The effect of varying stimulus rate and duration on brain activity during reading

The effect of the presentation rate and exposure duration of visually presented words on brain activity was investigated using positron emission tomography. Subjects either read aloud or silently mouthed the names of words. In regions associated with early visual analysis, activity increased with both rate and duration; in regions associated with response generation, activity increased with increasing rate but was unaffected by duration; and in regions associated with word recognition, activity decreased with increasing duration. The variable responses of different brain regions illustrate the functional segregation of these regions. Of particular interest was the dissociation between activity in the posterior fusiform gyri and that in the medial lingual gyrus--in the former, activity increased with rate and duration but the latter was unaffected by either variable. This finding suggests that word processing in the lingual gyrus during reading is distinct from that in the posterior fusiform gyri. A further observation was that during reading aloud, when subjects can hear the sound of their own voice, the response in the primary auditory cortices increased with stimulus rate, demonstrating that subjects process the sound of their own voice in a qualitatively similar way to words spoken by another.     

Towards Dynamic Drug Design: Identification and Optimization of β‐Galactosidase Inhibitors from a Dynamic Hemithioacetal System

A discovery strategy relying on the identification of fragments through resolution of a constitutional dynamic system, coupled to subsequent static ligand design and optimization, is demonstrated. The strategic design and synthesis of the best molecular fragments identified from a dynamic hemithioacetal system into static ligand structures yielded a range of β‐galactosidase inhibitors. Two series of structures mimicking the hemithioacetal motif were envisaged: thioglycosides and C‐glycosides. Inhibition studies provided important structural information for the two groups, and 1‐thiobenzyl‐β‐D ‐galactopyranoside demonstrated the best inhibitory effects.     

Oxidizing dissolution of spent MOX47 fuel subjected to water radiolysis: Solution chemistry and surface characterization by Raman spectroscopy

The mechanisms of oxidizing dissolution of spent MOX fuel (MIMAS TU2®) subjected to water radiolysis were investigated experimentally by leaching spent MOX47 fuel samples in pure water at 25 °C under different oxidizing conditions (with and without external gamma irradiation); the leached surfaces were characterized by Raman spectroscopy. The highly oxidizing conditions resulting from external gamma irradiation significantly increased the concentration of plutonium (Pu(V)) and uranium (U(VI)) compared with a benchmark experiment (without external irradiation). The oxidation behavior of the plutonium-enriched aggregates differed significantly from that of the UO₂ matrix after several months of leaching in water under gamma irradiation. The plutonium in the aggregates appears to limit fuel oxidation. The only secondary phases formed and identified to date by Raman spectroscopy are uranium peroxides that generally precipitate on the surface of the UO₂ grains. Concerning the behavior of plutonium, solution analysis results appear to be compatible with a conventional explanation based on an equilibrium with a Pu(OH)_4(am) phase. The fission product release - considered as a general indicator of matrix alteration - from MOX47 fuel also increases under external gamma irradiation and a change in the leaching mode is observed. Diffusive leaching was clearly identified, coinciding with the rapid onset of steady-state actinide concentrations in the bulk solution.     

Serotyping of Streptococcus pneumoniae by coagglutination with 12 pooled antisera

We report on the performance of a recently introduced commercial chessboard method using 12 antisera, in comparison with that of the 55-antiserum panel used in determining the serogroups and types (SGTs) of Streptococcus pneumoniae, both of which were carried out by a coagglutination technique. Of a total of 150 strains of S. pneumoniae studied, 135 (90%) belonged to the SGTs represented in the 23-valent pneumococcal vaccine; of these, 130 (96.3%) were identified as the same SGTs by both typing methods. The remaining five strains showed cross-reactivity with more than two pools by the chessboard method, but could be assigned to a single SGT by the Quellung test. The 96.3% concordance of the chessboard method suggests it can be adopted for determination of the SGTs of S. pneumoniae in laboratories.     

Sequence database searches via de novo peptide sequencing by tandem mass spectrometry

A method is described for searching protein sequence databases using tandem mass spectra of tryptic peptides. The approach uses a de novo sequencing algorithm to derive a short list of possible sequence candidates which serve as query sequences in a subsequent homology-based database search routine. The sequencing algorithm employs a graph theory approach similar to previously described sequencing programs. In addition, amino acid composition, peptide sequence tags and incomplete or ambiguous Edman sequence data can be used to aid in the sequence determinations. Although sequencing of peptides from tandem mass spectra is possible, one of the frequently encountered difficulties is that several alternative sequences can be deduced from one spectrum. Most of the alternative sequences, however, are sufficiently similar for a homology-based sequence database search to be possible. Unfortunately, the available protein sequence database search algorithms (e.g. Blast or FASTA) require a single unambiguous sequence as input. Here we describe how the publicly available FASTA computer program was modified in order to search protein databases more effectively in spite of the ambiguities intrinsic in de novo peptide sequencing algorithms.     

Influence of the Disintegrant on the Drug Percolation Threshold in Tablets

Previous papers studied ternary tablets containing different concentrations of polyvinylpyrrolidone cross-link (PVP-CL) as disintegrant. The drug percolation threshold, p_cl, for these tablets was estimated to fall in the range 0.26-0.31 of total porosity. The aim of the present paper is to study if the presence of the disintegrant agent (PVP-CL) in these tablets, exerts an important effect on the drug percolation threshold obtained. For this purpose, binary tablets containing the same model drug and excipient have been prepared in identical technological conditions. The drug percolation threshold in these matrix tablets has been calculated following the method of Bonny and Leuenberger (5). The results obtained show no significant difference between p_cl in the binary matrix tablets and the drug percolation threshold found in the tablets containing the disintegrant agent. This result supposes a stimulus for the application of the principles of percolation theory to a great number of pharmaceutical systems containing disintegrant agents or substances which cause a strong change in its release behavior.