

  16. Imaging amyloid in Parkinson's disease dementia and dementia with Lewy bodies with positron emission tomography.

    PubMed

    Brooks, David J

    2009-01-01

    Although Parkinson's disease with later dementia (PDD) and dementia with Lewy bodies (DLB) are pathologically characterized by the presence of intraneuronal Lewy inclusion bodies, amyloid deposition is also associated to varying degrees with both these disorders. Fibrillar amyloid load can now be quantitated in vivo with positron emission tomography (PET) using imaging biomarkers. Here the reported findings of 11C-PIB PET studies concerning the amyloid load associated with PD and its influence on dementia are reviewed. It is concluded that the presence of amyloid acts to accelerate the dementia process in Lewy body disorders, though has little influence on its nature. Anti-amyloid strategies could be a relevant approach for slowing dementia in a number of DLB and PDD cases.

  17. 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.

  18. 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.

  19. The NASA Langley building solar project and the supporting Lewis solar technology program

    NASA Technical Reports Server (NTRS)

    Ragsdale, R. G.; Namkoong, D.

    1974-01-01

    The use of solar energy to heat and cool a new office building that is now under construction is reported. Planned for completion in December 1975, the 53,000 square foot, single story building will utilize 15,000 square feet of various types of solar collectors in a test bed to provide nearly all of the heating demand and over half of the air conditioning demand. Drawing on its space-program-developed skills and resources in heat transfer, materials, and systems studies, NASA-Lewis will provide technology support for the Langley building project. A solar energy technology program underway at Lewis includes solar collector testing in an indoor solar simulator facility and in an outdoor test facility, property measurements of solar panel coatings, and operation of a laboratory-scale solar model system test facility. Based on results obtained in this program, NASA-Lewis will select and procure the solar collectors for the Langley test bed.

  20. A Frustrated Lewis Pair Catalyzed Asymmetric Transfer Hydrogenation of Imines Using Ammonia Borane.

    PubMed

    Li, Songlei; Li, Gen; Meng, Wei; Du, Haifeng

    2016-10-05

    Inspired by the zwitterion species generated from the splitting of H2 by frustrated Lewis pairs, we put forward a novel frustrated Lewis pair by the combination of H(δ-) and H(δ+) incorporated Lewis acid and base together. Piers' borane and chiral tert-butylsulfinamide were chosen as the FLP, and a metal-free asymmetric transfer hydrogenation of imines was realized with high enantioselectivities. Significantly, with ammonia borane as hydrogen source, a catalytic asymmetric reaction using 10 mol % of Piers' borane, chiral tert-butylsulfinamide, and pyridine additive, has been successfully achieved to furnish optically active amines in 78-99% yields with 84-95% ee's. Experimental and theoretical mechanistic studies reveal an interesting 8-membered ring hydrogen transfer transition state and an expected regeneration of reactive species with ammonia borane. Accordingly, a plausible catalytic pathway for this reaction is depicted.

  1. Two-Stage Indicators to Assess Learning Curves for Minimally Invasive Ivor Lewis Esophagectomy.

    PubMed

    Wang, Qi; Wu, Zixiang; Chen, Gang; Zhang, Sai; Shen, Gang; Wu, Ming

    2016-10-05

    Background Minimally invasive esophagectomy (MIE) Ivor Lewis has been increasingly performed over the last two decades. To guide the implementation of this technically demanding procedure, a comprehensive assessment of MIE-Ivor Lewis learning curves should include both the general competence to accomplish the procedure and the ability to generate oncological benefits. These objectives are believed to be associated with different phases of the learning curve. Methods A retrospective review of the first 109 patients who underwent MIE-Ivor Lewis by a single qualified surgeon was conducted. Relevant variables were collected and assessed by regression analysis to identify suitable indicators for patient stratification and learning curve assessment. Thereafter, the differential analysis was performed among groups to validate the learning curve model. Results Two variables, intrathoracic gastroesophageal anastomosis time and bilateral recurrent laryngeal nerve (RLN) lymphadenectomy number, which plateaued, respectively, after the 26th and 88th cases, were selected as meaningful indicators to identify different competence levels. Therefore, 109 patients were chronologically subcategorized into three groups (the first 26 MIEs as the early group, the next 62 cases as the middle group, and 21 most recent cases as the late group). Perioperative data were compared between groups with positive results to indicate a three-phase model for a learning curve for MIE-Ivor Lewis. Conclusions An MIE-Ivor Lewis learning curve should include three discrete phases that indicate, successively, unskilled operation (general competence to accomplish, less proficiency), surgical proficiency, and oncological efficacy. Intrathoracic anastomosis time and bilateral RLN lymphadenectomy were identified as suitable indicators delineate the different stages of an MIE-Ivor Lewis learning curve.

  2. Dementia With Lewy Bodies: Diagnosis and Management for Primary Care Providers

    PubMed Central

    Mahajan, Aman; Handa, Kamna

    2011-01-01

    Objective: The purpose of this review is to aid primary care providers in distinguishing dementia with Lewy bodies (DLB) from Alzheimer's disease and from Parkinson's disease with dementia. Differentiating these entities has important treatment implications. Data Sources: A PubMed search was undertaken using the keywords Lewy body dementia, dementia with Lewy bodies, and Lewy body disease. There were no date restrictions. Only articles in the English language were reviewed. References of selected articles were reviewed for additional sources. Data Selection and Extraction: Initially, 2,967 articles were retrieved. All 3 authors participated in data selection and extraction. Articles were further selected for content specific to epidemiology, clinical presentation, diagnostic studies, treatment, and prognosis. For articles with repetitive information, the most current article was used. This resulted in a total of 62 articles included in the review. Data Synthesis: Dementia with Lewy bodies is the second leading cause of dementia after Alzheimer's disease. The core symptoms of DLB, including cognitive fluctuations, visual hallucinations, and parkinsonism, may not always be present as a triad, and clinicians may be unaware of associated symptoms. Thus, this diagnosis is frequently missed by primary care providers. Often, DLB is misdiagnosed as Alzheimer's disease, Parkinson's disease, or a primary psychiatric illness. Treatments for DLB include cholinesterase inhibitors and N-methyl-D-aspartate antagonists. Antipsychotics should be avoided or used with caution. Conclusions: Dementia with Lewy bodies is an often missed diagnosis. Symptoms are often attributed to other disorders. A high clinical suspicion is helpful in accurate diagnosis, and presence of any of the core symptoms should initiate clinical suspicion of DLB. Distinguishing DLB from other disorders has important treatment implications. PMID:22295275

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 2-kW Solar Dynamic Space Power System Tested in Lewis' Thermal Vacuum Facility

    NASA Technical Reports Server (NTRS)

    1995-01-01

    Working together, a NASA/industry team successfully operated and tested a complete solar dynamic space power system in a large thermal vacuum facility with a simulated sun. This NASA Lewis Research Center facility, known as Tank 6 in building 301, accurately simulates the temperatures, high vacuum, and solar flux encountered in low-Earth orbit. The solar dynamic space power system shown in the photo in the Lewis facility, includes the solar concentrator and the solar receiver with thermal energy storage integrated with the power conversion unit. Initial testing in December 1994 resulted in the world's first operation of an integrated solar dynamic system in a relevant environment.

  9. Structural diversity and biological importance of ABO, H, Lewis and secretor histo-blood group carbohydrates.

    PubMed

    de Mattos, Luiz Carlos

    ABO, H, secretor and Lewis histo-blood system genes control the expression of part of the carbohydrate repertoire present in areas of the body occupied by microorganisms. These carbohydrates, besides having great structural diversity, act as potential receptors for pathogenic and non-pathogenic microorganisms influencing susceptibility and resistance to infection and illness. Despite the knowledge of some structural variability of these carbohydrate antigens and their polymorphic levels of expression in tissue and exocrine secretions, little is known about their biological importance and potential applications in medicine. This review highlights the structural diversity, the biological importance and potential applications of ABO, H, Lewis and secretor histo-blood carbohydrates.

  10. "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…

  11. Lewis base catalyzed [4+2] annulation of electron-deficient chromone-derived heterodienes and acetylenes.

    PubMed

    Dückert, Heiko; Khedkar, Vivek; Waldmann, Herbert; Kumar, Kamal

    2011-04-26

    Lewis base catalyzed [4+2] annulation reactions between electron-deficient chromone oxa- and azadienes and acetylene carboxylates provide tricyclic benzopyrones inspired by natural products. An asymmetric synthesis of the tricyclic benzopyrones was developed by using modified cinchona alkaloids as enantiodifferentiating Lewis base catalysts.

  12. Room-Temperature Activation of Hydrogen by Semi-immobilized Frustrated Lewis Pairs in Microporous Polymer Networks.

    PubMed

    Trunk, Matthias; Teichert, Johannes F; Thomas, Arne

    2017-03-15

    Porous polymer networks based on sterically encumbered triphenylphosphine motifs, mimicking the basic sites employed in frustrated Lewis pair (FLP) chemistry, were synthesized via Yamamoto polymerization and their interactions with the strong Lewis acid B(C6F5)3 probed. The combinations yield semi-immobilized FLPs, which are able to cleave dihydrogen heterolytically at ambient temperature and low hydrogen pressure.

  13. 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…

  14. Dietary supplementation with methylseleninic acid, but not selenomethionine, reduces spontaneous metastasis of Lewis lung carcinoma in mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Dietary supplementation with methylseleninic acid reduces spontaneous metastasis of Lewis lung carcinoma in mice Lin Yan*, Lana C. DeMars The present study investigated the effects of dietary supplementation with methylseleninic acid (MSeA) on spontaneous metastasis of Lewis lung carcinoma (LLC) in...

  15. 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

  16. The first autopsied case of diffuse Lewy body disease (DLBD): re-examination by recent immunostaining methods: The 50th Anniversary of Japanese Society of Neuropathology.

    PubMed

    Kosaka, Kenji; Manabe, Yuta

    2010-10-01

    Materials from our first autopsied case of diffuse Lewy body disease (DLBD), that was originally reported in 1976, were re-examined using recent immunohistochemical methods. Lewy pathology consisting of Lewy bodies and Lewy neurites appeared much more marked with alpha-synuclein immunostaining than had been detected with classical stainings. This case and our other similar cases prompted us to propose the terms "Lewy body disease" in 1980 and "diffuse Lewy body disease" in 1984. We also reported in 1990 that DLBD was classified into two forms: a pure form and a common form. Based on these studies the term "dementia with Lewy bodies (DLB)" was proposed in 1996. Since 1980, we have insisted that DLB, Parkinson disease (PD), and PD with dementia (PDD) should be understood within the spectrum of Lewy body disease. This insistence has been recently accepted by the International Workshop and the International Working Group on DLB and PDD in 2005 and in 2006, respectively.

  17. Evidence for the Sialylation of PilA, the PI-2a Pilus-Associated Adhesin of Streptococcus agalactiae Strain NEM316

    PubMed Central

    Morello, Eric; Mallet, Adeline; Konto-Ghiorghi, Yoan; Chaze, Thibault; Mistou, Michel-Yves; Oliva, Giulia; Oliveira, Liliana; Di Guilmi, Anne-Marie; Trieu-Cuot, Patrick; Dramsi, Shaynoor

    2015-01-01

    Streptococcus agalactiae (or Group B Streptococcus, GBS) is a commensal bacterium present in the intestinal and urinary tracts of approximately 30% of humans. We and others previously showed that the PI-2a pilus polymers, made of the backbone pilin PilB, the tip adhesin PilA and the cell wall anchor protein PilC, promote adhesion to host epithelia and biofilm formation. Affinity-purified PI-2a pili from GBS strain NEM316 were recognized by N-acetylneuraminic acid (NeuNAc, also known as sialic acid) specific lectins such as Elderberry Bark Lectin (EBL) suggesting that pili are sialylated. Glycan profiling with twenty different lectins combined with monosaccharide composition by HPLC suggested that affinity-purified PI-2a pili are modified by N-glycosylation and decorated with sialic acid attached to terminal galactose. Analysis of various relevant mutants in the PI-2a pilus operon by flow-cytometry and electron microscopy analyses pointed to PilA as the pilus subunit modified by glycosylation. Double labeling using PilB antibody and EBL lectin, which specifically recognizes N-acetylneuraminic acid attached to galactose in α-2, 6, revealed a characteristic binding of EBL at the tip of the pilus structures, highly reminiscent of PilA localization. Expression of a secreted form of PilA using an inducible promoter showed that this recombinant PilA binds specifically to EBL lectin when produced in the native GBS context. In silico search for potentially glycosylated asparagine residues in PilA sequence pointed to N427 and N597, which appear conserved and exposed in the close homolog RrgA from S. pneumoniae, as likely candidates. Conversion of these two asparagyl residues to glutamyl resulted in a higher instability of PilA. Our results provide the first evidence that the tip PilA adhesin can be glycosylated, and suggest that this modification is critical for PilA stability and may potentially influence interactions with the host. PMID:26407005

  18. 78 FR 59966 - Notice of Inventory Completion: Fort Lewis College, Durango, CO; Correction

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... National Park Service Notice of Inventory Completion: Fort Lewis College, Durango, CO; Correction AGENCY...., Durango, CO 81301, telephone (970) 247-7500, email MULHERN_D@fortlewis.edu SUPPLEMENTARY INFORMATION... were removed from La Plata, CO. This notice is published as part of the National Park...

  19. DOE large horizontal axis wind turbine development at NASA Lewis Research Center

    NASA Astrophysics Data System (ADS)

    Linscott, B. S.

    Large wind turbine activities managed by NASA Lewis are reviewed. These activities include results from the first and second generation field machines (Mod-OA, -1, and -2), the status of the Department of Interior WTS-4 machine for which NASA is responsible for technical management, and the design phase of the third generation wind turbines (Mod-5).

  20. NASA Lewis Research Center low-gravity fluid management technology program

    NASA Technical Reports Server (NTRS)

    Aydelott, J. C.; Carney, M. J.; Hochstein, J. I.

    1985-01-01

    A history of the Lewis Research Center in space fluid management technology program is presented. Current programs which include numerical modeling of fluid systems, heat exchanger/radiator concept studies, and the design of the Cryogenic Fluid Management Facility are discussed. Recent analytical and experimental activities performed to support the Shuttle/Centaur development activity are highlighted.

  1. Lost in Lewis Structures: An Investigation of Student Difficulties in Developing Representational Competence

    ERIC Educational Resources Information Center

    Cooper, Melanie M.; Grove, Nathaniel; Underwood, Sonia M.; Klymkowsky, Michael W.

    2010-01-01

    Because Lewis structures provide a direct connection between molecular structure and properties, the ability to construct and use them is an integral component of many chemistry courses. Although a great deal of time and effort has been dedicated to development of "foolproof" rules, students still have problems with the skill. What is more, many…

  2. Organo-Lewis acid as cocatalyst for cationic homogeneous Ziegler-Natta olefin polymerizations

    DOEpatents

    Marks, Tobin J.; Chen, You-Xian

    2001-01-01

    Organo-Lewis acids of the formula BR'R".sub.2 wherein B is boron, R' is fluorinated biphenyl, and R" is a fluorinated phenyl, fluorinated biphenyl, or fluorinated polycyclic fused ring group, and cationic metallocene complexes formed therewith. Such complexes are useful as polymerization catalysts.

  3. Curcumin reduces trabecular and cortical bone in naive and Lewis lung carcinoma-bearing mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The present study investigated the effects of dietary supplementation with curcumin on bone microstructural changes in female C57BL/6 mice in the presence or absence of Lewis lung carcinoma. Morphometric analysis showed that in tumor-bearing mice curcumin at 2% and 4% dietary levels (w/w) significa...

  4. DOE large horizontal axis wind turbine development at NASA Lewis Research Center

    NASA Technical Reports Server (NTRS)

    Linscott, B. S.

    1982-01-01

    Large wind turbine activities managed by NASA Lewis are reviewed. These activities include results from the first and second generation field machines (Mod-OA, -1, and -2), the status of the Department of Interior WTS-4 machine for which NASA is responsible for technical management, and the design phase of the third generation wind turbines (Mod-5).

  5. Advanced chemical propulsion at NASA Lewis: Metallized and high energy density propellants

    NASA Technical Reports Server (NTRS)

    Palaszewski, Bryan A.

    1991-01-01

    Two of the programs at the NASA Lewis Research Center investigating advanced systems for future space missions are the Metallized Propellant Program and the Advanced Concepts Program. Each program includes both experimental and theoretical studies of future propellants and the associated vehicle impacts and significant payload benefits for many types of space transportation. These programs are described.

  6. Learning without Education. An Interview with Lewis J. Perelman. Background Briefing Paper.

    ERIC Educational Resources Information Center

    Easterling, Douglas

    This interview with Lewis J. Perelman examines issues raised by his recent book, "School's Out" (1992), which describes the current educational system as an obsolete technology that is rapidly being replaced by the new metaprocess of hyperlearning. Hyperlearning will combine teaching and learning with artificial intelligence, broadband…

  7. Pre-mixed flame simulations for non-unity Lewis numbers

    NASA Technical Reports Server (NTRS)

    Rutland, C. J.; Trouve, A.

    1990-01-01

    A principal effect of turbulence on premixed flames in the flamelet region is to wrinkle the flame fronts. For non-unity Lewis numbers (Le), the local flame structure is altered in curved regions. This effect is examined using direct numerical simulations of the three dimensional, constant density, decaying isotropic turbulence with a single step, finite rate chemical reaction. Simulations of Lewis numbers 0.8, 1.0, and 1.2 are compared. The turbulent flame speed, S(sub T), increases as Le decreases. The correlation between S(sub T) and u prime found in previous Le = 1 simulations has a strong Lewis number dependency. The variance of the pdf of the flame curvature increases as Le decreases, indicating that the flames become more wrinkled. A strong correlation between local flame speed and curvature was found. For Le greater than 1, the flame speed increases in regions concave towards the products and decreases in convex regions. The opposite correlation was found for Le less than 1. The mean temperature of the products was also found to vary with Lewis number. For Le = 0.8, it is less than the adiabatic flame temperature and for Le = 1.2 it is greater.

  8. 32 CFR Appendix C to Part 552 - Authorized Activities for Fort Lewis Maneuver Area Access

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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 Military... vehicle tracks Walking, distance running Model airplane and rocket flying Model boating Orienteering...

  9. 32 CFR Appendix C to Part 552 - Authorized Activities for Fort Lewis Maneuver Area Access

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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 Military... vehicle tracks Walking, distance running Model airplane and rocket flying Model boating Orienteering...

  10. 32 CFR Appendix C to Part 552 - Authorized Activities for Fort Lewis Maneuver Area Access

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 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 Military... vehicle tracks Walking, distance running Model airplane and rocket flying Model boating Orienteering...

  11. 32 CFR Appendix D to Part 552 - Unauthorized Activities in Fort Lewis Maneuver Areas

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 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...

  12. 32 CFR Appendix D to Part 552 - Unauthorized Activities in Fort Lewis Maneuver Areas

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 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...

  13. 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...

  14. 32 CFR Appendix D to Part 552 - Unauthorized Activities in Fort Lewis Maneuver Areas

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 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...

  15. A Rhodium Nanoparticle-Lewis Acidic Ionic Liquid Catalyst for the Chemoselective Reduction of Heteroarenes.

    PubMed

    Karakulina, Alena; Gopakumar, Aswin; Akçok, İsmail; Roulier, Bastien L; LaGrange, Thomas; Katsyuba, Sergey A; Das, Shoubhik; Dyson, Paul J

    2016-01-04

    We describe a catalytic system composed of rhodium nanoparticles immobilized in a Lewis acidic ionic liquid. The combined system catalyzes the hydrogenation of quinolines, pyridines, benzofurans, and furan to access the corresponding heterocycles, important molecules present in fine chemicals, agrochemicals, and pharmaceuticals. The catalyst is highly selective, acting only on the heteroaromatic ring, and not interfering with other reducible functional groups.

  16. Highlighting High Performance Buildings: Adam Joseph Lewis Center for Environmental Studies

    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 that are local, non-toxic, and durable.

  17. The Lewis-acid-catalyzed synthesis of hyperbranched poly(glycerol-diacid)s in toluene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The first examples of monomeric glycerol-derived hyperbranched polyesters produced in a non-polar solvent system are reported here. The polymers were made by the Lewis acid (dibutyltin(IV)oxide)-catalyzed polycondensation of glycerol with either succinic acid (n (aliphatic chain length)=2), glutari...

  18. Lewis acid/CpRu dual catalysis in the enantioselective decarboxylative allylation of ketone enolates.

    PubMed

    Linder, David; Austeri, Martina; Lacour, Jérôme

    2009-10-07

    The addition of a Lewis acidic metal triflate salt Mg(OTf)(2) as co-catalyst in the CpRu-catalyzed decarboxylative allylation of in situ-generated ketone enolates allows the reaction to proceed at lower temperature with higher regio- and enantioselectivity. Even so-far-unreactive substrates react.

  19. Lewis basicity modulation of N-heterocycles: a key for successful cross-metathesis.

    PubMed

    Lafaye, Kevin; Nicolas, Lionel; Guérinot, Amandine; Reymond, Sébastien; Cossy, Janine

    2014-10-03

    Cross-metathesis involving N-heteroaromatic olefinic derivatives is disclosed. The introduction of an appropriate substituent on the heteroaromatic ring decreases the Lewis basicity of the nitrogen atom, thus preventing the deactivation of the ruthenium-centered catalyst. The reaction is quite general in terms of both N-heterocycles and olefinic partners.

  20. 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)