Unraveling Thermodynamic and Kinetic Contributions to the Stability of Doped Nanocrystalline Alloys using Nanometallic Multilayers.

Targeted doping of grain boundaries is widely pursued as a pathway for combating thermal instabilities in nanocrystalline metals. However, certain dopants predicted to produce grain-boundary-segregated nanocrystalline configurations instead form small nanoprecipitates at elevated temperatures that act to kinetically inhibit grain growth. Here, thermodynamic modeling is implemented to select the Mo-Au system for exploring the interplay between thermodynamic and kinetic contributions to nanostructure stability. Using nanoscale multilayers and in situ transmission electron microscopy thermal aging, evolving segregation states and the corresponding phase transitions are mapped with temperature. The microstructure is shown to evolve through a transformation at lower homologous temperatures (<600 °C) where solute atoms cluster and segregate to the grain boundaries, consistent with predictions from thermodynamic models. An increase in temperature to 800 °C is accompanied by coarsening of the grain structure via grain boundary migration but with multiple pinning events uncovered between migrating segments of the grain boundary and local solute clustering. Direct comparison between the thermodynamic predictions and experimental observations of microstructure evolution thus demonstrates a transition from thermodynamically preferred to kinetically inhibited nanocrystalline stability and provides a general framework for decoupling contributions to complex stability transitions while simultaneously targeting a dominant thermal stability regime.

Potential use of a Yersinia ruckeri O1 auxotrophic aroA mutant as a live attenuated vaccine.

The aroA gene of Yersinia ruckeri, which encodes 5-enolpyruvylshikimate 3-phosphate synthase, was insertionally inactivated with a DNA fragment containing a kanamycin resistance determinant and reintroduced by allelic exchange into the chromosome of Y. ruckeri 21102 O1 by means of the suicide vector pIVET8. The Y. ruckeri aroA::Kan(r) mutant was highly attenuated when inoculated intraperitoneally into rainbow trout, with a 50% lethal dose of >5 x 10(7) CFU. The mutants were not recoverable from the internal organs 48 h post-inoculation or later. The vaccination of rainbow trout with the AroA mutant as a live vaccine conferred significant protection (relative percentage survival = 90%) against the pathogenic wild-type strain of Y. ruckeri.

Conversion of pipecolic acid into lysine in Penicillium chrysogenum requires pipecolate oxidase and saccharopine reductase: characterization of the lys7 gene encoding saccharopine reductase.

Pipecolic acid is a component of several secondary metabolites in plants and fungi. This compound is useful as a precursor of nonribosomal peptides with novel pharmacological activities. In Penicillium chrysogenum pipecolic acid is converted into lysine and complements the lysine requirement of three different lysine auxotrophs with mutations in the lys1, lys2, or lys3 genes allowing a slow growth of these auxotrophs. We have isolated two P. chrysogenum mutants, named 7.2 and 10.25, that are unable to convert pipecolic acid into lysine. These mutants lacked, respectively, the pipecolate oxidase that converts pipecolic acid into piperideine-6-carboxylic acid and the saccharopine reductase that catalyzes the transformation of piperideine-6-carboxylic acid into saccharopine. The 10.25 mutant was unable to grow in Czapek medium supplemented with alpha-aminoadipic acid. A DNA fragment complementing the 10.25 mutation has been cloned; sequence analysis of the cloned gene (named lys7) revealed that it encoded a protein with high similarity to the saccharopine reductase from Neurospora crassa, Magnaporthe grisea, Saccharomyces cerevisiae, and Schizosaccharomyces pombe. Complementation of the 10.25 mutant with the cloned gene restored saccharopine reductase activity, confirming that lys7 encodes a functional saccharopine reductase. Our data suggest that in P. chrysogenum the conversion of pipecolic acid into lysine proceeds through the transformation of pipecolic acid into piperideine-6-carboxylic acid, saccharopine, and lysine by the consecutive action of pipecolate oxidase, saccharopine reductase, and saccharopine dehydrogenase.

Sangrado gastrointestinal por estrongiloides estercolaris en pacientes pediátricos / Gastrointestinal hemorrhage

Se describe una serie de 4 pacientes en edad pediátrica con sangrado gastrointestinal causado por la infestación de Estrongiloides estercolaris, atendidos en el Hospital la Misericordia, entre 1992 y 2000. Los 4 pacientes eran procedentes de la misma región geográfica. 3 casos se diagnosticaron mediante examen de la pieza quirúrgica, el cuarto como hallazgo de autopsia

Efficacy of ribavirin in patients with chronic hepatitis B.

This study aimed to evaluate the efficacy and safety of a 6-month course of ribavirin (Rb) (1200 mg/day) in the treatment of chronic hepatitis B (CHB). Sixty patients with CHB were randomly assigned in a double-blind placebo (Pl) controlled study; 30 patients received oral Rb (1200 mg/day) and 30 received Pl for 24 weeks. Patients were hepatitis B surface antigen (HBsAg); hepatitis B envelope antigen (HBeAg); and hepatitis B virus (HBV)-DNA-positive, with alanine aminotransferase (ALT) levels 1.5 times higher than normal values. Clinical evaluations and laboratory tests were carried out at regular intervals; tests included total blood cell count, liver function tests, and HBV serum markers. Baseline and control liver biopsies were carried out. HBeAg seroconversion occurred in 50.0% of the patients in the Rb group (vs 6.6% in the Pl group; P = 0.00019); HBV DNA negativization occurred in 33.3% in the Rb group (vs 6.6% in the Pl group; P = 0.009); and improvement in the necroinflammatory index occurred in 53.3% in the Rb group (vs 23.3% in the Pl group; P = 0.02). The drug was well tolerated; the most important side effect in the Rb group was hemoglobin reduction, which was reversible once the treatment was stopped. Ribavirin was an effective treatment, demonstrated by decreased ALT levels, alleviation of histological damage, seroconversion of HBeAg, and HBV-DNA negativization; Rb may be an alternative agent in the treatment of CHB, without significant side effects.

The specific transport system for lysine is fully inhibited by ammonium in Penicillium chrysogenum: an ammonium-insensitive system allows uptake in carbon-starved cells.

The regulation exerted by ammonium and other nitrogen sources on amino acid utilization was studied in swollen spores of Penicillium chrysogenum. Ammonium prevented the L-lysine, L-arginine and L-ornithine utilization by P. chrysogenum swollen spores seeded in complete media, but not in carbon-deficient media. Transport of L-[14C]lysine into spores incubated in presence of carbon and nitrogen sources was fully inhibited by ammonium ions (35 mM). However, in carbon-derepressed conditions (growth in absence of sugars, with amino acids as the sole carbon source) L-[14C]lysine transport was only partially inhibited. Competition experiments showed that L-lysine (1 mM) inhibits the utilization of L-arginine, and vice versa, L-arginine inhibits the L-lysine uptake. High concentrations of L-ornithine (100 mM) prevented the L-lysine and L-arginine utilization in P. chrysogenum swollen spores. In summary, ammonium seems to prevent the utilization of basic amino acids in P. chrysogenum spores by inhibiting the transport of these amino acids through their specific transport system(s), but not through the general amino acid transport system that is operative under carbon-derepression conditions.