1,287 research outputs found
Simulation Application for the LHCb Experiment
We describe the LHCb detector simulation application (Gauss) based on the
Geant4 toolkit. The application is built using the Gaudi software framework,
which is used for all event-processing applications in the LHCb experiment. The
existence of an underlying framework allows several common basic services such
as persistency, interactivity, as well as detector geometry description or
particle data to be shared between simulation, reconstruction and analysis
applications. The main benefits of such common services are coherence between
different event-processing stages as well as reduced development effort. The
interfacing to Geant4 toolkit is realized through a facade (GiGa) which
minimizes the coupling to the simulation engine and provides a set of abstract
interfaces for configuration and event-by-event communication. The Gauss
application is composed of three main blocks, i.e. event generation, detector
response simulation and digitization which reflect the different stages
performed during the simulation job. We describe the overall design as well as
the details of Gauss application with a special emphasis on the configuration
and control of the underlying simulation engine. We also briefly mention the
validation strategy and the planing for the LHCb experiment simulation.Comment: Talk from the 2003 Computing in High Energy and Nuclear Physics
(CHEP03), La Jolla, Ca, USA, March 2003, 6 pages, LaTeX, 9 eps figures. PSN
TUMT00
Incommensurate instability and lattice dynamics of potassium selenate within a semiempirical rigid-ion model
The lattice dynamics of potassium selenate is analyzed using a rigid-ion model with the selenate groups reduced to rigid bodies. The interatomic forces have been adjusted only using static structural data. The number of adjustable parameters varies from two to five. Such a simple model is already sufficient to reproduce semiquantitatively the phonon dynamics of the real system. In particular, the model exhibits the lattice instability leading to the existence of an incommensurate phase. The characteristics of the resulting soft mode agree with those observed experimentally. The calculated eigenvector, in excellent agreement with the experimental one, is rather insensitive to the details of the interactions. This explains the strong similarities of the incommensurate modulations in most A2BX4 compounds. On the other hand, the form of the soft-phonon branch strongly depends on the force model. It is sufficient to fit the model to the static structure observed at 145 K instead of the one at room temperature, to provoke a conspicuous softening of the branch. The branch minimum is specially sensitive to some potassium-oxygen interactions. The relative size of the cations plays an essential role in the origin of the incommensurate instability. For comparison the results of a similar analysis for Cs2SeO4 are presented. In this case, the unstable or soft character of the lowest 2 branch disappears.Dirección General de Investigación Científica y Técnica PB87-074
Methionine adenosyltransferase S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target thiol
S-Adenosylmethionine serves as the methyl donor for many biological methylation reactions and provides the propylamine group for the synthesis of polyamines. S-Adenosylmethionine is synthesized from methionine and ATP by the enzyme methionine adenosyltransferase. The cellular factors regulating S-adenosylmethionine synthesis have not been well defined. Here we show that in rat hepatocytes S-nitrosoglutathione monoethyl ester, a cell-permeable nitric oxide donor, markedly reduces cellular S-adenosylmethionine content via inactivation of methionine adenosyltransferase by S-nitrosylation. Removal of the nitric oxide donor from the incubation medium leads to the denitrosylation and reactivation of methionine adenosyltransferase and to the rapid recovery of cellular S-adenosylmethionine levels. Nitric oxide inactivates methionine adenosyltransferase via S-nitrosylation of cysteine 121. Replacement of the acidic (aspartate 355) or basic (arginine 357 and arginine 363) amino acids located in the vicinity of cysteine 121 by serine leads to a marked reduction in the ability of nitric oxide to S-nitrosylate and inactivate hepatic methionine adenosyltransferase. These results indicate that protein S-nitrosylation is regulated by the basic and acidic amino acids surrounding the target cysteine
Folding of dimeric methionine adenosyltransferase III: identification of two folding intermediates
Methionine adenosyl transferase (MAT) is an essential enzyme that synthesizes AdoMet. The liver-specific MAT isoform, MAT III, is a homodimer of a 43.7-kDa subunit that organizes in three nonsequential alpha-beta domains. Although MAT III structure has been recently resolved, little is known about its folding mechanism. Equilibrium unfolding and refolding of MAT III, and the monomeric mutant R265H, have been monitored using different physical parameters. Tryptophanyl fluorescence showed a three-state folding mechanism. The first unfolding step was a folding/association process as indicated by its dependence on protein concentration. The monomeric folding intermediate produced was the predominant species between 1.5 and 3 m urea. It had a relatively compact conformation with tryptophan residues and hydrophobic surfaces occluded from the solvent, although its N-terminal region may be very unstructured. The second unfolding step monitored the denaturation of the intermediate. Refolding of the intermediate showed first order kinetics, indicating the presence of a kinetic intermediate within the folding/association transition. Its presence was confirmed by measuring the 1,8-anilinonaphtalene-8-sulfonic acid binding in the presence of tripolyphosphate. We propose that the folding rate-limiting step is the formation of an intermediate, probably a structured monomer with exposed hydrophobic surfaces, that rapidly associates to form dimeric MAT III
Biochemical basis for the dominant inheritance of hypermethioninemia associated with the R264H mutation of the MAT1A gene. A monomeric methionine adenosyltransferase with tripolyphosphatase activity
Methionine adenosyltransferase (MAT) catalyzes the synthesis of S-adenosylmethionine (AdoMet), the main alkylating agent in living cells. Additionally, in the liver, MAT is also responsible for up to 50% of methionine catabolism. Humans with mutations in the gene MAT1A, the gene that encodes the catalytic subunit of MAT I and III, have decreased MAT activity in liver, which results in a persistent hypermethioninemia without homocystinuria. The hypermethioninemic phenotype associated with these mutations is inherited as an autosomal recessive trait. The only exception is the dominant mild hypermethioninemia associated with a G-A transition at nucleotide 791 of exon VII. This change yields a MAT1A-encoded subunit in which arginine 264 is replaced by histidine. Our results indicate that in the homologous rat enzyme, replacement of the equivalent arginine 265 by histidine (R265H) results in a monomeric MAT with only 0.37% of the AdoMet synthetic activity. However the tripolyphosphatase activity is similar to that found in the wild type (WT) MAT and is inhibited by PP(i). Our in vivo studies demonstrate that the R265H MAT I/III mutant associates with the WT subunit resulting in a dimeric R265H-WT MAT unable to synthesize AdoMet. Tripolyphosphatase activity is maintained in the hybrid MAT, but is not stimulated by methionine and ATP, indicating a deficient binding of the substrates. Our data indicate that the active site for tripolyphosphatase activity is functionally active in the monomeric R265H MAT I/III mutant. Moreover, our results provide a molecular mechanism that might explain the dominant inheritance of the hypermethioninemia associated with the R264H mutation of human MAT I/III
uPAR-controlled oncolytic adenoviruses eliminate cancer stem cells in human pancreatic tumors
Abstract Pancreatic tumors contain cancer stem cells highly resistant to chemotherapy. The identification of therapies that can eliminate this population of cells might provide with more effective treatments. In the current work we evaluated the potential of oncolytic adenoviruses to act against pancreatic cancer stem cells (PCSC). PCSC from two patient-derived xenograft models were isolated from orthotopic pancreatic tumors treated with saline, or with the chemotherapeutic agent gemcitabine. An enrichment in the number of PCSC expressing the cell surface marker CD133 and a marked enhancement on tumorsphere formation was observed in gemcitabine treated tumors. No significant increase in the CD44, CD24, and epithelial-specific antigen (ESA) positive cells was observed. Neoplastic sphere-forming cells were susceptible to adenoviral infection and exposure to oncolytic adenoviruses resulted in elevated cytotoxicity with both Adwt and the tumor specific AduPARE1A adenovirus. In vivo, intravenous administration of a single dose of AduPARE1A in human-derived pancreatic xenografts led to a remarkable anti-tumor effect. In contrast to gemcitabine AduPARE1A treatment did not result in PCSC enrichment. No enrichment on tumorspheres neither on the CD133+ population was detected. Therefore our data provide evidences of the relevance of uPAR-controlled oncolytic adenoviruses for the elimination of pancreatic cancer stem cells
New Symmetries in Crystals and Handed Structures
For over a century, the structure of materials has been described by a
combination of rotations, rotation-inversions and translational symmetries. By
recognizing the reversal of static structural rotations between clockwise and
counterclockwise directions as a distinct symmetry operation, here we show that
there are many more structural symmetries than are currently recognized in
right- or left-handed handed helices, spirals, and in antidistorted structures
composed equally of rotations of both handedness. For example, though a helix
or spiral cannot possess conventional mirror or inversion symmetries, they can
possess them in combination with the rotation reversal symmetry. Similarly, we
show that many antidistorted perovskites possess twice the number of symmetry
elements as conventionally identified. These new symmetries predict new forms
for "roto" properties that relate to static rotations, such as rotoelectricity,
piezorotation, and rotomagnetism. They also enable symmetry-based search for
new phenomena, such as multiferroicity involving a coupling of spins, electric
polarization and static rotations. This work is relevant to structure-property
relationships in all material structures with static rotations such as
minerals, polymers, proteins, and engineered structures.Comment: 15 Pages, 4 figures, 3 Tables; Fig. 2b has error
La formación docente del profesorado de la Universidad de Barcelona: satisfacción, transferencia e impacto
Este estudio analiza el efecto que los programas de formación del Instituto de Ciencias de la Educación (ICE) de la Universidad de Barcelona (UB) tiene sobre la acción docente del profesorado que recibe esta formación. Se ha valorado la satisfacción del profesorado sobre los cursos recibidos, el nivel de transferencia de los conocimientos adquiridos a la docencia y su repercusión en el rendimiento académico, en la motivación y en la participación de los estudiantes. También se analizan las dificultades para transferir a la práctica los conocimientos y las habilidades adquiridas en la formación. Los indicadores utilizados para la recogida y el análisis de datos forman parte del Sistema Interno de Garantía de Calidad (SIGC) de los programas de formación del ICE de la UB. Los datos muestran una alta satisfacción del profesorado con la formación recibida. Indican que los programas diseñados favorecen la adquisición de competencias docentes y proporcionan a los profesores una mayor capacidad para introducir cambios en su docencia Dichos cambios repercuten en la mejora del rendimiento académico, así como en la participación y motivación de los estudiantes. La percepción de que algunos aspectos organizativos de la institución obstaculizan la transferencia es mayor en el profesorado que ha recibido más formación. Así mismo, se pone de manifiesto que el SIGC es una buena herramienta para el seguimiento y la evaluación de los programas de formación, para su acreditación, y en consecuencia, para acreditar también el desarrollo docente del profesorado
Creation of a functional S-nitrosylation site in vitro by single point mutation
Here we show that in extrahepatic methionine adenosyltransferase replacement of a single amino acid (glycine 120) by cysteine is sufficient to create a functional nitric oxide binding site without affecting the kinetic properties of the enzyme. When wild-type and mutant methionine adenosyltransferase were incubated with S-nitrosoglutathione the activity of the wild-type remained unchanged whereas the activity of the mutant enzyme decreased markedly. The mutant enzyme was found to be S-nitrosylated upon incubation with the nitric oxide donor. Treatment of the S-nitrosylated mutant enzyme with glutathione removed most of the S-nitrosothiol groups and restored the activity to control values. In conclusion, our results suggest that functional S-nitrosylation sites can develop from existing structures without drastic or large-scale amino acid replacement
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