Independent component analysis: A flexible nonlinearity and decorrelating manifold approach

Independent component analysis (ICA) finds a linear transformation to variables that are maximally statistically independent. We examine ICA and algorithms for finding the best transformation from the point of view of maximizing the likelihood of the data. In particular, we discuss the way in which scaling of the unmixing matrix permits a "static" nonlinearity to adapt to various marginal densities. We demonstrate a new algorithm that uses generalized exponential functions to model the marginal densities and is able to separate densities with light tails. We characterize the manifold of decorrelating matrices and show that it lies along the ridges of high-likelihood unmixing matrices in the space of all unmixing matrices. We show how to find the optimum ICA matrix on the manifold of decorrelating matrices, and as an example we use the algorithm to find independent component basis vectors for an ensemble of portraits.     

ECOLOGICAL RISK-ASSESSMENT METHODOLOGY: A UK CASE STUDY FOR LANDFILLS

The paper presents an ecological risk-assessment methodology which (a) addresses surface-water exposures to aquatic mammals and birds, and (b) accounts for long-term accumulation and biomagnification of pollutants. The methodology has been adapted from those developed in the USA for compliance with US Environmental Protection Agency requirements, and combines predicted or measured surface-water concentration data with information on the natural history of wildlife species and chemical-specific bioaccumulation factors, to determine whether estimated exposures would exceed toxicological criteria. Whilst the methodology is applied to metals in leachate discharges from landfill sites, the general approach is applicable to other industrial sites. The approach could provide the basis for a shift towards more numerical risk-based ecological assessments in a wide variety of contexts.     

Silicon and aluminium interactions in haemodialysis patients

BACKGROUND: Aluminium toxicity in dialysis patients is well described. Aluminium has a close chemical affinity with silicon. Silicon may have a role in protection against aluminium toxicity. METHODS: We measured serum aluminium and silicon levels from haemodialysis patients from four different centres. RESULTS: Though no relationship was seen across all centres combined, in one centre there was a reciprocal relationship in patients on home haemodialysis (who did not require reverse osmosis). Median (range) aluminium levels were higher, 2.2 (0.4-9.6) micromol/l when serum silicon was less than 150 micromol/l, and lower, 1.1 (0.2-2.8) micromol/l when serum silicon levels were greater than 150 micromol/l (P = 0.03). CONCLUSIONS: In patients treated by haemodialysis without reverse osmosis high serum silicon concentrations were associated with lower serum aluminium concentrations than those with low serum silicon. Further work needs to confirm a preventative role for silicon in the accumulation and subsequent toxicity of aluminium in dialysis patients.     

Estrous cycle effects on operant responding for ethanol in female rats

Human females have been reported to be uniquely sensitive to the deleterious effects of ethanol, thus it is important to study the characteristics of and mechanisms underlying alcohol consumption that may be specific to females. Models of ethanol self-administration in female rats that take into consideration the estrous cycle have the potential to provide important information concerning these characteristics and mechanisms. The purpose of this study was to explore the effect of the cycle on ethanol self-administration using a limited access operant paradigm. Female Wistar rats were trained to lever press for 10% ethanol versus water using a saccharin fading procedure. Responses were examined across the four phases of the estrous cycle. No effects of estrous cycle phase were observed when these rats were allowed to cycle freely. Subsequently, estrous phase effects were investigated in females whose cycles had been synchronized. Under this condition, an effect of estrous phase was present, with lower ethanol intake observed in estrus (and in some cases proestrus). Synchronized rats all showed at least one very clear 4-day estrous cycle, whereas free-running rats' cycles ranged from 3 to 5 days. Thus, it is more likely that synchronized rats were tested in the identical portion of each phase, when hormone levels were less variable. These results suggest that ethanol may be more reinforcing during diestrus than proestrus and estrus in female rats.     

Computerized documentation for a rural nursing intervention project

Complex traits are generally taken to be under the influence of multiple genes, which may interact with each other to confer susceptibility to disease. Statistical methods in current use for localizing such genes essentially work under single-gene models, either implicitly or explicitly. In genomic screens for complex disease genes, some of the marker loci must be in tight linkage with disease susceptibility genes. We developed a general multi-locus approach to identify sets of such marker loci. Our approach focuses on affected sib pair data and employs a nonparametric pattern recognition technique using artificial neural networks. This technique analyzes all markers simultaneously in order to detect patterns of locus interactions. When applied to previously published sib pair data on type I diabetes, our approach finds the same genes as in the published report in addition to some new loci. For a specific two-locus model of inheritance, the power of our approach is higher than that of the currently used analysis standard.     

Solution structure of the motile major sperm protein (MSP) of Ascaris suum - evidence for two manganese binding sites and the possible role of divalent cations in filament formation

The major sperm protein (MSP) of Ascaris suum mediates amoeboid motility by forming an extensive intermeshed system of cytoskeletal filaments analogous to that formed by actin in many other amoeboid cells. MSP is a dimeric molecule that polymerizes to form non-polar filaments constructed from two helical subfilaments that wind round one another. Moreover, MSP filaments can interact with one another to form higher-order assemblies without requiring the range of accessory proteins usually employed in actin-based systems. A knowledge of how MSP polymerizes and forms the hierarchical series of helical MSP macromolecular assemblies is fundamental to understanding locomotion in these cells. Here we describe the solution structure of MSP dimers determined by NMR spectroscopy under conditions where MSP does not polymerize to form filaments. The solution structure is indistinguishable from that observed in putative MSP subfilament helices by X-ray crystallography, indicating that MSP polymerization is not accompanied by a major conformational change. We also show that the rate of MSP polymerization associated with movement of vesicles in an in vitro motility assay is enhanced by the presence of magnesium and manganese ions and use NMR to show that the primary residues that bind these ions are 24-25 and 83-86. These residues are distant from the interface formed between MSP dimers in subfilament helices, and so are probably not involved in this level of polymerization. Instead the manganese and magnesium ion binding appears to be associated with the assembly of subfilaments into filaments and their subsequent aggregation into bundles.     

The relation between arterial oxygen tension and cerebral blood flow during cardiopulmonary bypass

BACKGROUND: The precise mechanisms involved in islet xenograft rejection remain unknown. The purpose of the present study was to determine cellular mechanisms responsible for islet xenograft rejection in the liver to facilitate finding a procedure for prevention of immune rejection. METHODS: Hepatic mononuclear cells (MNC) as well as splenocytes, peripheral blood MNC, and thymocytes from streptozotocin-induced diabetic mice (BALB/c) rejecting the intrahepatic rat (Lewis) islet xenografts were isolated and examined by two-color FACS analysis. RESULTS: The characteristic finding of the hepatic MNC from the mice rejecting islet xenografts compared with mice receiving isografts was a significant increase in the yield as well as in the percentage of the cells expressing CD3+ interleukin-2 receptor (IL-2R) alpha- beta+, CD3+ CD8alpha+ beta+, and T cell receptor (TCR) alphabeta+ lymphocyte function-associated antigen-1+. The expression of CD3 and TCR alphabeta of these T cells was found to be of intermediate intensity (TCR(int) cells). The expansion of these TCR(int) cells occurred predominantly in the liver. There was no significant difference in the cells expressing CD3+ IL-2R alpha+, CD3+ CD4+, CD3+ TCRgammadelta+, CD3- IL-2Rbeta+ (natural killer cells), and B220+ (B cells). In vivo administration of anti-IL-2Rbeta monoclonal antibody directed to the expanded cells produced a prevention of rejection. CONCLUSIONS: These findings suggest that islet xenograft rejection in the liver from rat to mouse is an event for which the TCR(int) cells are responsible.