Microwave Rejection Networks

This is an extension of the Bridged-T infinite rejection network idea transformed into microwave concepts. These devices achieve approximately 100db of attenuation with skirt attenuations approximately 5db. The tuning range between 1 KMc and 10 KMc is continuously covered with 4 units at present. Work is continuing to reduce the number of units to 2. Design parameters, performance curves, and application to MILSTD 826 will be discussed.     

Relationships between accident investigations, risk analysis, and safety management

Several different approaches to achieve safety are in common use, and examples are accident investigations (AI), risk analysis (RA), and safety management systems (SMS). The meaning of these concepts and their practical applications vary quite a lot, which might cause confusion. A summary of definitions is presented. A general comparison is made of application areas and methodology. A proposal is made how to indicate parameters of variation. At one end of the scale there are organisations, which are highly organised in respect to safety. At the other end are small companies with informal safety routines. Although the three concepts differ in a number of respects, there are many links between them which is illustrated in a model. A number of relations have been described mainly concerned with more advanced organisations. Behind the practical safety work, there are varying sets of more or less explicit explanations and theories on safety and accident causation. Depending on the theory applied, the relations between approaches can be more or less clear and essential.     

Synthesis of branched 'nanotrees' by controlled seeding of multiple branching events

The formation of nanostructures with controlled size and morphology has been the focus of intensive research in recent years. Such nanostructures are important in the development of nanoscale devices and in the exploitation of the properties of nanomaterials. Here we show how tree-like nanostructures ('nanotrees') can be formed in a highly controlled way. The process involves the self-assembled growth of semiconductor nanowires via the vapour-liquid-solid growth mode. This bottom-up method uses initial seeding by catalytic nanoparticles to form the trunk, followed by the sequential seeding of branching structures. Each level of branching is controlled in terms of branch length, diameter and number, as well as chemical composition. We show, by high-resolution transmission electron microscopy, that the branching mechanism gives continuous crystalline (monolithic) structures throughout the extended and complex tree-like structures. The controlled seeding method that we report here has potential as a generic means of forming complex branching structures, and may also offer opportunities for applications, such as the mimicking of photosynthesis in nanotrees.     

The study of control methods for the robotic testing system for human musculoskeletal joints

Biomechanical testing of human musculoskeletal joints not only requires qualified testing machines and devices, but also needs an excellent control method to obtain better experimental results. In this paper, we take the human functional spinal unit (FSU) as an example to study how to improve the performance of the robotic testing system. First, the mechanical characteristics of the FSU are described and the simplified model (a rigid body-spring system) for the specimen is given. Because the location of the center of rotation (COR) of the specimen affects the performance of the system, so a comprehensive analysis on the location of the COR is carried out. Furthermore, the performance of the robotic testing system can be also improved through the improvement of the control methods. Two control methods have been proposed, one is the improved hybrid control and the other is fuzzy logic control (FLC).     

Detection of skin cancer by classification of Raman spectra

Skin lesion classification based on in vitro Raman spectroscopy is approached using a nonlinear neural network classifier. The classification framework is probabilistic and highly automated. The framework includes a feature extraction for Raman spectra and a fully adaptive and robust feedforward neural network classifier. Moreover, classification rules learned by the neural network may be extracted and evaluated for reproducibility, making it possible to explain the class assignment. The classification performance for the present data set, involving 222 cases and five lesion types, was 80.5%+/-5.3% correct classification of malignant melanoma, which is similar to that of trained dermatologists based on visual inspection. The skin cancer basal cell carcinoma has a classification rate of 95.8%+/-2.7%, which is excellent. The overall classification rate of skin lesions is 94.8%+/-3.0%. Spectral regions, which are important for network classification, are demonstrated to reproduce. Small distinctive bands in the spectrum, corresponding to specific lipids and proteins, are shown to hold the discriminating information which the network uses to diagnose skin lesions.     

Screening for noncovalent ligand-receptor interactions by electrospray ionization mass spectrometry-based diffusion measurements

The application of a novel method for the identification of low-molecular-weight noncovalent ligands to a macromolecular target is reported. This technique is based on the measurement of analyte diffusion coefficients by electrospray mass spectrometry (ESI-MS) (Clark et al., Rapid Commun. Mass Spectrom. 2002, 16, 1454-1462). Potential ligands have large diffusion coefficients as long as they are free in solution. Binding to a macromolecular target, however, drastically reduces the diffusional mobility of any ligand species. Mixtures containing six different saccharides [ribose, rhamnose, glucose, maltose, maltotriose, and N,N',N'-triacetylchitotriose (NAG(3))] were screened for noncovalent binding to lysozyme. Of these six compounds, only NAG(3) is known to bind to the protein. In "direct" binding tests, NAG(3) shows a significantly reduced diffusion coefficient in the presence of the protein. No changes were observed for any of the other saccharides. In a second set of experiments, the use of a "competition" screening method was explored in which mixtures of candidate saccharides were tested for their ability to displace a reference ligand from the target. The addition of NAG(3)-containing mixtures significantly increased the diffusion coefficient of the reference ligand NAG(4) (N,N',N',N'-tetraacetylchitotetrose), whereas mixtures that did not contain NAG(3) had no effect. These data clearly indicate the potential of ESI-MS-based diffusion measurements as a novel tool to screen compound libraries for binding to proteins and other macromolecular targets. In contrast to conventional ESI-MS-based ligand-receptor binding studies, this method does not rely on the preservation of noncovalent interactions in the gas phase.     

Real-time nucleic acid sequence-based amplification in nanoliter volumes

Real-time nucleic acid sequence-based amplification (NASBA) is an isothermal method specifically designed for amplification of RNA. Fluorescent molecular beacon probes enable real-time monitoring of the amplification process. Successful identification, utilizing the real-time NASBA technology, was performed on a microchip with oligonucleotides at a concentration of 1.0 and 0.1 microM, in 10- and 50-nL reaction chambers, respectively. The microchip was developed in a silicon-glass structure. An instrument providing thermal control and an optical detection system was built for amplification readout. Experimental results demonstrate distinct amplification processes. Miniaturized real-time NASBA in microchips makes high-throughput diagnostics of bacteria, viruses, and cancer markers possible, at reduced cost and without contamination.     

Mechanistic studies on enzymatic reactions by electrospray ionization MS using a capillary mixer with adjustable reaction chamber volume for time-resolved measurements

Mass spectrometry (MS)-based techniques have enormous potential for kinetic studies on enzyme-catalyzed processes. In particular, the use of electrospray ionization (ESI) MS for steady-state measurements is well established. However, there are very few reports of MS-based studies in the pre-steady-state regime, because it is difficult to achieve the time resolution required for this type of experiment. We have recently developed a capillary mixer with adjustable reaction chamber volume for kinetic studies by ESI-MS with millisecond time resolution (Wilson, D. J.; Konermann, L. Anal. Chem. 2003, 75, 6408-6414). Data can be acquired in kinetic mode, where the concentrations of selected reactive species are monitored as a function of time, or in spectral mode, where entire mass spectra are obtained for selected reaction times. Here, we describe the application of this technique to study the kinetics of enzyme reactions. The hydrolysis of p-nitrophenyl acetate by chymotrypsin was chosen as a simple chromophoric model system. On-line addition of a "makeup solvent" immediately prior to ionization allowed the pre-steady-state accumulation of acetylated chymotrypsin to be monitored. The rate constant for acetylation, as well as the dissociation constant of the enzyme-substrate complex obtained from these data, is in excellent agreement with results obtained by conventional stopped-flow methods. Bradykinin was chosen to illustrate the performance of the ESI-MS-based method with a nonchromophoric substrate. In this case, the unfavorable rate constant ratio for acylation and deacylation of the enzyme precluded measurements in the pre-steady-state regime. Steady-state experiments were carried out to determine the turnover number and the Michaelis constant for bradykinin. The methodologies used in this work open a wide range of possibilities for future ESI-MS-based kinetic assays in enzymology.     

Determination of ligand-protein dissociation constants by electrospray mass spectrometry-based diffusion measurements

A novel approach for the quantification of ligand-protein interactions is presented. Electrospray ionization mass spectrometry (ESI-MS) is used to monitor the diffusion behavior of noncovalent ligands in the presence of their protein receptors. These data allow the fraction of free ligand in solution to be determined, such that the corresponding dissociation constants can be calculated. A set of conditions is developed that provides an "allowable range" of concentrations for this type of assay. The method is tested by applying it to two different inhibitor-enzyme systems. The dissociation constants measured for benzamidine-trypsin and for N,N',N' '-triacetylchitotriose-lysozyme are (50 +/- 10) and (6 +/- 1) mM, respectively. Both of these results are in good agreement with previous data from the literature. In contrast to traditional ESI-MS-based methods, the approach used in this work does not rely on the preservation of specific solution-type noncovalent interactions in the gas phase. It is shown that this method allows an accurate determination of dissociation constants, even in cases in which the ion abundance ratio of free to ligand-bound protein in ESI-MS does not reflect the corresponding concentration ratio in solution.