1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine as a substrate of cytochrome P450 2D6: allosteric effects of NADPH-cytochrome P450 reductase

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that produces Parkinsonism symptoms in man, has been examined as a substrate of recombinant human cytochrome P450 2D6. When cumene hydroperoxide is used as an oxygen and electron donor, a single product is formed, identified as 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) for formation of this product (130 microM) is in agreement with the dissociation constants for MPTP binding to the enzyme determined by optical and nuclear magnetic resonance (NMR) spectroscopy. When the reaction is carried out with nicotinamide adenine dinucleotide phosphate (reduced) (NADPH) and recombinant human NADPH-cytochrome P450 reductase, a second product, identified as 1-methyl-4-(4'-hydroxyphenyl)-1,2,3,6-tetrahydropyridine, is formed in addition to 4-phenyl-1,2,3,6-tetrahydropyridine. The K(m) values for formation of these two products are 19 microM and 120 microM, respectively. Paramagnetic relaxation experiments have been used to measure distances between the protons of bound MPTP and the heme iron, and these have been used to construct models for the position and orientation of MPTP in the active site. For the cytochrome alone, a single mode of binding was observed, with the N-methyl close to the heme iron in a position appropriate for the observed N-demethylation reaction. In the presence of the reductase, the data were not consistent with a single mode of binding but could be explained by the existence of two alternative orientations of MPTP in the active site. One of these, characterized by a dissociation constant of 150 microM, is essentially identical to that observed in the absence of the reductase. In the second, which has a K(d) of 25 microM, the MPTP is oriented so that the aromatic ring is close to the heme iron, in a position appropriate for p-hydroxylation leading to the formation of the product seen only in the presence of the reductase. In the case of codeine, another substrate for cytochrome P450 2D6, the addition of reductase had no effect on the nature of the product formed, the dissociation constant, or the orientation in the binding site. These observations show that NADPH-cytochrome P450 reductase has an allosteric effect on the active site of cytochrome P450 2D6 that affects the binding of some substrates but not others.     

Mössbauer spectroscopic studies of Fe-substituted YIG

Compositional dependence of hyperfine parameters, determined through Mössbauer spectral analysis has been studied for Y_3−xFe_5+xO₁₂ (x = 0.0, 0.1, 0.3 and 0.5) garnet system at 300 K. The Mössbauer spectra have been fitted with three sextets in the ferrimagnetic state corresponding to Fe³⁺ ions at tetrahedral (d), octahedral (a) and dodecahedral (c) sites of the crystal structure. It is observed that isormershift, quadrupole shift and hyperfine field of d-site show no significant variation with Fe³⁺ concentration. The change in hyperfine fields of a- and c-sites with composition (x) has been explained on the basis of strength of exchange integrals, change in isomershift can be understood due to s-electron charge distribution and asymmetric displacement of oxygen ions surrounding the a- and c-sites seems to be responsible for observable quadrupole shift. The magneton number values obtained from magnetization and Mossbauer data are in agreement to those calculated using Neel's three sublattice model of ferrimagnetism.     

A design advisor for the optimal inspection of circularity tolerance

In the wake of growing importance for quality and the need to reduce inspection costs simultaneously, the need for a scientific method of selecting an optimum inspection strategy for coordinate measuring machine (CMM) based inspection has become very important. The inspection error resulting from CMM inspection is greatly affected by the profile irregularities and the sampling strategy, which includes sample size, sampling methods, and algorithms used for form evaluation. This paper describes a system that can recommend an optimal inspection plan based on the needs of the user. A design of experiments (DOE) based approach is used to relate the inspection error with sampling strategies. Surface irregularities are included in the form of lobes formed on the profile. A new two-way model is proposed that works in both directions between the sampling strategy and the performance metrics. The results indicate that the number of lobes and the sampling method used have little impact on the inspection error, while the sample size and form evaluation algorithms have a significant influence. An inspection plan advisor is presented, which provides an inspection plan based on the estimated shape and acceptable measurement error.     

Infrared study of salt free and salt treated cellulose pyrolysis under nitrogen atmosphere

The pyrolysis under nitrogen of salt free and salt treated cellulose was studied by infrared spectroscopy. The results confirm the unzipping mechanism suggested by DTA and TGA studies, and show this mechanism to apply to the untreated and salt treated samples. The results also show the unzipping to stop at the stage of char formation. The onset of this stage was found to occur after the volatilization of only 45–50% of the initial sample of the borax treated cellulose, compared with 65–70% of the KCl treated cellulose and 80–85% of the untreated cellulose.     

A closed-loop cross-correlation method for detecting model mismatch in MIMO model-based controllers

Correlation between a dithering signal and the prediction error has been used for detecting model mismatch in univariate model based control systems. This paper extends that approach to MIMO control systems. A closed-loop cross-correlation method is presented to detect which specific input-output pairings of a model-based controller are mismatched. This method may be used in screening the complete set of models and in selecting candidate models for re-identification. The method first finds the rows and columns of the transfer function matrix that contain mismatch, and then the candidates are found by the intersection of the said rows and columns. Placing the system under partial control, whereby one or more of the manipulated variables are held constant, can be used to further reduce the set of candidate models.     

Acetals as nucleating agents for polypropylene

Nucleating agents increase the impact strength, tensile strength, and tensile elasticity modulus of semicrystalline polymers. Nucleating agents also decrease product cycle times, resulting in a cost savings per product unit. We have synthesized and tested 15 compounds as nucleactors for polypropylene. Of these, trinapthylidene sorbitol, tri-(4-methyl-1-naphthylidene)sorbitol, tri-(4-methoxy-1-naphthylidene) sorbitol, and dibenzylidene xylitol are efficient nucleators of polypropylene. Trinaphthylidene sorbitol (tns) has two major diastereomers: The “S” diastereomer yields a faster crystallization rate for polypropylene than does the commercial nucleator dibenzylidene sorbitol (Millad 3905). Crystallization rates are 208 and 88, respectively (t min^?1 × 1000). The “R” diastereomer, however, is a poor nucleator and interferes with the nucleating activity of the “S” diastereomer. A 52/48 mixture of diastereomers does not nucleate polypropylene, even at twice the concentration. This is first time that the importance of stereochemistry has been demonstrated in the nucleating action. © 1994 John Wiley & Sons, Inc.     

On routing in large WDM networks

An important problem in WDM network design is to construct a logical topology and determine an optimal routing over that topology. Mixed Integer Linear Program (MILP) formulations to generate optimal solutions for this problem have been presented. Such formulations are computationally intractable, even for moderate sized networks. A standard approach is to decouple the problem of logical topology design and the problem of routing the traffic on this logical topology. Heuristics for finding the logical topology exist and a straight-forward linear program (LP), based on the node-arc formulation can be used to solve the routing problem over a given logical topology. We have found that such LP formulations become computationally infeasible for large networks. In this paper, we present a new formulation, based on the arc-chain representation, for optimally routing the specified traffic over a given logical topology to minimize the congestion of the network. We have used the revised simplex method incorporating an implicit column generation technique, and exploited the special Generalized Upper Bounding structure as well as the possibility of eta-factorization for efficiently updating the dual variables and finding the solution. Experimental results on a number of networks demonstrate the suitability of this approach.     

Implementation of bubble sort and the odd-even transposition sort on a rack of transputers

In this short note we discuss implementation of bubble sort and its variant the odd-even transposition sort in a parallel environment consisting of a network of transputers, with the accompanying OCCAM language.