Advances in manufacturing process technology are key ensembles for the production of integrated circuits in the sub-micrometer region. It is of paramount importance to assess the effects of tolerances in the manufacturing process on the performance of modern integrated circuits. The polynomial chaos expansion has emerged as a suitable alternative to standard Monte Carlo-based methods that are accurate, but computationally cumbersome. This paper provides an overview of the most recent developments and challenges in the application of polynomial chaos-based techniques for uncertainty quantification in integrated circuits, with particular focus on high-dimensional problems.

Abstract-We present a novel technique to perform variability analysis of multiport systems. The versatility of the proposed technique makes it suitable for the analysis of different types of modern electrical systems (e.g., interconnections, filters, connectors). The proposed method, based on the calculation of a set of univariate macromodels and on the use of the polynomial chaos expansion, produces a macromodel of the transfer function of the multiport system including its statistical properties. The accuracy and the significant speed up with respect to the classical Monte Carlo analysis are verified by means of two numerical examples.

1 The potency (pD2) and maximal contractile effect (Emax) of histamine, acetylcholine, carbachol and K+ were assessed from cumulative concentration-effect curves in guinea-pig isolated tracheal ring preparations with and without an intact epithelium. 3 Estimates of potency and Emax were also determined for the smooth muscle relaxants isoprenaline, forskolin and theophylline (which increase intracellular cyclic AMP) and for nitroglycerin (which increases cyclic GMP) in both intact and epithelium-stripped tracheal rings. The pD2 values for these relaxants were not significantly altered by the removal of the epithelium. However, with the exception of nitroglycerin, Emax values for these relaxants were significantly lower in stripped than in intact tracheal rings that had been maximally precontracted with carbachol. 4 The autoradiographic localisation of binding sites for the non-selective ,B-adrenoceptor ligand ['251]-iodocyanopindolol (I-CYP) showed that the epithelium ofthe guinea-pig trachea had a 75 ± 16% greater density of P-adrenoceptors than the smooth muscle. Removing the epithelium did not significantly alter either the density of smooth muscle binding sites or the affinity of I-CYP binding. It was concluded that the reduced functional response of guinea-pig trachea to isoprenaline was probably not due to smooth muscle P-adrenoceptor dysfunction.5 Results indicate that the epithelium plays an important roie in the modulation of responsiveness of guinea-pig trachea to histamine and relaxants that mediate their effects by selectively increasing intracellular cyclic AMP levels.

Pulmonary inflammation can contribute to the development of lung cancer in humans. We investigated whether pulmonary inflammation alters the genotoxicity of polycyclic aromatic hydrocarbons (PAHs) in the lungs of mice and what mechanisms are involved. To model nonallergic acute inflammation, mice were exposed intranasally to lipopolysaccharide (LPS; 20 µg/mouse) and then instilled intratracheally with benzo[a]pyrene (BaP; 0.5 mg/mouse). BaP-DNA adduct levels, measured by 32P-postlabeling analysis, were approximately 3-fold higher in the lungs of LPS/BaP-treated mice than in mice treated with BaP alone. Pulmonary Cyp1a1 enzyme activity was decreased in LPS/BaP-treated mice relative to BaP-treated mice suggesting that pulmonary inflammation impacted on BaP-induced Cyp1a1 activity in the lung. Our results showed that Cyp1a1 appears to be important for BaP detoxification in vivo and that the decrease of pulmonary Cyp1a1 activity in LPS/BaP-treated mice results in a decrease of pulmonary BaP detoxification, thereby enhancing BaP genotoxicity (ie, DNA adduct formation) in the lung. Because less BaP was detoxified by Cyp1a1 in the lungs of LPS/BaP-treated mice, more BaP circulated via the blood to extrapulmonary tissues relative to mice treated with BaP only. Indeed, we observed higher BaP-DNA adduct levels in livers of LPS/BaP-treated mice compared with BaP-treated mice. Our results indicate that pulmonary inflammation could be a critical determinant in the induction of genotoxicity in the lung by PAHs like BaP. Cyp1a1 appears to be involved in both BaP bioactivation and detoxification although the contribution of other enzymes to BaP-DNA adduct formation in lung and liver under inflammatory conditions remains to be explored.

1 The endogenous cannabinoid agonist, anandamide produced a modest contractile response in guinea-pig isolated bronchus compared with the vanilloid receptor agonist capsaicin. The contractile response to both anandamide and capsaicin was inhibited by the vanilloid receptor antagonist, capsazepine. Furthermore, the NK 2 -selective antagonist, SR48968 but not the NK 1 -selective antagonist, SR140333 inhibited contractile responses to anandamide. 2 The contractile response to anandamide was abolished in tissues desensitized by capsaicin. However, anandamide failed to cross-desensitize the contractile response to capsaicin. 3 The contractile response to anandamide was not signi®cantly altered in the presence of the CB 1 receptor antagonist, SR141716A, nor the amidase inhibitor, phenylmethylsulphonyl¯uoride (PMSF) but was signi®cantly increased in the presence of the neutral endopeptidase inhibitor, thiorphan. 4 The cannabinoid agonist, CP55,940 failed to signi®cantly attenuate the excitatory non-adrenergic non-cholinergic (eNANC) response in guinea-pig airways. In contrast, the ORL 1 receptor agonist, nociceptin, signi®cantly inhibited this response. 5 The results demonstrate that anandamide induces a modest contractile response in guinea-pig isolated bronchus that is dependent upon the activation of vanilloid receptors on airway sensory nerves. However, cannabinoid receptors do not appear to play a role in this regard, nor in regulating the release of neuropeptides from airway sensory nerves under physiological conditions.