Biomedical subjects

P L Taylor

Publications and source records attributed to P L Taylor.

At least 19 recordsLinked to original sources

PubMed2005

Phase sequences and long-range interactions in ferroelectric liquid crystals.

The origin of the long-range interlayer interactions responsible for the variety of phases exhibited by ferroelectric liquid crystals is discussed. It is shown that the anisotropy of the elastic constants that govern layer bending in smectic- C liquid crystals results in an effective long-range interaction between the smectic layers. The nature of this interaction is such as to favor a mutual alignment of the c directors of the layers in either a parallel or antiparallel orientation. The free energy of the system is the sum of the contributions of these long-range interlayer interactions and the short-range interaction between nearest-neighboring layers, which favors a purely helical structure for the c directors. The long-range interaction is found to favor commensurate structures while the short-range term favors incommensurate helices. The resulting structure is of the type characterized in the "distorted clock model." The phase diagrams that result from the application of this theory are consistent with the experimentally observed phase sequences.

Journal Article↗

PubMed2005

Impact of heat on nanocrystalline silver dressings. Part I: Chemical and biological properties.

Thermal stability of heat-treated nanocrystalline silver dressings was investigated using chemical techniques and biological assays. Dressings were heat-treated for 24h at temperatures from 23 to 110 degrees C. Bactericidal efficacy of heat-treated dressings was measured using a log reduction assay, while antibacterial longevity was determined via plate-to-plate transfer corrected zone of inhibition assays. Over the temperature range tested, biological activity dropped from excellent to negligible. Biological longevity results showed that controlled release properties of the dressings were significantly reduced by heat treatments above 75 degrees C. These data illustrate nanocrystalline silver sensitivity to heat. Further, it was clear that dressing efficacy is determined by total available soluble silver, not total silver in the dressing. It was determined that the quantity of soluble silver decreased significantly with increased heat treatment temperatures. These results should be considered in developing new nanocrystalline drug delivery systems.

Anti-Bacterial Agents↗

PubMed2005

Impact of heat on nanocrystalline silver dressings. Part II: Physical properties.

This work explores the effects of elevated temperature on the physical and chemical properties of nanocrystalline silver, and relates it to previously observed thermally induced changes in biological activity [Taylor PL et al. Biomaterials, in press, doi:10.1016/j.biomaterials.2005.05.040]. Microstructural evolution of nanocrystalline silver dressings, heat-treated for 24 h at temperatures from 23 to 110 degrees C, was studied in detail using X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photoelectron spectroscopy (XPS). These analyses indicated that silver nanocrystalline coatings undergo significant changes in structure when exposed to elevated temperature. XRD analysis showed a rapid increase in crystallite size above 75 degrees C along with decomposition of crystalline silver oxide (Ag2O) at the onset of crystallite growth. SEM imaging showed a loss of fine features and sintering of the structure at elevated temperatures. The XPS data indicated that silver-oxygen bonds disappeared completely, with the initial decomposition occurring between 23 and 37 degrees C, and total oxygen in the coating decreased from 16-17% to 6.5% over the temperature range of 75-110 degrees C. A comparison of these results to the data of Taylor et al. [Biomaterials, in press, doi:10.1016/j.biomaterials.2005.05.040] indicates that the unique biological properties of nanocrystalline silver are related to its nanostructure. This should guide future development of therapeutic nanocrystalline silver delivery systems.

Anti-Bacterial Agents↗

PubMed2004

Long-range interlayer interactions in ferroelectric liquid crystals.

Some smectic liquid crystals exhibit a series of phases, including ferroelectric, antiferroelectric, and ferrielectric commensurate structures as well as an incommensurate phase. A long-standing problem has been to understand the origin of the long-range interaction responsible for this rich variety of phases. We study a model that incorporates thermal fluctuations in the flexing of layers and find that it supports commensurate and incommensurate structures. The vibrational entropy competes with an assumed helical interaction between nearest-neighbor layers. An increase in temperature then leads to an unwinding of the helix that proceeds at first through commensurate phases and then into an incommensurate phase. This result is consistent with the experimentally observed "distorted clock model."

Journal Article↗

PubMed2003

Theory of layer structure in ferroelectric liquid crystal devices in applied electric fields.

We propose a model for the free energy of a ferroelectric liquid crystal formed by cooling a sample from the smectic-A phase between parallel substrates. Under these circumstances the smectic layers may deform into V-shaped structures known as chevrons. Application of a strong electric field causes the layers to return to a flat shape, but this can occur in a number of ways. In the model presented here, it is a parameter related to the layer compression modulus that is the principal factor in determining the nature of the field-induced transition from chevrons to flat layers. When this parameter is large, the transition is sudden, but when it is small the chevron first takes on a rounded form before flattening. At intermediate values the tip of the chevron first flattens, and then this flat region gradually grows to encompass the entire layer.

Journal Article↗

PubMed2002

Mitigation of tokamak disruptions using high-pressure gas injection.

High-pressure gas-jet injection of neon and argon is shown to be a simple and robust method to mitigate the deleterious effects of disruptions on the DIII-D tokamak. The gas jet penetrates to the central plasma at its sonic velocity. The deposited species dissipates >95% of the plasma by radiation and substantially reduces mechanical stresses on the vessel caused by poloidal halo currents. The gas-jet species-charge distribution can include >50% fraction neutral species which inhibits runaway electrons. The favorable scaling of this technique to burning fusion plasmas is discussed.

Journal Article↗

PubMed2002

Simulation study of the glass transition temperature in poly(methyl methacrylate).

The glass transition in syndiotactic poly (methyl methacrylate) has been studied through atomistic molecular dynamics simulations performed at temperatures in the range from 297 K to 684 K. The mean squared deviations of atoms, monomers, and molecules from their initial positions were analyzed by means of a technique that separates the effects of diffusive motion from the underlying vibrational motion. The diffusive motion shows a novel power-law variation with time, with an exponent that varies continuously from 0.5 below the glass transition temperature T(g) to 1 at high temperatures. The self part of the van Hove correlation functions for both hydrogen atoms and monomers shows structural arrest at the lowest temperature studied. A second peak in the atomic van Hove correlation is attributed to rotation of the CH3 group.

Journal Article↗

PubMed2002

Stability of connected cylindrical liquid bridges.

Two cylindrical liquid bridges, with a conduit to facilitate flow of liquid from one bridge to the other, were levitated against gravity in a magnetic field gradient. The stability limit of the bridges subjected to near zero total body force was measured as a function of their slenderness ratios, and found to be in good agreement with theoretical predictions.

Journal Article↗

PubMed2000

The rat gonadotropin-releasing hormone receptor internalizes via a beta-arrestin-independent, but dynamin-dependent, pathway: addition of a carboxyl-terminal tail confers beta-arrestin dependency.

This study examined the mechanism underlying the rat GnRH receptor (GnRH-R) internalization pathway by investigating the role of added/extended C-terminal tails and the effect of beta-arrestins and dynamin. The internalization of the wild-type (WT) rat GnRH-R, stop codon mutants, GnRH-R/TRH receptor (TRH-R) chimera, rat TRH-R, and catfish GnRH-R was examined using radioligand binding assay. Overexpression of beta-arrestin in COS-7 cells expressing each of the receptor constructs substantially increased endocytosis rate constants (k(e)) of the TRH-R, catfish GnRH-R, and GnRH-R/TRH-R chimera, but not of the WT rat GnRH-R and stop codon mutants. The beta-arrestin-promoted increase in the k(e) value was diminished by cotransfecting cells with the dominant negative beta-arrestin-(319-418) mutant, whereas WT GnRH-R and stop codon mutant internalization were unaffected. Additionally, confocal microscopy showed that activated GnRH-Rs failed to induce time-dependent redistribution of either beta-arrestin-1- or beta-arrestin-2-green fluorescent protein conjugate to the plasma membrane. However, the dominant negative dynamin (DynK44A) mutant impaired internalization of all of the receptors regardless of their beta-arrestin dependency, indicating that they internalize via a clathrin-mediated pathway. We conclude that the mammalian GnRH-R uses a beta-arrestin-independent, dynamin-dependent internalization mechanism distinct from that employed by the other receptors studied.

Amino Acid Sequence↗

PubMed2000

Internalization kinetics of the gonadotropin-releasing hormone (GnRH) receptor.

This study quantified the agonist-induced endocytotic and recycling events of the mammalian gonadotropin releasing hormone receptor (GnRH-R) and investigated the role of the intracellular carboxyl (C)-terminal tail in regulating agonist-induced receptor internalization kinetics. The rate of internalization for the rat GnRH-R was found to be exceptionally low when compared with G-protein coupled receptors (GPCRs) which possess a cytoplasmic C-terminal tail (thyrotropin-releasing hormone receptor (TRH-R), catfish GnRH-R (cfGnRH-R) and GnRH/TRH-R chimeric receptor). These data provide evidence that the presence of a functional intracellular cytoplasmic C-terminal tail is essential for rapid internalization of the studied GPCRs.

Animals↗

PubMed1999

Clinical integration and new options for academic medical institutions in network development.

The author outlines two options, made possible by developments in antitrust law, that can create a favored role for academic health science centers as well as for stand-alone medical schools and teaching hospitals, using the unique strengths of these institutions that are often considered weaknesses by the marketplace. The first option is the development of clinically integrated collaborations that need not be either system-wide or necessarily governed by total quality management processes, or involve the characteristics of ownership typical of the usual integrated delivery systems. The second option is the development of new clinical "products." Each option encourages creative financing, legal, medical, and governance approaches and makes it possible for centers, medical schools, and teaching hospitals to build multi-provider collaborations that are in harmony with their missions and different from the less-compatible integrated delivery systems that they often seek to build. The author provides an extensive background on antitrust law to explain the two options and the criteria for crafting them within antitrust law. He then describes how antitrust law applies to multi-provider networks and in particular to academic health science centers and free-standing medical schools and teaching hospitals, and gives examples of the kinds of fruitful collaborations these institutions could engage in. He urges those institutions to realize that if they keep faith with their best characteristics in creative new ways (such as those suggested by his article), they will thrive in the years ahead.

Academic Medical Centers↗

PubMed1999

Scattered fractions of dose from 6,10,18, and 25 MV linear accelerator x rays in radiotherapy facilities.

Data for computation of primary and secondary shielding barriers in radiotherapy facilities are presented in the National Council on Radiation Protection and Measurements Report 49, which covers primary barriers for accelerating voltages up to 10 MV and secondary barriers up to 6 MV. Inconsistencies in reported scattered fraction values found in the literature for megavoltage accelerators are due, in part, to differences in measurement techniques. A consistent approach was used to measure the scattered fractions of 6, 10, 18, and 25 MV photon dose. A reference ion chamber was placed on the symmetry axis of a cylindrical water phantom, approximating the human torso, 25.6 cm diameter, at the gantry isocenter. Measurements were made with a second ion chamber at 2m from the isocenter at angles ranging from 10 degrees through 150 degrees from the beam central axis with a field size of 20 cm x 20 cm at the isocenter. The dose measured at each angle is reported as a fraction of the reference chamber dose at the center of the phantom and as calculated to a reference chamber depth of d(max), also at the isocenter. The results of these measurements were compared with Monte Carlo calculations and show reasonable agreement. A comparison with previously published data was not as good due to the differences in measurement techniques. However, after some adjustments to correct for the differences, the comparison is very good. Scattered fractions beyond 30 degrees are highest for the lowest energy beam investigated. This indicates that the scattered fraction values reported in NCRP 49 for 6 MV are sufficient for use in conservative shielding calculations for the higher energy x rays beyond 30 degrees. For angles smaller than 30 degrees, the new data are more appropriate and show the scatter fractions are larger for higher MV x rays.

Air Pollution, Indoor↗

PubMed1999

Field-induced phase transitions in antiferroelectric liquid crystals.

A theoretical study is made of the process by which an antiferroelectric smectic liquid crystal undergoes a field-induced transition to ferroelectric alignment. We find that for cells of moderate thickness the initial departure from antiferroelectric alignment occurs as a continuous Fréedericksz transition. The following transition from partial alignment to complete ferroelectric ordering may occur as either a first-order or continuous transition, depending on the relative strength of some of the model parameters. The case where the transition is continuous provides a possible mechanism for some recently observed thresholdless transitions in these systems.

Journal Article↗

PubMed1999

Nematic order in nanoscopic liquid crystal droplets.

We have used atomistic molecular-dynamics simulations to model the detailed molecular configuration of 5CB (4-n-pentyl-4'-cyanobiphenyl) molecules in the form of a nanoscopic liquid crystal droplet in a vacuum microgravity environment. We find the equilibrium state of droplets consisting of as few as 26 or 50 molecules to exhibit significant nematic ordering. The shape of the droplets is also anisotropic, but there is little angular correlation between the nematic director and the long axis of the droplet. Some tendency to micelle formation is observed in droplets of 50 molecules.

Journal Article↗

PubMed1999

Scatter fractions from linear accelerators with x-ray energies from 6 to 24 MV.

Computation of shielding requirements for a linear accelerator must take into account the amount of radiation scattered from the patient to areas outside the primary beam. Currently, the most frequently used data are from NCRP 49 that only includes data for x-ray energies up to 6 MV and angles from 30 degrees to 135 degrees. In this work we have determined by Monte Carlo simulation the scattered fractions of dose for a wide range of energies and angles of clinical significance including 6, 10, 18, and 24 MV and scattering angles from 10 degrees to 150 degrees. Calculations were made for a 400 cm2 circular field size impinging onto a spherical phantom. Scattered fractions of dose were determined at 1 m from the phantom. Angles from 10 degrees to 30 degrees are of concern for higher energies where the scatter is primarily in the forward direction. An error in scatter fraction may result in too little secondary shielding near the junction with the primary barrier. The Monte Carlo code ITS (Version 3.0) developed at Sandia National Laboratory and NIST was used to simulate scatter from the patient to the barrier. Of significance was the variation of calculated scattered dose with depth of measurement within the barrier indicating that accurate values may be difficult to obtain. Mean energies of scatter x-ray spectra are presented.

Biophysical Phenomena↗

PubMed1999

Isolation and characterisation of the marmoset gonadotrophin releasing hormone receptor: Ser(140) of the DRS motif is substituted by Phe.

In order to facilitate the understanding of gonadotrophin-releasing hormone (GnRH) agonist and antagonist action in the primate animal model, the marmoset GnRH receptor (GnRH-R) was cloned and characterised. It was shown to have 95% and 85% sequence identity with the human and rat GnRH-Rs, respectively, and, when transiently expressed in COS-7 cells, it exhibited high-affinity des-Gly(10), [d-Trp(6)]-GnRH binding, with a K(d) value similar to those of both the rat and human forms, but with a greatly reduced B(max) value. The ED(50) for production of GnRH-induced total inositol phosphate (IP) for the marmoset GnRH-R was also similar to those of the rat and the human, but the maximal response compared with the rat receptor was markedly reduced. In all mammalian forms of the GnRH-R cloned to date, the conserved DRY region of G-protein-coupled receptors is substituted with DRS. The most interesting feature of the marmoset GnRH-R was the substitution of this motif with DRF. In order to investigate the DRS to DRF substitution, a Ser(140)Phe rat GnRH-R mutant was generated. The mutant had a K(d) value similar to that of the wild-type rat receptor, although the B(max) value was slightly lower, indicating that expression of functional mutant receptor at the cell surface was reduced. The ED(50) value for IP production was also similar to that of the wild-type receptor, with a reduction in maximal response. The level of internalisation for the rat wild-type and mutant GnRH-R constructs was also assessed and the Ser(140)Phe mutant was shown to have an increased rate of receptor internalisation, suggesting a role for this residue in regulating internalisation. These results show that the marmoset GnRH-R exhibits a substitution in the DRS motif and that this substitution may play a part in desensitisation and internalisation events.

Amino Acid Sequence↗

PubMed1998

Functional analysis of GnRH receptor ligand binding using biotinylated GnRH derivatives.

The objective of this study was to determine whether the gonadotrophin-releasing hormone (GnRH) ligand binds to the GnRH receptor (GnRH-R) with either the N- and C-termini or the beta-II turn pointing towards the cell. The functionality of GnRH and two biotinylated GnRH derivatives, biotin [D-Lys6]GnRH and biotin [Gln1]GnRH biotinylated at positions 6 and 1, respectively was assessed. Streptavidin was also used in combination with these peptides to investigate the effects of the steric hindrance caused by this molecule on ligand binding when bound to the biotin molecules at the two positions. GnRH bound to the receptor with high affinity, which was not affected by the addition of streptavidin. Both the biotinylated derivatives bound to the receptor though with lower affinities than GnRH. The biotin [D-Lys6]GnRH-streptavidin complex bound to the receptor albeit with lower affinity compared to biotin [D-Lys6]GnRH only, although it maintained its ability to cause receptor internalisation. The ability of the biotin [Gln1]GnRH to bind to the receptor was abolished in the presence of excess streptavidin. Both GnRH and biotin [D-Lys6]GnRH stimulated total inositol phosphate production whereas biotin [Gln1]GnRH exhibited GnRH antagonist activity. It appears that the small biotin molecule can be accommodated within the binding pore when attached to position 1 of the ligand but not when complexed to streptavidin. The fact that biotin [D-Lys6]GnRH maintains functionality when complexed to streptavidin while biotin [Gln1]GnRH does not, suggests that the N- and possibly the C-termini are required for receptor binding. Thus the most likely binding orientation for the ligand is with the N- and C-termini pointing inwards with the residue at position 6 pointing away from the binding site.

Animals↗

PubMed1998

Gonadotropin-releasing hormone receptors with intracellular carboxyl-terminal tails undergo acute desensitization of total inositol phosphate production and exhibit accelerated internalization kinetics.

The mammalian gonadotropin-releasing hormone receptor (GnRH-R) is the only G-protein-coupled receptor (GPCR) in which the intracellular C-terminal tail is completely absent. In contrast to other GPCRs, the GnRH-R does not show rapid desensitization of total inositol (IP) production, and the rates of internalization are exceptionally slow. We investigated whether the incorporation of a cytoplasmic tail into the C terminus of the GnRH-R affects desensitization events and receptor internalization rates. A GnRH-R/TRH-R chimera was created where the intracellular tail of the rat thyrotropin-releasing hormone receptor (TRH-R) was engineered into the C terminus of the rat GnRH-R. Three different rat GnRH-R cDNA stop codon mutations (one for each reading frame) were also made. The GnRH-stimulated IP production of the wild-type rat GnRH-R expressed in either COS-7 or HEK 293 cells did not desensitize even after prolonged stimulation with GnRH. In contrast, the catfish GnRH-R (which does possess an intracellular tail) and the TRH-R rapidly (<10 min) desensitized following agonist stimulation. The GnRH-R/TRH-R chimera also desensitized following treatment with GnRH, resembling the pattern shown by the TRH-R and the catfish GnRH-R. Two of the stop codon mutants did not show desensitization of IP production, and the third mutant with the longest tail was not functional. Internalization experiments showed that the rat GnRH-R had the slowest endocytosis and recycling rates compared with the TRH-R, the catfish GnRH-R, and the chimeric GnRH/TRH-R. This study demonstrates that the addition of a functional intracellular C-terminal tail to the GnRH-R produces rapid desensitization of IP production and significantly increases internalization rates.

Amino Acid Sequence↗