Phencyclidine metabolite irreversible binding in the rat: gonadal steroid regulation and CYP2C11

These studies were conducted to determine the effect of hormones on sex-related differences in phencyclidine (PCP) metabolite irreversible binding and to determine the cytochrome P450 isoform(s) involved in this process. Sprague-Dawley male rats were castrated or administered estradiol and Sprague-Dawley female rats were ovarectomized or ovarectomized and given testosterone. Liver microsomal metabolism studies demonstrated that PCP metabolite binding to proteins was significantly altered by testosterone and estrogen administration. Castration of male rats decreased metabolite binding to 57% of sham-operated male levels, and administration of testosterone to ovarectomized female rats increased metabolite binding to 41 % of normal male levels. No metabolite adducts could be detected in microsomes from male rats administered estradiol or from sham-operated females given vehicle. These hormone-induced changes in metabolite binding closely matched the hormone-induced changes in CYP2C11 function and expression in these same microsomes. PCP metabolite irreversible binding to microsomal proteins was highly correlated with CYP2C11 function (as assessed by the formation of 2alpha-OH-testosterone, r = 0.91) and with CYP2C11 expression (as assessed by Western blot analysis, r = 0.95). In addition, an anti-CYP2C11 monoclonal antibody almost completely inhibited PCP metabolite binding (down to 7% of control male values) in an antibody concentration-dependent manner. These data strongly implicate CYP2C11 as an isoform involved in PCP metabolism and the formation and/or binding of a reactive PCP metabolite to microsomal proteins.     

The structural origin of nonplanar heme distortions in tetraheme ferricytochromes c3

Resonance Raman (RR) spectroscopy, molecular mechanics (MM) calculations, and normal-coordinate structural decomposition (NSD) have been used to investigate the conformational differences in the hemes in ferricytochromes c3. NSD analyses of heme structures obtained from X-ray crystallography and MM calculations of heme-peptide fragments of the cytochromes c3 indicate that the nonplanarity of the hemes is largely controlled by a fingerprint peptide segment consisting of two heme-linked cysteines, the amino acids between the cysteines, and the proximal histidine ligand. Additional interactions between the heme and the distal histidine ligand and between the heme propionates and the protein also influence the heme conformation, but to a lesser extent than the fingerprint peptide segment. In addition, factors that influence the folding pattern of the fingerprint peptide segment may have an effect on the heme conformation. Large heme structural differences between the baculatum cytochromes c3 and the other proteins are uncovered by the NSD procedure [Jentzen, W., Ma, J.-G., and Shelnutt, J. A. (1998) Biophys. J. 74, 753-763]. These heme differences are mainly associated with the deletion of two residues in the covalently linked segment of hemes 4 for the baculatum proteins. Furthermore, some of these structural differences are reflected in the RR spectra. For example, the frequencies of the structure-sensitive lines (nu4, nu3, and nu2) in the high-frequency region of the RR spectra are lower for the Desulfomicrobium baculatum cytochromes c3 (Norway 4 and 9974) than for the Desulfovibrio (D.) gigas, D. vulgaris, and D. desulfuricans strains, consistent with a more ruffled heme. Spectral decompositions of the nu3 and nu10 lines allow the assignment of the sublines to individual hemes and show that ruffling, not saddling, is the dominant factor influencing the frequencies of the structure-sensitive Raman lines. The distinctive spectra of the baculatum strains investigated are a consequence of hemes 2 and 4 being more ruffled than is typical of the other proteins.     

Synthesis of platinum nanowire networks using a soft template

Platinum nanowire networks have been synthesized by chemical reduction of a platinum complex using sodium borohydride in the presence of a soft template formed by cetyltrimethylammonium bromide in a two-phase water-chloroform system. The interconnected polycrystalline nanowires possess the highest surface area (53 +/- 1 m2/g) and electroactive surface area (32.4 +/- 3.6 m2/g) reported for unsupported platinum nanomaterials; the high surface area results from the small average diameter of the nanowires (2.2 nm) and the 2-10 nm pores determined by nitrogen adsorption measurements. Synthetic control over the network was achieved simply by varying the stirring rate and reagent concentrations, in some cases leading to other types of nanostructures including wormlike platinum nanoparticles. Similarly, substitution of a palladium complex for platinum gives palladium nanowire networks. A mechanism of formation of the metal nanowire networks is proposed based on confined metal growth within a soft template consisting of a network of swollen inverse wormlike micelles.     

Binary ionic porphyrin nanosheets: electronic and light-harvesting properties regulated by crystal structure

Crystalline solids self-assembled from anionic and cationic porphyrins provide a new class of multifunctional optoelectronic micro- and nanomaterials. A 1?:?1 combination of zinc(II) tetra(4-sulfonatophenyl)porphyrin (ZnTPPS) and tin(IV) tetra(N-methyl-4-pyridiniumyl)porphyrin (SnTNMePyP) gives porphyrin nanosheets with high aspect ratios and varying thickness. The room temperature preparation of the nanosheets has provided the first X-ray crystal structure of a cooperative binary ionic (CBI) solid. The unit cell contains one and one-half molecules of aquo-ZnTPPS(4-) (an electron donor) and three half molecules of dihydroxy-SnTNMePyP(4+) (an electron acceptor). Charge balance in the solid is reached without any non-porphyrinic ions, as previously determined for other CBI nanomaterials by non-crystallographic means. The crystal structure reveals a complicated molecular arrangement with slipped π-π stacking only occurring in isolated dimers of one of the symmetrically unique zinc porphyrins. Consistent with the crystal structure, UV-visible J-aggregate bands indicative of exciton delocalization and extended π-π stacking are not observed. XRD measurements show that the structure of the Zn/Sn nanosheets is distinct from that of Zn/Sn four-leaf clover-like CBI solids reported previously. In contrast with the Zn/Sn clovers that do exhibit J-aggregate bands and are photoconductive, the nanosheets are not photoconductive. Even so, the nanosheets act as light-harvesting structures in an artificial photosynthesis system capable of reducing water to hydrogen but not as efficiently as the Zn/Sn clovers.     

Using Total Quality Principles for Strategic Planning and Curriculum Revision

This paper describes the long-term strategic planning process of the College of Engineering at the University of North Carolina at Charlotte, a process that began in the Fall of 1992 and continues today. The chronology of activities comprising this process, as well as the output of the process thus far, are presented in enough detail that they may serve as a blue print for others. First, we discuss some of the forces driving the college's educational reform efforts, especially those related to the use of TQM as the vehicle for change. Throughout the case study, we point out how (and why) certain Total Quality principles, including customer relationships, shared vision, assessment and continuous improvement, and sub-systems alignment, became integral parts of the strategic planning process.     

Shear-induced mechanochromism in polydiacetylene monolayers

We use atomic force microscopy to actuate and characterize the nanoscale mechanochromism of polydiacetylene monolayers on atomically-flat silicon oxide substrates. We find explicit evidence that the irreversible blue-to-red transformation is caused by shear forces exerted normal to the polydiacetylene polymer backbone. The anisotropic probe-induced transformation is characterized by a significant change in the tilt orientation of the side chains with respect to the surface normal. We discuss preliminary molecular dynamics simulations and electronic structure calculations on twelve-unit polydiacetylene oligomers that allow us to correlate the transformation with bond-angle changes in the conjugated polymer backbone.     

Raman difference spectroscopy of tertiary and quaternary structure changes in methaemoglobins

There have been several resonance Raman scattering investigations of the effect of inositol hexaphosphate (IHP) on methaemoglobins. In those studies the sensitivity for detecting frequency differences was limited to 1-2 cm-1, and consequently frequency differences were not detected although spectral intensity differences due to changes in spin equilibria were. Shelnutt et al. recently reported on the observation of frequency differences induced by changes in the quaternary structure of chemically modified deoxyhaemoglobins. An improved Raman difference spectroscopic technique with 0.1 cm-1 sensitivity allowed the detection of these differences. We report here the application of this technique to a series of methaemoglobins with and without the addition of IHP. In addition to the intensity changes resulting from changes in the spin equilibria, we have observed frequency differences. In all liganded methaemo-globins that we examined a decrease in frequency of the mode in the 1,370 cm-1 region was observed on addition of IHP. In those in which a quaternary structure change is known to occur the frequency difference is greater than 0.5 cm-1. In those in which no quaternary structure change occurs [metHbA(CN-) and methHbA(N-3)] the frequency difference is smaller (approximately 0.15 cm-1).     

Linear Estimation of the Scale Parameter of the First Asymptotic Distribution of Extreme Values

A Lagrange multiplier technique is used to obtain linear, minimum-variance, unbiased estimators for the scale parameters of the first asymptotic distributions of smallest and largest values with known mode. Coefficients for multiplying ordered observations are computed for complete and censored samples of size n = 1(1) 15. Each sample of size n is censored from above and all m-order-statistic estimators are obtained where m ? n. Then the smallest subset of # order statistics from the set of m available order statistics is found which yields a 99% efficiency relative to the m-order-statistic estimator. The Cramér-Rao lower bound for the variances of the estimators for complete samples is derived and tabled for n = 1(1) 15. For censored samples the asymptotic variances of the maximum-likelihood m-order-statistic estimators are presented for comparative purposes.     

Quality Improvement Partnerships with Industry Using Student Teams

The 1993 Quality Challenge is a cooperative partnership between Milliken and Company, the National Science Foundation and three North Carolina Universities. The project goal was to activate a multidisciplinary team of students, faculty, and industry representatives in a real-world quality improvement project. The 1993 project was an expanded follow-up to the 1992 University Challenge Project, also sponsored by Milliken. Based upon past experience, project coordinators broke the 1993 project into three components: Preparation, Identification, and Action. Preparation included a preliminary course held in the Spring to teach students fundamental Total Quality Management tools, team building skills and communication skills needed in industry. A team of students was selected from the course to participate in the summer Identification and Action phases of the project. The Identification phase included introduction to project goals, team process training, specialized team formation and project focus. The Action phase of the project included process capability studies, shade variation studies, root cause trials and a statistical design of experiment on shade variables. The project resulted in many recommendations to improve the process and reduce shade variation. The overall project methodology and approach can be applied to industries other than textile manufacturing. Educational benefits for all participants included: team building and teamwork experience, enhancement of effective communication skills, experience in design of experiments, engineering design and practice, greater self confidence, and industrial experience with real-world quality improvement opportunities.     

Effect of answer format and review method on college students' learning

Interactive instructional methods are characterized by engaging students with the course material and involve delivering feedback for their efforts. Using a mixed 2 × 2 factorial experiment, we compared the effects of multiple choice answer formats (word versus letter) and methods (automated versus manual) on 70 undergraduate students' acquisition of instructional material. Although there was no significant difference in participants' gain scores between automated (“clickers”) and manual (holding up response cards) methods, significantly greater learning occurred when participants used the word rather than letter answer format. Despite participants' preference for letter over word format, instructors may still want to require students to write out answers to review questions given the improved performance it yields.