Biomedical subjects
Publications and source records attributed to R P Taylor.
We report that liquids perform self-propelled motion when they are placed in contact with hot surfaces with asymmetric (ratchetlike) topology. The pumping effect is observed when the liquid is in the Leidenfrost regime (the film-boiling regime), for many liquids and over a wide temperature range. We propose that liquid motion is driven by a viscous force exerted by vapor flow between the solid and the liquid.
We use magnetoconductance fluctuation measurements of phase-coherent semiconductor billiards to quantify the contributions to the nonlinear electric conductance that are asymmetric under reversal of magnetic field. We find that the average asymmetric contribution is linear in magnetic field (for magnetic flux much larger than 1 flux quantum) and that its magnitude depends on billiard geometry. In addition, we find an unexpected asymmetry in the power spectrum of the magnetoconductance with respect to reversal of magnetic field and bias voltage.
BACKGROUND: Medicines and Healthcare products Regulatory Agency's (MHRA's) Medical Device Alert MDA/2004/048 described bias in some endocrine test results obtained on a few immunoassay platforms, particularly the Bayer Advia Centaur instrument, when using blood specimens collected into Becton Dickinson (BD) Vacutainer SSTII Advance tubes. As users of BD tubes and the Advia Centaur instrument, we addressed our concerns about the quality of the results that we had previously reported by undertaking an independent study. METHOD: We compared the results of 15 immunoassays performed on Bayer Advia Centaur using blood specimens collected into four different BD Vacutainer tubes (plain, old and newly released BD SSTII Advance, and BD PSTII). RESULTS: Compared with plain tubes, old SSTII Advance tube results showed no bias for testosterone, CA15-3, follicle-stimulating hormone and folate assays, but gave a positive bias for cortisol and a negative bias for vitamin-B12. Compared with plain tubes, BD PSTII tubes gave no significant bias for thyroid function tests, prolactin, parathyroid hormone, and CA125, but gave a negative bias for steroid assays, and a positive bias for gonadotrophins. The results obtained using new BD SSTII Advance tubes were generally comparable with those on plain tubes. CONCLUSIONS: Only for cortisol did our findings support the bias described by MHRA. Based on our results, apart from vitamin-B12 and possibly cortisol, there may have been no significant influence on clinical decisions as a result of using the old BD SSTII Advance specimen tubes. New BD SSTII Advance tubes and plain tubes give generally comparable results. BD PSTII tubes should not be used for steroid hormone measurements on the Bayer Advia Centaur instrument.
Fractals have experienced considerable success in quantifying the complex structure exhibited by many natural patterns and have captured the imagination of scientists and artists alike. With ever widening appeal, they have been referred to both as "fingerprints of nature" and "the new aesthetics." Our research has shown that the drip patterns of the American abstract painter Jackson Pollock are fractal. In this paper, we consider the implications of this discovery. We first present an overview of our research from the past five years to establish a context for our current investigations of human response to fractals. We discuss results showing that fractal images generated by mathematical, natural and human processes possess a shared aesthetic quality based on visual complexity. In particular, participants in visual perception tests display a preference for fractals with mid-range fractal dimensions. We also present recent preliminary work based on skin conductance measurements that indicate that these mid-range fractals also affect the observer's physiological condition and discuss future directions based on these results.
The well-established symmetry relations for linear transport phenomena cannot, in general, be applied in the nonlinear regime. Here we propose a set of symmetry relations with respect to bias voltage and magnetic field for the nonlinear conductance of two-terminal electric conductors. We experimentally confirm these relations using phase-coherent, semiconductor quantum dots.
For many years investigators have been researching methods of preconditioning the myocardium against ischaemia-induced damage; however, a majority of this research has been carried out in young animals and cells. Normal ageing is accompanied by changes in the human myocardium that decrease its capacity to tolerate and respond to various forms of stress. Also, the likelihood of experiencing an ischaemic stress and other cardiovascular complications increases as an individual ages; therefore, an aged population would benefit most from cardioprotective treatments. Methods currently known to provide cardioprotection (or preconditioning) include exercise, heat stress, oxidative stress, brief ischaemia, stretch and certain pharmacological interventions. It is unclear whether the aged myocardium can adapt to a preconditioning stimulus; however, many researchers have observed age-related alterations in the expression and activation of proteins key to the cardioprotective process. These proteins include heat shock protein 70 (HSP70), nitric oxide synthase (NOS), the sodium-hydrogen exchanger (NHE), and the mitogen-activated protein (MAP) kinases c-Jun N-terminal Kinase (JNK), extracellular signal-regulated kinase (ERK), and p38. Therefore, the purpose of the current review will be to outline the current knowledge of these cardioprotective agents in an aged myocardium. Interactions among the cardioprotective agents outlined herein suggest that age-related changes in the myocardium will need to be better understood before cardioprotective interventions that have been proved effective in young animals can be applied to an aged human population.
Brownian heat engines use local temperature gradients in asymmetric potentials to move particles against an external force. The energy efficiency of such machines is generally limited by irreversible heat flow carried by particles that make contact with different heat baths. Here we show that, by using a suitably chosen energy filter, electrons can be transferred reversibly between reservoirs that have different temperatures and electrochemical potentials. We apply this result to propose heat engines based on mesoscopic semiconductor ratchets, which can quasistatically operate arbitrarily close to Carnot efficiency.
OBJECTIVE-Assessment and follow-up of early renal dysfunction is important in diabetic nephropathy. Plasma creatinine is insensitive for a glomerular filtration rate (GFR) >50 ml/min and creatinine clearance is unwieldy and subject to collection inaccuracies. We aimed to assess the reproducibility, reliability, and accuracy of plasma cystatin C as a measure of GFR ranging from normal to moderate impairment due to type 1 diabetes in the presence of a normal plasma creatinine concentration. RESEARCH DESIGN AND METHODS-A sensitive immunoturbidimetric cystatin C assay was examined in 29 subjects with type 1 diabetes and 11 nondiabetic subjects. Duplicate measurements of the following were collected from each subject, 2 weeks apart: cystatin C, enzymatic plasma creatinine, 24-h creatinine clearance, GFR estimated from plasma creatinine by the Cockcroft-Gault equation, and iohexol clearance as a gold standard. RESULTS-Iohexol clearance ranged from 35 to 132 ml. min(-1). 1.73 m(-2). Plasma cystatin C compared well with the other clinically used tests. The reliability of cystatin C, as assessed by the discriminant ratio, was superior to creatinine clearance (3.4 vs. 1.5, P < 0.001) and the correlation of cystatin C with iohexol clearance (Rs -0.80) was similar to that of creatinine clearance (Rs -0.74) and superior to that of plasma creatinine and the Cockcroft-Gault estimate (Rs -0.54 and 0.66, respectively). Duplicate estimations were used to provide an unbiased equation to convert plasma cystatin C to GFR. CONCLUSIONS-Based on this study, cystatin C is a more reliable measure of GFR than creatinine clearance, is more highly correlated with iohexol clearance than plasma creatinine, and is worthy of further investigation as a clinical measure of GFR in type 1 diabetes.
We present a fourth-order finite difference (FD) method for solving two-dimensional partial differential equations. The FD operator uses a compact nine-point stencil on a regular square grid. Despite the regular grid, Dirichlet boundary conditions can be applied on an arbitrarily shaped boundary without resorting to the usual stepped approximation. We demonstrate the superior convergence of the method over second-order techniques by solving the Schrödinger equation for an electron in a semiconductor quantum dot with a smoothly varying potential which generates classically chaotic dynamics.
We examined the ability of a bispecific mAb reagent, consisting of a mAb specific for the primate erythrocyte complement receptor cross-linked with an anti-bacterial mAb, to target bacteria in the bloodstream in an acute infusion model in monkeys. In vitro studies demonstrated a variable level of complement-mediated binding (immune adherence) of Pseudomonas aeruginosa (strain PAO1) to primate E in serum. In vivo experiments in animals depleted of complement revealed that binding of bacteria to E was <1% before administration of the bispecific reagent, but within 5 min of its infusion, >99% of the bacteria bound to E. In complement-replete monkeys, a variable fraction of infused bacteria bound to E. This finding may have significant implications in the interpretation of animal models and in the understanding of bacteremias in humans. Treatment of these complement-replete monkeys with the bispecific reagent led to >99% binding of bacteria to E. Twenty-four-hour survival studies were conducted; several clinical parameters, including the degree of lung damage, cytokine levels, and liver enzymes in the circulation, indicate that the bispecific mAb reagent provides a degree of protection against the bacterial challenge.
Electromagnetic analogies of quantum chaos are investigated in two-dimensional optical cavities which have reflective surfaces and contain a gradient refractive index medium. As the shape of the cavity is transformed continuously from a rectangle to a parallelogram, the geometrical ray paths undergo a transition from stable to chaotic dynamics. In the chaotic regime, the spectral statistics of the cavity are accurately described by random matrix theory. In addition, the electromagnetic mode spectrum of the cavity is modulated by both real and ghost periodic ray paths. These paths also "scar" the electric field intensity distributions of regular subsets of cavity eigenmodes.
We investigate how fractals evolve into nonfractal behavior as the generation process is gradually suppressed. Fractals observed in the conductance of semiconductor billiards are of particular interest because the generation process is semiclassical and can be suppressed by transitions towards either fully classical or fully quantum-mechanical conduction. Investigating a range of billiards, we identify a "universal" behavior in the changeover from fractal to nonfractal conductance, which is described by a smooth evolution rather than deterioration in the fractal scaling properties.
Electromagnetic wave chaos is investigated using two-dimensional optical cavities formed in a cylindrical gradient refractive index lens with reflective surfaces. When the planar ends of the lens are cut at an angle to its axis, the geometrical ray paths are chaotic. In this regime, the electromagnetic mode spectrum of the cavity is modulated by both real and ghost periodic ray paths, which also "scar" the electric field intensity distributions of many modes. When the cavity is coupled to waveguides, the eigenmodes generate complex series of resonant peaks in the electromagnetic transmission spectrum.
High avidity anti-dsDNA IgG antibodies are believed to play an important role in the pathogenesis of the autoimmune disease systemic lupus erythematosus (SLE) and therefore attempts have been made to reduce the concentration of these antibodies in the bloodstream of SLE patients. Previously we reported the development of an antigen based heteropolymer (AHP), a bispecific complex prepared by using the avidin-biotin system to crosslink dsDNA to a mAb specific for the human erythrocyte (E) complement receptor. Our studies indicated that this AHP could bind anti-dsDNA antibodies to E and facilitate clearance of these autoantibodies from the circulation of a monkey without E destruction. Here we report an improved covalent crosslinking procedure and purification scheme in which the AHP construct is isolated by precipitation in 50% saturated ammonium sulfate. We used a dsDNA binding dye, PicoGreen, to demonstrate specificity of binding of dsDNA to E via the AHP. The efficacy of the AHP in binding IgG anti-dsDNA antibodies to E was demonstrated in a sensitive and quantitative assay, based on the time resolved fluorescence properties of europium-labeled anti-human IgG mAbs used to probe the E. We also used this assay to screen SLE patient and normal plasmas for levels of anti-dsDNA IgG. The results of this assay correlate very well with the Farr assay, and therefore this approach may be useful in the development of informative and specific assays for a variety of autoantibodies. Treatment of SLE plasmas with E-AHP under conditions close to physiological led to substantial reductions (> or = 90%) in anti-dsDNA titers. It should be possible to test these new AHP for their ability to target and safely remove IgG anti-dsDNA antibodies from the circulation in animal models.
Dengue viruses (DEN), causative agents of dengue fever (DF) and more severe dengue hemorrhagic fever (DHF)/dengue shock syndrome, infect over 100 million people every year. Among those infected, up to one-half million people develop DHF, which requires an extensive hospital stay. Recent reports indicate that there is a significant correlation between virus titer in the bloodstream of infected individuals and the severity of the disease, especially the development of DHF. This suggests that if there is a procedure to reduce viremia in infected subjects, then the severity of the disease may be controlled during the critical early stages of the disease before it progresses to DHF. We have generated bispecific mAb complexes (heteropolymer(s), HP), which contain a mAb specific for the DEN envelope glycoprotein cross-linked with a second mAb specific for the primate E complement receptor 1. These HP facilitate rapid binding of DEN to human and monkey E in vitro, with approximately 90% bound within 5 min. Furthermore, in a passive viremia monkey model established by continuous steady state infusion of DEN, injection of HP during the steady state promoted rapid binding of DEN to the E, followed by subsequent clearance from the vascular system. Moreover, HP previously infused into the circulation is capable of efficiently capturing a subsequent challenge dose of DEN and binding it to E. These data suggest that HP potentially can be useful for alleviating DEN infection-associated symptoms by reducing titers of free virus in the vascular system.
Opsonization of particulate pathogens by antibodies and complement can lead to their binding to the complement receptor (CR1), specific for C3b, on primate erythrocytes (E). This process of immune adherence may play a role in immunologic defense by immobilizing bacteria and viruses, thus preventing them from leaving the bloodstream to invade susceptible tissue and organs. Immune adherence of C3b-opsonized and immune complexed pathogens to E may also facilitate their transfer to, and destruction by, fixed tissue macrophages. We have used mAbs specific for CR1 crosslinked with pathogen specific mAbs to generate heteropolymers (HP) which can bind a wide range of substrates to primate erythrocytes. Both prototype and bonafide pathogens bound to primate E via HP are handled in the circulation of non-human primates in a manner which appears to be virtually identical to the mechanism by which C3b-opsonized substrates bound to E CR1 are cleared. In this process of focused phagocytosis, Fc receptors on the phagocytic cell engage the E-bound complex, CR1 is removed by proteolysis, and the entire immune complex and CR1 are internalized while sparing the E. It may be possible to use HP to target pathogens in the bloodstream in a wide range of therapeutic applications.
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Two complementary techniques were employed to assess the soft tissue response to applied pressure. The noninvasive methods involve the simultaneous measurement of the local tensions of oxygen and carbon dioxide (tcPO2 and tcPCO2) and the collection and subsequent analysis of sweat collected from the sacrum, a common site for the development of pressure sores. All tests were performed on able-bodied subjects. Results have indicated that oxygen levels (tcPO2) were lowered in soft tissues subjected to applied pressures of between 40 (5.3 kPa) and 120 mmHg (16.0 kPa). At the higher pressures, this decrease was generally associated with an increase in carbon dioxide levels (tcPCO2) well above the normal basal levels of 45 mmHg (6 kPa). There were also considerable increases, in some cases up to twofold, in the concentrations of both sweat lactate and urea at the loaded site compared with the unloaded control. By comparing selected parameters, a threshold value for loaded tcPO2 was identified, representing a reduction of ~60% from unloaded values. Above this threshold, there was a significant relationship between this parameter and the loaded/unloaded concentration ratios for both sweat metabolites. These parameters may prove useful in identifying those subjects whose soft tissue may be compromised during periods of pressure ischemia.