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Biomedical subjects

J Hone

Publications and source records attributed to J Hone.

At least 19 recordsLinked to original sources

Optical spectroscopy of individual single-walled carbon nanotubes of defined chiral structure.

We simultaneously determined the physical structure and optical transition energies of individual single-walled carbon nanotubes by combining electron diffraction with Rayleigh scattering spectroscopy. These results test fundamental features of the excited electronic states of carbon nanotubes. We directly verified the systematic changes in transition energies of semiconducting nanotubes as a function of their chirality and observed predicted energy splittings of optical transitions in metallic nanotubes.

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Probing electronic transitions in individual carbon nanotubes by Rayleigh scattering.

Rayleigh scattering spectra were obtained from individual single-walled carbon nanotubes with the use of a laser-generated visible and near-infrared supercontinuum. This diagnostic method is noninvasive and general for nanoscale objects. The approach permits clear identification of excited states in arbitrary metallic and semiconducting nanotubes. We analyzed spectral lineshapes in relation to the role of excitonic effects and correlated the results with Raman scattering data on individual tubes. The nanotube structure remained the same over distances of tens of micrometers. Small nanotube bundles retained distinct Rayleigh spectroscopic signatures of their component nanotubes, thus allowing the probing of nanotube-nanotube interactions.

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How should pathogen transmission be modelled?

Host-pathogen models are essential for designing strategies for managing disease threats to humans, wild animals and domestic animals. The behaviour of these models is greatly affected by the way in which transmission between infected and susceptible hosts is modelled. Since host-pathogen models were first developed at the beginning of the 20th century, the 'mass action' assumption has almost always been used for transmission. Recently, however, it has been suggested that mass action has often been modelled wrongly. Alternative models of transmission are beginning to appear, as are empirical tests of transmission dynamics.

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Metal-insulator and structural phase transition observed by ESR spectroscopy and x-ray diffraction in KC60.

We have performed electron spin resonance (ESR) spectroscopy and x-ray diffraction experiments at low temperature on KC60 single crystals. ESR data reveal the occurrence of a metal-insulator phase transition at about 50 K. In the same temperature range, we observe the stabilization of a superstructure which doubles the volume of the unit cell. We suggest that displacements of the K atoms and a modulation of the C60 charge may be involved in the mechanism of this phase transition. These results shed new light on the subtle interplay of structure, dimensionality, and electronic properties in the AC60 fullerides.

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The relationship between prevalence of Mycobacterium bovis infection in feral ferrets and possum abundance.

AIM: To determine the relationship between the prevalence of macroscopic Mycobacterium bovis infection in feral ferrets (Mustela furo) and the abundance of brushtail possums (Trichosurus vulpecula). METHODS: The predictive power of a previously reported positive association between the prevalence of macroscopic M. bovis infection in ferrets and possum abundance was examined by undertaking surveys of M. bovis infection in ferrets at sites of low and high possum abundance. The association was then tested by a manipulative experiment that measured changes in the prevalence of macroscopic M. bovis infection in feral ferrets after reducing possum abundance. RESULTS: The positive relationship between the prevalence of macroscopic M. bovis infection in ferrets and possum abundance remained valid for new survey data, although the goodness of fit of the relationship was reduced. Experimentally reducing possum abundance reduced the odds of macroscopic M. bovis infection in ferrets by 80% in the years immediately following possum control (Odds Ratio=0.23, p=0.003). CONCLUSIONS: There is a causal link between possum abundance and the prevalence of macroscopic M. bovis infection in feral ferrets in areas in which M. bovis infection is known to occur in ferret populations. This suggests that possum-to-ferret transmission of disease occurs and accounts for most of the disease evident in ferret populations, though does not determine whether ferrets are spillover or maintenance hosts of M. bovis. Management to reduce the prevalence of M. bovis infection in ferrets should consider reducing possum abundance as a control tactic.

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Is the intrinsic thermoelectric power of carbon nanotubes positive?

The thermoelectric power (TEP) of single-walled carbon nanotubes (SWNTs) is extremely sensitive to gas exposure history. Samples exposed to air or oxygen have an always positive TEP, suggestive of holelike carriers. However, at fixed temperature the TEP crosses zero and becomes progressively more negative as the SWNTs are stripped of oxygen. The time constant for oxygen adsorption/desorption is strongly temperature dependent and ranges from seconds to many days, leading to apparently "variable" TEP for a given sample at a given temperature. The saturated TEP can be accounted for within a model of strong oxygen doping of the semiconducting nanotubes.

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Quantized phonon spectrum of single-wall carbon nanotubes

The electronic spectra of carbon nanotubes and other nanoscale systems are quantized because of their small radii. Similar quantization in the phonon spectra has been difficult to observe because of the far smaller energy scale. We probed this regime by measuring the temperature-dependent specific heat of purified single-wall nanotubes. The data show direct evidence of one-dimensional quantized phonon subbands. Above 4 kelvin, they are in excellent agreement with model calculations of individual nanotubes and differ markedly from the specific heat of two-dimensional graphene or three-dimensional graphite. Detailed modeling yields an energy of 4.3 millielectron volts for the lowest quantized phonon subband and a tube-tube (or "lattice") Debye energy of 1.1 millielectron volts, implying a small intertube coupling in bundles.

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Electron spin density distribution in the polymer phase of CsC60: assignment of the NMR spectrum.

We present high resolution 133Cs-13C double resonance NMR data and 13C-13C NMR correlation spectra of 13C enriched samples of the polymeric phase of CsC60. These data lead to a partial assignment of the lines in the 13C NMR spectrum of CsC60 to the carbon positions on the C60 molecule. A plausible completion of the assignment can be made on the basis of an ab initio calculation. The data support the view that the conduction electron density is concentrated at the C60 "equator," away from the interfullerene bonds.

Journal Article↗

Graphical simulation of early development of the cerebral cortex.

Much experimental data exists concerning the development of the cerebral cortex. There is a need for a common vehicle to integrate this data and to allow the testing of hypotheses concerning development. Computer simulation and visualization are powerful mechanisms for hypothesis testing. Our long-term goal is to create a robust, extensible, portable tool for simulation and visualization of cortical development to serve both research and educational purposes. This paper describes a simulation program, SimCortex, which models the early stages of development of the cerebral cortex of the mouse. Version 1.0 of SimCortex models the proliferation of progenitor cells in the pseudostratified ventricular epithelium (PVE), the generation of young neurons and their migration into the cortical plate, which is the forerunner of cell layers II through VI of the adult cortex. We present an overview of the design and implementation of SimCortex, sample output of the system and a comparison of our results with experimental data. We conclude with a brief overview of proposed future enhancements of the system.

Animals↗

Homozygosity for a null allele of the insulin receptor gene in a patient with leprechaunism.

Mutations in the insulin receptor gene can cause genetic syndromes associated with extreme insulin resistance. We have investigated a patient with leprechaunism (leprechaun/Qatar-1) born of a consanguineous marriage. Postnatally, the proband had episodes of severe hypoglycemia and hyperinsulinernia, with blood glucose levels ranging from 0.9 to 9.9 mmol/L. The C peptide concentration with 1880 nmol/L, and the total insulin concentration was 1409 mU/L. The patient died outside the hospital at the age of four months. All 22 exons of the patient's insulin receptor gene were screened for mutations using denaturing gradient gel electrophoresis. Thereafter, the nucleotide sequences of selected exons were determined directly. The patient was homozygous for a mutation in exon 13; thirteen base pairs were deleted and replaced by a 5 b.p. sequence. This mutation shifts the reading frame and introduces a premature chain termination codon downstream in exon 13. Thus, the mutant allele is predicted to be a null allele that encodes a truncated receptor lacking both transmembrane and tyrosine kinase domains.

Alleles↗

A mathematical model of detection and dynamics of porcine transmissible gastroenteritis.

Transmissible gastroenteritis (TGE) is a viral disease causing dehydration, diarrhoea and death in pigs. The disease is widespread in pig-producing areas of the world but does not occur in Australia. A mathematical model of TGE spread within a pig herd is proposed and calibrated by reference to published data. The model is then applied to two situations of special interest; first to estimate the delay before detection of TGE (6 to over 30 days) when infection is first introduced into a herd of domestic or feral pigs, and second the effect of the disease in a population of feral pigs (could become endemic if transmission is high).

Animals↗

Mechanisms of hormone resistance: lessons from insulin-resistant patients.

Hormones are secreted by endocrine glands and transported to the target cell at which the hormone acts. The hormone binds to its receptor, thereby eliciting various biological responses within the target cell. Examples of disease mechanisms that function at the different stages in the development of the insulin receptor, and result in insulin resistance, are discussed in this review. Antibodies to insulin can impair delivery of the hormone to the target cell, and can desensitize that target cell to insulin action. In recent years, several genetic diseases have been identified that result from mutations in the genes encoding the relevant receptors. Studies of syndromes of insulin resistance provide illustrations of the multiple types of defects in receptor function that can generally cause hormone resistance (12, 13). For example, mutations in the receptor can decrease the number of receptors on the cell surface by inhibiting receptor biosynthesis, impairing receptor transport to the cell surface, or accelerating the rate of receptor degradation. Alternatively, mutations have been identified that decrease the affinity of insulin binding or inhibit receptor tyrosine kinase activity. In recent years, there has been considerable progress toward elucidating post-receptor mechanisms in the biochemical pathways of hormone action. At present, there are a limited number of examples of mutations in genes encoding proteins that function in this part of the pathway, but it seems likely that additional examples will be discovered in the future. It is likely that these insights into biochemical mechanisms of disease will ultimately lead to an improvement in our ability to treat human disease.

Genetic Diseases, Inborn↗

Homozygosity for a new mutation (Ile119-->Met) in the insulin receptor gene in five sibs with familial insulin resistance.

Mutations in the insulin receptor gene can cause genetic syndromes such as leprechaunism that are associated with extreme insulin resistance. We have investigated a patient with leprechaunism born of a consanguineous marriage. All 22 exons of the insulin receptor gene were screened for mutations using denaturing gradient gel electrophoresis. Thereafter, the nucleotide sequences of selected exons were determined directly. The patient was homozygous for a point mutation in exon 2 of the insulin receptor gene which results in the substitution of methionine for isoleucine at codon 119. Thus, the mutant allele encodes a receptor that has a mutation in the putative insulin binding domain. Accordingly, the mutant receptor would be predicted not to transduce the insulin signal effectively. In spite of a homozygous abnormality of the insulin receptor gene and many of the clinical features of severe insulin resistance, the proband's clinical syndrome was noticeably different from previously described patients with leprechaunism who usually die within the first six months of life. There are a total of nine children in the family, five of whom are homozygous for the Ile119-->Met mutation in the insulin receptor gene, and are clinically affected with varying degrees of severity. Four unaffected sibs are clinically normal; two are heterozygous carriers of the mutant allele, one is homozygous for the normal allele, and one unaffected sib was not available for molecular studies.

Exons↗

Estimation of the dynamics and rate of transmission of classical swine fever (hog cholera) in wild pigs.

Infectious diseases establish in a population of wildlife hosts when the number of secondary infections is greater than or equal to one. To estimate whether establishment will occur requires extensive experience or a mathematical model of disease dynamics and estimates of the parameters of the disease model. The latter approach is explored here. Methods for estimating key model parameters, the transmission coefficient (beta) and the basic reproductive rate (RDRS), are described using classical swine fever (hog cholera) in wild pigs as an example. The tentative results indicate that an acute infection of classical swine fever will establish in a small population of wild pigs. Data required for estimation of disease transmission rates are reviewed and sources of bias and alternative methods discussed. A comprehensive evaluation of the biases and efficiencies of the methods is needed.

Animals↗

A distinct glucocorticoid hormone response regulates phosphoprotein maturation in rat hepatoma cells.

Glucocorticoid hormone-dependent maturation of the mouse mammary tumor virus (MMTV) phosphorylated polyprotein (Pr74) allows experimental access to certain posttranslational regulatory circuits under steroid control in M1.54 cells, an MMTV-infected rat hepatoma cell line. Pulse-chase experiments revealed that [35S]methionine-labeled Pr74 synthesized in uninduced cells could be converted posttranslationally into p24, a stable phosphorylated maturation product, only after 4 h of exposure to 1 microM dexamethasone, a synthetic glucocorticoid. This regulated processing could be prevented by prior exposure, during the chase period, to inhibitors of RNA (actinomycin D) or protein (cycloheximide or puromycin) synthesis. Moreover, half-maximal production of p24 occurred at 10 nM dexamethasone, a concentration that approximated half-maximal receptor binding and stimulation of MMTV transcript synthesis. Kinetic, hormonal, and genetic evidence suggest that p24 expression did not require or result from the overall glucocorticoid-dependent increase in polyprotein concentration. First, 20 h after dexamethasone withdrawal, Pr74 maturation was completely deinduced, whereas the absolute level of this MMTV precursor remained 10-fold over its basal level. Second, progesterone, which competes with dexamethasone for receptor binding, facilitated the regulated production of p24 but prevented the steroid-mediated accumulation of functional MMTV mRNA. Lastly, certain glucocorticoid-responsive variants, derived from M1.54 cells by resistance to complement cytolysis, expressed p24 in the presence or absence of glucocorticoid-induced levels of Pr74. Taken together, our results suggest that the glucocorticoid-regulated maturation of MMTV phosphopolyproteins resulted from an independent hormone response that required normal receptor function and de novo RNA and protein synthesis.

Animals↗