Robust DNA microarray image analysis

DNA microarrays are an increasingly important tool that allow biologists to gain insight into the function of thousands of genes in a single experiment. Common to all array-based approaches is the necessity to analyze digital images of the scanned DNA array. The ultimate image analysis goal is to automatically quantify every individual array element (spot), providing information about the amount of DNA bound to a spot. Irrespective of the quantification strategy, the preliminary information to extract about a spot includes the mapping between its location in the digital image and its possibly distorted position in the spot array (gridding). We present a gridding approach divided into a spot-amplification step (matched filter), a rotation estimation step (Radon transform), and a grid spanning step. Quantification of the spots is performed by robustly fitting of a parametric model to pixel intensities with the help of M-estimators. The main advantage of parametric spot fitting is its ability to cope with overlapping spots. If the goodness-of-fit is too bad, a semiparametric spot fitting is employed. We show that our approach is superior to simple quantification strategies such as averaging of the pixel intensities. The system was extensively tested on 1740 images resulting from two DNA libraries.Received: 15 June 2001, Accepted: 21 July 2002, Published online: 3 June 2003 Correspondence to: Norbert Brändle     

Pharmacokinetics of Gadomer-17, a new dendritic magnetic resonance contrast agent

Rationale and objectives: Gadomer-17 is a new magnetic resonance (MR) contrast medium presently in clinical development. It is a dendritic gadolinium (Gd) chelate carrying 24 Gd ions. This study investigated the pharmacokinetic behavior of this contrast medium. Methods: The pharmacokinetics of Gadomer-17 were investigated in different species (rat, rabbit, dog, monkey) for up to 7 days after intravenous (i.v.) injection of 25–100 μmol/kg body weight. In addition, elimination and biodistribution were evaluated after single i.v. injection of Gadomer-17 in rats. Results: After i.v. injection Gadomer-17 distributes almost exclusively within the intravascular space without significant diffusion into the interstitial space. The volume of distribution (Vc) in the initial or α-phase ranged from 0.04 1/kg (rats, rabbits) to 0.06 1 kg (monkeys) and 0.07 1/kg (dogs), which reflects mainly the plasma volume. The blood/plasma concentration profile was found to be biphasic. The volume of distribution at a steady state is clearly smaller than that of other contrast media, which distribute to the extracellular space. After single i.v. injection in rats, the dendritic contrast medium was rapidly and completely eliminated from the body, mainly via glomerular filtration. No long-term accumulation or retention of the nonmetabolized agent was detectable in organs or tissues. Conclusions: Gadomer-17 is a promising new MR contrast medium that has an intravascular distribution and a rapid renal elimination.     

A DIALOG-ORIENTED AND GRADIENT-BASED STABILITY MARGIN IN UNCERTAIN SYSTEMS

ABSTRACT

Gradients and matricial gradients for optimally increasing the stability margin and the admissible uncertainty of a dynamic system are the targets of this presented article. To design a dynamic system, the gradients are used in a dialog between a system scientist and gradient-based computer support. The stability margin is derived for output state controllers, including regular state controllers. The resonant frequency and the damping factors are investigated as a direct function of the maximum admissible uncertainty. The resulting gradients are extended to observer-assisted controllers, to minimum-order observers, and to dynamic-output state controllers.     

LEAP EFFECTS AMONG ROBUST ROOT TRAJECTORIES

The set of closed-loop eigenvalues in the presence of the worst uncertainty is termed robust root trajectory. The open-loop gain or some other system parameter is changed monotonically. The admissible uncertainties are considered along their envelope. The worst uncertainty is denoted as that one where a specified function of the eigenvalues leads to the maximum disadvantageous effect on the closed-loop stability performance. Leaps in the dynamic behavior occur even for infinitesimally small changes in the gain parameter when system uncertainties are considered that are located especially at their bounds.     

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Ohne Zusammenfassung     

Deformation-morphology correlations in electrically conductive carbon nanotube—thermoplastic polyurethane nanocomposites

Addition of small amounts (0.5-10 vol%) of multiwall carbon nanotubes (CNT) to thermoplastic elastomer Morthane produced polymer nanocomposites with high electrical conductivity (σ∼1-10 S/cm), low electrical percolation (?∼0.005) and enhancement of mechanical properties including increased modulus and yield stress without loss of the ability to stretch the elastomer above 1000% before rupture. In situ X-ray scattering during deformation indicated that these mechanical enhancements arise not only from the CNTs, but also from their impact on soft-segment crystallization. The deformation behavior after yielding of the nanocomposites, irrespective of CNT concentration, is similar to the unfilled elastomer, implying that the mechanistics of large deformation is mainly governed by the matrix. The relative enhancement of the Young's modulus of the nanocomposites is comparable to other elastomeric nanocomposites, implying that to the first order specific chemical details of the elastomeric system is unimportant.     

Soft eigenvalue assignment with limited disturbance feedforward and state controller norm

The method of softly assigning eigenvalues is attractive for design problems where constraining the control effort and disturbance feedforward is more important than following the exact pole location.     

Ray tracing with PO/PTD for RCS modeling of large complex objects

The present paper deals with a new efficient approach in order to assess the simulation of scattered fields from arbitrary metallic objects. The basic idea is to combine a ray tracing algorithm with the principles of physical optics (PO) and the physical theory of diffraction (PTD). The ray tracing algorithm stochastically launches discrete rays and uses a ray density normalization. In order to perform simulations at finite objects the PO/PTD formulation is required. Thus, fast intersection routines can be implemented, while the ray density formulation reduces the PO and PTD integrals to a pure sum of ray contributions. Simulation results obtained with this model are verified by comparison with both exact simulations using a method of moments (MoM) code and measurement results, proving an excellent accuracy and fast computation even at complex objects. With this asymptotic approach, scattering properties of large objects that are too complex for exact methods can be analyzed with rather moderate computation efforts. Typical applications include the simulation of low observability (LO) designs as well as the generation of databases for identifying unknown aircraft by their radar signature.