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Differential Analysis (differential + analysis)
Selected AbstractsWHAT SIN IS: A DIFFERENTIAL ANALYSISMODERN THEOLOGY, Issue 4 2009JESSE COUENHOVEN Sin is clearly evil, but what differentiates sin from evil? The idea that sin is moral evil is widely held, but important theological arguments have been posed against it. Theologians who reject sin moralism have, however, found it hard to distinguish sin from evil,partially because they share hidden assumptions with sin moralists. Helped by a philosophical theology of deep responsibility, I propound sin responsibilism: sin is culpable evil. This analysis of sin is open to multiple accounts of sin's relation to morality or theories of responsibility, and thus of sin's scope,but I defend a non-moralistic, compatibilist sin responsibilism. [source] Differential analysis of DNA microarray gene expression dataMOLECULAR MICROBIOLOGY, Issue 4 2003G. Wesley Hatfield Summary Here, we review briefly the sources of experimental and biological variance that affect the interpretation of high-dimensional DNA microarray experiments. We discuss methods using a regularized t -test based on a Bayesian statistical framework that allow the identification of differentially regulated genes with a higher level of confidence than a simple t -test when only a few experimental replicates are available. We also describe a computational method for calculating the global false-positive and false-negative levels inherent in a DNA microarray data set. This method provides a probability of differential expression for each gene based on experiment-wide false-positive and -negative levels driven by experimental error and biological variance. [source] Differential analysis of Bacillus anthracis after pX01 plasmid curing and comprehensive data on Bacillus anthracis infection in macrophages and glial cellsPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 20 2007Sung-Ha Park Abstract Bacillus anthracis is a gram-positive bacterial organism responsible for anthrax. This organism has two pathogenic plasmids: pX01 and pX02. The genetic function of pX01, which comprises about 198,kb, is not known, except for a region called the pathogenic island, which contains three genes,pag, lef, and cya,that code for three toxic proteins. A 2-D difference gel electrophoresis (2-D DIGE) system was used to verify the existence of proteins controlled by the pX01 plasmid, and protein regulation data were obtained using DeCyder software. A total of 1728 proteins were identified in the wild-type strain of this organism and 1684 in the pX01 plasmid. Twenty-seven of these proteins disappeared and eight appeared when the pX01 plasmid was removed. An additional 52 proteins were downregulated and 15 were upregulated when this plasmid was removed. A total of 102 proteins have been identified using the MALDI-TOF method of analysis, including 49 whose functions are unknown. Among these, 31 participate in metabolic processes, two in cellular processes, 15 in the processing of genetic information, and five in the processing of extracellular information. Another seven proteins participate in bacterial virulence and pathogenesis. We investigated the functions of these proteins in other bacteria, particularly the B. anthracis derivative H9041. Bacterial growth differed between pX01+/pX02+ B. anthracis and its pX01,/pX02+ derivative as did the cytotoxicity of macrophages infected by pX01+/pX02+ B. anthracis and the pX01,pX02+ derivative. We also found that S100B protein levels increased in the host infected with pX01+/pX02+ B. anthracis or its pX01,/pX02+ derivative. These data suggest that the pX01 plasmid plays a key role in the regulation of protein functions in B. anthracis. [source] Pedigree analysis of an elite rice hybrid using proteomic approachPROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 2 2006Zhensheng Xie Abstract The definition of dominance or epistasis is generally on the basis of a descriptive characterization for these crops in the field, such as yield per hectare and the weight of grain. Since these trait examinations lack molecular information, how to precisely predict the phenotypic changes in filial generation is still a problem in heterosis studies. For rice, the genetic information caused by hybridization can be archived through analyzing of proteomes of rice seeds. Differential analysis of proteomes was introduced for the rice seeds of three cultivars, 9311, PA64S and LYP9, an elite rice hybrid from cross between 9311 and PA64S. In the three rice endosperms, the expression profiles of proteins were similar with the stained spots of 47,±,1, 46,±,0.6 and 44,±,0.6, for 9311, PA64S and LYP9, respectively; however, the number of proteins expressed in the rice embryos was significantly increased with the stained spots of 395.3,±,12.9, 350,±,9.2, and 389.3,±,16.4, for 9311, PA64S and LYP9, respectively. Importantly, the image comparisons and protein identifications have revealed in significantly different embryo protein spots among the three rice cultivars. By carefully analyzing these different 2-DE spots, many of them from the three embryos were shown to display a mirrored relationships between parents and the first filial generation. Furthermore, all of stained spots in LYP9 embryo were found on the 2-DEs from its parents, indicating that there was a genetic linkage. These results suggest that proteomic approach is able to serve pedigree analysis and functional prediction for new rice breeds. [source] Dynamic urinary proteomic analysis reveals stable proteins to be potential biomarkersPROTEOMICS - CLINICAL APPLICATIONS, Issue 3 2009Wei Sun Abstract Human urinary proteome analysis is a convenient and efficient approach for understanding disease processes affecting the kidney and urogenital tract. Many potential biomarkers have been identified in previous differential analyses; however, dynamic variations of the urinary proteome have not been intensively studied, and it is difficult to conclude that potential biomarkers are genuinely associated with disease rather then simply being physiological proteome variations. In this paper, pooled and individual urine samples were used to analyze dynamic variations in the urinary proteome. Five types of pooled samples (first morning void, second morning void, excessive water-drinking void, random void, and 24,h void) collected in 1,day from six volunteers were used to analyze intra-day variations. Six pairs of first morning voids collected a week apart were used to study inter-day, inter-individual, and inter-gender variations. The intra-day, inter-day, inter-individual, and inter-gender variation analyses showed that many proteins were constantly present with relatively stable abundances, and some of these had earlier been reported as potential disease biomarkers. In terms of sensitivity, the main components of the five intra-day urinary proteomes were similar, and the second morning void is recommended for clinical proteome analysis. The advantages and disadvantages of pooling samples are also discussed. The data presented describe a pool of stable urinary proteins seen under different physiological conditions. Any significant qualitative or quantitative changes in these stable proteins may mean that such proteins could serve as potential urinary biomarkers. [source] Induced and repressed genes after irradiation sensitizing by pentoxyphylline,INTERNATIONAL JOURNAL OF CANCER, Issue 6 2007Waldemar Waldeck Abstract Aim in cancer therapy is to increase the therapeutic ratio eliminating the disease while minimizing toxicity to normal tissues. Radiation therapy is a main component in targeting cancer. Radiosensitizing agents like pentoxyphylline (PTX) have been evaluated to improve radiotherapy. Commonly, cells respond to radiation by the activation of specific early and late response genes as well as by inhibition of genes, which are expressed under normal conditions. A display of the genetic distinctions at the level of transcription is given here to characterize the molecular events underlying the radiosensitizing mechanisms. The method of suppression subtractive hybridization allows the visualization of both induced and repressed genes in irradiated cells compared with cells sensitized immediately after irradiation. The genes were isolated by cDNA-cloning, differential analysis and sequence similarity search. Genes involved in protein synthesis, metabolism, proteolysis and transcriptional regulation were detected. It is important that genes like KIAA280, which were only known as unidentified EST sequences before without function, but inaccessible by array technology were recovered as functional genes. Database searches for PTX-induced genes detected a human mRNA completely unknown. In case of suppressed genes, we detected several mRNAs; one thereof shows homology to a hypothetical protein possibly involved in signal transduction. A further mRNA encodes the protein BM036 supposed to associate with the E2F transcription factor. A hypothetical protein H41 was detected, which may repress the Her-2/neu receptor influencing breast cancer, gliomas and prostate tumors. Radiation combined with PTX may lead to a better prognosis by down regulation of the Her-2/neu, which will be proven by clinical studies in the near future. © 2006 Wiley-Liss, Inc. [source] A study of methods for evaluating the integrity of plate type heat exchangers used in the dairy industryINTERNATIONAL JOURNAL OF DAIRY TECHNOLOGY, Issue 1 2000A A DOWMAN An overview of leak testing methods for heat exchangers is presented. The problems associated with the presence of residual liquid during testing were assessed as it was shown experimentally that complete drainage of plate type heat exchangers is very difficult. A theoretical modelling of small leaks in heat exchanger plates was combined with laboratory experiments. The strengths and weaknesses of electrolytic differential analysis and helium leak detection methods are presented. The electrolytic differential analysis method is capable of detecting smaller leak volumes than the helium leak detection method, in the presence of water, assuming , 0.5 ,S/cm and 0.1 ppm helium detection limit for the former and latter cases respectively. The test pressure was shown to be a significant factor in the detection of very small holes; this was a particularly important criterion for gas based hole detection methods in the presence of water. [source] Improved detection of reactive metabolites with a bromine-containing glutathione analog using mass defect and isotope pattern matchingRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 9 2010André LeBlanc Drug bioactivation leading to the formation of reactive species capable of covalent binding to proteins represents an important cause of drug-induced toxicity. Reactive metabolite detection using invitro microsomal incubations is a crucial step in assessing potential toxicity of pharmaceutical compounds. The most common method for screening the formation of these unstable, electrophilic species is by trapping them with glutathione (GSH) followed by liquid chromatography/mass spectrometry (LC/MS) analysis. The present work describes the use of a brominated analog of glutathione, N -(2-bromocarbobenzyloxy)-GSH (GSH-Br), for the invitro screening of reactive metabolites by LC/MS. This novel trapping agent was tested with four drug compounds known to form reactive metabolites, acetaminophen, fipexide, trimethoprim and clozapine. Invitro rat microsomal incubations were performed with GSH and GSH-Br for each drug with subsequent analysis by liquid chromatography/high-resolution mass spectrometry on an electrospray time-of-flight (ESI-TOF) instrument. A generic LC/MS method was used for data acquisition, followed by drug-specific processing of accurate mass data based on mass defect filtering and isotope pattern matching. GSH and GSH-Br incubations were compared to control samples using differential analysis (Mass Profiler) software to identify adducts formed via the formation of reactive metabolites. In all four cases, GSH-Br yielded improved results, with a decreased false positive rate, increased sensitivity and new adducts being identified in contrast to GSH alone. The combination of using this novel trapping agent with powerful processing routines for filtering accurate mass data and differential analysis represents a very reliable method for the identification of reactive metabolites formed in microsomal incubations. Copyright © 2010 John Wiley & Sons, Ltd. [source] Screening for disulfide-rich peptides in biological sources by carboxyamidomethylation in combination with differential matrix-assisted laser desorption/ionization time-of-flight mass spectrometryRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 17 2001Susanne Neitz Peptides with biological functions often contain disulfide bridges connecting two cysteine residues. In an attempt to screen biological fluids for peptides containing cysteine residues, we have developed a sensitive and specific method to label cysteines selectively and detect the resulting molecular mass shift by differential mass spectrometry. First, reduction of disulfide bridges and carboxyamidomethylation of free thiols is adjusted to quantitatively achieve cysteine alkylation for complex peptide extracts. In a second step, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) before and after chemical derivatization is performed, followed by differential analysis to determine shifted peaks; shifted peaks belong to cysteine-containing peptides, other peaks remain unchanged. The number of cysteines can then be determined by the resulting molecular mass shift. Free, reduced cysteines are shifted by 57,u, two oxidized cysteines involved in disulfide bridges (cystine) result in a shift to higher mass per disulfide bridge of 116,u. Disulfide bridges connecting different amino acid chains like insulin break up during reduction. In this case, two peaks with lower molecular masses result from a single one in the unmodified sample. With this technique, we were able to identify cysteine-containing peptides and short fragments of proteins present in human blood filtrate. Copyright © 2001 John Wiley & Sons, Ltd. [source] On-Line HPLC-UV-mass spectrometry and tandem mass spectrometry for the rapid delineation and characterization of differences in complex mixtures: a case study using toxic oil variantsBIOMEDICAL CHROMATOGRAPHY, Issue 5 2002Frank W. Crow An integrated differential approach to the characterization of complex mixtures is presented which includes the targeting of liquid chromatography (LC) peaks for identification using characteristic UV adsorption of the LC peak, subsequent molecular weight and formula determination using accurate mass LC mass spectrometry (MS), and structure characterization using accurate mass LC-tandem mass spectrometry. The use of differential UV adsorption aids in narrowing the scope of the study to only specific peaks of interest. Accurate mass measurement of the molecular ion species provides molecular weight information as well as atomic composition information. The tandem MS (MS/MS) spectra provide fragmentation information which allows for structural characterization of each component. Accurate mass assignment of each of the fragment ions in the MS/MS spectrum provides atomic composition for each of the fragment ions and thus further aids in the structural characterization. These experiments are facilitated through the use of on-line LC-MS and LC-MS/MS with in-line UV detection. A synthetic toxic oil (STO) related to Toxic Oil Syndrome is studied with a focus on possible contaminants resulting from the interaction of aniline, used as a denaturant, with the normal components of the oil. A differential analysis between the STO and a control oil is performed. LC peaks were targeted using UV absorbance to indicate the possible presence of the aniline moiety. Further differential analysis was performed through the determination of the MS signals associated with each component separated on the LC. Finally, the MS/MS data was also used to determine if the fragmentation of the targeted components indicated the presence of aniline. The MS/MS and accurate mass data were used to assign the structures for the targeted components. Copyright © 2002 John Wiley & Sons, Ltd. [source] Good modeling practice for PAT applications: Propagation of input uncertainty and sensitivity analysisBIOTECHNOLOGY PROGRESS, Issue 4 2009Gürkan Sin Abstract The uncertainty and sensitivity analysis are evaluated for their usefulness as part of the model-building within Process Analytical Technology applications. A mechanistic model describing a batch cultivation of Streptomyces coelicolor for antibiotic production was used as case study. The input uncertainty resulting from assumptions of the model was propagated using the Monte Carlo procedure to estimate the output uncertainty. The results showed that significant uncertainty exists in the model outputs. Moreover the uncertainty in the biomass, glucose, ammonium and base-consumption were found low compared to the large uncertainty observed in the antibiotic and off-gas CO2 predictions. The output uncertainty was observed to be lower during the exponential growth phase, while higher in the stationary and death phases - meaning the model describes some periods better than others. To understand which input parameters are responsible for the output uncertainty, three sensitivity methods (Standardized Regression Coefficients, Morris and differential analysis) were evaluated and compared. The results from these methods were mostly in agreement with each other and revealed that only few parameters (about 10) out of a total 56 were mainly responsible for the output uncertainty. Among these significant parameters, one finds parameters related to fermentation characteristics such as biomass metabolism, chemical equilibria and mass-transfer. Overall the uncertainty and sensitivity analysis are found promising for helping to build reliable mechanistic models and to interpret the model outputs properly. These tools make part of good modeling practice, which can contribute to successful PAT applications for increased process understanding, operation and control purposes. © 2009 American Institute of Chemical Engineers Biotechnol. Prog., 2009 [source] | |||||||||||||