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Biomedical subjects

S Cochran

Publications and source records attributed to S Cochran.

At least 19 recordsLinked to original sources

Imaging with lithium niobate/epoxy composites.

Lithium niobate, LiNbO3, is a very promising material for high temperature applications in non-destructive testing because of its high Curie temperature. However, for commercial applications LiNbO3 has often been neglected because of its low electromechanical coupling coefficients. This paper explores the potential of LiNbO3 composites, by means of room temperature characterization and measurements, for further use in operation in high temperature transducers. LiNbO3 composites of 1-3 connectivity in an epoxy matrix with volume fractions of LiNbO3 of 33% and 54% were fabricated. The composites were characterized by electrical impedance measurements and the results were compared with modelled impedance characteristics. Many parameters were predicted accurately, including an improvement of more than 75% in thickness mode electromechanical coupling coefficient, from kT=0.17 for bulk LiNbO3 to kT=0.32 for composite material. Some large discrepancies between simulation and experiment were also identified when a conventional one-dimensional model was used to calculate equivalent composite material parameters; however, finite element modelling was more accurate. After characterization, the composite was configured for use as a linear array. Functional measurements were conducted on steel blocks with a side drilled hole to represent a crack tip. This was detected by the array and visualized in time-of-flight diffraction B-scan images.

Journal Article↗

Multilayer piezocomposite structures with piezoceramic volume fractions determined by mathematical optimisation.

Piezocomposite materials are now widely used in broadband underwater sonar for ultrasound generation and detection because of their recognised advantages over piezoceramic devices. However, it is difficult to make single-layer piezocomposite devices to operate effectively at frequencies below 100 kHz. Instead, multilayer composite stacks can be used. If this solution is adopted, interesting effects can be achieved by choosing appropriate ceramic volume fractions for different layers in the stack, as volume fraction plays a key role in achieving the desired performance. In this paper we describe a theoretical study of 1-3 piezocomposite transducers with five layers each with a different volume fraction. Our work is based mainly on our own special purpose computer code which solves the one-dimensional wave equation by matrix manipulation, with additional support from the PZ Flex finite element analysis package. The choice of volume fractions is difficult because of the multifaceted nature of the problem, with a very large number of possible combinations and complex dependence of material properties, and hence transducer sensitivity and frequency response on the volume fractions. Therefore, we have used the stochastic optimisation technique of simulated annealing implemented in MATLAB code to determine the volume fraction of each layer. The optimisation cost function we have used is maximisation of gain-bandwidth product. We have found that significant increases in gain-bandwidth product can be achieved compared with the use of the same volume fraction in each layer, far exceeding the 35% reported previously with trial-and-error volume fraction adjustment. This suggests that improvements in practical device performance are possible.

Journal Article↗

Thick aluminium nitride films deposited by room-temperature sputtering for ultrasonic applications.

Materials in film form for electromechanical transduction have a number of potential applications in ultrasound. They are presently under investigation in flexural transducers for air-coupled ultrasound and underwater sonar operating at frequencies up to a few megahertz. At higher frequencies, they have the potential to be integrated with electronics for applications of ultrasound requiring high spatial resolution. However, a number of fabrication difficulties have arisen in studies of such films. These include the high temperatures required in many thick and thin film deposition processes, making them incompatible with other stages in transducer fabrication, and difficulties maintaining film quality when thin film--typically sub-1 microm--processes are extended to higher thicknesses. In this paper, we first outline a process which has allowed us to deposit aluminium nitride (AlN) films capable of electromechanical transduction at thicknesses up to more than 5 microm without substrate heating. As an ultrasonic transduction material, AlN has functional disadvantages, particularly a high acoustic velocity and weak electromechanical transduction. However, it also has a number of advantages relating to practicality of fabrication and functionality. These include the ability to be deposited on a variety of amorphous substrates, a very high Curie temperature, low permittivity, and low electrical and mechanical losses. Here, we present experimental results highlighting the transduction capabilities of AlN deposited on aluminium electrodes on glass and lithium niobate. We compare the results with those from standard simulation processes, highlighting the reasons for discrepancies and discussing the implications for incorporation of AlN into standard ultrasonic transducer design processes.

Journal Article↗

1-3 connectivity piezoelectric ceramic-polymer composite transducers made with viscous polymer processing for high frequency ultrasound.

Potential applications of high frequency ultrasound exist because of the high spatial resolution consequent upon short wavelength. The frequencies of interest, typically from 25 MHz upwards, are easily supported by modern instrumentation but the capabilities of ultrasonic transducers have not kept pace and the transducers in high frequency commercial ultrasonic systems are still made with single-phase crystal, ceramic or piezopolymer materials. Despite potential performance advantages, the 1-3 connectivity piezoelectric ceramic-polymer composite materials now widely used at lower ultrasonic frequencies have not been adopted because of manufacturing difficulties. These difficulties are centred on fabrication of the 1-3 piezoceramic bristle-block comprising tall, thin pillars upstanding from a supporting stock. Fabrication techniques which have been explored already include injection moulding, mechanical dicing, and laser machining. Here, we describe an alternative technique based on viscous polymer processing (VPP) to produce net shape ceramic bristle-blocks. VPP produces green-state ceramic with rheological properties suitable for embossing. We outline how this can be created then report on our work to fabricate PZT bristle-blocks with lateral pillar dimensions of the order of 50 microm and height-to-width ratios of the order of 10. These have been backfilled with low pre-cure viscosity polymer and made into complete 1-3 piezocomposite transducer elements. We outline the performance of the transducers in terms of electrical impedance and pulse-echo behaviour and show that it corresponds well with computer modelling. We conclude that VPP is a promising technique to allow the established advantages of piezocomposite material to be exploited at higher frequencies than have been possible so far.

Journal Article↗

Experimental investigation of alternative pre-stress components for a 3-1 connectivity multilayer piezoelectric-polymer composite ultrasonic transducer.

The most popular configuration for piezoelectric-polymer composites has pillars of piezoelectric ceramic supported by a polymer matrix and material with this structure is now widely available commercially. However, it has significant disadvantages for use in multilayer devices for non-mass-loaded operation below approximately 50 kHz. An alternative configuration is therefore reported here, in which interconnected fingers of piezoelectric ceramic surround polymer plates. This can be termed 3-1 connectivity, since the piezoceramic is fully connected in three dimensions and the polymer in only one. The configuration has been found to have significant manufacturing advantages which feed through to enhanced performance compared with practical 1-3 connectivity multilayer devices. For many potential applications, high-power operation is required, and it is unclear if the multilayer structure has sufficient internal strength to maintain its integrity at high strains. Therefore, an investigation has been carried out into alternative pre-stressing component designs. These comprise back and front stainless steel plates of different shapes, connected by a number of stainless steel rods. In this paper, the fundamental performance of a multilayer device is illustrated with electrical impedance and surface displacement measurements in air, without pre-stressing. Then measurements are reported from three different clamping configurations. It is shown that good results can be achieved at spot frequencies with a suitable clamp, but that unsuitable clamps prevent even this, and broadband performance is unlikely to be achieved easily.

Journal Article↗

The novel long PDE4A10 cyclic AMP phosphodiesterase shows a pattern of expression within brain that is distinct from the long PDE4A5 and short PDE4A1 isoforms.

In situ hybridisation methods were used to map the distribution of the novel long PDE4A10 isoform in the brain. PDE4A10 distribution was compared to that of the long PDE4A5 isoform and the short PDE4A1 isoform using probes specific for unique sequences within each of these isoforms. Coronal sections of the brain, taken at the level of the olfactory bulb, prefrontal cortex, striatum, thalamus, hippocampus and cerebellum, were analysed. Strongest expression of PDE4A isoforms was found in the olfactory bulb granular layer with high signals also in the piriform cortex, the dentate gyrus and the CA1 and CA2 pyramidal cells. For the two long forms, level general staining was noted throughout the striatum, thalamus and hippocampus but no signal was evident in the cerebellum. The long PDE4A10 and PDE4A5 isoforms localised to essentially the same regions throughout the brain, although PDE4A10 was uniquely expressed in the major island of Calleja. A signal for the short PDE4A1 isoform was found in regions in which the two long isoforms were both expressed, with the exception of the medial nucleus of the amygdala where weak signals for PDE4A5 and PDE4A10 were detected but PDE4A1 was absent. Uniquely, strong signals for PDE4A1 were detected in the glomerular layer of the olfactory bulb, the CA3 pyramidal cell region and the cerebellum; areas where signals for the two long forms were not evident. PDE4A transcripts for both PDE4A5 and PDE4A10 were not apparent in the brain stem and those for PDE4A1 were low. PDE4A isoforms are present in several key areas of the brain and therefore present valid targets for therapeutic interventions. Whilst the two long PDE4A isoforms show a remarkably similar distribution, in at least three regions there is clear segregation between their pattern of expression and that of the PDE4A1 short form. This identifies differential regulation of the expression of PDE4A long and short isoforms. We suggest that specific PDE4A isoforms may have distinct functional roles in the brain, indicating that PDE4A isoform-selective inhibitors may have specific therapeutic and pharmacologic properties.

3',5'-Cyclic-AMP Phosphodiesterases↗

Features of the auditory development of the short-tailed Brazilian opossum, Monodelphis domestica: evoked responses, neonatal vocalizations and synapses in the inferior colliculus.

The onset of hearing in anesthetized South American opossums (Monodelphis domestica) was determined by the measurement of evoked potentials to click stimuli from the vertex of the skull immediately over the inferior colliculus. Evoked potentials were first recorded at postnatal day 24 at a threshold of 83 dB SPL; thresholds declined over subsequent weeks to below 58 dB at 40 days. Isolation calls emitted by the pups had stereotypic spectra with peaks at near 13 kHz and an octave higher. Such calls declined in frequency by day 32 and were not emitted at day 40. The peak frequency of the calls matched very closely the best frequency of hearing of adult Monodelphis. The number of synapses in the inferior colliculus increased at day 26; when plotted in relation to the number of cells, synaptic density increased steeply from day 27 after the animal had begun to hear. This suggests that environmental sound has a potent effect on the development of synapses in the auditory system.

Acoustic Stimulation↗

Modulation of idiotypic and antiidiotypic immunoglobulin G responses in an alloimmune thrombocytopenic patient associated with extracorporeal protein A immunoadsorption.

In the present case study, a patient with Non-Hodgkin. Lymphoma underwent combination chemotherapy resulting in severe pancytopenia requiring transfusion support with blood products. The patient became refractory to random donor platelet transfusions and subsequently received five immunoadsorption treatments. The patient's clinical response to immunoadsorption therapy was assessed by monitoring platelet transfusion recovery and survival. In addition, changes in antibody responses were assessed. Early during the course of immunoadsorption therapy, antiplatelet immunoglobulin G (IgG) alloantibody was detected. There was a decline in antiplatelet IgG alloantibody levels by the last immunoadsorption treatment associated with increases to platelet correct count increments after completion of immunoadsorption therapy. In addition, elevated levels of antiidiotypic IgG antibody detected early during the course of therapy were significantly reduced by the last immunoadsorption treatment. This case study suggests that specific alloimmune idiotypic IgG antibody and corresponding antiidiotypic IgG antibody responses may be modulated in association with extracorporeal immunoadsorption employing protein A/silica columns.

Adolescent↗

Cloning and sequencing of a human thioredoxin reductase.

The DNA sequence encoding human placental thioredoxin reductase has been determined. Of the 3826 base pairs sequenced, 1650 base pairs were in an open reading frame encoding a mature protein with 495 amino acids and a calculated molecular mass of 54,171. Sequence analysis showed strong similarity to glutathione reductases and other NADPH-dependent reductases. Human thioredoxin reductase contains the redox-active cysteines in the putative FAD binding domain and has a dimer interface domain not previously seen with prokaryote and lower eukaryote thioredoxin reductases.

Amino Acid Sequence↗

Brominated polyacetylenic acids from the marine sponge Xestospongia muta: inhibitors of HIV protease.

The EtOAc extract of the sponge Xestospongia muta collected in Colombus Island, Bahamas, yielded eleven straight-chain unsaturated, polyacetylenic, brominated acids, seven of which were identified on the basis of spectral data, including the unknown acids 2-7. These acetylenic acids are the first known examples that have been shown to inhibit HIV protease, a critical enzyme in the replication of human immunodeficiency virus.

Animals↗

Detection of renal stones with real-time sonography: effect of transducers and scanning parameters.

Three experiments with a variety of transducers and scanning parameters were designed to investigate if renal stones could be detected with greater certainty by using particular transducers or scanning parameters. First, the lateral resolution, derived from the -6-dB size of the beam profile, was measured at various depths for five transducers commonly used for renal sonography. Second, an in vitro test object was constructed from bovine liver, porcine kidneys, and two renal calculi to access gray-scale map effects on shadow visibility before and after storage in the digital scan converter. The third experiment combined 15 lithotripsy patients with known renal stones with 16 patients in whom the results of renal sonography and other radiographic procedures suggested renal calculi. The group of 15 patients was scanned several times with the transducers and gray-scale maps studied earlier, and the group of 16 patients was scanned only with one transducer and one gray-scale map. On radiographs, 12 of the 16 patients did not have renal calculi. Sonograms of the test object showed that low-contrast images were best for detection of posterior shadows. Three radiologists interpreted the 31 sonograms with a sensitivity of 81% and a specificity of 86% for detecting renal stones. For the 15 cases of renal stones scanned with a variety of transducers, the three radiologists found that annular-array transducers depicted stone shadowing with less ambiguity than mechanical sector transducers did 81% of the time.

Animals↗

Factors influencing the accumulation in fibrous plaques of lipid derived from low density lipoprotein. II. Preferential immobilization of lipoprotein (a) (Lp(a)).

The extracellular lipid that accumulates in fibrous atherosclerotic lesions appears to be derived directly from plasma low density lipoprotein (LDL). One factor that may influence the lipid deposition is immobilization of part of the LDL in lesions, and an immobilized fraction can be released by incubation with the fibrinolytic enzyme, plasmin, suggesting that it is associated with fibrin. The lipoprotein variant Lp(a) is associated with increased risk of arterial disease, and its characteristic apoprotein, apo(a), is structurally related to plasminogen, suggesting that it might bind to the plasminogen binding sites on fibrin. In this study we have compared blood Lp(a) and the soluble and plasmin-releasable Lp(a) in 45 samples of normal intima and different types of lesion. Levels of soluble and plasmin-releasable Lp(a) were dependent on both blood level and type of tissue sample. Although the amount of soluble LDL was 5-20 times higher than Lp(a) in intima, the amounts released by plasmin were similar, and Lp(a) appears to account for most of the apo B-containing lipoprotein that is immobilized in lesions.

Aorta↗

The inter-relation of fibrin, lipoprotein(a) and plasminogen in human atherosclerotic lesions.

The low density lipoprotein (LDL) variant, lipoprotein(a) (Lp(a)) is a risk factor for coronary heart disease, and in this study we have examined its interaction with the arterial wall. Samples of normal intima and atherosclerotic lesions were extracted with buffer containing EDTA and protease inhibitors and assayed for LDL and Lp(a) by radial immunodiffusion. The extract tissues were washed, then incubated with plasmin and the amounts of LDL and Lp(a) released into the digest were measured. Intimal Lp(a) concentrations were compared to Lp(a) in the patients' blood. Levels of both soluble and plasmin-releasable Lp(a) were related to type of intimal sample and blood Lp(a) level. In early proliferative lesions there was a significant correlation between plasmin-releasable Lp(a) and blood Lp(a) (r = 0.631, P less than 0.002). Highest levels of plasmin-releasable Lp(a) were found in more advanced lesions that had accumulated some lipid. In extracts the amounts of LDL were 5-20 fold greater than Lp(a) but in the plasmin digests Lp(a) could account for most of the apoB detected, suggesting that Lp(a) may bind to fibrin in the lesion through its plasminogen-like structures and thus contribute to lipid accumulation in fibrous plaques. Plasminogen cannot be detected by rocket immunoelectrophoresis in samples from about two-thirds of aortas, and it seemed possible that the large plasminogen-like apo(a) component of Lp(a) was interfering with intimal uptake or retention of plasminogen, or its immunoassay. However, in 28 samples of intima or thrombi from 16 patients there was no relation between amounts of Lp(a) and plasminogen.

Aorta↗

Detection, isolation and characterization of staphylococcal enterotoxin B in protein A preparations purified by immunoglobulin G affinity chromatography.

Studies were performed to detect and isolate trace contaminants of staphylococcal enterotoxin B (SEB) in various protein A preparations isolated by affinity chromatography employing human IgG covalently bound to Sepharose 4B. Utilizing an ELISA technique, trace amounts (0.018-0.138%) of SEB could be detected in protein A preparations after separation of the SEB employing a molecular sizing column in a high pressure liquid chromatography (HPLC) system. Trace contamination by SEB could be removed from protein A preparations by an additional DEAE ion exchange chromatography step employing a low ionic strength buffer system (0.005 M NaCl in 0.01 phosphate buffer, pH 7.50). The resulting protein A preparations possessed a purity higher than that observed prior to the final purification step. Polyacrylamide gel electrophoresis (PAGE) analyses of the trace contamination removed from protein A preparations by ion exchange chromatography revealed, in addition to SEB, several additional contaminating polypeptides of an unknown nature. These studies indicate that protein A preparations of high purity can be prepared by employing DEAE ion exchange chromatography in addition to affinity chromatography utilizing immobilized human IgG.

Chromatography, Affinity↗