Improved Principal Component Monitoring of Large-Scale Processes

This is the first paper that shows and theoretically analyses that the presence of auto-correlation can produce considerable alterations in the Type I and Type II errors in univariate and multivariate statistical control charts. To remove this undesired effect, linear inverse ARMA filter are employed and the application studies in this paper show that false alarms (increased Type I errors) and an insensitive monitoring statistics (increased Type II errors) were eliminated.

Introduction of a Nonlinearity Measure for Principal Component Models

This is the first paper that introduces a nonlinearity test for principal component models. The methodology involves the division of the data space into disjunct regions that are analysed using principal component analysis using the cross-validation principle. Several toy examples have been successfully analysed and the nonlinearity test has subsequently been applied to data from an internal combustion engine.

Nitric Oxide Produced in Response to Engagement of beta 2 Integrins on Human Neutrophils Activates the Monomeric GTPases Rap1 and Rap2 and Promotes Adhesion

We found that engagement of beta 2 integrins on human neutrophils increased the levels of GTP-bound Rap1 and Rap2. Also, the activation of Rap1 was blocked by PP1, SU6656, LY294002, GF109203X, or BAPTA-AM, which indicates that the downstream signaling events in Rap1 activation involve Src tyrosine kinases, phosphoinositide 3-kinase, protein kinase C, and release of calcium. Surprisingly, the integrin-induced activation of Rap2 was not regulated by any of the signaling pathways mentioned above. However, we identified nitric oxide as the signaling molecule involved in beta 2 integrin-induced activation of Rap1 and Rap2. This was illustrated by the fact that engagement of beta 2 integrins increased the production of nitrite, a stable end-product of nitric oxide. Furthermore, pretreatment of neutrophils with N-monomethyl-L-arginine, or 1400W, which are inhibitors of inducible nitric-oxide synthase, blocked integrin-induced activation of Rap1 and Rap2. Similarly, Rp-8pCPT-cGMPS, an inhibitor of cGMP-dependent serine/threonine kinases, also blunted the integrin-induced activation of Rap GTPases. Also nitric oxide production and its downstream activation of cGMP-dependent serine/threonine kinases were essential for proper neutrophil adhesion by beta 2 integrins. Thus, we made the novel findings that beta 2 integrin engagement on human neutrophils triggers production of nitric oxide and its downstream signaling is essential for activation of Rap GTPases and neutrophil adhesion.

Th2 lymphoproliferative disorder of LatY136F mutant mice unfolds independently of TCR-MHC engagement and is insensitive to the action of Foxp3+ regulatory T cells.

Mutant mice where tyrosine 136 of linker for activation of T cells (LAT) was replaced with a phenylalanine (Lat(Y136F) mice) develop a fast-onset lymphoproliferative disorder involving polyclonal CD4 T cells that produce massive amounts of Th2 cytokines and trigger severe inflammation and autoantibodies. We analyzed whether the Lat(Y136F) pathology constitutes a bona fide autoimmune disorder dependent on TCR specificity. Using adoptive transfer experiments, we demonstrated that the expansion and uncontrolled Th2-effector function of Lat(Y136F) CD4 cells are not triggered by an MHC class II-driven, autoreactive process. Using Foxp3EGFP reporter mice, we further showed that nonfunctional Foxp3(+) regulatory T cells are present in Lat(Y136F) mice and that pathogenic Lat(Y136F) CD4 T cells were capable of escaping the control of infused wild-type Foxp3(+) regulatory T cells. These results argue against a scenario where the Lat(Y136F) pathology is primarily due to a lack of functional Foxp3(+) regulatory T cells and suggest that a defect intrinsic to Lat(Y136F) CD4 T cells leads to a state of TCR-independent hyperactivity. This abnormal status confers Lat(Y136F) CD4 T cells with the ability to trigger the production of Abs and of autoantibodies in a TCR-independent, quasi-mitogenic fashion. Therefore, despite the presence of autoantibodies causative of severe systemic disease, the pathological conditions observed in Lat(Y136F) mice unfold in an Ag-independent manner and thus do not qualify as a genuine autoimmune disorder.

Improved Process Monitoring Using Nonlinear Principal Component Models

This paper presents two new approaches for use in complete process monitoring. The firstconcerns the identification of nonlinear principal component models. This involves the application of linear
principal component analysis (PCA), prior to the identification of a modified autoassociative neural network (AAN) as the required nonlinear PCA (NLPCA) model. The benefits are that (i) the number of the reduced set of linear principal components (PCs) is smaller than the number of recorded process variables, and (ii) the set of PCs is better conditioned as redundant information is removed. The result is a new set of input data for a modified neural representation, referred to as a T2T network. The T2T NLPCA model is then used for complete process monitoring, involving fault detection, identification and isolation. The second approach introduces a new variable reconstruction algorithm, developed from the T2T NLPCA model. Variable reconstruction can enhance the findings of the contribution charts still widely used in industry by reconstructing the outputs from faulty sensors to produce more accurate fault isolation. These ideas are illustrated using recorded industrial data relating to developing cracks in an industrial glass melter process. A comparison of linear and nonlinear models, together with the combined use of contribution charts and variable reconstruction, is presented.