Effect of deviation from plane wave conditions on the Doppler spectrum from an ultrasonic blood flow detector.

Deviation from plane wave conditions within the ultrasound beam of a Doppler blood flow detector leads to a non-linear relationship between the phase angle of the back-scattered signal and the scatterer position. This in turn leads to frequency modulation of the Doppler signal and an increase in the Doppler spectrum width. The relationship between the ultrasound beam and the observed signal spectrum has been investigated by employing a computer-based model of the ultrasound field which enabled the calculation of: 1, pressure (amplitude and phase angle) field distributions from plane disc and focused transducers with unapodized and apodized aperture field distributions; 2, the Doppler signal from a scatterer moving through the field; and 3, the spectrum of this signal. The increase in spectral width resulting from deviations from plane wave conditions was calculated by comparing this spectrum with that of the signal from which frequency modulation had been removed.     

PICOSECOND FLUORESCENCE OF R3230AC MAMMARY CARCINOMA MITOCHONDRIA AFTER TREATMENT WITH HEMATOPORPHYRIN DERIVATIVE and PHOTOFRIN® II in vivo

Hematoporphyrin derivative (HPD) and other porphyrin samples were excited by 20-ps 532-nm laser pulses. Fluorescence was detected using a low-jitter streak camera. Data were fitted to a sum of exponential decay times on the order of picoseconds. Fluorescence of porphyrins in aqueous solution show various behaviors depending on the hydrophobicity of the porphyrins. The most hydrophilic porphyrins show long decays only (greater than 500 ps). Porphyrins intermediate in hydrophobicity have intensity-dependent fast decays. The most hydrophobic have fast decays (less than 20 ps). Picosecond fluorescences of mitochondria prepared from rat tumors treated in vivo with HPD or Photofrin II show an increase in the ratio of fast to slow decays when compared to the injected porphyrins. These results are consistent with the concentration of the more hydrophobic porphyrins in mitochondria in photosensitization treatment. Thus picosecond fluorescence studies of porphyrins may provide a means to obtain photoproperties which differentiate between effective and ineffective in vivo photosensitizers.     

The acquisition of new technology and its impact on a firm's competitive position

The strategic decision concerning the optimal and dynamic acquisition of new technology is examined. The model focuses on a profit maximizing firm that optimally derives its price, level of output, and its level and composition of productive capacity over time. The acquisition of new technology and reduction of existing capacity may occur simultaneously, so that the composition of the firm's productive resources may be upgraded over time. It is assumed that the acquisition of new technology causes a reduction in production costs and a direct increase in the firm's demand. The demand experienced by the firm may be directly increased as a result of acquiring new technology due to benefits such as expanded product-mix or volume capabilities, improved quality of output, or improved customer service (shorter production lead time). In addition, it is shown that demand is indirectly increased due to the reduced production costs that enable the firm to charge a lower price. Therefore, the strategic impact of acquiring new technology is captured, since its effect on future demand and the firm's ability to meet the demand are considered. The importance of capturing the increased demand potential offered by the new technology is demonstrated through the analysis of numerical examples. In addition, the effect on the optimal solution caused by a variety of environmental conditions is examined. For example, the impact of technological innovation is observed by defining (i) the cost of acquiring technology as a decreasing function of time, and (ii) the effectiveness of new technology on reducing operating costs as an increasing function of time.     

Chromatographic screening for drugs of abuse using capillary columns. I. Comparison of open tubular columns and support coated open tubular columns for the analysis of central nervous system stimulant drugs

Summary Extraction of urine samples containing central nervous system stimulant drugs and analysis of the extracts on metal and glass open tubular columns and on support coated open tubular glass columns are discussed.     

Non-Cayley Vertex-Transitive Graphs of Order Twice the Product of Two Odd Primes

For a positive integer n, does there exist a vertex-transitive graph Γ on n vertices which is not a Cayley graph, or, equivalently, a graph Γ on n vertices such that Aut Γ is transitive on vertices but none of its subgroups are regular on vertices? Previous work (by Alspach and Parsons, Frucht, Graver and Watkins, Marusic and Scapellato, and McKay and the second author) has produced answers to this question if n is prime, or divisible by the square of some prime, or if n is the product of two distinct primes. In this paper we consider the simplest unresolved case for even integers, namely for integers of the form n = 2pq, where 2 < q < p, and p and q are primes. We give a new construction of an infinite family of vertex-transitive graphs on 2pq vertices which are not Cayley graphs in the case where p ≡ 1 (mod q). Further, if p ? 1 (mod q), p ≡ q ≡ 3(mod 4), and if every vertex-transitive graph of order pq is a Cayley graph, then it is shown that, either 2pq = 66, or every vertex-transitive graph of order 2pq admitting a transitive imprimitive group of automorphisms is a Cayley graph.     

Automated MEMS-based Drosophila embryo injection system for high-throughput RNAi screens

We have developed an automated system based on microelectromechanical systems (MEMS) injectors for reliable mass-injection of Drosophila embryos. Targeted applications are high-throughput RNA interference (RNAi) screens. Our injection needles are made of silicon nitride. The liquid to be injected is stored in an integrated 500 nl reservoir, and an externally applied air pressure pulse precisely controls the injected volume. A steady-state water flow rate per applied pressure of 1.2 nl s(-1) bar(-1) was measured for a needle with channel width, height and length of 6.1 microm, 2.3 microm and 350 microm, respectively. A typical volume of 60 pl per embryo can be reliably and rapidly delivered within tens of milliseconds. Theoretical predictions of flow rates match measured values within +/-10%. Embryos are attached to a glass slide surface and covered with oil. Packages with the injector chip and the embryo slide are mounted on motorized xyz-stages. Two cameras allow the user to quickly align the needle tip to alignment marks on the glass slide. Our system then automatically screens the glass slide for embryos and reliably detects and injects more than 98% of all embryos. Survival rates after deionized (DI) water injection of 80% and higher were achieved. A first RNAi experiment was successfully performed with double-stranded RNA (dsRNA) corresponding to the segment polarity gene armadillo at a concentration of 0.01 microM. Almost 80% of the injected embryos expressed an expected strong loss-of-function phenotype. Our system can replace current manual injection technologies and will support systematic identification of Drosophila gene functions.     

QSAR modeling of in vitro inhibition of cytochrome P450 3A4

We report the QSAR modeling of cytochrome P450 3A4 (CYP3A4) enzyme inhibition using four large data sets of in vitro data. These data sets consist of marketed drugs and drug-like compounds all tested in four assays measuring the inhibition of the metabolism of four different substrates by the CYP3A4 enzyme. The four probe substrates are benzyloxycoumarin, testosterone, benzyloxyresorufin, and midazolam. We first show that using state-of-the-art QSAR modeling approaches applied to only one of these four data sets does not lead to predictive models that would be useful for in silico filtering of chemical libraries. We then present the development and the testing of a multiple pharmacophore hypothesis (MPH) that is formulated as a conceptual extension of the traditional QSAR approach to modeling the promiscuous binding of a large variety of drugs to CYP3A4. In the simplest form, the MPH approach takes advantage of the multiple substrate data sets and identifies the binding of test compounds as either proximal or distal relative to that of a given substrate. Application of the approach to the in silico filtering of test compounds for potential inhibitors of CYP3A4 is also presented. In addition to an improvement in the QSAR modeling for the inhibition of CYP3A4, the results from this modeling approach provide structural insights into the drug-enzyme interactions. The existence of multiple inhibition data sets in the BioPrint database motivates the original development of the concept of a multiple pharmacophore hypothesis and provides a unique opportunity for formulating alternative strategies of QSAR modeling of the inhibition of the in vitro metabolism of CYP3A4.     

Cationic phosphorus-carbon-pnictogen cages isolobal to [C5R5]+

The cationic cages nido-[C2Bu(t)2P2E]+ (E = As, Sb), which are isolobal to the cyclopentadienyl cation, adopt square based pyramidal structures with the heavy pnictogen atom at the apex; NMR and computational methods have been used to probe the dynamic behaviour of the complexes.