Protein fold recognition without Boltzmann statistics or explicit physical basis

We present a fast method for finding optimal parameters for a low-resolution (threading) force field intended to distinguish correct from incorrect folds for a given protein sequence. In contrast to other methods, the parameterization uses information from >10(7) misfolded structures as well as a set of native sequence-structure pairs. In addition to testing the resulting force field's performance on the protein sequence threading problem, results are shown that characterize the number of parameters necessary for effective structure recognition.

The relationship between multiple birth children's early phonological skills and later literacy

Previous studies have shown that multiple ; birth children (MBC) are prone to early phonological ;difficulties and later literacy problems. However, to date, ;there has been no systematic long-term follow-up of MBC with phonological difficulties in the preschool years to determine whether these difficulties predict later literacy problems. In this study, 20 MBC whose early speech and language skills had been previously documented were compared to normative data and 20 singleton controls on tasks assessing phonological ; processing and literacy. The major findings indicated that MBC performed significantly more poorly on some tasks :df phonological processing than singleton controls did. Further, the early phonological skills of MBC (i.e., the number of inappropriate phonological processes used) correlated with poor performance on visual rhyme recognition, word repetition, and phoneme detection tasks 5 years later. There was no significant relationship between early biological factors (birth weight and gestation period) and performance on the phonological processing and literacy-related subtests. These results cl-support the hypothesis that MBC's early speech and language difficulties are not merely a transient phase;of; development, but a real disorder, with consequences for later academic achievement.

Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination

Development of CD8 alpha beta CTL epitope-based vaccines requires an effective strategy capable of co-delivering large numbers of CTL epitopes, Here we describe a DNA plasmid encoding a polyepitope or polytope protein, which contained multiple contiguous minimal murine CTL epitopes, Mice vaccinated with this plasmid made MHC-restricted CTL responses to each of the epitopes, and protective CTL were demonstrated in recombinant vaccinia virus, influenza virus, and tumor challenge models, CTL responses generated by polytope DNA plasmid vaccination lasted for 1 yr, could be enhanced by co-delivering a gene for granulocyte-macrophage CSF, and appeared to be induced in the absence of CD4 T cell-mediated help, The ability to deliver large numbers of CTL epitopes using relatively small polytope constructs and DNA vaccination technology should find application in the design of human epitope-based CTL vaccines, in particular in vaccines against EBV, HIV, and certain cancers.

Data analysis in multiple-frequency bioelectrical impedance analysis

The performance of three analytical methods for multiple-frequency bioelectrical impedance analysis (MFBIA) data was assessed. The methods were the established method of Cole and Cole, the newly proposed method of Siconolfi and co-workers and a modification of this procedure. Method performance was assessed from the adequacy of the curve fitting techniques, as judged by the correlation coefficient and standard error of the estimate, and the accuracy of the different methods in determining the theoretical values of impedance parameters describing a set of model electrical circuits. The experimental data were well fitted by all curve-fitting procedures (r = 0.9 with SEE 0.3 to 3.5% or better for most circuit-procedure combinations). Cole-Cole modelling provided the most accurate estimates of circuit impedance values, generally within 1-2% of the theoretical values, followed by the Siconolfi procedure using a sixth-order polynomial regression (1-6% variation). None of the methods, however, accurately estimated circuit parameters when the measured impedances were low (<20 Omega) reflecting the electronic limits of the impedance meter used. These data suggest that Cole-Cole modelling remains the preferred method for the analysis of MFBIA data.

Simultaneous detection of multiple antigens with triple immunolabeling

Immunolabeling is commonly used to localize antigens within frozen or paraffin tissue sections. We modified existing immunolabeling techniques to allow the detection of three antigens simultaneously within the one tissue section. The approach relies on the use of three monoclonal antibodies in sequential immunoperoxidase staining steps, each with colored substrates, resulting in the deposition of black, brown, and rose stains. The method is rapid and does not require novel techniques or materials. In this report, we demonstrate the colocalization of mast cell tryptase, neurofilament protein, and CD31 (platelet-endothelial cell adhesion molecule) or laminin in normal human skin and normal buccal mucosa, as an illustration of the power and simplicity of the multiple antigen localization technique.

Suicide in urban New South Wales, Australia 1985-1994: Socio-economic and migrant interactions

Variation of suicide with socio-economic status (SES) in urban NSW (Australia) during 1985-1994, by sex and country or region of birth, was examined using Poisson regression analysis of vital statistics and population data (age greater than or similar to 15 yr). Quintiles of SES were defined by municipality of residence and comparisons of suicide by SES were adjusted for age and country (or region) of birth (COB), and examined by COB. Risk of suicide in females was 28% that of males for all adults and 21% for youth (age 15-24 yr). Suicide risk was lower in males from southern Europe, Middle East and Asia, and higher in northern and eastern European males, compared to the Australian-born. Risks for suicide increased significantly with decreasing SES in males, but not in females. The relationship of male suicide and SES was stronger when controlled for COB. For males, the relative risk of suicide, adjusted for age and COB, was 66% higher in the lowest SES quintile compared to the highest quintile, and 39% higher for youth (age 15-24 yr). For male suicide, the population attributable fraction for SES (less than the highest quintile) was 27%. Analysis of SES differentials in male suicide according to COB indicated a significant inverse suicide gradient in relation to SES for the Australian-born and those burn in New Zealand and the United Kingdom or fire. but not in non-English speaking COB groups, except for Asia. For Australian-born males, suicide risk was 71% higher in the lowest SES group (compared to the highest), adjusted for age. These findings indicate that SES plays an important role in male suicide rates among the Australian-born and migrants from English-speaking countries and Asia, and among youth; but not in female suicide, nor suicide in most non-English speaking migrant groups. Reduction in SES differentials through economic and social policies may reduce male suicide in lower SES groups and should be seen to be at least as important as individual level interventions. (C) 1998 Elsevier Science Ltd. All rights reserved.

Dehydromonocrotaline generates sequence-selective N-7 guanine alkylation and heat and alkali stable multiple fragment DNA crosslinks

Monocrotaline is a pyrrolizidine alkaloid known to cause toxicity in humans and animals. Its mechanism of biological action is still unclear although DNA crosslinking has been suggested to a play a role in its activity. In this study we found that an active metabolite of monocrotaline, dehydromonocrotaline (DHM), alkylates guanines at the N7 position of DNA with a preference for 5'-GG and 5'-GA sequences; In addition, it generates piperidine- and heat-resistant multiple DNA crosslinks, as confirmed by electrophoresis and electron microscopy. On the basis of these findings, we propose that DHM undergoes rapid polymerization to a structure which is able to crosslink several fragments of DNA.

Evidence of multiple transcription initiation and termination sites within the rDNA intergenic spacer and rRNA readthrough transcription in the urochordate Herdmania curvata

Analysis of the structure of the urochordate Herdmania curvata ribosomal DNA intergenic spacer (IGS) and its role in transcription initiation and termination suggests that rRNA gene regulation in this chordate differs from that in vertebrates. A cloned H, curvata IGS is 1881 bp and composed predominantly of two classes of similar repeat sequences that largely alternate in a tandem array. Southern blot hybridization demonstrates that the IGS length variation within an individual and population is largely the result of changes in internal repeat number. Nuclease S1 mapping and primer extension analyses suggest that there are two transcription initiation sites at the 3' end of the most 3' repetitive element; these sites are 6 nucleotides apart. Unlike mouse, Xenopus, and Drosophila, there is no evidence of transcription starting elsewhere in the IGS. Most sequence differences between the promoter repeat and the other internal repeats are in the vicinity of the putative initiation sites. As in Drosophila, nuclease S1 mapping of transcription termination sites suggest that there is not a definitive stop site and a majority of the pre-rRNAs read through a substantial portion of the IGS. Some transcription appears to proceed completely through the promoter repeat into the adjacent rDNA unit. Analysis of oocyte RNA by reverse transcription-polymerase chain reaction (RT-PCR) confirms that readthrough transcription into the adjacent rDNA unit is occurring in some small IGS length variants; there is no evidence of complete readthrough of IGSs larger than 1.0 kb.

Critical values for unit root and cointegration test statistics - the use of response surface equations

This note considers the value of surface response equations which can be used to calculate critical values for a range of unit root and cointegration tests popular in applied economic research.

Towards a validation of multiple features in the assessment of emotions

This study extends previous attempts to assess emotion with single adjective descriptors, by examining semantic as well as cognitive, motivational, and intensity features of emotions. The focus was on seven negative emotions common to several emotion typologies: anger, fear, sadness, shame, pity, jealousy, and contempt. For each of these emotions, seven items were generated corresponding to cognitive appraisal about the self, cognitive appraisal about the environment, action tendency, action fantasy, synonym, antonym, and intensity range of the emotion, respectively. A pilot study established that 48 of the 49 items were linked predominantly to the specific emotions as predicted. The main data set comprising 700 subjects' ratings of relatedness between items and emotions was subjected to a series of factor analyses, which revealed that 44 of the 49 items loaded on the emotion constructs as predicted. A final factor analysis of these items uncovered seven factors accounting for 39% of the variance. These emergent factors corresponded to the hypothesized emotion constructs, with the exception of anger and fear, which were somewhat confounded. These findings lay the groundwork for the construction of an instrument to assess emotions multicomponentially.

A numerical study of large sparse matrix exponentials arising in Markov chains

Krylov subspace techniques have been shown to yield robust methods for the numerical computation of large sparse matrix exponentials and especially the transient solutions of Markov Chains. The attractiveness of these methods results from the fact that they allow us to compute the action of a matrix exponential operator on an operand vector without having to compute, explicitly, the matrix exponential in isolation. In this paper we compare a Krylov-based method with some of the current approaches used for computing transient solutions of Markov chains. After a brief synthesis of the features of the methods used, wide-ranging numerical comparisons are performed on a power challenge array supercomputer on three different models. (C) 1999 Elsevier Science B.V. All rights reserved.AMS Classification: 65F99; 65L05; 65U05.

Optics of the developing fish eye: comparisons of Matthiessen's ratio and the focal length of the lens in the black bream Acanthopagrus butcheri (Sparidae, Teleostei)

Matthiessen's ratio (distance from centre of lens to retina: lens radius) was measured in developing black bream, Acanthopagrus butcheri (Sparidae, Teleostei). The value decreased over the first 10 days post-hatch from 3.6 to 2.3 along the nasal and from four to 2.6 along temporal axis. Coincidentally, there was a decrease in the focal ratio of the lens (focal length:lens radius). Morphologically, the accommodatory retractor lentis muscle appeared to become functional between 10-12 days post-hatch. The results suggest that a higher focal ratio compensates for the relatively high Matthiessen's ratio brought about by constraints of small eye size during early development. Combined with differences in axial length, this provides a means for larval fish to focus images from different distances prior to the ability to accommodate. (C) 1999 Elsevier Science Ltd. All rights reserved.