A eukaryotic enzyme that can disjoin dead-end covalent complexes between DNA and type I topoisomerases.

The covalent joining of topoisomerases to DNA is normally a transient step in the reaction cycle of these important enzymes. However, under a variety of circumstances, the covalent complex is converted to a long-lived or dead-end product that can result in chromosome breakage and cell death. We have discovered and partially purified an enzyme that specifically cleaves the chemical bond that joins the active site tyrosine of topoisomerases to the 3' end of DNA. The reaction products made by the purified enzyme on a variety of model substrates indicate that the enzyme cleanly hydrolyzes the tyrosine-DNA phosphodiester linkage, thereby liberating a DNA terminated with a 3' phosphate. The wide distribution of this phosphodiesterase in eukaryotes and its specificity for tyrosine linked to the 3' end but not the 5' end of DNA suggest that it plays a role in the repair of DNA trapped in complexes involving eukaryotic topoisomerase I.

Antigenic peptides containing large PEG loops designed to extend out of the HLA-A2 binding site form stable complexes with class I major histocompatibility complex molecules.

Recognition of peptides bound to class I major histocompatibility complex (MHC) molecules by specific receptors on T cells regulates the development and activity of the cellular immune system. We have designed and synthesized de novo cyclic peptides that incorporate PEG in the ring structure for binding to class I MHC molecules. The large PEG loops are positioned to extend out of the peptide binding site, thus creating steric effects aimed at preventing the recognition of class I MHC complexes by T-cell receptors. Peptides were synthesized and cyclized on polymer support using high molecular weight symmetrical PEG dicarboxylic acids to link the side chains of lysine residues substituted at positions 4 and 8 in the sequence of the HLA-A2-restricted human T-lymphotrophic virus type I Tax peptide. Cyclic peptides promoted the in vitro folding and assembly of HLA-A2 complexes. Thermal denaturation studies using circular dichroism spectroscopy showed that these complexes are as stable as complexes formed with antigenic peptides.

Interleukin 3 enhances cytotoxic T lymphocyte development and class I major histocompatibility complex "re-presentation" of exogenous antigen by tumor-infiltrating antigen-presenting cells.

We show that interleukin 3 (IL-3) enhances the generation of tumor-specific cytotoxic T lymphocytes (CTLs) through the stimulation of host antigen-presenting cells (APCs). The BALB/c (H-2d) spontaneous lung carcinoma line 1 was modified by gene transfection to express ovalbumin as a nominal "tumor antigen" and to secrete IL-3, a cytokine enhancing myeloid development. IL-3-transfected tumor cells are less tumorigenic than the parental cell line, and tumor-infiltrating lymphocytes isolated from these tumors contain increased numbers of tumor-specific CTLs. By using B3Z86/90.14 (B3Z), a unique T-cell hybridoma system restricted to ovalbumin/H-2b and implanting the tumors in (BALB/c x C57BL/6)F1 (H-2d/b) mice, we demonstrate that the IL-3-transfected tumors contain an increased number of a rare population of host cells that can process and "re-present" tumor antigen to CTLs. Electron microscopy allowed direct visualization of these host APCs, and these studies, along with surface marker phenotyping, indicate that these APCs are macrophage-like. The identification of these cells and their enhancement by IL-3 offers a new opportunity for tumor immunotherapy.

Chiral gold(I) vs chiral silver complexes as catalysts for the enantioselective synthesis of the second generation GSK-hepatitis C virus inhibitor

The synthesis of a GSK 2nd generation inhibitor of the hepatitis C virus, by enantioselective 1,3-dipolar cycloaddition between a leucine derived iminoester and tert-butyl acrylate, was studied. The comparison between silver(I) and gold(I) catalysts in this reaction was established by working with chiral phosphoramidites or with chiral BINAP. The best reaction conditions were used for the total synthesis of the hepatitis C virus inhibitor by a four step procedure affording this product in 99% ee and in 63% overall yield. The origin of the enantioselectivity of the chiral gold(I) catalyst was justified according to DFT calculations, the stabilizing coulombic interaction between the nitrogen atom of the thiazole moiety and one of the gold atoms being crucial.

Binap-gold (I) versus Binap-silver trifluoroacetate complexes as catalysts in 1,3-dipolar cycloadditions of axomethine ylides

The 1,3-dipolar cycloaddition between azomethine ylides and alkenes is efficiently catalysed by [{(Sa)-Binap-Au(tfa)}2] (Binap=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl; tfa=trifluoroacetyl). Maleimides, 1,2-bis(phenylsulfonyl)ethylene, chalcone and nitrostyrene were suitable dipolarophiles even when using sterically hindered 1,3-dipole precursors. The results obtained in these transformations improve the analogous ones obtained in the same reactions catalysed by [Binap–Ag(tfa)]. In addition, computational studies have also been carried out to demonstrate both the high enantioselectivity exhibited by the chiral gold(I) complex, and the non-linear effect observed in this transformation.

Enantioselective Synthesis of exo-4-Nitroprolinates from Nitro­alkenes and Azomethine Ylides Catalyzed by Chiral Phosphor­amidite·Silver(I) or Copper(II) Complexes

Chiral complexes formed by privileged phosphoramidites derived from chiral binol and optically pure Davies’ amines, and copper(II) triflate, silver(I) triflate or silver(I) benzoate are excellent catalysts for the general 1,3-dipolar cycloaddition between nitroalkenes and azomethine ylides generated from α-amino acid derived imino esters. These three methods can be conducted at room temperature to afford the exo-cycloadducts (4,5-trans-2,5-cis-4-nitroprolinates) with high diastereoselectivity and high enantioselectivity. In general, the three procedures are complementary but silver catalysts are more versatile and less sensitive to sterically congested starting materials.

Proyecto RE-Sahara: taller cooperativo entre las asignaturas de Proyectos I, Estructuras II y Construcción III de la titulación de Arquitectura

Tras los sustanciales cambios en el plan de estudios actual debido a la futura implantación del nuevo Título de Grado de Arquitectura, es preciso dar cabida a metodologías docentes que potencien las habilidades y competencias específicas del arquitecto al tiempo que respondan a las prestaciones que demanda la sociedad de la Arquitectura. Por ello, se ha propuesto, en distintas asignaturas de la titulación, un taller multidisciplinar que engloba tres de las áreas de conocimiento fundamentales para el desarrollo del alumno de arquitectura como son Proyectos, Estructuras y Construcción. Con ejercicios de este tipo, se pretende contribuir a una mayor coordinación entre estas áreas con el fin de que los estudiantes no perciban la docencia fragmentada en disciplinas estancas. La metodología docente empleada ha consistido en la realización de un trabajo práctico común con un tema de carácter social, con el objetivo de involucrar a los futuros arquitectos en el desarrollo de propuestas reales. Trabajo supervisado mediante correcciones conjuntas con la participación del profesorado de las tres asignaturas de manera coordinada. En conclusión, el alumnado ha mostrado una preferencia mayoritaria por esta metodología docente ya que proporciona una visión conjunta entre asignaturas, englobadas en un único trabajo vinculado a la práctica profesional real.

Panowanie Kazimierza Jagiellończyka, króla polskiego i.w. księcia litewskiego. Wyjęte z rękopisow Jana Albertrandego;

Vol. 2 has title: Panowanie Kazimierza, Jana Alberta i Alexandra Jagiellończyków, królów polskich i w. książąt litewskich.

Cronica breue de i fatti illustri de Re di Francia, con le loro effigie dal naturale, cominciando da Faramondo Primo Re di Francia ... sino ad Henrico III ...

Mode of access: Internet.

Praeclarissimum opus diui Isidori Hyspalensis, quod aetimologiarum inscribitur ... : quasi i hoc volumine solu[m] de re gra[m]matica, atq[ue] vocabulor[m] interpretationibus ...

Mode of access: Internet.

Esequie di Luigi I cattolico Re delle Spagne celebrate in Firenze nella chiesa di S. Maria Nouella de' PP. predicatori il dì XXVI di Ottobre MDCCXXIV dal ... padre Fr. Saluatore Ascanio ... /

Mode of access: Internet.

Delle lodi di Luigi I cattolico Re delle Spagne /

Mode of access: Internet.

I progetti degli increduli sulla distruzione dei regolari e sulla invasione dei beni ecclesiastici : disvelati nelle opere di Federico il Grande Re di Prussia. Con un'Appendice di alcuni Decreti dell'Assemblea nazionale de' francesi sul medesimo argomento /

Contiene con portadilla propia :Appendice Saggio de decreti dell'Assemblea Nazionale de Francesi, sul medesimo Argomento.

Del Mappamondo istorico tomo quinto, parte terza : che contiene le vite de i Re di Danimarca e Noruega dal cominciamento della monarchia sino all'anno 1705 /

Mode of access: Internet.