Effect of vitamin D on Epstein-Barr (EBV)-specific CD8+T cells in patients with early multiple sclerosis (MS)

Background: Infection with EBV and a lack in vitamin D may be important environmental triggers of MS. 1,25-(OH)2D3 mediates a shift of antigen presenting cells (APC) and CD4+ T cells to a less inflammatory profile. Although CD8+ T cells do express the vitamin D receptor, a direct effect of 1,25(OH)2D3 on these cells has not been demonstrated until now. Since CD8+ T cells are important immune mediators of the inflammatory response in MS, we examined whether vitamin D directly affects the CD8+ T cell response, and more specifically if it modulates the EBV-specific CD8+ T cell response. Material and Methods: To explore whether the vitamin D status may influence the pattern of the EBV-specific CD8+ T cell response, PBMC of 10 patients with early MS and 10 healthy controls (HC) were stimulated with a pool of immunodominant 8-10 mer peptide epitopes known to elicit CD8+ T cell responses. PBMC were stimulated with this EBV CD8 peptide pool, medium (negative control) or anti- CD3/anti-CD28 beads (positive control). The following assays were performed: ELISPOT to assess the secretion of IFN-gamma by T cells in general; cytometric beads array (CBA) and ELISA to determine whichcytokines were released by EBV-specific CD8+ T cells after six days of culture; and intracellular cytokine staining assay to determine by which subtype of T cells secreted given cytokines. To examine whether vitamin D could directly modulate CD8+ T cell immune responses, we depleted CD4+ T cells using negative selection. Results: We found that pre-treatment of vitamin D had an antiinflammatory action on both EBV-specific CD8+ T cells and on CD3/ CD28-stimulated T cells: secretion of pro-inflammatory cytokines (IFNgamma and TNF-alpha) was decreased, whereas secretion of antiinflammatory cytokines (IL-5 and TGF-beta) was increased. At baseline, CD8+ T cells of early MS patients showed a higher secretion of TNFalpha and lower secretion of IL-5. Addition of vitamin D did not restore the same levels of both cytokines as compared to HC. Vitamin D-pretreated CD8+T cells exhibited a decreased secretion of IFN-gamma and TNF-alpha, even after depletion of CD4+ T cells from culture. Conclusion: Vitamin D has a direct anti-inflammatory effect on CD8+ T cells independently from CD4+ T cells. CD8+ T cells of patients with earlyMS are less responsive to the inflammatory effect of vitamin D than HC, pointing toward an intrinsic dysregulation of CD8+ T cells. The modulation of EBV-specific CD8+T cells by vitaminDsuggests that there may be interplay between these twomajor environmental factors of MS. This study was supported by a grant from the Swiss National Foundation (PP00P3-124893), and by an unrestricted research grant from Bayer to RDP.

The Literary relations between La Fontaine and the "Astrée" of Honoré d'Urfé : a dissertation presented to the faculty of the department of philosophy of the university of Pennsylvania in partial fulfilment of the requirements for the degree of doctor of philosophy / by Walther P. Fischer

Collection : Publications of the University of Pennsylvania ; n° 6

Legendarius per circulum anni, pars.

Légendier disposé dans l'ordre du calendrier liturgique du 20 juillet au 25 novembre et contenant les saints suivants: ss. Margarita, Maria Magdelene, Jacobus major ap., Stephanus, Laurentius, Hippolytus, assumptio b. Mariae, Bartholomaeus, Augustinus, Johannes Baptista, Aegidius, nativitas b. Mariae, Gorgonius, Protus et Hyacinthus, exaltatio s. Crucis, Euphemia, Matthaeus, Mauritius, Cosmas et Damianus, Michael archangelus, Hieronymus, Leodegarius, Dionysius, Lucas, Simon et Judas, Martinus, Caecilia, Clemens, Catharina. F. 1-130. Legendarius. F. 1-3v. "... passio sancte Margarete virginis"; cf. B.H.L. n° 5306. F. 3v-6v. "... vita sancte Marie Magdalene" [ODO Cluniacensis abbas, sermo 2, excerptum] (P.L. 133, 714B-719C); cf. B.H.L. n° 5440. F. 6v-8v. "... passio sancti Jacobi [majoris] apostoli" incomplet des lignes finales par lacune matérielle, à partir de "decollandi erant dixit [Jacobus...]" [Virtutes apostolorum, de s. Jacobo majore] (Mombritius, 2a ed., II, 37-40 lig. 15); cf. B.H.L. n° 4057; C.A.N.T. n° 272. F. 9-12. "Inventio sancti Stephani prothomartyris" [LUCIANUS presbyter, interprete AVITO presbytero Bracarensi ]. "Domino venerabili Nimpsio [sic] episcopo... [Julianus exponctué et corrigé en] Lucianus... Revelationem que mihi ostensa est...-... aperire dignatus est..." recensio mixta suivie d'un court épilogue: "Bovem appellatum... declarata sunt"; cf. C.P.L. n° 575; B.H.L. Suppl. n° 7851n (E. Vanderlinden, Rev. des études byzantines, IV, 1946, 190-216, version A'; ne fait pas partie des mss. recensés pour l'édition). F. 12-16. "... passio sancti [Sixti et sancti] Laurentii". "In illo tempore Decius Caesar et Valerianus prefectus jusserunt...-... participati sunt omnes"; cf. B.H.L. Suppl. n° 7801 avec var. incipit et n° 4754. F. 16-18. "... passio sancti Ypoliti et sociorum ejus". "Egressus itaque Ypolitus post tercium diem...-... vivere male et regnare cum Christo "; cf. B.H.L. n° 3961 avec var. incipit et explicit. F. 18-31. "... [sermo] beati Ieronimi in assumptione sancte Virginis" [PASCHASIUS RADBERTUS, De Adsumptione b. Mariae] (C.C.C.M., LVI C 109-162; édité aussi parmi les apocryphes de saint Jérôme, P.L., XXX, 126-147); cf. C.P.L. n° 633, ep. 9 (18-29). F. 29-31. Addition contemporaine : "In vigilia assumptionis beate Marie legatur: Secundum Lucam (Lc 11, 27). [M]agne devocionis et fidei...-... ubera que suxisti" [BEDA, In Lc, l. IV, excerptum] divisé en trois paragraphes, correspondant sans doute à trois leçons (P.L., XCII, 479 C-480 B; C.C.S.L., CXX, 236-237 lig. 213-244) (29). — "Sermo iste legatur in nativitate beate Marie virginis"; cf. infra f. 56v. "[A]pprobate consuetudinis est apud christianos...-... pacta cessare" [FULBERTUS CARNOTENSIS, sermo 4] incomplet de la fin qui a été laissée en blanc (P.L. CXLI, 320-324 A; J.M. Canal, dans Rech. théol. anc. méd., XXX (1963), 56-61 lig. 168); ne fait pas partie des mss. répertoriés par J.M. Canal, ibid., XXIX (1962), 36-37; division marginale en neuf, puis en trois fois trois leçons; en marge du titre, une note difficilement lisible identifie l'auteur: "sermo Fulberti ep. Carnotensis" (29v-31). F. 32-35. "... vita [sic pro passio] sancti Bartholomei apostoli" [Virtutes apostolorum, de s. Bartholomaeo]; cf. B.H.L. Suppl. n° 1002a; C.A.N.T. n° 259. F. 35-49v. "[Vita s.] Augustini episcopi", sans prologue [POSSIDIUS]. "Ex provincia affricana civitate...-... perfruar"; cf. B.H.L. n° 785; C.P.L. n° 358 (35-49a lig. 7); suivi de la liste des livres de s. Augustin dans l'ordre des Retractations : "Libros vero quod edidit hic breviter enumerare vel annotare non omissi. Et hoc indicium librorum omnium sancti Augustini. Contra paganos achademicos [sic] libri III. De beata vita liber I. De ordine sacro libri II. De soliloquiis...-... et gratia liber. Requievit autem... V. kal. septembris..." (C.C.S.L., LVII (1984), 1-4, var.); texte proche du ms. lat. 5276, ff. 136v-137, répertorié par A. Wilmart, Miscellanea Agostiniana, Roma, 1931, 157 (Testi e studi, 2) (49a lig. 7-49v). F. 49v-52v. "Inventio capitis sancti Johannis Baptiste"; cf. B.H.L. n° 4296 (49v-51). — "De translatione ejusdem [Angeriacum]"; cf. B.H.L. n° 4297 (51-52v). F. 52v-56v. "... vita sancti Egidii"; cf. B.H.L. n° 93. F. 56v-59v. "De nativitate sancte Marie". "Petis a me petitiunculam opere...-... prefationem habuisse"; cf. B.H.L. Suppl. n° 5345 (56v a-b lig. 27) ; suivi de: "Petitis a me...-... scribi potuerunt. Igitur beata et gloriosissima semper virgo Maria..-... docuerunt Dominum..." (éd. parmi les apocryphes de s. Jérôme, P.L., XXX, 2a ed., 307-317); cf. B.H.L. n° 5344-5343; C.P.L., n° 633, ep. 50 (56v b lig. 27-59v). L'attribution à Paschase Radbert des deux lettres regroupées en une seule faite par C. Lambot, dans Rev. bénéd., XLVI (1934), 271-282, est réfutée par R. Beyers, dans Rev. Théol. et Philos., CXXII (1990), 171-188. Voir sa nouv. éd. dans CC Apocrypha, 10. F. 59v-61v. "Passio sancti Gorgonii [et Dorothei]; cf. B.H.L. n° 3617. F. 61v-62. "[Passio ss.] Prothi et Jacincti"; cf. B.H.L. n° 6977. F. 62-63v. "De exaltatione sancte Crucis". "Tempore illo postquam Constantino Augusto contra Maxentium..."; cf. B.H.L. n° 4178, avec var. incipit. F. 64-68v. "[Passio s.] Eufemie virginis". "Quinto persecutionis anno Diocletiani...-... Completum est autem martyrium... Prisco proconsule Europe..."; cf. B.H.L. n° 2709, avec var. explicit. F. 68v-72v. "[Passio] sancti Mathei apostoli" [Virtutes apostolorum, de s. Jacobo majore]; cf. C.A.N.T. n° 270; B.H.L. n° 5690, avec var. explicit de l'épilogue: "Zaroes autem...-... passio eorum ostendit". F. 72v-76. "[Passio s.] [Marcii corrigé en] Mauricii con [sic] sociis suis" [s. EUCHERIUS LUGDUNENSIS] sans le prologue; cf. B.H.L. n° 5738; C.P.L. n° 490. F. 76-79v. "[Passio ss.] Cosme et Damiani"; cf. B.H.L. Suppl. n° 1975. F. 79v-80. "[In festivitate s.] Michaelis archangeli". "Angelorum quippe et hominum naturam...-... medicina Dei." [GREGORIUS MAGNUS, Hom. in Ev., 34, excerptum]; C.P.L. n° 1711 (P.L., LXXVI, 1249 C-1251 A, §§ 6, fin-9 début) divisé en 8 paragraphes; une interpolation a été ajoutée dans la marge inférieure du f. 79v par une main contemporaine qui a également numéroté les paragraphes en IX leçons, le texte ajouté formant la lectio IIa : "[N]ovem esse angelorum ordines ad Dei judicia...-... principantur."; il s'agit d'un court extrait du sermon Legimus in ecclesiasticis historiis édité par J. E. Cross, dans Traditio, 33 (1977), 108-109 lig. 41-47 (Beda, Homilia subditia 71, P.L., XCIV, 453 C); cf. C.P.P.M., I, 4046. F. 80-82v. "[Vita s.] Jeronimi presbiteri". "Hieronimus noster [corrigé en: presbiter] in oppido Stridonis...-... etatis sue anno in Domino requievit cui..." extraits de la Vie apocryphe de Gennadius (P.L., XXII, 175-184, passim, avec var.); cf. C.P.L. n° 623; B.H.L. n° 3869; Lambert, B.H.M., IIIA, 630 (80-81b lig. 26); suivi du miracle du lion extrait de la Vie du Ps. Sebastianus Casinensis: "Contigit autem hujusmodi miraculum in monasterio... Quadam namque die ingens leo... - asserendo narrantur" (P.L., XXII, 210 lig. 11-213 lig. 11); cf. C.P.L. n° 622; B.H.L. n° 3872 avec var. incipit; Lambert, B.H.M., IIIA, 630 (81b lig. 26-82v). F. 82v-88v. "[Vita s.] Leodegarii". "Igitur sanctus Leodegarius ex progenie...-... postmodum cecum. ... adnecteret opera ibidem" [URSINUS LOGOGIACENSIS] sans le prologue et incomplet de la fin (C.C.S.L., CXVII, 589-632 lig. 14, avec var.); cf. C.P.L. n° 1079a; B.H.L. n° 4851; suivi d'un court extrait omis à sa place plus haut dans le texte: "Deinde vero ire ceperunt... Dei opera ibidem" (ed. cit., 631 § 31 lig. 3-7). F. 88v-98. "[Passio] sancti Dyonisii martyris", texte incomplet par suite de la perte de 2 ff. entre les ff. 96 et 97, le texte s'arrête à "...fideliter adhe[-rebat]" et reprend à "[Domitia-]no per tres Cesares..." (P.L., CVI, 23-40 C et 48 A-50); cf. B.H.L. n° 2175. F. 98-100v. "[Laudatio s.] Luce evvangeliste". "Gloriosus igitur evvangelista Jhesu Christi Lucas natione Syrus...-... ubique confluunt qui ..." [PAULUS DIACONUS, hom. 59] incomplet du prologue (P.L., XCV, 1530-1535, avec var.); cf. B.H.L. n° 4974, d'après ce ms. F. 100v-106. "[Passio ss.] Symonis et Jude apostolorum" avec l'épilogue [ABDIAS, Virtutes Simonis et Judae Thaddaei]; cf. B.H.L. n° 7750-7751; C.A.N.T. n° 284. F. 106-107v. "[Laudatio] sancti Martini archiepiscopi" [ALCUINUS, De vita s. Martini, pars I]; cf. B.H.L. n° 5625. — GREGORIUS TURONENSIS, De virtutibus s. Martini; cf. B.H.L. n° 5618; seule l'adresse du prologue, introduite par une initiale filigranée, a été copiée au bas du f. 107v, col. b: "Domnis sanctis et in Christi amore dulcissimis fratribus... Gregorius peccator", le texte lui-même manque, soit en raison de la perte du cahier suivant, soit qu'il n'ait pas été copié. F. 108-115v. "[Passio s.] Cecilie virginis et martyris"; cf. B.H.L. Suppl. n° 1495a. F. 115v-118v. "[Passio s.] Clementis pape". [Prologus] "Postquam igitur beatus Petrus apostolus in Antiochia cathedram... -... passio secuta est"; cf. B.H.L. Suppl. n° 1849, d'après ce ms. (115v-116a, lig. 11); — "Tunc sanctus Clemens romane ecclesie episcopus disciplinam...-... Cersone Licie provincie"; C.P.L. n° 2177; B.H.L. n° 1848 (Mombritius, 2a ed., I, 341-344, var. à l'incipit et à l'explicit); suivi de: "Oremus fratres ut Dominus... participes. Per..." (116a, lig. 11-118v). F.118v-130. "[Passio] sancte Katerine virginis et martyris"; cf. B.H.L. n° 1663, sans le prologue. F. 130-130v. Additions. Table des saints contenus dans le volume, XIVe s. (130). — Prière latine en 10 strophes de deux vers, XVe s.: "Jhesu tue matris prece ab Orci me serva nece...-... ab inferi atris" (130v).

Arsenic speciation by ion-exchange chromatography with on- line determination by hydride generation: electronic modification of the D.C. plasma by photon counting

A method using L-cysteine for the determination of arsenous acid (As(III)), arsenic acid (As(V)), monomethylarsonic acid (MMAA), and dimethylarsinic acid (DMAA) by hydride generation was demonstrated. The instrument used was a d.c. plasma atomic emission spectrometer (OCP-AES). Complete recovery was reported for As(III), As(V), and DMAA while 86% recovery was reported for MMAA. Detection limits were determined, as arsenic for the species listed previously, to be 1.2, 0.8, 1.1, and 1.0 ngemL-l, respectively. Precision values, at 50 ngemL-1 arsenic concentration, were f.80/0, 2.50/0, 2.6% and 2.6% relative standard deviation, respectively. The L-cysteine reagent was compared directly with the conventional hydride generation technique which uses a potassium iodide-hydrochloric acid medium. Recoveries using L-cysteine when compared with the conventional method provided the following results: similar recoveries were obtained for As(III), slightly better recoveries were obtained for As(V) and MMAA, and significantly better recoveries for DMAA. In addition, tall and sharp peak shapes were observed for all four species when using L-cysteine. The arsenic speciation method involved separation by ion exchange .. high perfonnance liquid chromatography (HPLC) with on-line hydride generation using the L.. cysteine reagent and measurement byOCP-AES. Total analysis time per sample was 12 min while the time between the start of subsequent runs was approximately 20 min. A binary . gradient elution program, which incorporated the following two eluents: 0.01 and 0.5 mM tri.. sodium citrate both containing 5% methanol (v/v) and both at a pH of approximately 9, was used during the separation by HPLC. Recoveries of the four species which were measured as peak area, and were normalized against As(III), were 880/0, 290/0, and 40% for DMAA, MMAA and As(V), respectively. Resolution factors between adjacent analyte peaks of As(III) and DMAA was 1.1; DMAA and MMAA was 1.3; and MMAA and As(V) was 8.6. During the arsenic speciation study, signals from the d.c. plasma optical system were measured using a new photon-signal integrating device. The_new photon integrator developed and built in this laboratory was based on a previously published design which was further modified to reflect current available hardware. This photon integrator was interfaced to a personal computer through an AID convertor. The .photon integrator has adjustable threshold settings and an adjustable post-gain device.

Iridium(I) complexes of phenanthroline-derived benzimidazolylidenes : synthetic, structural and catalytic studies

N-heterocyclic carbenes (NHCs) have undergone rapid development in recent years. Due to their strong a-electron donation and structural variability properties, NHCs are becoming a major class of ligands in organometallic chemistry. Compared with the other two types of NHCs (imidazolylidenes and imidazolinylidenes), benzimidazolylidenes have not been well represented. Limited synthetic approaches may impede the development ofbenzimidazolylidenes. This thesis is focused on the synthesis of phenanthroline-derived benzimidazolylidene ligands and their metal complexes. A series of benzimidazolylidene-iridium complexes were synthesized and characterized spectroscopically and crystallographic ally. All of the new complexes showed varying degrees of catalytic activity and enantioselectivity toward transfer hydrogenation and asymmetric hydrogenation. The best results were achieved in hydrogenation of methyl-2-acetamidoacrylate, which afforded (-)-(R)-methyl-2-acetamidopropanoate in 97% yield and 81 % ee.

Beyond child's play : wealth, status, and the death of children in the MH-LH I periods of the Argolid, Greece

This study explores the mortuary remains of children from the MH-LH I periods of the Argolid, Greece. This examination concentrates on how the child in death acted as a tool for wealth and status display. Here, children are understood to have perpetuated, maintained, and reinforced status distinctions between families in their community. The analysis of one hundred child burials that date to these periods illustrates how the burials of children were important opportunities used by the families of children to display wealth and status. Thus, children can be viewed as important factors in the reorganization of social structure in the transition from the Middle to Late Helladic.

Asymmetric hydrogenation of alkenes with cationic iridium(I) complexes of 2-phosphino-1-aminoferrocene ligands

Iridium complexes with bidentate P,N ligands represent a class of catalysts that significantly expand the application range of asymmetric hydrogenation. New substrate classes, for which there have previously been no suitable catalysts, can now be efficiently hydrogenated in high conversion and enantioselectivity. These substrates are often of synthetic importance, thus iridium catalysis represents a significant advance in the field of asymmetric catalysis. Planar chiral ferrocenyl aminophosphine ligands in which both heteroatoms were directly bound to the cyclopentadienyl ring were prepared by BF3-activated lithiationsubstitution in the presence of a chiral diamine in 49-59% yield and 75-85% enantiomeric excess. Some of these ligands were recrystallized to enantiomeric purity via ammonium fluoroborate salt formation of the phosphine sulfide. A crystal structure of one of these compounds was obtained and features an intramolecular hydrogen bond between the nitrogen, hydrogen, and sulfur atoms. Neutralization, followed by desulfurization, provided the free ligands in enantiomeric purity. Iridium complexes with these ligands were formed via reaction with [Ir(COD)Clh followed by anion exchange with NaBArF. These complexes were successfully applied in homogeneous hydrogenation of several prochiral substrates, providing products in up to 92% enantiomeric excess. Variation of the dimethyl amino group to a pyrrolidine group had a negative effect on the selectivity of hydrogenation. Variation of the substituents on phosphorus to bulkier ortho-tolyl groups had a positive effect, while variation to the more electron rich dicyclohexyl phosphine had a negative effect on selectivity.

Photograph - B Squadron of the G.G.B.G. [Governor General’s Body Guard] at Niagara

Black and white photograph, mounted on board, 13 cm x 20 cm of the B Squadron of the G.G.B.G. [Governor General’s Body Guard] at Niagara.