Novel approaches to the discovery of antimicrobial agents

OBJECTIVE: To examine the cost-effectiveness of prenatal carrier screening for cystic fibrosis. METHODS: A cost-benefit equation was developed that was based on the hypothesis that the cost of prenatal diagnosis required to diagnose and prevent one case of cystic fibrosis should be equal to or less than the lifetime cost generated from the birth of a neonate with cystic fibrosis. The formula was adjusted because a woman's positive or negative carrier status remains unchanged, thus eliminating the need for testing in subsequent pregnancies. The formula was manipulated to identify the optimal cost per screening test, as well as the net cost savings per prenatally diagnosed case of cystic fibrosis for various racial or ethnic groups. Sensitivity analyses included some key assumptions regarding the cost per screening test ($50-150), patient screening acceptance rates (25-100%), and therapeutic abortion rates (50-100%). RESULTS: Assuming therapeutic abortion rates of 50-100%, the net savings per prenatally diagnosed case of cystic fibrosis are $58,369-$382,369 among whites. Given the previously reported patient screening acceptance rates of 50-78%, the overall annual cost savings in the United States for whites are $161-251 million. However, the screening program was not found to be cost-effective for blacks, Asians, or Hispanics. CONCLUSION: Under most assumptions and sensitivity analyses, a prenatal cystic fibrosis-carrier screening program appears to be cost-effective.     

A unified method for optimal arbitrary pole placement

We consider the classic problem of pole placement by state feedback. We offer an eigenstructure assignment algorithm to obtain a novel parametric form for the pole-placing feedback matrix that can deliver any set of desired closed-loop eigenvalues, with any desired multiplicities. This parametric formula is then exploited to introduce an unconstrained nonlinear optimisation algorithm to obtain a feedback matrix that delivers the desired pole placement with optimal robustness and minimum gain. Lastly we compare the performance of our method against several others from the recent literature.     

On the interrelation of rubber elastic stress-strain curves under different types of strain

With specially shaped samples it is possible to study the stress-strain relation σ(γ) in simple shear up to large shear deformation γ. Measurements of σ(γ) on synthetic polyisoprene, IR 305, differently crosslinked with dicumylperoxide, are reported and compared with those for uniaxial extension on the same materials. Using the simple deformation geometry including shearbands proposed in the meander model (1), both stress-strain relations can be converted into each other. These results favor the applied superstructural model and moreover show that the deformation behavior of rubbers is governed by one material law, σ(γ).     

A Complete and Highly Effective Mothproofing Agent Comprising a Pyrethroid and a Hexahydropyrimidine

Pyrethroids, considered as a general class of compounds, have been shown to provide effective protection from the larvae of the keratin-digesting insects Tineola bisselliella H., Tinea pellionella Linn., Hofmannophila pseudo-spretella Station and Attagenus piceus Oliv. The position regarding the susceptibility of the furniture carpet beetle to pyrethroids is less clear, however. It has been reported that both deltamethrin and permethrin are effective against Anthrenus flavipes Le Conte, whilst permethrin is also reported elsewhere to be effective against the same species. Results obtained in our laboratory, however, have indicated that pyrethroids may offer inadequate protection against Anthrenus vorax Waterh. [1, 2]. This latter species is identical to Anthrenus flavipes var. seminiveus Casey, a colour variety of Anthrenus flavipes Le Conte. The 1,3-disubstituted5-phenylcarbamoyl-2,4,6-trioxo- and 4,6-dioxo-2-thione-hexahydropyrimidine derivatives described in this paper exhibit a surprisingly high and selective toxicity to the Anthrenus species. Thus, a combination of an appropriate hexahydropyrimidine with a suitable pyrethroid, e.g. permethrin, provides complete control of a wide range of commonly encountered textile insect pests. The influence of substituents on the mothproofing activity is discussed.     

The distribution and phylogenetic significance of desmethylsterols inChenopodium andAtriplex: Coexistence of Δ7- and Δ5 -sterols

Twenty-one species in the Chenopodiaceae were analyzed for sterol composition. In ten of eleven species ofChenopodium, the major desmethylsterols were Δ⁷-sterols accompanied by lower proportions of Δ⁵-sterols. InC. fremontii this pattern was reversed. The sterol profiles of five species ofAtriplex were characterized by the coexistence of Δ⁷- and Δ⁵-sterols in ratios of 0.3∶1 to 0.4∶1. MaleAtriplex plants contained higher proportions of Δ⁵-sterols than femaleAtriplex plants. OneCeratoides and twoSalicornia species contained Δ⁵-sterols as their predominant sterols.     

Evaluation of electron beam welding technique for the integration of robust sensor elements into high-pressure automotive systems

For “on board” diagnosis purposes of the injected fuel quantity flow sensitive elements based on the thermo-resistive measurement principle were integrated into finished Common Rail injection nozzles of valve-covered orifice (VCO) or mini-sac hole (MSH) class. Electron-discharge machining as well as electron beam welding technique are key technologies for a reliable integration procedure. To demonstrate negligible influence on the hydraulic performance of the nozzle after modification an optical measurement set-up is used to record temporally resolved the propagation of the spray patterns ejected from the six injection holes simultaneously. From these investigations the impact on the structural distortion of the valve caused by the welding seam is proved as its position can be directly linked to any chances in spray performance of each individual injection hole. Reducing the energy input during the electron beam welding lowers substantially the asymmetry in spray patterns from hole to hole as the needle uncovers the six injection holes more symmetrically. Besides this important finding, the numerical calculations indicate that the implementation of the sensor chip slightly amplifies the asymmetry induced by the welding process due to an additional weakening of the nozzle body which is confirmed experimentally. Despite these challenges, however, it is demonstrated that appropriate parameters for the integration procedure can be found affecting the hydraulic performance negligible compared to the original state.     

Nematic polymer liquid-crystal wave plate for high-power lasers at 1054 nm

A nematic polymer liquid crystal is used to construct wave plates for use at 1054 nm. Three methods of wave-plate construction are discussed: double substrate with fiber spacers in homogeneous distribution, double substrate with fiber spacers in annular distribution, and single substrate. The polymer liquid crystal shows high laser-damage resistance, making it particularly useful for high-peak-power laser applications. Alignment techniques and measurement of birefringence for the highly viscous polymer are described.     

From Images to Shape Models for Object Detection

We present an object class detection approach which fully integrates the complementary strengths offered by shape matchers. Like an object detector, it can learn class models directly from images, and can localize novel instances in the presence of intra-class variations, clutter, and scale changes. Like a shape matcher, it finds the boundaries of objects, rather than just their bounding-boxes. This is achieved by a novel technique for learning a shape model of an object class given images of example instances. Furthermore, we also integrate Hough-style voting with a non-rigid point matching algorithm to localize the model in cluttered images. As demonstrated by an extensive evaluation, our method can localize object boundaries accurately and does not need segmented examples for training (only bounding-boxes).