Plasma current start-up by the outer ohmic heating coils in the Saskatchewan TORus Modified (STOR-M) iron core tokamak.

A plasma current up to 15 kA has been driven with outer ohmic heating (OH) coils in the STOR-M iron core tokamak. Even when the inner OH coil is disconnected, the outer OH coils alone can induce the plasma current as primary windings and initial breakdown are even easier in this coil layout. This result suggests a possibility to use an iron core in a spherical tokamak to start up the plasma current without a central solenoid. The effect of the iron core saturation on the extension of the discharge pulse length has been estimated for further experiments in the STOR-M tokamak.

Ozone therapy for the treatment of dental caries.

BACKGROUND: Dental caries is a bacterially mediated disease characterised by demineralisation of the tooth surface, which may lead to cavitation, discomfort, pain and eventual tooth loss. Ozone is toxic to certain bacteria in vitro and it has been suggested that delivering ozone into a carious lesion might reduce the number of cariogenic bacteria. This possibly could arrest the progress of the lesion and may, in the presence of fluoride, perhaps allow remineralisation to occur. This may in turn delay or prevent the need for traditional dental conservation by 'drilling and filling'. OBJECTIVES: To assess whether ozone is effective in arresting or reversing the progression of dental caries. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (to 7 November 2003); Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2003); MEDLINE and PREMEDLINE (OVID, 1966 to November 2003); EMBASE (OVID, 1980 to November 2003); CINAHL (OVID, 1982 to November 2003); AMED (OVID, 1985 to November 2003). Quintessence was handsearched through 2002 and KaVo were contacted as manufacturers of the HealOzone apparatus for any additional published or unpublished trials. SELECTION CRITERIA: Inclusion was assessed independently by at least two reviewers. Trials were only included if they met the following criteria: randomisation in a controlled trial; single surface in vivo carious lesion accessible to ozone application; clear allocation concealment; ozone application to the lesions in the intervention group; no such application of ozone in the control group; outcomes measured after at least 6 months. DATA COLLECTION AND ANALYSIS: Reviewers independently extracted information in duplicate. A paucity of comparable data did not allow meta-analytic pooling of the included studies. MAIN RESULTS: Three trials were included, with a combined total of 432 randomised lesions (137 participants). Forty-two conference papers, abstracts and posters were excluded (from an unknown number of studies). The risk of bias in all studies appeared high. The analyses of all three studies were conducted at the level of the lesion, which is not independent of the person, for this reason pooling of data was not appropriate or attempted. Individual studies showed inconsistent effects of ozone on caries, across different measures of caries progression or regression. Few secondary outcomes were reported, but one trial reported an absence of adverse events. REVIEWERS' CONCLUSIONS: Given the high risk of bias in the available studies and lack of consistency between different outcome measures, there is no reliable evidence that application of ozone gas to the surface of decayed teeth stops or reverses the decay process. There is a fundamental need for more evidence of appropriate rigour and quality before the use of ozone can be accepted into mainstream primary dental care or can be considered a viable alternative to current methods for the management and treatment of dental caries.

Characterization of nitride thin films by electron backscatter diffraction.

Thin films incorporating GaN, InGaN and AlGaN are presently arousing considerable excitement because of their suitability for UV and visible light-emitting diodes and laser diodes. However, because of the lattice mismatch between presently used substrates and epitaxial nitride thin films, the films are of variable quality In this paper we describe our preliminary studies of nitride thin films using electron backscattered diffraction (EBSD). We show that the EBSD technique may be used to reveal the relative orientation of an epitaxial thin film with respect to its substrate (a 90 degrees rotation between a GaN epitaxial thin film and its sapphire substrate is observed) and to determine its tilt (a GaN thin film was found to be tiltedby 13 +/- 1 degrees towards [1010]GaN), where the tilt is due to the inclination of the sapphire substrate (cut off-axis by 10 degrees from (0001)sapphire towards (1010)sapphire). We compare EBSD patterns obtained from As-doped GaN films grown by plasma-assisted molecular beam epitaxy (PA-MBE) with low and high As4 flux, respectively. Higher As4 flux results in sharper, better defined patterns, this observation is consistent with the improved surface morphology observed in AFM studies. Finally, we show that more detail can be discerned in EBSD patterns from GaN thin films when samples are cooled.

Properties of the Plasmodium falciparum homologue of a protective vaccine candidate of Plasmodium yoelii.

We describe an unusual tryptophan-rich protein of Plasmodium falciparum that contains threonine-rich repeats. The protein is encoded by a 2.5 kb gene with a two-exon structure including a short AT-rich intron that is spliced out of the mature message. The 5' end of the gene encodes a hydrophobic region, which is assumed to be a signal peptide. The peptide sequence is characterised by a tryptophan-rich region and a block of degenerate threonine repeats. The protein is synthesised throughout the asexual life cycle and has an apparent molecular weight of approximately 94 kDa. It has a variable molecular weight in different strains of P. falciparum. Length polymorphisms can be found in the intron region and the second exon. Four single nucleotide mutations are localised in the tryptophan-rich region and two were found in the threonine-repeat block. Homology searches based on gene structure and amino acid sequence revealed a relationship with a P. yoelii antigen that has been used successfully in vaccine studies. Thus, this P. falciparum antigen should be considered an additional candidate for assessment in vaccination against the asexual blood-stages of P. falciparum.

Increased oxidative stress in Alzheimer's disease as assessed with 4-hydroxynonenal but not malondialdehyde.

Oxidative stress is thought to play a major role in the pathogenesis of Alzheimer's disease (AD). Although there is strong post-mortem and experimental evidence of oxidative damage occurring in AD brains, the use of markers in the peripheral circulation to show oxidative stress is less convincing. We examined plasma from AD patients for markers of increased oxidative stress. We report elevated levels of 4-hydroxy-nonenal (4-HNE) in AD patients compared to controls (median 20.6, IQR 6.0-25.2 vs. 7.8, 3.3-14.5 micomol/l, respectively; p=0.001) but not malondialdehyde (MDA), and lower levels of ascorbate in AD plasma when compared to age-matched controls (9.9, 6.0-33.7 vs. 24.2, 13.9-48.6 micromol/l; p<0.05). Levels of 4-HNE in AD patients were inversely related to ascorbate (r=-0.337; p=0.07) and Folstein Mini-Mental State Examination (MMSE) (r=-0.474; p=0.015). The concentration of protein sulphydryls, free-radical scavengers, was directly related to the MMSE result (r=0.427; p=0.03). Increased production of 4-HNE indicates increased oxidative stress (lipid peroxidation), which is not evident using the more common marker MDA. This elevation of 4-HNE was related to the degree of cognitive impairment (MMSE).

Structure-based design of an RNA-binding zinc finger.

A structure-based approach was used to design RNA-binding zinc fingers that recognize the HIV-1 Rev response element (RRE). An arginine-rich alpha-helix from HIV-1 Rev was engineered into the zinc finger framework, and the designed fingers were shown to bind specifically to the RRE with high affinity and in a zinc-dependent manner, and display cobalt absorption and CD spectra characteristic of properly folded fingers. The results indicate that a monomeric zinc finger can recognize a specific nucleic acid site and that the alpha-helix of a finger can be used to recognize the major groove of RNA as well as DNA. The RRE-binding zinc fingers demonstrate how structure-based approaches may be used in the design of potential RNA-binding therapeutics and provide a framework for selecting RNA-binding fingers with desired specifications.

The subgaleal pulley suture.

The repair of scalp defects is often complicated by moderate tension on the wound edges. A subgaleal version of the 'pulley' suture, which may be helpful in closing wounds in this setting, is described.

Comparison of magnitude estimation and interval scaling of loudness.

To identify whether equal-appearing interval or magnitude estimation scaling resulted in a data set with a closer correlation to the physical stimuli involved 20 young adults completing two tasks. In Task 1 subjects used a 7-point equal-appearing interval loudness of 18 10-sec. samples of babble speech, presented randomly at intensities of 5 to 90 dB SPL. In Task 2 subjects used magnitude estimation scaling to rate these stimuli, presented in a randomized order. Analysis showed significantly high correlations for both scaling methods and the stimuli (Spearman rho = 1.00 and .99, respectively). Subjects can use either form of scaling to rate changes in loudness.

Comparisons of magnitude estimation scaling of rock music by children, young adults, and older people.

The present study concerned the perceptual processing of complex auditory stimuli in 10 children (M age = 8.1) as compared to 10 young adults (M age = 19.3) and 10 older adult subjects (M age = 54.2). The auditory stimulus used was 10 sec. of rock music (Led Zeppelin, 1969). All three groups provided numerical responses to nine intensities of the rock music stimulus (10, 20, 30, 40, 50, 60, 70, 80, 90 dB above threshold). Analysis showed that the children reported a wider range of numerical responses than both adult groups. The mean numerical responses for the children ranged from .54 to 54.24. For the young adults the range was .76 to 11.37, and for the older subjects it was 1.6 to 23.31. Results suggest that the children were not bound by the same set of rules as the adults with regard to magnitude estimation scaling of the loudness of the rock music stimulus. Their internal scaling mechanisms appeared to be more flexible and broader based than those of the adults who participated in this study.

Listener ratings of the intelligibility of tracheoesophageal speech in noise.

The purpose of this investigation was to determine the extent to which listener ratings of the intelligibility of tracheoesophageal puncture (TEP) speech vary as a function of different signal-to-noise ratios. Fifty college students, 25 men and 25 women (Median age = 19.7 years) participated in the study. They were instructed to assign numbers to audio-recorded speech samples in each of nine signal-to-noise ratio conditions (+65 dB, +20 dB, +15 dB, +10 dB, +5 dB, 0 dB, -5 dB, -10 dB, and -15 dB) in two separate magnitude estimation scaling tasks. During Task 1 the subjects rated the intelligibility of a TEP speech sample. In Task 2 the subjects rated the intelligibility of a normal speech sample. The results indicated that as the levels of background noise increased, listener ratings of intelligibility decreased (F 8,392 = 37.84; p < or = .0001).

Factors related to magnitude estimation scaling of complex auditory stimuli: aging.

The purpose of this study was to examine the effects of aging on magnitude estimation scaling of the loudness of complex auditory stimuli in the form of rock music. The subjects were 10 young adults (M age = 19.3 yr.), and 10 older individuals (M age = 54.2 yr.). The older individuals' mean numerical responses suggested that they perceived the rock music stimuli as louder for all nine suprathreshold intensities tested. The older group of subjects may have perceived the suprathreshold stimulus intensities as being louder because of physical and affective changes that naturally occur in central auditory processing during the aging process.

Magnitude estimation scaling of the loudness of a wide range of auditory stimuli.

The study of the perception of loudness lends itself well to the psychophysical scaling technique of magnitude estimation. This study was designed to extend the range of auditory stimuli used to study the magnitude estimation scaling of loudness. The five stimuli chosen were a 1000-Hz pure tone, narrow band noise (700-1300 Hz band width), broad band noise (100-10,000 Hz band width), rock music, and babble speech, i.e., speech in which meaning is not discernible because several individuals are talking at once. Subjects were 30 normal young women (M = 19 yr.). During the auditory magnitude-estimation task for each of the five stimuli, a subject was instructed to assign numbers to stimulus presented in a randomly ordered series of nine sensation levels (10, 20, 30, 40, 50, 60, 70, 80, and 90 dB SL). Multivariate analysis of variance for repeated measures indicated there were no significant differences in the numerical responses of the subjects for the five stimuli. A possible explanation for these results is the presence of an underlying stabilizing factor (internal scaling mechanism) that allows adults to scale loudness consistently irrespective of the type of auditory stimulus.

A second merozoite surface protein (MSP-4) of Plasmodium falciparum that contains an epidermal growth factor-like domain.

Merozoite surface proteins of Plasmodium falciparum play a critical role in the invasion of human erythrocytes by the malaria parasite. Here we describe the identification of a novel protein with a molecular mass of 40 kDa that is found on the merozoite surface of P. falciparum. We call this protein merozoite surface protein 4 (MSP-4). Evidence for the surface location of MSP-4 includes (i) a staining pattern that is consistent with merozoite surface location in indirect immunofluorescent studies of cultured parasites, (ii) localization of MSP-4 in the detergent phase in Triton X-114 partitioning studies, and (iii) nucleotide sequencing studies which predict the presence of an N-terminal signal sequence and a hydrophobic C-terminal sequence in the protein. Immunoprecipitation studies of biosynthetically labelled parasites with [3H] myristic acid indicated that MSP-4 is anchored on the merozoite surface by a glycosylphosphatidylinositol moiety. Of considerable interest is the presence of a single epidermal growth factor-like domain at the C terminus of the MSP-4 protein, making it the second protein with such a structure to be found on the merozoite surface.

A putative Plasmodium falciparum exported serine/threonine protein kinase.

An 8kb gene coding for a putative serine/threonine protein kinase from Plasmodium falciparum has been cloned and sequenced. It is arranged in two exons: exon I is 2 kb and exon II is 5.6 kb. The gene codes for a large protein of 2510 amino acids. Antibodies raised against a fusion protein were used to localize the putative kinase. By immunofluorescence microscopy, it was found in the cytoplasm of infected red cells. By immunoelectron microscopy it was associated with membranous structures in the red cell and with the red cell membrane, particularly at parasite-induced knobs. This is the first putative protein kinase of P. falciparum to be exported from the parasite into its host cell.

Conservation of structural motifs and antigenic diversity in the Plasmodium falciparum merozoite surface protein-3 (MSP-3).

Merozoite surface protein-3 (MSP-3) is a secreted polymorphic antigen associated with erythrocytic schizonts and merozoites of Plasmodium falciparum asexual blood-stages. A prominent structural feature of MSP-3 is a domain composed of three blocks of tandemly-repeated heptads with the consensus sequence AXXAXXX. The three blocks of four alanine heptad-repeats are separated by short stretches of non-repetitive sequence unrelated to the heptad-repeat. C-terminal to the heptad-repeats, MSP-3 contains a glutamic acid-rich domain followed by another heptad-repeat similar to a leucine-zipper motif. An analysis of the msp-3 gene from four P. falciparum isolates shows that polymorphism in MSP-3 is predominantly due to sequence diversity in the N-terminal half of the predicted polypeptide within and flanking the heptad-repeats. Mutations in the region of the gene that encodes the alanine heptad-repeats appear to be of two types. Unique mutations in non-repetitive sequence have generated amino acid substitutions and deletions that result in unique sequences among MSP-3 variants. In contrast, mutations in the heptad-coding sequence are largely dimorphic and are clustered in one or two heptads in each of the three blocks of heptads. Despite the diversity within and flanking the heptad domain the AXXAXXX motif is highly conserved as are other features of the sequence that predict the formation of alpha-helical secondary structure. Recombinant proteins and a synthetic peptide were used to raise antisera to conserved and variable regions of MSP-3. Differential reactivity of these reagents with the parasite antigen identified the alanine heptad-repeat domain as a site of antigenic diversity among MSP-3 polypeptides.

Magnitude-estimation scaling of complex auditory stimuli: native and nonnative languages.

50 subjects used magnitude-estimation scaling to rate 11 languages on two subjective perceptual tasks. On Task 1, the subjects rated languages according to how similar they were to their native language (English). In Task 2, the subjects rated languages according to how much they like them. Analysis showed a high over-all correlation between how similar subjects felt the languages were to their native language and how much they liked them (Pearson product-correlation r = .86). The high correlation indicates consistency in subjects' scaling responses. This consistency may suggest that magnitude estimation is an appropriate method for scaling complex auditory stimuli represented by various attributes of native and nonnative languages.

Nuclear magnetic resonance solution structure of the human Hsp40 (HDJ-1) J-domain.

The J-domain is a highly conserved domain found in all members of the DnaJ family of molecular chaperones. The three-dimensional structure of a recombinant, uniformly 15N-labeled 77-residue polypeptide containing the complete J-domain from human Hsp40 (HDJ-1) has been determined by nuclear magnetic resonance (NMR) spectroscopy in solution. On the basis of 876 upper distance constraints derived from nuclear Overhauser effects (NOE) and 173 dihedral angle constraints, a group of 20 conformers representing the solution structure of the HDJ-1 J-domain was computed with the program DIANA and energy-minimized with the program OPAL. The average of the pairwise root-mean-square deviations of the individual NMR conformers relative to the mean coordinates for the backbone atoms N, C2 and C' of residues 4 to 54 and 4 to to 66 is 0.88 and 0.99 A respectively. The molecular architecture includes four helices composed of residues 5 to 9, 15 to 28, 40 to 54 and 60 to 66. A turn composed of residues 10 to 14 links helices I and II, and a loop composed of residues 29 to 39 containing a highly conserved tripeptide HPD (residues 31 to 33) connects the antiparallel helices II and III. The tertiary fold formed by helix I-turn-helix II-loop-helix III forms a closed structural core; the less defined helix IV stands away from the core of the domain. The side-chains of the tripeptide HPD extend out from the core of the structure in the opposite direction from helix IV. The structure supports the hypothesis that the highly conserved tripeptide could play a key role in the interaction of Hsp40 with the molecular chaperone, Hsp70.

Solution structure of a polypeptide containing four heptad repeat units from a merozoite surface antigen of Plasmodium falciparum.

The Plasmodium falciparum antigen SPAM (secreted polymorphic antigen associated with merozoites) contains an unusual set of heptad repeat units with alanine at the a and d positions. Twelve heptads with the consensus sequence AXXAXXX occur in three blocks of four, linked by short nonrepetitive sequences. A 38-residue polypeptide comprising the first block of four heptad units and five flanking residues at either end, SPAM-H1, has been synthesized and its structure in aqueous solution determined from 1H NMR data. Sedimentation equilibrium showed the peptide to be monomeric in aqueous solution. Its structure was determined from 1H NMR-derived distance and dihedral angle constraints by using distance geometry calculations, restrained simulated annealing, and conjugate gradient energy minimization in the CHARMm force field. The polypeptide contains an alpha-helix extending from Ser10 (position e of the first heptad) to at least Lys32 (position f of the fourth heptad) and possibly as far as Val35. The helix is bent, partly as result of a kink around residues 19-20. The conformations of the nine N-terminal residues and the six C-terminal residues are not well defined by the NMR data. The rms deviation from the average of the 20 best structures over the well-defined region (residues 11-31, which have backbone angular order parameters > 0.8) was 1.56 A for backbone heavy atoms (N, C alpha, and C) and 2.12 A for all heavy atoms. 2H2O exchange experiments identified slowly exchanging amide protons near the C-terminus and the last two turns of the helix. The unusual stability of the C-terminus reflects the presence of a new C-capping motif, which may involve the side chain of an asparagine in a position external to the C-cap residue. Possible interactions of the H1 sequence with the other two heptad repeat units in the intact merozoite antigen are discussed.