584 research outputs found
Human melanomas and ovarian cancers overexpressing mechanical barrier molecule genes lack immune signatures and have increased patient mortality risk
No full textWe have identified eight genes whose expression in human melanoma metastases and ovarian cancers is associated with a lack of Th1 immune signatures. They encode molecules with mechanical barrier function in the skin and other normal tissues and include filaggrin (FLG), tumor-associated calcium signal transducer 2 (TACSTD2), and six desmosomal proteins (DST, DSC3, DSP, PPL, PKP3, and JUP). This association has been validated in an independent series of 114 melanoma metastases. In these, DST expression alone is sufficient to identify melanomas without immune signatures, while FLG and the other six putative barrier molecules are overexpressed in a different subset of melanomas lacking immune signatures. Similar associations have been identified in a set of 186 ovarian cancers. RNA-seq data from 471 melanomas and 307 ovarian cancers in the TCGA database further support these findings and also reveal that overexpression of barrier molecules is strongly associated with early patient mortality for melanoma (p = 0.0002) and for ovarian cancer (p < 0.01). Interestingly, this association persists for FLG for melanoma (p = 0.012) and ovarian cancer (p = 0.006), whereas DST overexpression is negatively associated with CD8(+) gene expression, but not with patient survival. Thus, overexpression of FLG or DST identifies two distinct patient populations with low immune cell infiltration in these cancers, but with different prognostic implications for each. These data raise the possibility that molecules with mechanical barrier function in skin and other tissues may be used by cancer cells to protect them from immune cell infiltration and immune-mediated destruction
MAGE-6 encodes HLA-DRbeta1*0401-presented epitopes recognized by CD4+ T cells from patients with melanoma or renal cell carcinoma
No full textCD4+ T cells modulate the magnitude and durability of CTL responses in vivo and may serve as potent effector cells within the tumor microenvironment. The current study was undertaken to define novel epitopes from the broadly expressed tumor antigen MAGE-6 that are recognized by CD4+ T cells. We have combined the use of a HLA-DR4/peptide binding algorithm with the IFN-gamma enzyme-linked immunospot assay to identify four nonoverlapping sequences derived from the MAGE-6 protein that served as CD4+ T-cell epitopes in HLA-DR4+ donors. Strikingly, patients with active melanoma or renal cell carcinoma failed to secrete IFN-gamma in response to MAGE-6-derived epitopes, whereas both normal donors and cancer patients with no current evidence of disease were responsive, particularly after short-term in vitro stimulations with peptide-pulsed dendritic cells. Importantly, peptide-specific CD4+ T cells also recognized HLA-DRbeta1*0401+ tumor cells that constitutively expressed the MAGE-6 protein and autologous HLA-DRbeta1*0401+ dendritic cells transfected with MAGE-6 cDNA-elicited CD4+ T cells that reacted against individual peptide epitopes in vitro. These data suggest that MAGE-6-derived epitopes could serve as useful vaccine candidate components and may provide an immune-monitoring index of clinically important Th1-type immunity in patients with renal cell carcinoma or melanoma
Formation of Methane versus Benzene in the Reactions of (C5Me5)(2)Th(CH3)(2) with [CH3PPh3]X (X=Cl, Br, I) Yielding Thorium-Carbene or Thorium-Ylide Complexes
No full textbibtex: ISI:000412189700021 bibtex\location:'POSTFACH 101161, 69451 WEINHEIM, GERMANY',publisher:'WILEY-V C H VERLAG GMBH',type:'Article',affiliation:'Walensky, JR (Reprint Author), Univ Missouri, Dept Chem, Columbia, MO 65211 USA. Maron, L (Reprint Author), Univ Toulouse, 135 Ave Rangueil, F-31077 Toulouse, France. Maron, L (Reprint Author), LPCNO, CNRS, INSA, UPS,UMR,UMR 5215, 135 Ave Rangueil, F-31077 Toulouse, France. Rungthanaphatsophon, Pokpong; Bathelier, Adrien; Barnes, Charles L.; Walensky, Justin R., Univ Missouri, Dept Chem, Columbia, MO 65211 USA. Bathelier, Adrien; Castro, Ludovic; Maron, Laurent, Univ Toulouse, 135 Ave Rangueil, F-31077 Toulouse, France. Bathelier, Adrien; Castro, Ludovic; Maron, Laurent, LPCNO, CNRS, INSA, UPS,UMR,UMR 5215, 135 Ave Rangueil, F-31077 Toulouse, France.','author-email':'[email protected] [email protected]',da:'2018-12-05','doc-delivery-number':'FI7PR',eissn:'1521-3773','funding-acknowledgement':'U.S. Department of Energy, Office of Science, Early Career Research Program [DE-SC-0014174]; Humboldt Foundation; Chinese Academy of Science; CalMip','funding-text':'J.R.W. gratefully acknowledges support for this work from the U.S. Department of Energy, Office of Science, Early Career Research Program under Award Number DE-SC-0014174. L.M. is member of the Instiut Universitaire de France. The Humboldt Foundation, the Chinese Academy of Science and CalMip is acknowledged for either financial support or computing time.','journal-iso':'Angew. Chem.-Int. Edit.','keywords-plus':'CARBON MULTIPLE BOND; MOLECULAR-STRUCTURE; METALLA-ALLENES; URANIUM COMPLEX; TRANS-INFLUENCE; U-IV=C; REACTIVITY; LIGAND; CHEMISTRY; PH2PNSIME3','number-of-cited-references':'42',oa:'Bronze','orcid-numbers':'Walensky, Justin/0000-0003-0221-2675','research-areas':'Chemistry','times-cited':'5','unique-id':'ISI:000412189700021','usage-count-last-180-days':'0','usage-count-since-2013':'9','web-of-science-categories':'Chemistry, Multidisciplinary'\International audienceThe reaction of (C5Me5)(2)Th(CH3)(2) with the phosphonium salts [CH3PPh3]X (X=Cl, Br, I) was investigated. When X=Br and I, two equivalents of methane are liberated to afford (C5Me5)(2)Th[CHPPh3]X, rare terminal phosphorano-stabilized carbenes with thorium. These complexes feature the shortest thorium-carbon bonds (approximate to 2.30 angstrom) reported to date, and electronic structure calculations show some degree of multiple bonding. However, when X = Cl, only one equivalent of methane is lost with concomitant formation of benzene from an unstable phosphorus(V) intermediate, yielding (C5Me5)(2)Th[kappa(2)-(C,C')-(CH2)(CH2)PPh2]Cl. Density functional theory (DFT) investigations of the reaction energy profiles for [CH3PPh3]X, X = Cl and I showed that in the case of iodide, thermodynamics prevents the production of benzene and favors formation of the carbene
Strict coupling between CFTR's catalytic cycle and gating of its Cl- ion pore revealed by distributions of open channel burst durations
No full textCFTR, the ABC protein defective in cystic fibrosis, functions as an anion channel. Once phosphorylated by protein kinase A, a CFTR channel is opened and closed by events at its two cytosolic nucleotide binding domains (NBDs). Formation of a head-to-tail NBD1/NBD2 heterodimer, by ATP binding in two interfacial composite sites between conserved Walker A and B motifs of one NBD and the ABC-specific signature sequence of the other, has been proposed to trigger channel opening. ATP hydrolysis at the only catalytically competent interfacial site is suggested to then destabilize the NBD dimer and prompt channel closure. But this gating mechanism, and how tightly CFTR channel opening and closing are coupled to its catalytic cycle, remains controversial. Here we determine the distributions of open burst durations of individual CFTR channels, and use maximum likelihood to evaluate fits to equilibrium and nonequilibrium mechanisms and estimate the rate constants that govern channel closure. We examine partially and fully phosphorylated wild-type CFTR channels, and two mutant CFTR channels, each bearing a deleterious mutation in one or other composite ATP binding site. We show that the wild-type CFTR channel gating cycle is essentially irreversible and tightly coupled to the ATPase cycle, and that this coupling is completely destroyed by the NBD2Walker B mutation D1370N but only partially disrupted by the NBD1 Walker A mutation K464A
HYPERFINE STRUCTURE IN THE MICROWAVE SPECTRUM OF CHLORINE DIOXIDE AND THE MICROWAVE SPECTRUM OF
No full textR. F. Curl, James L. Kinsey, John G. Baker, James C. Baird, George R. Bird, Robert F Heidelberg, T. M. Sugden, P. R. Jenkins, and C. N. Kenney, Phys. Rev. 121. 1119 (1961).Author Institution: Dept. of Chemistry, Rice University; Dept. of Chemistry, University of CaliforniaThe microwave spectrum of chlorine dioxide has already been assigned and a crude hyperfine structure analysis The approximate interaction parameters have been found to be indeed approximately correct, but have been refined. The hyperfine structure can now be fitted nearly to experimental error. Hyperfine structure matrix elements off-diagnoal in the rotational quantum numbers have been found to give a small but significant effect through second order perturbation. Some discussion of the interpretation of the hyperfine interaction constants will be given. The rotational assignment and geometrical structure previously have been completely confirmed by the spectrum of . Isotope effects on the hyperfine constants will be discussed
Total synthesis of N-(benzyloxycarbonyl)didemnin A
No full textDidemnin A, a cyclic depsipeptide isolated from a Caribbean tunicate, was synthesized by coupling two key fragments, (Boc-(3S,4R,5S)-Ist(TBDMS)-(2R,S;4S)-Hip-Leu-Pro-OH (Fragment I)) and (Z- scD-MeLeu-Thr(H-Me\sb2Tyr)-OTMSe) (Fragment II). Fragment I was synthesized, in turn, from Boc-(3S,4R,5S)-Ist(TBDMS)-OH, Bn-(2R,S;4S)-Hip-OH, Boc- scL-Leu-OH and H- scL-Pro-OMe by stepwise elongation of the peptide chain, starting from H-Pro-OMe. Fragment II was synthesized from Z- scD-MeLeu-OH, H- scL-Thr-OMe and Boc- scL-Me\sb2Tyr-OH, starting from Z- scD-MeLeu-OH. The heptapeptide Z- scD-MeLeu-Thr(Boc-(3S,4R,5S)-Ist-(2R,S;4S)-Hip-Leu-Pro-Me\sb2Tyr) -OTMSe was synthesized by coupling the two fragments between proline and dimethyltyrosine using Bop-Cl. After deprotection of TMSe and Boc groups, the cyclization was accomplished between threonine and isostatine, again using Bop-Cl. The \sp1H NMR and mass spectra and rotation of the synthesized N-Z-didemnin A are the same as those of natural N-Z-didemnin A.Made available in DSpace on 2011-05-07T12:46:28Z (GMT). No. of bitstreams: 2
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William Scoresby, Jr. (1789-1857) and the Open Polar Sea - Myth and Reality
No full textWilliam Scoresby, Jr., whaler and eminent natural scientist, was denied a role in the British Government\u27s renewal of polar exploration in 1818. Befriended by Sir Joseph Banks and a member of the most respected learned societies in Scotland, England and the Continent, Scoresby made detailed observations of ice conditions in the Arctic over a period of 17 years, aiding the government\u27s decision to search for new polar routes. However, Scoresby and Sir John Barrow, Second Secretary of the Admiralty, the main organizer of arctic exploration, had opposing perceptions of the nature of the northern regions. Barrow, until the end of his life, believed the polar regions harbored a warm water sea, while Scoresby considered the theory a ludicrous chimera. This is believed to be the source of Barrow\u27s illogical rejection of Scoresby. To support this thesis the author has contrasted Scoresby\u27s two major works, An Account of the Arctic Regions and Voyage to the Whale Fishery, with Barrow\u27s arctic writings, A Chronological History of Voyages into the Arctic Regions and Voyage in the Arctic Regions from 1818 to the Present Time, as well as looking at other literary visions of the Arctic contemporary to the period. Scoresby\u27s ability as a mariner, his years of arctic experience, his scientific education at the University of Edinburgh, his meticulous records and acute and sensitive observations in both prose and drawing, all provide a sound basis for perceiving the Admiralty\u27s autocratic rejection of Scoresby as a loss to arctic science in the 19th century. It also points up the underlying romantic vision of the northern regions in the mind of society at the time: a place harboring an earthly paradise. To Scoresby, the Arctic was nature\u27s laboratory, not a "playground for the imagination".Key words: William Scoresby, Jr., John Barrow, open polar sea, arctic exploration, perceptions of the Arctic Mots clés: William Scoresby fils, John Barrow, mer polaire libre, exploration arctique, perceptions de l’Arctiqu
THE MICROWAVE SPECTRUM OF ISO-BUTENYL CHLORIDE
No full textAuthor Institution: Department of Chemistry, Harvard UniversityThe microwave spectrum of iso-butenyl chloride (1-chloro-2-methyl-2-propene) has been studied in order to investigate rotational isomerism about the bond. It has been found that the spectrum is dominated by a-type transitions of a rotamer which has the Cl bond gauche with respect to the ethylenic group. A number of weaker lines have been tentatively assigned for the cis rotamer. Spectral assignment was assisted greatly by the use of radio frequency microwave double resonance techniques. Rotational constants have been determined for and isotopic species and structural parameters derived from these data will be compared with those for related molecules
Investigation of the Luminol Chemiluminescence Reaction as a Post-Column Reaction Detector for HPLC
No full textThe luminol chemiluminescence (CL) reaction has been used as a post-column reaction detector for high performance liquid chromatography (HPLC). The research reported here has progressed in two principle areas: first, the development of a method for the determination of amino acids and other complexing species based on suppression of the Cu(II)-catalyzed luminol CL reaction and second, the development of a method for the determination of -D-glucosides using immobilized enzymes and luminol CL detection of the enzymatically generated hydrogen peroxide.Free Cu(II) catalyzes the luminol CL reaction and the CL emission increases with increasing Cu(II) concentration. Amino acids were then detected by their complexation of Cu(II), resulting in negative signals (decreases in the observed CL emission) as the amount of free Cu(II) was decreased. Detection limits of 1 pmol-2 nmol were obtained using a flow injection system, and the method was demonstrated to be applicable to the determination of amino acids separated via ion-exchange chromatography. This method was extended to the determination of other species (such as amines, aminoglycosides, catecholamines, and cyanide) which also complex Cu(II), and detection limits in the low pmol range were obtained for several species. This method was also demonstrated to be applicable for the determination of catecholamines separated via reverse phase HPLC, and for the determination of the gentamicin C components in gentamicin sulfate separated via ion-pair chromatography.The determination of -D-glucosides utilized sequential immobilized enzyme reactors (IMER) to first hydrolyze -D-glucosides to -D-glucose (using -glucosidase) and then to produce hydrogen peroxide from the -D-glucose (using glucose oxidase); the hydrogen peroxide was then detected with luminol CL (the emitted light intensity is proportional to peroxide concentration). This method was used for the determination of individual -D-glucosides (phenyl, p-nitrophenyl, salicin, and metsulfuron methyl) via flow injection analysis and was extended to the determination of a mixture of glucosides following their separation via reverse phase HPLC. (Abstract shortened with permission of author.)Made available in DSpace on 2014-12-15T23:19:17Z (GMT). No. of bitstreams: 1
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Previous issue date: 1988Embargo set by: Seth Robbins for item 70577
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Reason: Restricted to the U of I community idenfinitely during batch ingest of legacy ETDsRestricted to the U of I community idenfinitely during batch ingest of legacy ETDsU of I Only164 p.Thesis (Ph.D.)--University of Illinois at Urbana-Champaign, 1988
A VIBRATIONAL SPECTROSCOPIC INVESTIGATION OF SOME SYMMETRICALLY SUBSTITUTED FLUROETHANES IN THE SOLID STATE
No full textAuthor Institution: Chemistry Department, East Carolina UniversityThe infrared and Raman spectra of , and are reported in the solid state. The 1, 2 halo-substituted species were recorded at liquid nitrogen temperature. The trans-form in each case appears to be the most stable from these studies. Band assignments have been made for fundamentals on the basis of symmetry. The elusive C-C stretching fundamental in these compounds appears from 702 to . The paucity of theoretical data for the fluoroethanes in general is discussed
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