PXR

Ratio of Zwittbrion Form to Hydroxy Form (pXr) fob Pyridines and Azines in Which a Benzo Ring Carries a Hydroxyl Group... 

Nuclear Receptor Regulation of Hepatic Cytochrome P450 Enzymes. Figure 1 General mechanism for transcriptional activation of CYP genes by xenochemicals that activate their cognate xeno-receptor proteins. In the case of Ah receptor, the receptor s heterodimerization partner is Arnt, whereas in the case of the nuclear receptors CAR, PXR, and PPARa, the heterodimerization partner is RXR. The coactivator and basal transcription factor complexes shown are each comprised of a large number of protein components. 

Stanley LA, Horsburgh BC, Ross J et al (2006) PXR and CAR nuclear receptors which play a pivotal role in drug disposition and chemical toxicity. Drug Metab Rev 38 515-597... 

Chang TKH, Waxman DJ (2006) Synthetic drugs and natural products as modulators of constitutive androstane receptor (CAR) and pregnane X receptor (PXR). Drug Metab Rev 38 51-73... 

Potassium Competitive Acid Blockers The pregnane X receptor (PXR) is a promiscuous nuclear receptor, that has evolved to protect the body from toxic chemicals. It is activated by a wide variety of xenobiotics including several diugs like rifampicin, hyperforin ( the active ingredient of St. John s wort), clotrimazole and others. PXR heterodimerizes with the... 

Proton Pump Inhibitors and Acid Pump Antagonists retinoid X receptor (RXR) and is also activated by various lipophilic compounds produced by the body such as bile acids and steroids. PXR heterodimerized with RXR stimulates the transcription of cytochrome P450 3A monooxygenases (CYP3A) and other genes involved in the detoxification and elimination of the... 

PP potentially harmful substances. PXR appears to be the key regulator of CYP3A induction by xenobiotics. 

Gene regulation by tocopherols has mainly been associated with PKC because of its deactivation by a-tocopherol and its contribution in the regulation of a number of transcription factors (NF-kappaB, API). A direct participation of the pregnane X receptor (PXR)/ retinoid X receptor (RXR) has been also shown. The antioxidant-responsive element (ARE) and the TGF-beta-responsive element appear in some cases to be implicated as well. The obser ved immunmodulatory function of a-tocopherol may also be attributed to the fact that the release of the proinflammatory cytokine interlukin-l 3 can be inhibited by a-tocopherol via... 

Four years after Doering s discovery of the hygroscopic bromide of the tropylium ion [3" ] (Doering and Knox, 1954), Vol pin et al. (1957) reported that the tropylium ion (pXr+ 3.88) gives a covalent compound with acetate ion (pXb 9.24) but not with isocyanate ion (pK 10.1). This suggests that an anion with pXb greater than 10.1 would give a salt with the tropylium ion. 

Thus far we have considered the eigenvalue decomposition of a symmetric matrix which is of full rank, i.e. which is positive definite. In the more general case of a symmetric positive semi-definite pxp matrix A we will obtain r positive eigenvalues where r general case we obtain a pxr matrix of eigenvectors V such that ... 

It should be noted that in the case of a singular matrix A, the dimensions of V and A are pxr and rxr, respectively, where r is smaller than p. The expression in eq. (29.53) allows us to compute the generalized inverse, specifically the Moore-Penrose inverse, of a symmetric matrix A from the expression ... 

In the previous section we have developed principal components analysis (PCA) from the fundamental theorem of singular value decomposition (SVD). In particular we have shown by means of eq. (31.1) how an nxp rectangular data matrix X can be decomposed into an nxr orthonormal matrix of row-latent vectors U, a pxr orthonormal matrix of column-latent vectors V and an rxr diagonal matrix of latent values A. Now we focus on the geometrical interpretation of this algebraic decomposition. 

In this case, the nxpxq three-way table X is decomposed into the nxr, pxr, qxr loading matrices A, B, C for the row-, column- and layer-items of X. 

From the latent vectors and singular values one can compute the nxr generalized score matrix S and the pxr generalized loading matrix L. These matrices contain the coordinates of the rows and columns in the space spanned by the latent vectors ... 

The application of principal components regression (PCR) to multivariate calibration introduces a new element, viz. data compression through the construction of a small set of new orthogonal components or factors. Henceforth, we will mainly use the term factor rather than component in order to avoid confusion with the chemical components of a mixture. The factors play an intermediary role as regressors in the calibration process. In PCR the factors are obtained as the principal components (PCs) from a principal component analysis (PC A) of the predictor data, i.e. the calibration spectra S (nxp). In Chapters 17 and 31 we saw that any data matrix can be decomposed ( factored ) into a product of (object) score vectors T(nxr) and (variable) loadings P(pxr). The number of columns in T and P is equal to the rank r of the matrix S, usually the smaller of n or p. It is customary and advisable to do this factoring on the data after columncentering. This allows one to write the mean-centered spectra Sq as ... 

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