Heuristic lipophilicity potential for computer-aided rational drug design

In this contribution we suggest a heuristic molecular lipophilicity potential (HMLP), which is a structure-based technique requiring no empirical indices of atomic lipophilicity. The input data used in this approach are molecular geometries and molecular surfaces. The HMLP is a modified electrostatic potential, combined with the averaged influences from the molecular environment. Quantum mechanics is used to calculate the electron density function rho(r) and the electrostatic potential V(r), and from this information a lipophilicity potential L(r) is generated. The HMLP is a unified lipophilicity and hydrophilicity potential. The interactions of dipole and multipole moments, hydrogen bonds, and charged atoms in a molecule are included in the hydrophilic interactions in this model. The HMLP is used to study hydrogen bonds and water-octanol partition coefficients in several examples. The calculated results show that the HMLP gives qualitatively and quantitatively correct, as well as chemically reasonable, results in cases where comparisons are available. These comparisons indicate that the HMLP has advantages over the empirical lipophilicity potential in many aspects. The HMLP is a three-dimensional and easily visualizable representation of molecular lipophilicity, suggested as a potential tool in computer-aided three-dimensional drug design.     

Comparison of Displacement and Mixing Diffusers

In order to cumpare the peformance of different supply diffuers of ventilation air, the airflow passern, temperature stratifiation and contaminant dispersion in a furnitured office ventilated by three kinds of air diffuer were numerically investigated. The air diffuers studied in this paper are a quarter-cylinder displacement diffuer on the floor and mixing diffuers (linear and vortex diffuers) on the ceiling. The heat sources in the of-fice are considered to be 50% convective and 50% radiative. The k-? two-equatwn model of turbulence is employed to predict the turbulent diffusion. The results show that the displacement diffuser provides a rather uniform flow field with low velocify in most areas, and the vertical temperature difference from floor to ceiling is as high as 6 K. With the linear diffuser, the air velociry is high, and the temperature is uniform both horizontally and vertically. The air velocity generated by the vortex diffuser is moderate. The distributions of the temperature and the contaminant are rather uniform.     

Inhibition of G1 cyclin-dependent kinase activity during growth arrest of human breast carcinoma cells by prostaglandin A2

Prostaglandin A2 (PGA2) potently inhibits cell proliferation and suppresses tumor growth in vivo, but little is known regarding the molecular mechanisms mediating these effects. Here we demonstrate that treatment of breast carcinoma MCF-7 cells with PGA2 leads to G1 arrest associated with a dramatic decrease in the levels of cyclin D1 and cyclin-dependent kinase 4 (cdk4) and accompanied by an increase in the expression of p21. We further show that these effects occur independent of cellular p53 status. The decline in cyclin D and cdk4 protein levels is correlated with loss in cdk4 kinase activity, cdk2 activity is also significantly inhibited in PGA2-treated cells, an effect closely associated with the upregulation of p21. Immunoprecipitation experiments verified that p21 was indeed complexed with cdk2 in PGA2-treated cells. Additional experiments with synchronized MCF-7 cultures stimulated with serum revealed that treatment with PGA2 prevents the progression of cells from G1 to S. Accordingly, the kinase activity associated with cdk4, cyclin E, and cdk2 immunocomplexes, which normally increases following serum addition, was unchanged in PGA2-treated cells. Furthermore, the retinoblastoma protein (Rb), a substrate of cdk4 and cdk2 whose phosphorylation is necessary for cell cycle progression, remains underphosphorylated in PGA2-treated serum-stimulated cells. These findings indicate that PGA2 exerts its growth-inhibitory effects through modulation of the expression and/or activity of several key G1 regulatory proteins. Our results highlight the chemotherapeutic potential of PGA2, particularly for suppressing growth of tumors lacking p53 function.     

Investigation of optical losses in photoelastic and ridge waveguides in GaAs-AlGaAs heterostructures

Two approaches have been used to fabricate stable photoelastic waveguides with planarized surfaces on GaAs-AlGaAs heterostructures. The first approach uses tensile Ni/sub 3/GaAs stressors formed by metal-semiconductor reactions. The second approach uses inert, refractory and compressive stressors, such as RF sputtered W and RF co-sputtered WNi films. For comparison purposes, ridge waveguides have also been fabricated using the same heterostructure by a dry etching technique. Optical losses of photoelastic waveguides, measured by Fabry-Perot (FP) method at a wavelength of 1.53 /spl mu/m, are comparable to or better than those of the ridge waveguides. Material loss appears to be the primary loss mechanism in both photoelastic and ridge waveguides. These results indicate that the photoelastic waveguide processing technique reported in this study is a promising alternative to commonly used dry etching techniques for planarization.     

c-KIT expression enhances the leukemogenic potential of 32D cells

The growth of human leukemic cells in culture and in vivo is dependent upon the presence of hematopoietic growth factors. Most populations of human leukemic acute myeloblastic leukemia (AML) cells express c-Kit on their surface and respond to Kit ligand (KL) in culture. To determine if this interaction was of potential significance in vivo we used a mouse model system. 32D cells, a murine IL-3-dependent myeloid cell line, were rendered KL responsive by transfection of the murine c-Kit. After injection of 32D or 32D-Kit cells into syngeneic hosts, animals bearing 32D-Kit cells, but not 32D cells, became moribund and were killed. These animals had circulating leukemic blast cells, infiltration of bone marrow, spleen, brain, liver, lung, and kidney. Cells recovered from some of the animals continued to be dependent upon IL-3 or KL for growth while in other cases the cells were factor independent. This model illustrates that the constitutive expression of c-Kit enhances the leukemic potential of 32D cells. The model will be useful for studying the progression of leukemia in vivo and testing whether interruption of the interaction of Kit and KL can affect the growth of leukemic cells.     

Trends in Hydrological Parameters of a Southern Brazilian Watershed and its Relation to Human Induced Changes

The Piracicaba river basin is a subtropical watershed located in the southeastern region of Brazil. With an area of 12 400 km², the basin is a typical example of new landscape resulting from development in tropical and sub-tropical regions: establishment of intensive industrial and agricultural processes were followed by significant population growth and water management. This scenario has led to significant increase in water demand and decrease in water quality. The main objective of this study is the detection of changes in the patterns of flow and precipitation in the basin, and its possible relation to man-induced changes. Statistical analyses were performed on records of precipitation, evapotranspiration and streamflow, from 1947 to 1991. Precipitation and evapotranspiration totals showed significant increasing trends for the entire basin. From eight streamflow gauge stations, half showed significant decreasing trend. The most probable cause of such trends is the export of water from the basin to the metropolitan region of São Paulo city.     

Triangular ray-tube analysis of dielectric lens antennas

A new method of analysis for the radiation characteristics of dielectric lens antennas with arbitrary inner and outer surfaces is presented. The analysis is based on representing the feed illumination by a contiguous set of ray tubes and including the effects of surface reflections and ray divergence. Radiation patterns and the antenna gain are then computed by evaluating the closed-form expressions developed for the Kirchhoff's integral of the aperture fields. The validity of the analysis method has been demonstrated by comparing the computations with measured results of two different spherical lenses and a shaped lens configurations. The analysis method presented takes into account some of the practical aspects associated with lens design such as surface zoning to reduce the mass and surface matching to minimize the reflection loss     

Synthesis and properties of 2,2,6,6-tetramethyl-1-(1-phenethyloxy)piperidine,an initiator for living free radical styrene polymerization

Summary An initiator for living free radical polymerization may be prepared by trapping the benzylic ethylbenzene radical with the stable 2,2,6,6-tetramethylpiperidinyl-1-oxy (TEMPO) radical. The adduct, 2,2,6,6-tetramethyl-1-(1-phenethyloxy)piperidine (TMPEP), smoothly undergoes thermal fragmentation at temperatures approaching 140° C to afford an active carbon radical capable of initiating polymerization and a passive mediating nitroxyl radical to reversibly cap and preserve the propagating polymer chain.     

Design of optimum signals for the simultaneous estimation of timedelay and Doppler shift

The problem of joint estimation of time delay and Doppler shift is considered from the point of view of the Wigner distribution of the signal. A very efficient method of obtaining the optimum signal with minimum estimation error based on the convexity of the design region is developed. Practical applications, however, require the signal to satisfy other constraints which present complications in acquiring the optimum signal. A design approach based on the method of simulated annealing is suggested to solve for the optimum signal under constraints. The performance of the signals so obtained is evaluated and compared with that of signals obtained by synthesis     

Preparation of Metal-Coated Carbon Fiber Reinforced Composites and Their Electromagnetic Properties

Medium temperature curing by infrared radiation was used to prepare electromagnetic wave absorbing multilayered plastic matrix composite materials containing metal-coated carbon fibers (MCFs). The electromagnetic properties of the materials were investigated by frequency scanning tests with microwave vector network analyzer. It is found that the electromagnetic parameters, mainly permittivity of the composites increase significantly with the addition of MCFs, which gives the composites good designability as thin, light-weight EM wave absorbers. It is also shown that MCFs can improve on the EM wave energy attenuating property of the composites by widening the work frequency band width and raising the absorptive peak