A mixture model-based approach to the clustering of microarray expression data

Motivation: This paper introduces the software EMMIX-GENE that has been developed for the specific purpose of a model-based approach to the clustering of microarray expression data, in particular, of tissue samples on a very large number of genes. The latter is a nonstandard problem in parametric cluster analysis because the dimension of the feature space (the number of genes) is typically much greater than the number of tissues. A feasible approach is provided by first selecting a subset of the genes relevant for the clustering of the tissue samples by fitting mixtures of t distributions to rank the genes in order of increasing size of the likelihood ratio statistic for the test of one versus two components in the mixture model. The imposition of a threshold on the likelihood ratio statistic used in conjunction with a threshold on the size of a cluster allows the selection of a relevant set of genes. However, even this reduced set of genes will usually be too large for a normal mixture model to be fitted directly to the tissues, and so the use of mixtures of factor analyzers is exploited to reduce effectively the dimension of the feature space of genes. Results: The usefulness of the EMMIX-GENE approach for the clustering of tissue samples is demonstrated on two well-known data sets on colon and leukaemia tissues. For both data sets, relevant subsets of the genes are able to be selected that reveal interesting clusterings of the tissues that are either consistent with the external classification of the tissues or with background and biological knowledge of these sets.

Molecular clocks in reptiles: Life history influences rate of molecular evolution

Life history has been implicated as a determinant of variation in rate of molecular evolution amongst vertebrate species because of a negative correlation between bode size and substitution rate for many Molecular data sets. Both the generality and the cause of the negative bode size trend have been debated, and the validity of key studies has been questioned (particularly concerning the failure to account for phylogenetic bias). In this study, a comparative method has been used to test for an association between a range of life-history variables-such as body size age at maturity, and clutch size-and DNA substitution rate for three genes (NADH4, cytochrome b, and c-mos). A negative relationship between body size and rate of molecular evolution was found for phylogenetically independent pairs of reptile species spanning turtles. lizards. snakes, crocodile, and tuatara. Although this Study was limited by the number of comparisons for which both sequence and lite-history data were available, the results, suggest that a negative bode size trend in rate of molecular evloution may be a general feature of reptile molecular evolution. consistent with similar studies of mammals and birds. This observation has important implications for uncovering the mechanisms of molecular evolution and warns against assuming that related lineages will share the same substitution rate (a local molecular clock) in order to date evolutionary divergences from DNA sequences.

Developmental expression of a class IV POU gene in the gastropod Haliotis asinina supports a conserved role in sensory cell development in bilaterians

POU-IV genes regulate neuronal development in a number of deuterostomes (chordates) and ecdysozoans (arthropods and nematodes). Currently their function and expression in the third bilaterian clade, the Lophotrochozoa, comprising molluscs, annelids and. their affiliates, is unclear. Herein we characterise the developmental expression of HasPOU-IV in the gastropod mollusc, Haliotis asinina. The POU-IV gene is transiently expressed in I I distinct larval territories during the first 3 days of development. HasPOU-IV is first expressed in sets of ventral epidermal cells in the newly hatched trochophore larvae. As larval morphogenesis proceeds, we observe HasPOU-IV transcripts in cells that putatively form a range of sensory systems including chemo- and mechanosensory cells in the foot, cephalic tentacles, the ctenidia. the geosensory statocyst and the eyes. By comparing HasPOU-IV expression with POU-IV genes in other bilaterians we infer that this class of POU-domain genes had an ancestral role in regulating sensory cell development.

An analysis of occupational outcomes for Indigenous and Asian employees in Australia

This paper examines occupational performance in Australia across three racial groups in Australia: Indigenous Australians; Asian people, defined as all those whose language spoken at home was either Chinese, Vietnamese or other forms of a South-east or East Asian language; and white people, defined as the residual category. The paper has as its starting point, observed differences in occupational attainment among the three groups in Australia and sets out to account for these observed differences on the basis of both race and non-racial attributes such as, age, education and area of residence.

Interactive expectations

In modeling expectation formation, economic agents are usually viewed as forming expectations adaptively or in accordance with some rationality postulate. We offer an alternative nonlinear model where agents exchange their opinions and information with each other. Such a model yields multiple equilibria, or attracting distributions, that are persistent but subject to sudden large jumps. Using German Federal Statistical Office economic indicators and German IFO Poll expectational data, we show that this kind of model performs well in simulation experiments. Focusing upon producers' expectations in the consumption goods sector, we also discover evidence that structural change in the interactive process occurred over the period of investigation (1970-1998). Specifically, interactions in expectation formation seem to have become less important over time.

Comparative analysis of genetic diversity in the mangrove species Avicennia marina (Forsk.) Vierh. (Avicenniaceae) detected by AFLPs and SSRs

Avicennia marina is an important mangrove species with a wide geographical and climatic distribution which suggests that large amounts of genetic diversity are available for conservation and breeding programs. In this study we compare the informativeness of AFLPs and SSRs for assessing genetic diversity within and among individuals, populations and subspecies of A. marina in Australia. Our comparison utilized three SSR loci and three AFLP primer sets that were known to be polymorphic, and could be run in a single analysis on a capillary electrophoresis system, using different-colored fluorescent dyes. A total of 120 individuals representing six populations and three subspecies were samplcd. At the locus level, SSRs were considerably more variable than AFLPs, with a total of 52 alleles and an average heterozygosity of 0.78. Average heterozygosity for AFLPs was 0.193, but all of the 918 bands scored were polymorphic. Thus, AFLPs were considerably more efficient at revealing polymorphic loci than SSRs despite lower average heterozygosities. SSRs detected more genetic differentiation between populations (19 vs 9%) and subspecies (35 vs 11%) than AFLPs. Principal co-ordinate analysis revealed congruent patterns of genetic relationships at the individual, population and subspecific levels for both data sets. Mantel testing confirmed congruence between AFLP and SSR genetic distances among, but not within, population comparisons, indicating that the markers were segregating inde- pendently but that evolutionary groups (populations and subspecies) were similar. Three genetic criteria of importance for defining priorities for ex situ collections or in situ conservation programs (number of alleles, number of locally common alleles and number of private alleles) were correlated between the AFLP and SSR data sets. The congruence between AFLP and SSR data sets suggest that either method, or a combination, is applicable to expanded genetic studies of mangroves. The codominant nature of SSRs makes them ideal for further population-based investigations, such as mating-system analyses, for which the dominant AFLP markers are less well suited. AFLPs may be particularly useful for monitoring propagation programs and identifying duplicates within collections, since a single PCR assay can reveal many loci at once.

Disease, habitat fragmentation and conservation

Habitat loss and the resultant fragmentation of remaining habitat is the primary cause of loss of biological diversity. How do these processes affect the dynamics of parasites and pathogens? Hess has provided some important insights into this problem using metapopulation models for pathogens that exhibit 'S-I' dynamics; for example, pathogens such as rabies in which the host population may be divided into susceptible and infected individuals. A major assumption of Hess's models is that infected patches become extinct, rather than recovering and becoming resistant to future infections. In this paper, we build upon this framework in two different ways: first, we examine the consequences of including patches that are resistant to infection; second, we examine the consequences of including a second species of host that can act as a reservoir for the pathogen. Both of these effects are likely to be important from a conservation perspective. The results of both sets of analysis indicate that the benefits of corridors and other connections that allow species to disperse through the landscape far outweigh the possible risks of increased pathogen transmission. Even in the commonest case, where harmful pathogens are maintained by a common reservoir host, increased landscape connectance still allows greater coexistence and persistence of a threatened or endangered host.

Partitioned Bremer support and multiple trees

Partitioned Bremer support (PBS) is a valuable means of assessing congruence in combined data sets, but some aspects require clarification. When more than one equally parsimonious tree is found during the constrained search for trees lacking the node of interest, averaging PBS for each data set across these trees can conceal conflict, and PBS should ideally be examined for each constrained tree. Similarly, when multiple most parsimonious trees (MPTs) are generated during analysis of the combined data, PBS is usually calculated on the consensus tree. However, extra information can be obtained if PBS is calculated on each of the MPTs or even suboptimal trees. (C) 2002 The Willi Hennig Society. Published by Elsevier Science (USA). All rights reserved.

Latin interchanges and direct products

In this paper we focus on the identification of latin interchanges in latin squares which are the direct product of latin squares of smaller orders. The results we obtain on latin interchanges will be used to identify critical sets in direct products. This work is an extension of research carried out by Stinson and van Rees in 1982.

Racialised schooling, 'ethnic success' and Asian-Australian students

Based on discussions with Asian-Australian young women at a mixed-sex, Australia State high school, this article argues that the pro-school conformity of Asian-Australian young women sets them in a problematic and precarious relationship to the material and symbolic and processes of racialisation. The first part of the article identifies the limitations of research into the pro-school/anti-school orientations of minority students, arguing that most accounts are based on theories of culture, acculturation, class and gender, and class and race that neglect an analysis of race and sex. I then argue that practices of racialisation and sexualisation actually sustain pro-school culture and Asian female group associations. While these formations are effective in securing Asian female educational success, they are also problematic because they limit the educational possibilities and employment opportunities of Asian young women in Australia.

Categorization and characterization of transcript-confirmed constitutively and alternatively spliced introns and exons from human

By spliced alignment of human DNA and transcript sequence data we constructed a data set of transcript-confirmed exons and introns from 2793 genes, 796 of which (28%) were seen to have multiple isoforms. We find that over one-third of human exons can translate in more than one frame, and that this is highly correlated with G+C content. Introns containing adenosine at donor site position +3 (A3), rather than guanosine (G3), are more common in low G+C regions, while the converse is true in high G+C regions. These two classes of introns are shown to have distinct lengths, consensus sequences and correlations among splice signals, leading to the hypothesis that A3 donor sites are associated with exon definition, and G3 donor sites with intron definition. Minor classes of introns, including GC-AG, U12-type GT-AG, weak, and putative AG-dependant introns are identified and characterized. Cassette exons are more prevalent in low G+C regions, while exon isoforms are more prevalent in high G+C regions. Cassette exon events outnumber other alternative events, while exon isoform events involve truncation twice as often as extension, and occur at acceptor sites twice as often as at donor sites. Alternative splicing is usually associated with weak splice signals, and in a majority of cases, preserves the coding frame. The reported characteristics of constitutive and alternative splice signals, and the hypotheses offered regarding alternative splicing and genome organization, have important implications for experimental research into RNA processing. The 'AltExtron' data sets are available at http://www.bit.uq.edu.au/altExtron/ and http://www.ebi.ac.uk/similar tothanaraj/altExtron/.

Ar-40/-Ar-39 geochronology at the Instituto de Geociencias, USP: instrumentation, analytical procedures, and calibration

Laser heating Ar-40/Ar-39 geochronology provides high analytical precision and accuracy, mum-scale spatial resolution. and statistically significant data sets for the study of geological and planetary processes, A newly commissioned Ar-40/Ar-39 laboratory at CPGeo/USP, Sao Paulo, Brazil, equips the Brazilian scientific community with a new powerful tool applicable to the study of geological and cosmochemical processes. Detailed information about laboratory layout, environmental conditions, and instrumentation provides the necessary parameters for the evaluation of the CPGeo/USp Ar-40/Ar-39 suitability to a diverse range of applications. Details about analytical procedures, including mineral separation, irradiation at the IPEN/CNEN reactor at USP, and mass spectrometric analysis enable potential researchers to design the necessary sampling and sample preparation program suitable to the objectives of their study. Finally, the results of calibration tests using Ca and K salts and glasses, international mineral standards, and in-house mineral standards show that the accuracy and precision obtained at the Ar-40/Ar-39 laboratory at CPGeo/USP are comparable to results obtained in the most respected laboratories internationally. The extensive calibration and standardization procedures under-taken ensure that the results of analytical studies carried out in our laboratories will gain immediate international credibility, enabling Brazilian students and scientists to conduct forefront research in earth and planetary sciences.

Reflections on onset-rime and phoneme sensitivity as predictors of beginning word reading

Rival claims have been made concerning the importance of rime sensitivity as a predictor of early word reading skill. Hulme et al. (2002) suggested that phoneme sensitivity is more strongly predictive of word reading ability than is onset-rime sensitivity. An examination of two independent data sets suggests that, although onset-rime sensitivity typically predicts school entrants' later word reading skill, phoneme sensitivity does predict more variation. However, multiple regression analyses do not reveal the level of phonological sensitivity that children need in order to understand alphabetic reading instruction. This issue is crucial to the detection of children at risk for reading failure and for the design of intervention programs for these children. A different analytic strategy is described for addressing this issue. (C) 2002 Elsevier Science (USA).

Testing the relationship between morphological and molecular rates of change along phylogenies

Molecular evolution has been considered to be essentially a stochastic process, little influenced by the pace of phenotypic change. This assumption was challenged by a study that demonstrated an association between rates of morphological and molecular change estimated for total-evidence phylogenies, a finding that led some researchers to challenge molecular date estimates of major evolutionary radiations. Here we show that Omland's (1997) result is probably due to methodological bias, particularly phylogenetic nonindependence, rather than being indicative of an underlying evolutionary phenomenon. We apply three new methods specifically designed to overcome phylogenetic bias to 13 published phylogenetic datasets for vertebrate taxa, each of which includes both morphological characters and DNA sequence data. We find no evidence of an association between rates of molecular and morphological rates of change.

Latent inhibition and schizophrenia: Pavlovian conditioning of autonomic responses

Latent inhibition (LI) is an important model for understanding cognitive deficits in schizophrenia, Disruption of LI is thought to result from an inability to ignore irrelevant stimuli. The study investigated LI in schizophrenic patients by using Pavlovian conditioning of electrodermal responses in a complete within-subject design. Thirty-two schizophrenic patients, ( 16 acute. unmedicated and 16 medicated patients) and 16 healthy control subjects (matched with respect to age and gender) participated in the study. The experiment consisted of two stages: preexposure and conditioning. During preexposure two visual stimuli were presented, one of which served as the to-be-conditioned stimulus (CSp +) and the other one was the not-to-be-conditioned stimulus (CSp -) during the following conditioning ( = acquisition). During acquisition. two novel visual stimuli (CSn + and CSn -) were introduced. A reaction time task was used as the unconditioned stimulus (US). LI was defined as the difference in response differentiation observed between proexposed and non-preexposed sets of CS + and CS -. During preexposure. the schizophrenic patients did not differ in electrodermal responding from the control subjects, neither concerning the extent of orienting nor the course of habituation. The exposure to novel stimuli at the beginning of the acquisition elicited reduced orienting responses in unmedicated patients compared to medicated patients and control subjects, LI was observed in medicated schizophrenic patients and healthy controls. but not in acute unmedicated patients. Furthermore LI was found to be correlated with the duration of illness: it was attenuated in patients who had suffered their first psychotic episode. (C) 2002 Elsevier Science B.V. All rights reserved.