DNA-binding properties of the yeast transcriptional activator, Gcr1p

In Saccharomyces cerevisiae the GCRI gene product is required for high-level expression of genes encoding glycolytic enzymes. In this communication, we extend our analysis of the DNA binding properties of Gcr1p. The DNA-binding domain of Gcr1p binds DNA with high affinity. The apparent dissociation constant of the Gcr1p DNA-binding domain for one of its specific binding sites (TTTCAGCTTCCTCTAT) is 2.9 x 10(-10) M. However, competition experiments showed that Gcr1p binds this site in vitro with a low degree of specificity. We measured a 33-fold difference between the ability of specific competitor and DNA of random sequence to inhibit the formation of nucleoprotein complexes between Gcr1p and a radiolabeled DNA probe containing its binding site. DNA band-shift experiments, utilizing probes of constant length in which the positions of Gcr1p-binding sites are varied relative to the ends, indicated that Gcr1p-DNA nucleoprotein complexes contain bent DNA. The implications of these findings in terms of the combinatorial interactions that occur at the upstream activating sequence elements of genes encoding glycolytic enzymes are discussed.     

Creating global software: A conspectus and review

Ten books on the development of international software are reviewed and used to develop a framework for the globalization of software. Most of the books are written or edited by practitioners of global software development and therefore are filled with practical knowledge and methodologies which can guide the novice or even the experienced developer to first internationalize and then localize software. The books span a six year time span, during which the resources available to support the global software development effort have expanded and standards have been established, resulting in reduced effort. This conspectus starts with an introduction that includes several definitions, spells out the issues of translation from one language to another, localization, organization, culture, interface design, documentation, and quality assurance, recommends approaches for development of micro-based software for Macintosh and Windows environments, and ends with a unifying summary.     

Management of acute otitis media caused by resistant pneumococci in infants

OBJECTIVES: To assess the clinical outcome and risk of failure after oral vs. intravenous treatment in otitis media caused by penicillin-resistant pneumococci. To determine the possible correlations between pneumococcal minimal inhibitory concentration (MIC) to penicillin and clinical outcome. DESIGN: Retrospective study of 156 cases collected between 1993 and 1995. Mean follow-up: 5 months. Setting. Two tertiary academic medical centers in Paris, France. PATIENTS AND METHODS: Pneumococcus was isolated from 191 of 570 ear samples obtained from children with otitis media and shown to be penicillin-resistant in 156. Medical history, antibiotic therapy during the previous 3 months and day-care center attendance were reviewed. For the current episode microbiologic characteristics of the isolated strains, type of treatment, therapy efficacy and clinical outcome were analyzed. Patients were predominantly young (76.3% were <1 year old) and bacteriologic samples were taken mainly because of previous treatment failure. RESULTS: Among 156 children with pneumococcal penicillin-resistant otitis media, 72.2% attended day-care centers, 71.8% had been previously treated with aminopenicillin and 52.5% with cephalosporins. Failure of previous empirical oral therapy was noted in 84% (one-third of these had been receiving amoxicillin-clavulanate). Patients treated intravenously had had a more protracted otitis but no greater number of previous episodes of acute otitis media than those receiving oral therapy. Acute mastoiditis occurred in 4 infants resulting in mastoidectomy. Oral treatment (mainly with high dose amoxicillin,120 to 150 mg/kg/day) and intravenous therapy (cephalosporin or glycopeptide) had been used in 59 and 41%, respectively. Mean duration of therapy was 10.7 days. Three failures (1.9%) and 10 recurrences (6.4%, average 28 days) occurred. No statistical difference was found between intravenous and oral therapy with respect to risk of recurrence. A high penicillin MIC value was correlated with previous antibiotic treatment but not with clinical outcome. CONCLUSIONS: Oral therapy appears to be as effective as intravenous therapy for the treatment of penicillin-resistant pneumococcal otitis media. Intravenous treatment should not necessarily be dictated by the penicillin susceptibility value but should be considered in cases of failure to thrive, persistent otitis or other complications.     

Photosystem I is an early target of photoinhibition in barley illuminated at chilling temperatures

Light-induced damage to photosystem I (PSI) was studied during low-light illumination of barley (Hordeum vulgare L.) at chilling temperatures. A 4-h illumination period induced a significant inactivation of PSI electron transport activity. Flash-induced P700 absorption decay measurements revealed progressive damage to (a) the iron-sulfur clusters FA and FB, (b) the iron-sulfur clusters FA, FB, and FX, and (c) the phylloquinone A1 and the chlorophyll AO or P700 of the PSI electron acceptor chain. Light-induced PSI damage was also evidenced by partial degradation of the PSI-A and PSI-B proteins and was correlated with the appearance of smaller proteins. Aggravated photodamage was observed upon illumination of barley leaves infiltrated with KCN, which inhibits Cu,Zn-superoxide dismutase and ascorbate peroxidase. This indicates that the photodamage of PSI in barley observed during low-light illumination at chilling temperatures arises because the defense against active oxygen species by active oxygen-scavenging enzymes is insufficient at these specific conditions. The data obtained demonstrate that photoinhibition of PSI at chilling temperatures is an important phenomenon in a cold-tolerant plant species.     

MF59 adjuvant enhances antibody responses of infant baboons immunized with Haemophilus influenzae type b and Neisseria meningitidis group C oligosaccharide-CRM197 conjugate vaccine

The ability of the adjuvant MF59 to enhance the immunogenicity of polysaccharide-protein conjugate vaccines was investigated in infant baboons. MF59 consists of stable droplets (<250 nm) of the metabolizable oil squalene and two surfactants, polyoxyethylene sorbitan monooleate and sorbitan trioleate, in an oil-in-water emulsion. In humans, MF59 is well tolerated and enhances the immunogenicity of recombinant protein subunit or particle vaccines. Its effect on the immunogenicity of polysaccharide-protein conjugate vaccines is unknown. Baboons 1 to 4 months of age were immunized intramuscularly with Neisseria meningitidis group C and Haemophilus influenzae type b (Hib) oligosaccharide-CRM197 conjugate vaccines. The lyophilized vaccines were reconstituted with phosphate-buffered saline (PBS), Al(OH)3 (alum), or MF59. Groups of five animals each were given three injections of the respective formulations, with one injection every 4 weeks. Four weeks after each immunization, the MF59 group had up to 7-fold-higher geometric mean anticapsular-antibody titers than the alum group and 5- to 10-fold-higher N. meningitidis group C bactericidal-antibody titers. Twenty-one weeks after the third immunization, the MF59 group still showed 5- to 10-fold-higher anticapsular-antibody titers. The antibody responses of the animals given the vaccines reconstituted with PBS were low at all times measured. Both the MF59 and alum groups, but not the PBS group, showed booster antibody responses to unconjugated Hib and N. meningitidis group C polysaccharides, results consistent with induction of memory B cells. Thus, MF59 may be useful for accelerating and augmenting immunity to polysaccharide-protein conjugate vaccines in infants.     

Role of meaningful subgroups in explaining differences in perceived variability for in-groups and out-groups.

Five aspects of the complexity of the knowledge representation of business and engineering majors were examined to see whether these differed by group memberships and whether these differences were related to differences in perceived variability. Significantly more subgroups were generated when describing the in-group than the out-group; this difference predicted the relative tendency to see the in-group as more variable, and when controlled for statistically, out-group homogeneity effects were eliminated. Familiarity, redundancy, number of attributes used to describe the group, and the deviance of the subgroups from the larger group generally showed differences for in-group and out-group but did not show consistent evidence of mediation. In a 2nd study, Ss who were asked to sort group members into meaningful subgroups perceived greater variability relative to those who did not perform the sorting task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Contrast media enhanced magnetic resonance angiography for determining patency of a coronary bypass. A comparison with coronary angiography]

BACKGROUND: More data on the efficacy and safety of ciprofloxacin in pediatric cystic fibrosis patients are needed. METHODS: One hundred eight pediatric cystic fibrosis patients (ages 5 to 17 years) with acute bronchopulmonary exacerbations entered a randomized multicenter trial designed to compare the safety and efficacy of antipseudomonas therapy with oral ciprofloxacin (15 mg/kg twice daily; maximum dosage 750 mg twice daily) or intravenous ceftazidime plus tobramycin (CAZ/TM) for 14 days. RESULTS: Clinical improvement was observed in 93% of patients treated with oral ciprofloxacin and in 96% of those receiving parenteral therapy. Transient suppression of Pseudomonas aeruginosa was achieved in 63% of patients at the end of the course of iv CAZ/TM therapy and in 24% receiving ciprofloxacin. Ultrasound examination and nuclear magnetic resonance imaging scans showed no evidence of cartilage toxicity in any of the ciprofloxacin-treated patients. Musculoskeletal adverse events were reported with similar frequency in the two groups of patients (7% in the group receiving ciprofloxacin therapy and 11% in the IV CAZ/TM group). The only sustained musculoskeletal symptom was a case of synovitis in a patient receiving parenteral CAZ/TM. CONCLUSION: Ciprofloxacin thus appears to be safe and effective for use in young patients with bronchopulmonary exacerbation of cystic fibrosis.     

A local cell quality metric and variational grid smoothing algorithm

A local cell quality metric is introduced and used to construct a variational functional for a grid smoothing algorithm. A maximum principle is proved and the properties of the local quality measure, which combines element shape and size control metrics, are investigated. Level set contours are displayed to indicate the effect of cell distortion. The approach is demonstrated for meshes of triangles and quadrilaterals in 2D and a test case with hexahedral cells in 3D. Issues such as the use of a penalty for folded meshes and the effect of valence change in the mesh patches are considered.     

Validating a five-factor marijuana motives measure: Relations with use, problems, and alcohol motives.

This study adapted and extended M. L. Cooper's (1994) Drinking Motives Measure to examine marijuana motives among 299 college students. An exploratory factor analysis supported the hypothesized 5-factor marijuana motives model, resulting in enhancement, conformity, expansion, coping, and social motives. Analyses supported the internal consistency and concurrent validity of the 5 marijuana motives. Marijuana motives were significant predictors of marijuana use and added to the prediction of use-related problems above and beyond the contribution of lifetime use. Motives and gender interacted in predicting use and use-related problems. Parallel regression analyses revealed that marijuana and alcohol motives predicted comparable amounts of variance in use and use-related problems. However, different patterns of relations emerged across drugs, supporting the discriminant validity of the marijuana and alcohol motives. (PsycINFO Database Record (c) 2010 APA, all rights reserved)