Data sources and processing The changes in gene expression in response to the addition of various compounds to Arabidopsis suspension cells were measured as outlined previously [32]. Data for the addition of chitin to 50 mg mL Sigma, Sydney ; and flagellen22 peptide to 1 M Auspep, Parkville, Victoria ; are included here and arrays were carried out as described in Clifton et al. 2005 [32]. Average gene expression levels were calculated across replicate chips; in each case, a minimum of two replicates was available. For each experimental variable or time point, the log ratio of expression under experimental conditions to appropriate control conditions was determined for each gene. These log ratios formed the input for ModuleFinder and CoReg analysis. Only a subset of the 22, 000 genes on the Affymetrix gene chips were analyzed in the examples presented here. This gene subset comprised 374 genes, derived from a set of proteins identified in isolated Arabidopsis mitochondria by liquid chromatography-tandem mass spectrometry [30]. For CoReg analysis, promoter sequences were taken as the 3000 base-pair sequences upstream of each gene, retrieved from TAIR. Programming in R ModuleFinder and CoReg were developed in R, a computer language and environment for statistical computing [57]. An advantage of R is that it is available as free software and runs on a wide variety of UNIX platforms and similar systems, Windows and MacOS. Most importantly R provides a variety of built-in statistical and graphical techniques, including a variety of cluster analysis methods and facilities for displaying cluster trees and heat maps, while also allowing users to extend R's capabilities by defining their own functions. Statistical methods used in ModuleFinder ModuleFinder filters out the genes whose expression did not change under all experiments in the initial subset. This is done by considering a matrix of p-values provided by the user, which reflects the results of a test for differential expression including correction for multiple testing if appropriate ; , and filtering out all genes whose p-values are above a user-defined cut-off in any of the experiments in the subset. The default p-value cut-off is 0.05, but can be set by the user to any value between zero and one. In the examples presented here, the p-values used were derived from two-sided t-tests comparing the robust multiarray analysis-processed expression measures from replicates of control and experimental conditions [5]. In each case, a minimum of two replicates was available. Note: this drug has the potential for significant infusion-related side effects, and the complete prescribing information should be reviewed before use in a particular patient. Rheumatoid arthritis RA ; is a debilitating autoimmune disease that affects more than 2 million Americans. Rituxan is a genetically-engineered therapeutic antibody rituximab ; that was initially approved in 1997 for treatment of certain types of non-Hodgkins lymphoma NHL ; . It was FDA-approved in May 2006, in combination with methotrexate, for the treatment of moderate to severe RA in adult patients who have had an inadequate response to one or more tumor necrosis factor antagonist therapies such as Humira, Enbrel, or Remicade. The phase 3 "REFLEX" clinical trial was the basis for the FDA's decision. Patients in this trial who received Rituxan had significant improvement in joint pain, inflammation and physical function at 24 weeks as compared to placebo ; from a single course of therapy 2 infusions ; , along with a stable dose of methotrexate. Rituxan binds to the antigen CD20, and selectively targets immune cells known as CD20-positive B-cells; it does not target stem cells or existing plasma cells. This drug may affect multiple pathways by which B-cells may contribute to the onset and progression of RA. It is the only agent with this mechanism of action that is approved for RA. Infusion-related reactions: "Black Box" warning It should be noted that extremely serious infusion reactions have been reported with Rituxan, some with fatal outcomes. The most severe symptoms of infusion-related reactions were pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, and anaphylactic-type reactions. In reported cases, the following factors were more frequently associated with fatal outcomes: female gender, pulmonary infiltrates, and chronic lymphocytic leukemia or mantle cell lymphoma. Most patients experience some type of infusion-related symptoms with their first Rituxan infusion. Such reactions may occur within 30-120 minutes of the start of the first dose, which should be infused in a hospital or clinic setting where medical intervention is readily available. These symptoms could include flulike illness, chills rigors, nausea, urticaria, headache, bronchospasm, angioedema, hypotension, and hypoxia. These symptoms vary in their severity and are generally reversible with medical intervention. Less than 1 percent of acute infusion reactions were judged to be serious in the REFLEX trial. Another potentially significant side effect of Rituxan is hypotension, which may occur during the infusion; therefore, it is recommended that antihypertensive agents be held for 12 hours prior to each dose. Also, about 5% of Rituxan-treated patients may develop anti-chimeric antibodies. The current recommended dose for RA is one treatment course, consisting of two 1000 mg IV infusions separated by 2 weeks, in combination with methotrexate. Solu-Medrol 100 mg IV or equivalent ; is given as a pre-infusion medication 30 minutes before each Rituxan dose. The safety and effectiveness of additional Rituxan doses has not been established; a few patients have received additional courses, but none received subsequent courses sooner than 16 weeks after the previous course and most had subsequent courses 24 weeks after the previous one. Further research may clarify the appropriate use of additional doses in RA patients. Rituxan is also being studied for treatment of other autoimmune diseases, including lupus nephritis, systemic lupus erythematosus SLE ; , and multiple sclerosis MS and rosuvastatin.
2-30 nL is typically injected into the capillary. sequently, five CE analyses 30 nL per injection ; Subof a.

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