Developing a Systems Approach to the Problems of Industry — Lessons Based on Experience at IIASA

This paper describes progress on a number of research projects initiated in the Management and Technology Area of the International Institute of Applied Systems Analysis in the period 1977/80. The projects were undertaken by an international, multi-disciplinary, team concerned with the study of management problems arising from technological change. The experience obtained is used to explore the need for, and feasibility of, undertaking such problem-oriented programme research at the national level. It is concluded that the need to conduct methodological research of this nature is great, though not always self-evident; that the financial and organisational problems would be severe, though not insuperable; and that it is time for practising operational researchers and applied systems analysts to flex their muscles to this end.     

Verification of CuInSe2 density of states features by reflection electron energy loss spectroscopy

Reflection electron energy loss measurements of CuInSe₂ single crystals are reported and when possible, the losses are compared with former results by Kazmerski and Jamjoum et al. Their identification of the transitions is confirmed and refined by spectrum simulations with total and partial densities of states from band structure calculations of Jaffe, Bendt, Zunger, and Bullett.New conduction-band maxima at energies not covered by the available calculations, are proposed and their consistency with the experimental loss energies is shown by another simulation with Lorentzian density peaks.     

Theory of the contribution of the electron-phonon interaction to the anisotropic electronic lifetime and transport properties of zine

Using pseudopotential theory for the phonons, electrons, and electron-phonon interaction of zine, we have calculated several electronic properties of this metal. Among these are the electron lifetime at three positions on the Fermi surface, the anisotropic electrical resistivity, the anisotropic thermal conductivity, and the ultrasonic attenuation, all due to the electron-phonon interaction, and all as a function of temperature. For the electrical resistivity, two solutions of the Boltzmann equation were obtained, one consisting of a single spherical harmonic, and the other made up of six spherical harmonics. The single spherical harmonic is not adequate at low temperatures.     

Electron interactions and transport between coupled quantum Hall edge states

We examine the effects of electron-electron interactions on transport between edge states in a multilayer integer quantum Hall system. The edge states of such a system, coupled by interlayer tunneling, form a two-dimensional, chiral metal at the sample surface. We calculate the temperature-dependent conductivity and the amplitude of conductance fluctuations in this chiral metal, treating Coulomb interactions and disorder exactly in the weak-tunneling limit. We find that the conductivity increases with increasing temperature, as observed in recent experiments, and we show that the correlation length characterizing conductance fluctuations varies inversely with temperature.     

Membrane preconcentration-capillary electrophoresis tandem mass spectrometry (mPC-CE-MS/MS) in the sequence analysis of biologically derived peptides

We demonstrate the use of membrane preconcentration capillary electrophoresis tandem mass spectrometry (mPC-CE-MS/MS) for sequencing peptides at the sub-100 femtomole level. In particular by loading the mPC-CE cartridge off-line with a pressurized bomb apparatus, 100 mul solutions can be loaded in <5 min. Furthermore, mPC-CE-MS in conjunction with on-line transient isotachophoresis carried out in 25 mum i.d. capillaries results in enhanced resolution and theoretical plate values as compared to convention 50-75 mum i.d. capillaries. We show that this is a powerful new approach in the sequencing of biologically derived compounds from complex mixtures such as MHC class I peptides.     

Formation of polypyrrole chains in alumina and chromia-pillared layered phosphates

The reaction of gaseous pyrrole (pyr) with Cu²⁺ exchanged alumina- and chromia-pillared -tin and -zirconium phosphates has been investigated. Preliminary exchange with Cu²⁺ reveals differences in ordering in the two types of oxide-pillared materials, ascribed to differences in precursor insertion during their preparation. In both oxide-pillared types, the pyr rapidly polymerises in the pores (not on the surface). Optical spectra and XPS evidence point to the presence of more than one type of pyr polymer, and hence of a porous system. The optical properties are typical of mixed neutral and bipolaron states with the presence of low-oxidation level polypyrrole. Based on similarities in optical properties with zeolite analogues, it is suggested that the starting materials contain porous systems similar to both zeolite-Y and mordenite present together. As for zeolite-Y and mordenite analogues, the materials have negligible conductances ( < 10^{–9 –1} cm^–1), which is ascribed to the presence of only short polymeric pyr units.     

Global proteome analysis of a human gastric carcinoma

An approach that combines analysis of global protein digests (GPDs) of various subcellular fractions with a novel chromatographic-based method to map protein expression profiles is described. The KATO III gastric carcinoma cell line was fractionated into membrane and cytosol fractions. Each subcellular fraction was digested with trypsin to yield complex mixtures of global protein tags (GPTs). These mixtures were fractionated by two dimensions of chromatography, and GPTs were sequenced by microcapillary liquid chromatography-tandem mass spectrometry (LC-MS/MS), using two further complementary dimensions of chromatography. Additionally, a novel method of protein expression profiling was used to map the KATO III human gastric carcinoma cell line. This method uses the cells' natural proteolytic processes to derive in vivo peptide tags that represent proteins of every functional class and from all subcellular compartments. In one example, expressed protein tags (EPTs) are naturally displayed on the surface of cells by multiligand receptors. Isolation and sequence identification of EPTs is an efficient approach for protein profiling that is complementary to GPT analysis. The EPT approach also provides a further unique subcellular fraction of the biological starting material. Isolation of the multiligand receptors was by immunoaffinity chromatography (IAC). In the current study, five individual peptide maps (two EPTs and three GPTs) of the KATO III cell line were fractionated by multimodal chromatography, and sequenced by on-line multimodal microcapillary LC-MS/MS. This analysis led to the identification of 4291 individual peptide sequences, which defined 1966 unique proteins expressed by this human carcinoma cell line.     

Direct INDO/SCI method for excited state calculations

Intermediate neglect of differential overlap (INDO) is the most commonly utilized semiempirical technique for performing excited state calculations on large organic systems such as organic semiconductors and fluorescent dyes. The calculations are typically done at the singles-configuration interaction (SCI) level. Direct methods provide a more efficient means of performing configuration interaction (CI) calculations, and the computational trade offs associated with various approaches to direct-CI theory have been well characterized for ab initio Hamiltonians and high-order CI. However, the INDO and SCI approximations lead to a new set of trade offs. In particular, application of the electron-electron interactions in the atomic basis leads to savings in computational time that scale as the number of atomic orbitals, which for a large organic system can be two to three orders of magnitude. These savings are largest when only a few low-lying excited states are generated and when a full SCI basis, which includes excitations between all filled and empty molecular orbitals, is used. In addition, substantial memory savings are achieved in the direct method by avoiding the evaluation of the two electron integrals in the molecular orbital basis. The method is demonstrated by calculating the absorption spectrum of a poly(paraphenylenevinylene) oligomer containing 16 phenyl rings.     

Creation of a productive, highly enantioselective nitrilase through gene site saturation mutagenesis (GSSM)

Gene site saturation mutagenesis (GSSM) technology is applied for the directed evolution of a nitrilase. The nitrilase effectively catalyzes the desymmetrization of the prochiral substrate 3-hydroxyglutaronitrile to afford (R)-4-cyano-3-hydroxybutyric acid, a precursor to the valuable cholesterol-lowering drug Lipitor. The discovered wild-type enzyme effectively performs the reaction at the industrially relevant 3 M substrate concentration but affords a product enantiomeric excess of only 87.6% ee. Through GSSM, a mutagenesis technique that effects the combinatorial saturation of each amino acid in the protein to each of the other 19 amino acids, combined with a novel high-throughput mass spectroscopy assay, a number of improved variants were identified, the best of which is the Ala190His mutant that yields product enantiomeric excess of 98.5% at 3 M substrate loading and a volumetric productivity of 619 g L-1 d-1.