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.     

An investigation of grain boundary sliding in superplasticity at high elongations

Experiments were performed on the superplastic Zn-22% Al eutectoid alloy to determine the contribution of grain boundary sliding at both low (35%) and high (235%) elongations. The tests were conducted at two different strain rates in the superplastic Region II, and the results show that, within the accuracy of the measurements, there is a large sliding contribution at both elongations. By taking detailed measurements of both the magnitude of the sliding offset and the type of interface, it is shown that the average offsets are generally a maximum at the Zn-Zn boundaries, there is less sliding at the Zn-Al interfaces, and the offsets are a minimum at the Al-Al boundaries. In addition, the distributions of the magnitudes of the sliding offsets are similar at both the low and high elongations. It is concluded that grain boundary sliding is an important deformation process in the superplastic Region II and that it remains important even when the elongation is very high. The nature of the results indicates also that experimental observations of the deformation behaviour in superplastic materials at low elongations (up to 50%) provide meaningful information on the behaviour at much higher (superplastic) elongations.On leave from Mechanical Engineering Department, Nanjing Aeronautical Institute, Nanjing, Jiang-su 210002, People's Republic of China.     

High temperature mechanical properties of single phase alumina

The creep properties of a commercial, single phase aIurnina have been determined in the temperature range of 1623 to 1723 K. The stress exponent,n, in the relationship ⁿ was determined to be 1.9 and the true activation energy was found to be 635 kJ mol^–1. Normal primary stage creep transients were observed up to strains of 1%. At low stresses, steady-state conditions were not obtained due to the occurrence of concurrent grain growth. It is shown that the steady state creep results are consistent with the occurrence of an interface controlled diffusionaI creep mechanism.     

Target following with motion prediction for unmanned surface vehicle operating in cluttered environments

The capability of following a moving target in an environment with obstacles is required as a basic and necessary function for realizing an autonomous unmanned surface vehicle (USV). Many target following scenarios involve a follower and target vehicles that may have different maneuvering capabilities. Moreover, the follower vehicle may not have prior information about the intended motion of the target boat. This paper presents a trajectory planning and tracking approach for following a differentially constrained target vehicle operating in an obstacle field. The developed approach includes a novel algorithm for computing a desired pose and surge speed in the vicinity of the target boat, jointly defined as a motion goal, and tightly integrates it with trajectory planning and tracking components of the entire system. The trajectory planner generates a dynamically feasible, collision-free trajectory to allow the USV to safely reach the computed motion goal. Trajectory planning needs to be sufficiently fast and yet produce dynamically feasible and short trajectories due to the moving target. This required speeding up the planning by searching for trajectories through a hybrid, pose-position state space using a multi-resolution control action set. The search in the velocity space is decoupled from the search for a trajectory in the pose space. Therefore, the underlying trajectory tracking controller computes desired surge speed for each segment of the trajectory and ensures that the USV maintains it. We have carried out simulation as well as experimental studies to demonstrate the effectiveness of the developed approach.     

Nucleation and Growth Characteristics of Cavities during the Early Stages of Tensile Creep Deformation in a Superplastic Zirconia–20 wt% Alumina Composite

Constant-stress tensile creep experiments on a superplastic 3-mol%-yttria-stabilized tetragonal zirconia composite with 20 wt% alumina revealed that cavities nucleate relatively early during tensile deformation. The number of cavities nucleated increases with increasing imposed stress. The cavities nucleate at triple points associated largely with an alumina grain, and then grow rapidly in a cracklike manner to attain dimensions on the order of the grain facet size. It is suggested that coarser-grained superplastic ceramics exhibit lower ductility due to the ease in formation of such grain boundary facet-cracks and their interlinkage to form a macroscopic crack of critical dimensions.     

Upper bound on singlet fraction of two-qubit mixed entangled states

We demonstrate a new method to achieve the maximum singlet fraction using an entangled mixed two-qubit state as a resource. For this, we establish a tight upper bound on singlet fraction and show that the maximal singlet fraction obtained in Verstraete and Verschelde (Phys Rev Lett 90:097901(1)–097901(4), 2003) does not attain the upper bound on the singlet fraction derived here. Interestingly, we found that the required upper bound can, in fact, be achieved using local filtering operations.