Potent piperazine hydroxyethylamine HIV protease inhibitors containing novel P3 ligands

The 2-isopropyl thiazolyl group is a highly optimized P3 ligand for C2 symmetry-based HIV protease inhibitors, as exemplified in the drug ritonavir. Here we report that incorporation of this P3 ligand into a piperazine hydroxyethylamine series also yielded novel, highly potent inhibitors. In tissue culture assays, the presence of human serum was less deleterious to the activity of these inhibitors than to that of ritonavir. Furthermore, potent activity against ritonavir resistant HIV was observed.     

Putting reader roles to the test: an ethnomethodological approach

That readers read within roles has long been argued by literary theorists and more recently by technical communication theorists. Yet few scholars have attempted to put their theories to a test. The study reported in this paper attempts to do by using a conversation analysis tool called ethnomethodology. In an experimental setting, subjects were videotaped reading and responding to a set of instructions. Their responses indicate that: readers will often choose to play a role different from the one embedded in a text, especially if the text role offends them in some way; readers with similar education and interest may display different reader roles, making these roles difficult to predict; and within a single reading, a reader may change roles frequently. The paper concludes by discussing the implications of the findings and the appropriateness of ethnomethodology for reader-role research     

An improved PCR-based method for site directed mutagenesis using megaprimers

The antimicrobial activity of a combination of lactic acid and whey permeate fermented by a nisin-producing Lactococcus lactis strain was tested by the agar diffusion method using bacteria isolated from fish as test organisms. Lactic acid inhibited all bacterial strains studied, but nisin whey permeate inhibited Gram-positive bacteria only. The combination was more effective than lactic acid alone against Pseudomonas fluorescens and Staphylococcus hominis isolated from fish, and Pseudomonas aeruginosa ATCC9721 and Micrococcus luteus ATCC9341.     

All-trans beta-carotene is absorbed preferentially to 9-cis beta-carotene, but the latter accumulates in the tissues of domestic ferrets (Mustela putorius puro)

The algae Dunaliella bardawil and Dunaliella salina naturally contain large concentrations of all-trans and 9-cis beta-carotene (betaC). The purpose of this study was to compare the relative serum and tissue accumulation of all-trans and 9-cis betaC in ferrets fed different ratios of all-trans/9-cis betaC derived from two commercial sources, D. bardawil or D. salina (Betatene). Male ferrets (7 wk old) were fed carotene-free, pelleted diets for 27 d. Beginning on d 18, groups of ferrets (n = 6 or 7) received daily, one of six oral supplements varying in ratios of 9-cis and all-trans betaC mixed with approximately 1.0mL of Ensure. Four supplements containing 5.2-8.3 micromol total betaC were prepared from a 20% Betatene preparation, D. bardawil, a high-cis Betatene preparation, and Betatene further enriched in 9-cis betaC with all-trans betaC/9-cis betaC ratios of 2.2, 1.5, 0.6 and 0.4, respectively. Two control supplements, high and low betaC, were prepared from commercial betaC beadlets. The high control supplement had an all-trans/9-cis ratio of 19.0, whereas 9-cis betaC was not detected in the low supplement. On d 27, serum and tissues were obtained for HPLC analysis of betaC and its isomers. Analysis of livers showed that all-trans betaC was the primary isomer present, but 9-cis and other isomers were also detected in all groups. The hepatic all-trans/9-cis ratios were 5.9, 4.9, 2.5, 1.4, 52.2 and47.5, respectively, for the groups listed above. Lower amounts of all-trans and 9-cis betaC were found in kidneys compared with the liver, but ratios of all-trans/9-cis were not different among groups. Only trace amounts of 9-cis betaC were found in serum. These results demonstrate that the algae D. bardawil and D. salina provide a bioavailable source of betaC isomers, but, as in humans, absorption of 9-cis betaC is poor and any 9-cis betaC absorbed is apparently cleared by the liver.     

Two-dimensional ultrasonic tomography in nondestructive evaluation by using area functions

It is shown that the (normalized) area function based on the Born approximation offers a simple connection between the ultrasonic scattering response and the monochromatic ray sum in X-ray CT (computerized tomography). Because of this simple association, it is possible to apply the ultrasonic signals in the computationally direct and efficient parallel-beam X-ray CT algorithm to reproduce the vertical thickness function of an ultrasonic scatterer. The development of this imaging methodology is demonstrated for flaws of simple geometry; theoretical as well as experimental results for two model scatterers using this imaging technique are reported. Specifically, the area functions for a two-to-one spheroid and a circular cylinder are calculated and applied to a filtered backprojection algorithm of X-ray CT to obtain the vertical thickness function images. These images are then compared with the true vertical thickness functions of the targets based on their geometry. With theoretical data, this method was found to work very well. Even when experimental data containing creeping waves were used, the method produced satisfactory results for objects with continuously smooth surface.     

Design optimization of supersonic jet pumps using high fidelity flow analysis

Supersonic jet pumps are simple devices with no moving parts, where a high velocity (primary) flow is used to pump a second fluid. In this paper, Computational Fluid Dynamics (CFD) is combined with an optimization framework in order to develop a tool for the rapid generation of jet pump designs. A key feature of the problem formulation is the transformation of the jet pump design parameters in terms of geometric ratios. This approach dramatically reduces the number of unrealistic designs covered by the Design of Experiments. Optimal Latin Hypercubes for surrogate model building and model validation points are constructed using a permutation genetic algorithm and design points are evaluated using CFD. Surrogate models of primary and entrained flow rates are built using a Moving Least Squares approach. A series of optimizations for various pump sizes are performed using a genetic algorithm and Sequential Quadratic Programming, with responses calculated from the surrogates. This approach results in a set of optimized designs, from which pumps for a wide range of flow rates can be interpolated.     

Microstructural changes during ageing of Cu-2.5 wt% Ti

Microstructural changes in Cu-2.5wt % Ti during ageing at 573 and 773 K have been studied by transmission electron microscopy. Ageing times ranged from 60 sec to 200 h. Ordering of the precipitates was observed after very short ageing treatments at 773 K, and coarsening according tot ^1/3 was also observed from very early times. The particles were observed to become increasingly aligned into rod-like groups along 10 0 as ageing progressed. These results permit a new interpretation of the strengthening mechanisms in this alloy.     

Recognition of moving objects using feature signatures

An important application of machine vision systems is the recognition of known three-dimensional objects. A major difficulty arises when two or more objects project the same or similar two-dimensional image, often resulting in misclassification and degradation of system performance. The changes in images which result from the motion of objects provide a source of three-dimensional information which can greatly aid the classification process, but this three-dimensional analysis is computationally complex and subject to many sources of error. This work develops a methodology which utilizes the information derived from the apparent changes in object features over time to facilitate the recognition task, without the need to actually recover the three-dimensional structure of the objects under view. The basic approach is to generate a ``feature signature' by combining the feature measurements of the individual regions in a long sequence of images. The static information in the individual frames is analyzed along with the temporal information from the entire sequence. These techniques are particularly applicable in situations where static image processing methods cannot discriminate between ambiguous objects. Two example implementations are presented to illustrate the application of the techniques of object recognition using motion information.