Solid-state 2H NMR study of methyl-d3-cobalamin

A solid-state 2H NMR study of methyl-d3-cobalamin has been performed as a function of temperature to provide information concerning the character and energetics of the motion performed by this unique bioorganometallic methyl group. Analysis of the 2H NMR line shape indicates that the methyl group undergoes rapid three-fold rotation, and that the Co-C-2H angle lies between 105.9 and 109.5 degrees. Determination of the spin-lattice relaxation times T1 shows that the relaxation is anisotropic, consistent with a "jumping" motion of the methyl group rather than rotational diffusion. This also provides the activation energy to methyl jumps as 8.3 +/- 1.3 kJ/mol. It is proposed that this energetic barrier may be a useful probe of changes in the electronic character of the Co-C bond that accompany the biological role of this molecule in such enzymes as methionine synthase.     

Auditory system plasticity in children after long periods of complete deafness

Separation and identification of proteins by two-dimensional (2-D) electrophoresis can be used for protein-based gene expression analysis. In this report single protein spots, from polyvinylidene difluoride blots of micropreparative E. coli 2-D gels, were rapidly and economically identified by matching their amino acid composition, estimated pI and molecular weight against all E. coli entries in the SWISS-PROT database. Thirty proteins from an E. coli 2-D map were analyzed and identities assigned. Three of the proteins were unknown. By protein sequencing analysis, 20 of the 27 proteins were correctly identified. Importantly, correct identifications showed unambiguous "correct" score patterns. While incorrect protein identifications also showed distinctive score patterns, indicating that protein must be identified by other means. These techniques allow large-scale screening of the protein complement of simple organisms, or tissues in normal and disease states. The computer program described here is accessible via the World Wide Web at URL address (http:@expasy.hcuge.ch/).     

Induced candidosis in mice with artificially established oral flora

The aim of this study was to gauge the effect of an artificially established flora, unnatural for mice, on the induction of oral candidosis in mice. Four groups of BALB/c mice were compared; conventional Candida albicans-free mice, "germ-free" mice which had been inoculated with Candida-free human saliva, germ-free mice which had been exposed to a cocktail of Streptococcus mitis, S. sobrinus and S. sanguis, and uncontaminated germ-free mice. After exposure to C. albicans via drinking water, the four groups of mice were killed and their oral cavities examined for candidal growth and oral lesions. Conventional mice yielded significantly less candidal growth and exhibited significantly fewer oral lesions than the other three groups. Candidal lesions in the two groups of contaminated germ-free mice were significantly fewer than in the uncontaminated germ-free mice. The latter exhibited extensive candidal lesions with little inflammatory infiltrate. It is concluded that mice with human oral micro-organisms have some resistance against candidal infection albeit at a reduced level, that mice with natural oral flora are highly resistant, and that germ-free mice are extremely susceptible to C. albicans infection.     

Yearly stepwise increments of the growth hormone dose results in a better growth response after four years in girls with Turner syndrome. Dutch Working Group on Growth Hormone

To optimize the growth promoting effect of growth hormone (GH), 65 previously untreated girls with Turner syndrome (TS), chronological age (CA) 2-11 yr, were randomized into 3 dosage regimen groups: A, B, and C, with a daily recombinant-human GH dose during 4 study years of 4-4-4-4, 4-6-6-6, and 4-6-8-8 IU/m2 b.s. The first GH dosage increase in groups B and C resulted in a significantly higher mean height velocity (HV) compared with constant dose group A. During the third year, when the dose was raised again only in group C, mean HV was significantly higher in groups B and C than in group A, and in group C compared with group B. In year 4 only group C mean HV remained significantly higher than group A. The pattern of change in HSDSCA (Dutch-Swedish-Danish Turner references) was identical; however, in year 4 mean delta HSDSCA in group B also remained significantly higher than group A. After 4 yr GH treatment, the following was determined. 1) The mean delta HSDSCA was significantly higher for groups B and C compared with group A, but not significantly different between groups B and C. 2) Although significantly higher compared with estimated values for untreated Dutch girls with TS, bone maturation of the GH treated girls was not significantly different between groups. 3) It was positively related with the degree of bone age (BA) retardation at start of study and negatively with baseline CA. 4) Both the modified Index of Potential Height (mIPHRUS) and a recently developed Turner-specific final height (FH) prediction method (PTSRUS), based on regression coefficients for H, CA, and bone age, showed significant increases in mean FH prediction, without significant differences between groups. PTSRUS values were markedly higher than the mIPHRUS values. Dose dependency could be shown for the area under the curve (AUC) for GH, but delta HSDSCA was not linearly related with AUC. Baseline GH binding protein (BP) levels were in 84% of the cases within the normal age range; the decrease in mean levels after 6 months GH was not significant. Mean insulin-like growth factor I (IGF-I) and IGFBP-3 plasma levels increased significantly, without significant differences between groups. delta HSDSCA during GH was dependent on IGF-I plasma levels at baseline and during the study period, beta-0.002 and beta-0.0004. Thus, a stepwise GH-dosing approach reduced the "waning" effect of the growth response after 4 yr treatment without undue bone maturation. FH prediction was not significantly different between treatment groups. Irrespective of the GH dose used, initiation of GH treatment at a younger age was beneficial after 4 yr GH when expressed as actual cm gained or as gain in FH prediction, but was not statistically significant when expressed as delta HSDSCA over the study period.     

Online handwriting recognition: the NPen++ recognizer

This paper presents the online handwriting recognition system NPen++ developed at the University of Karlsruhe and Carnegie Mellon University. The NPen++ recognition engine is based on a multi-state time delay neural network and yields recognition rates from 96% for a 5,000 word dictionary to 93.4% on a 20,000 word dictionary and 91.2% for a 50,000 word dictionary. The proposed tree search and pruning technique reduces the search space considerably without losing too much recognition performance compared to an exhaustive search. This enables the NPen++ recognizer to be run in real-time with large dictionaries. Initial recognition rates for whole sentences are promising and show that the MS-TDNN architecture is suited to recognizing handwritten data ranging from single characters to whole sentences. Received September 3, 2000 / Revised October 9, 2000     

The clinical assessment of cancer tests: a statistical approach to the prediction of "false positive" rates from controls

As the sensitivity of the new in vitro cancer detection techniques increases, a larger number of "false positive" results can be expected from control populations apparently free from malignant disease at the time of the test. An attempt is made to predict the number of unexplained positives, together with the expected age and sex distribution, using published cancer registration statistics. The predicted numbers are compared with the observed numbers of unexplained positives in two clinical trials of the MEM test.     

Effect of tinidazole, metronidazole and nitrofurazone on nucleic acid synthesis in Clostridium bifermentans

Coplanar lines of different orientations rotating in depth and viewed in parallel projection may appear to rotate in different directions and reverse independently of each other, or they may appear coplanar and all reverse together. The frequency of the latter "grouped" appearance for lines with an orientation range of 30 degrees was a function of the number of lines in a given space. Grouping was greater for lines converging to an implicit vanishing point and for lines with collinear edges regardless of their orientations. Line length, and by inference, interline separation also had effect of the nature of the response.     

Advanced neutron imaging methods with a potential to benefit from pulsed sources

During the last decade neutron imaging has seen significant improvements in instrumentation, detection and spatial resolution. Additionally, a variety of new applications and methods have been explored. As a consequence of an outstanding development nowadays various techniques of neutron imaging go far beyond a two- and three-dimensional mapping of the attenuation coefficients for a broad range of samples. Neutron imaging has become sensitive to neutron scattering in the small angle scattering range as well as with respect to Bragg scattering. Corresponding methods potentially provide spatially resolved and volumetric data revealing microstructural inhomogeneities, texture variations, crystalline phase distributions and even strains in bulk samples. Other techniques allow for the detection of refractive index distribution through phase sensitive measurements and the utilization of polarized neutrons enables radiographic and tomographic investigations of magnetic fields and properties as well as electrical currents within massive samples. All these advanced methods utilize or depend on wavelength dependent signals, and are hence suited to profit significantly from pulsed neutron sources as will be discussed.     

Advances in neutron imaging

Imaging techniques based on neutron beams are rapidly developing and have become versatile non-destructive analyzing tools in many research fields. Due to their intrinsic properties, neutrons differ strongly from electrons, protons or X-rays in terms of their interaction with matter: they penetrate deeply into most common metallic materials while they have a high sensitivity to light elements such as hydrogen, hydrogenous substances, or lithium. This makes neutrons perfectly suited probes for research on materials that are used for energy storage and conversion, e.g., batteries, hydrogen storage, fuel cells, etc. Moreover, their wave properties can be exploited to perform diffraction, phase-contrast and dark-field imaging experiments. Their magnetic moment allows for resolving magnetic properties in bulk samples. This review will focus on recent applications of neutron imaging techniques in both materials research and fundamental science illustrated by examples selected from different areas.