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Mutations in human genes are often associated with disease or altered gene expression level, which in turn influences a variety of biological functions. Thus, finding a mutation of a given gene from a large dataset of sequence variants is crucial for finding a potential disease-related gene. Over the past few decades, statistical methods have been developed to measure the effect of a single nucleotide variant on gene expression level. However, most of these methods, which include linear regression, logistic regression and ordinary t-statistics, have the limitation of being incapable of handling large-scale gene expression data. Hence, there is an urgent need for developing alternative analysis methods to enhance the analysis power of gene expression data. In this study, we developed a novel analysis method called linear adaptive regression (LAR), which can effectively measure the effect of a single nucleotide variant on gene expression level from the large-scale gene expression data. Instead of using a large set of single nucleotide variants to explore the effect of the mutation, LAR models the relationship between single nucleotide variants and gene expression levels using a linear regression model. A modified t-statistic is introduced for model testing, which is capable of handling the large-scale gene expression data and the large number of tests in functional genomics studies. We also proposed a multiple testing correction strategy, which includes two main phases to control the false discovery rate: controlling the false discovery rate at the level of genes and controlling the false discovery rate at the level of single nucleotide variants. The performance of LAR is compared with two other methods (sparse linear regression, logistic regression and ordinary t-statistics), using real and simulated data. Using both real and simulated data, we show that LAR is capable of modeling the relationship between single nucleotide variants and gene expression levels, while keeping the statistical power as high as logistic regression and ordinary t-statistics. Compared with standard linear regression, the multiple testing correction in the variant-level test of LAR, which controls the false discovery rate at the level of individual single nucleotide variants, is more power-efficient. Furthermore, LAR is
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A cDNA library from Theileria annulata sporozoites was constructed by using oligo-dT primed reverse transcription of poly(A)+RNA followed by PCR amplification. The cloned cDNA was characterized using 5′ and 3′ rapid amplification of cDNA ends (RACE). This cDNA had an open reading frame of 1072 bp encoding a 37.3 kDa protein of 372 amino acids, the deduced amino acid sequence of which shares 84% identity with the recently identified Theileria bovis P67 antigen. The mature protein contains a putative hydrophobic signal sequence, a single transmembrane domain and a glycosylphosphatidylinositol (GPI) anchor, and has a molecular weight of 42-46 kDa in immunoblots of a detergent soluble T. annulata sporozoite extract. Recombinant parasite transgenic expressing a GPI-anchored T. annulata protein showed no growth inhibition to the cultured cells. The immunogenicity of this cDNA cloned from the Theileria parasite was compared with that of a recombinant protein by stimulating the secretion of gamma interferon (IFN-gamma) by rat splenocytes. Both T. annulata cDNA and recombinant P67 protein could be used to stimulate IFN-gamma production. The mean concentration of IFN-gamma induced by recombinant T. annulata protein was five-fold greater than that induced by cDNA. This level of IFN-gamma production was significantly higher than that obtained with a weakly immunogenic (19 kDa) recombinant Theileria perspecsa protein.Q:
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Much research has been carried out in the field of membrane filtration to extend the capabilities of existing membrane technologies, e.g. reverse osmosis and nanofiltration. Major progress has been made but practical methods of producing membranes with ultra small pores have not yet been developed. Theoretically ultra small pores could be produced by etching pore-deterioration away from the pore surfaces, but in practice this has not been possible with any degree of repeatability.
Much progress has been made by the addition of small amounts of solids to the base fluid to swell the pores and produce a skin or layer of impurities or filter cake. This layer prevents the passage of smaller particles into the membrane. However, large particles also cause a thick layer to form and this has to be removed by filtration until the normal size of the particles is reached. The time required to obtain this critical size may be very long and it may also take a lot of pressure to remove the layer.
Therefore, it is one object of the invention to provide a faster method of producing ultra small pores.
It is another object of the invention to provide a method of producing ultra small pores which is substantially more economical than presently used methods.
It is still another object of the invention to provide a method of producing ultra small pores which does not require a large applied pressure.
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