Study of hemodynamics using a flow-pressure transducer

A method for simultaneous measuring the pressure and blood flow through the vascular wall is described. It is based on the application of a miniature pressure transducer combined with an ultrasonic blood flow transducer. The tests were performed in a Pitotube by means of pulsing flows. The flow-pressure transducer was applied to studying the hemodynamics of the cat thoracic aorta.     

Protein family classification using sparse markov transducers.

We present a method for classifying proteins into families based on short subsequences of amino acids using a new probabilistic model called sparse Markov transducers (SMT). We classify a protein by estimating probability distributions over subsequences of amino acids from the protein. Sparse Markov transducers, similar to probabilistic suffix trees, estimate a probability distribution conditioned on an input sequence. SMTs generalize probabilistic suffix trees by allowing for wild-cards in the conditioning sequences. Since substitutions of amino acids are common in protein families, incorporating wild-cards into the model significantly improves classification performance. We present two models for building protein family classifiers using SMTs. As protein databases become larger, data driven learning algorithms for probabilistic models such as SMTs will require vast amounts of memory. We therefore describe and use efficient data structures to improve the memory usage of SMTs. We evaluate SMTs by building protein family classifiers using the Pfam and SCOP databases and compare our results to previously published results and state-of-the-art protein homology detection methods. SMTs outperform previous probabilistic suffix tree methods and under certain conditions perform comparably to state-of-the-art protein homology methods.     

Automated identification of field-recorded songs of four British grasshoppers using bioacoustic signal recognition

Recognition of Orthoptera species by means of their song is widely used in field work but requires expertise. It is now possible to develop computer-based systems to achieve the same task with a number of advantages including continuous long term unattended operation and automatic species logging. The system described here achieves automated discrimination between different species by utilizing a novel time domain signal coding technique and an artificial neural network. The system has previously been shown to recognize 25 species of British Orthoptera with 99% accuracy for good quality sounds. This paper tests the system on field recordings of four species of grasshopper in northern England in 2002 and shows that it is capable of not only correctly recognizing the target species under a range of acoustic conditions but also of recognizing other sounds such as birds and man-made sounds. Recognition accuracies for the four species of typically 70-100% are obtained for field recordings with varying sound intensities and background signals.     

3-dimensional registration of micro-movements of vertebral implants by a specially adapted measuring system using magnetic transducers]

The aim of this study was to develop a biomechanical experimental set-up to quantify motion of ventrally inserted spinal implants at the implant/bone interface. The model we used was the vertebral column of the calf. Lumbar vertebrae L2 to L4 were "instrumented" with a screw-rod system. The adjacent vertebrae L1 and L5 were connected to a servohydraulic testing machine and axial compression applied. Shortening of the specimen and three-dimensional movement of the most cranial implant relative to the bone was recorded using 3 electromagnetic transducers. 100,000 cycles of axial loading varying between -0.5 kN and -1 kN were applied. Static shortening of the specimen of 8.5 mm and an elastic movement of 180 to 280 microns were measured. The greatest amplitude of single-plane motion was recorded in the sagittal plane in both static and elastic modes. Implant motion within each cycle was recorded accurately as load-displacement curves within a range of 1.35 to 30 microns. With this test set-up, primary stability of different spinal implant systems can be compared. The use of electromagnetic transducers permits three-dimensional implant motion analysis even when only a mono-axial servohydraulic testing machine is available.     

Phosphorylase: a biological transducer.

A transducer is a device that receives energy from one system and transmits it, often in a different form, to another. Glycogen phosphorylase receives information from the cell or organism in the form of metabolic signals. The energy associated with the binding of these ligand signals is integrated and transmitted at an atomic level, allowing precise adjustment of the enzymatic activity. Understanding this elegant allosteric control has required several different approaches, but the structural requirements of allostery are being defined.     

Volume-dependent variations of regional lung sound, amplitude, and phase.

Acoustic imaging of the respiratory system demonstrates regional changes of lung sounds that correspond to pulmonary ventilation. We investigated volume-dependent variations of lung sound phase and amplitude between two closely spaced sensors in five adults. Lung sounds were recorded at the posterior right upper, right lower, and left lower lobes during targeted breathing (1.2 +/- 0.2 l/s; volume = 20-50 and 50-80% of vital capacity) and passive sound transmission (< or =0.2 l/s; volumes as above). Average sound amplitudes were obtained after band-pass filtering to 75-150, 150-300, and 300-600 Hz. Cross correlation established the phase relation of sound between sensors. Volume-dependent variations in phase (< or =1.5 ms) and amplitude (< or =11 dB) were observed at the lower lobes in the 150- to 300-Hz band. During inspiration, increasing delay and amplitude of sound at the caudal relative to the cranial sensor were also observed during passive transmission in several subjects. This previously unrecognized behavior of lung sounds over short distances might reflect spatial variations of airways and diaphragms during breathing.     

Evaluation of a microprocessor-controlled exercise testing system

We evaluated a new exercise-testing system (Beckman Horizon MMC), incorporating a microprocessor that controls the acquisition of data, corrects for time delays, applies calibration factors, ensures quality control, and presents results in a variety of formats. Precision of measurements of ventilation (VE) and mixed expired gas concentrations was high. In steady-state exercise (n = 100) VO2 was measured with a precision (+/- SD) of 66 ml/min (4.3%), (r = 0.991); there was a small (4.62%) systematic underestimation of VCO2, but precision was comparable with VO2, with SD being 67 ml/min (4.55%) (r = 0.993). Good agreement was obtained between measurements made in progressive incremental exercise in healthy subjects with correlation coefficients of 0.997 for VE, 0.995 for VO2, and 0.994 for VCO2. Agreement in patients with cardiorespiratory disorders (n = 10) was similar, except in three patients in whom a variable pattern of breathing limited strict comparisons. Comparison with a breath-by-breath analysis system (n = 5) showed that rapid changes in VE, VCO2, and VO2 were followed accurately; the half time for a change in VO2 was not systematically different between the two systems (SD, 3.34 s, r = 0.951). The incorporation of microprocessor-controlled calibration procedures, which are simple to carry out frequently, was judged to be an important feature of this system.     

Comparison of pathway analysis approaches using lung cancer GWAS data sets

Pathway analysis has been proposed as a complement to single SNP analyses in GWAS. This study compared pathway analysis methods using two lung cancer GWAS data sets based on four studies: one a combined data set from Central Europe and Toronto (CETO); the other a combined data set from Germany and MD Anderson (GRMD). We searched the literature for pathway analysis methods that were widely used, representative of other methods, and had available software for performing analysis. We selected the programs EASE, which uses a modified Fishers Exact calculation to test for pathway associations, GenGen (a version of Gene Set Enrichment Analysis (GSEA)), which uses a Kolmogorov-Smirnov-like running sum statistic as the test statistic, and SLAT, which uses a p-value combination approach. We also included a modified version of the SUMSTAT method (mSUMSTAT), which tests for association by averaging χ² statistics from genotype association tests. There were nearly 18000 genes available for analysis, following mapping of more than 300,000 SNPs from each data set. These were mapped to 421 GO level 4 gene sets for pathway analysis. Among the methods designed to be robust to biases related to gene size and pathway SNP correlation (GenGen, mSUMSTAT and SLAT), the mSUMSTAT approach identified the most significant pathways (8 in CETO and 1 in GRMD). This included a highly plausible association for the acetylcholine receptor activity pathway in both CETO (FDR≤0.001) and GRMD (FDR = 0.009), although two strong association signals at a single gene cluster (CHRNA3-CHRNA5-CHRNB4) drive this result, complicating its interpretation. Few other replicated associations were found using any of these methods. Difficulty in replicating associations hindered our comparison, but results suggest mSUMSTAT has advantages over the other approaches, and may be a useful pathway analysis tool to use alongside other methods such as the commonly used GSEA (GenGen) approach.     

Development of a novel liquid crystal based cell traction force transducer system

Keratinocyte traction forces play a crucial role in wound healing. The aim of this study was to develop a novel cell traction force (CTF) transducer system based on cholesteryl ester liquid crystals (LC). Keratinocytes cultured on LC induced linear and isolated deformation lines in the LC surface. As suggested by the fluorescence staining, the deformation lines appeared to correlate with the forces generated by the contraction of circumferential actin filaments which were transmitted to the LC surface via the focal adhesions. Due to the linear viscoelastic behavior of the LC, Hooke's equation was used to quantify the CTFs by associating Young's modulus of LC to the cell induced stresses and biaxial strain in forming the LC deformation. Young's modulus of the LC was profiled by using spherical indentation and determined at approximately 87.1±17.2kPa. A new technique involving cytochalasin-B treatment was used to disrupt the intracellular force generating actin fibers, and consequently the biaxial strain in the LC induced by the cells was determined. Due to the improved sensitivity and spatial resolution (～1μm) of the LC based CTF transducer, a wide range of CTFs was determined (10-120nN). These were found to be linearly proportional to the length of the deformations. The linear relationship of CTF-deformations was then applied in a bespoke CTF mapping software to estimate CTFs and to map CTF fields. The generated CTF map highlighted distinct distributions and different magnitude of CTFs were revealed for polarized and non-polarized keratinocytes.     

Bacteriorhodopsin: a picosecond optoelectric signal transducer.

This paper summarizes the results found in our laboratory investigating the ultrafast light-induced charge separation in bacteriorhodopsin. A special technique was elaborated for dried oriented samples of long term stability. An upper limit of 21 ps was found by a direct electric method for the early charge separation processes. A permanent electric field on the surface of illuminated samples was demonstrated. The potential application of such samples as ultrafast optoelectric signal transducers is discussed.     

Establishment of paternity testing system using microsatellite markers in Chinese Holstein

To estimate the efficiency of microsatellite markers in paternity testing among Chinese Holstein, 30 microsatellite loci were used to differentiate 330 Chinese Holstein genotypes, according to the calculation of the allele frequency, number of alleles, effective number of alleles, genetic heterozygosity, polymorphic information content (PIC), and the exclusion probability in this cattle population. The results demonstrated that the exclusion probability ranged from 0.620 in locus BM1818 to 0.265 in locus INRA005 with the average of 0.472 and 11 microsatellite markers exceeding 0.5. The combined exclusion probability of nine microsatellite markers was over 0.99. The result showed that paternity testing of Chinese Holstein was basically resolved using the nine microsatellite markers selected.     

Model system using coliphage phi X174 for testing virus removal by air filters.

Short-term (15-min-duration) and long-term (5- to 6-day-duration) test procedures have been developed for determining the efficiency of the removal of bacteriophage phi X174 by air-sterilizing filters. These procedures were sensitive enough to measure a 10(8)-fold reduction in the number of bacteriophage. A filter commonly used in industrial air sterilizations (Domnick-Hunter Bio-X borosilicate glass) effected a 10(8)-fold removal of viable phage in both short-term and long-term tests. A prototype low-flux, hollow-fiber membrane gave similar results; however, a prototype high-flux, hollow-fiber membrane removed only about 99.999% of the bacteriophage in short-term tests.     

Model system using coliphage phi X174 for testing virus removal by air filters.

Short-term (15-min-duration) and long-term (5- to 6-day-duration) test procedures have been developed for determining the efficiency of the removal of bacteriophage phi X174 by air-sterilizing filters. These procedures were sensitive enough to measure a 10(8)-fold reduction in the number of bacteriophage. A filter commonly used in industrial air sterilizations (Domnick-Hunter Bio-X borosilicate glass) effected a 10(8)-fold removal of viable phage in both short-term and long-term tests. A prototype low-flux, hollow-fiber membrane gave similar results; however, a prototype high-flux, hollow-fiber membrane removed only about 99.999% of the bacteriophage in short-term tests.     

Characterization of a cell-free protein synthesizing system from rat lung.

1. A cell-free protein synthesizing system has been developed from a novel source, namely the rat lung. 2. The system translates endogenous mRNA at a linear rate for up to 10 min at approx 5% of the in vivo rate. 3. With the use of edeine and 7-methylguanosine-5'-triphosphate (m7GTP), specific blockers of peptide chain initiation, we have demonstrated that 40-60% of total amino acid incorporation is attributable to reinitiation on nascent polypeptide chains. 4. The lung cell-free system will be a valuable asset when investigating the mechanisms involved in the regulation of pulmonary protein synthesis.     

Evaluation of a new anaerobic power testing system

The purpose of this study was to evaluate the reliability of a new anaerobic athletic performance system. This system is proposed to assess vertical jump height, anaerobic power through repetitive jumping, and reaction to both an auditory and visual stimulus. One hundred twenty-three subjects (92 men and 31 women; mean +/- SD: age, 20.5 +/- 2.1 years; body weight, 83.1 +/- 20.4 kg; height, 176.0 +/- 9.2 cm) volunteered to participate. To assess reliability of the new testing device, subjects were tested on 3 separate occasions (T1, T2, and T3). At least 72 hours but not more than 1 week separated each laboratory visit. During each testing session subjects performed a countermovement jump (CMJ), a 30 consecutive jumps anaerobic power test (30JT), and reaction to both an auditory and visual stimulus. Results showed no differences between T1, T2, and T3 in either CMJ height or 30JT assessments. However, reaction to an audible or visual stimulus significantly improved during each testing session. Intraclass reliability of the CMJ and the 30JT was greater than 0.96 across the 3 trials. Pearson correlation coefficients of r > 0.90 were seen for the CMJ and 30JT, indicating a high test-retest reliability. The test-retest reliability for the reaction tests were lower (r ranging from 0.72 to 0.83). A Bland-Altman plot showed limited agreement between methods of vertical jump height assessment. Results indicate that this new testing device shows high reliability to assess both CMJ height and anaerobic power. In addition, anaerobic power assessment in a jump test provides a specific measure of anaerobic power for many sports incorporating similar performance patterns.     

A cell-based sensor system for toxicity testing using multiwavelength fluorescence spectroscopy

A novel cell-based fluorometric sensor system for toxicity monitoring is described, which uses functional spontaneously contracting cardiomyocytes (HL-1 cell line) as the biological recognition element. Based on these highly specialized cells, it has the potential of providing a sensitive and relevant analytical in vitro toxicity testing method. The system was configured by propagating the surface-attaching HL-1 cardiomyocytes in the wells of a 96-well microtiter plate and connecting the plate via an optical fiber to a fluorescence spectrometer capable of excitation-emission matrix scanning. The fluorescence data were analyzed using a conventional spectral analysis software program. The performance of the system for detection of general cytotoxicity to the cells was evaluated using three well-known drugs: verapamil, quinidine, and acetaminophen. The dose-response curves were assessed and the EC₅₀ values were determined (0.10 ± 0.007, 0.23 ± 0.025, and 12.32 ± 2.40 mM, respectively). Comparison with in vitro and in vivo reference data for the drugs showed good correlations, suggesting that this cell-based sensor system could be a useful tool in pharmacological in vitro drug testing.