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Biomedical subjects

R G Clark

Publications and source records attributed to R G Clark.

At least 19 recordsLinked to original sources
PubMed2006

Microsecond resolution of quasiparticle tunneling in the single-Cooper-pair transistor.

We present radio-frequency measurements on a single-Cooper-pair-transistor in which individual quasiparticle poisoning events were observed with microsecond temporal resolution. Thermal activation of the quasiparticle dynamics is investigated, and consequently, we are able to determine energetics of the poisoning and unpoisoning processes. In particular, we are able to assign an effective quasiparticle temperature to parametrize the poisoning rate.

Journal Article↗
PubMed2006

Spin-dependent quasiparticle transport in aluminum single-electron transistors.

We investigate the effect of Zeeman splitting on quasiparticle transport in normal-superconducting-normal (NSN) aluminum single-electron transistors (SETs). In the above-gap transport, the interplay of Coulomb blockade and Zeeman splitting leads to spin-dependence of the sequential tunneling. This creates regimes where either one or both spin species can tunnel onto or off the island. At lower biases, spin-dependence of the single quasiparticle state is studied, and operation of the device as a bipolar spin filter is suggested.

Journal Article↗
PubMed2004

Maximizing the Hilbert space for a finite number of distinguishable quantum states.

Given a particular quantum computing architecture, how might one optimize its resources to maximize its computing power? We consider quantum computers with a number of distinguishable quantum states, and entangled particles shared between those states. Hilbert-space dimensionality is linked to nonclassicality and, hence, quantum computing power. We find that qutrit-based quantum computers optimize the Hilbert-space dimensionality and so are expected to be more powerful than other qudit implementations. In going beyond qudits, we identify structures with much higher Hilbert-space dimensionalities.

Journal Article↗
PubMed2004

Salmonella Brandenburg - emergence of a new strain affecting stock and humans in the South Island of New Zealand.

AIMS: To report information on the spread of a new strain of Salmonella Brandenburg, which affected livestock and humans in the South Island of New Zealand, and a series of small case studies designed to investigate potential transmission of infection. METHODS: Information on the occurrence and spread of S. Brandenburg in livestock was gathered from laboratory diagnostic submissions, from case studies on the faecal excretion rate in ewes, carrier status of black-backed gulls (Larus dominicanus), spread of S. Brandenburg organisms in sheep yards, infection in lambs going to meat plants, and from post-abortion pathological changes in the reproductive tract of ewes. RESULTS: A newly recognised strain of S. Brandenburg was first diagnosed in aborting sheep from a flock in mid Canterbury in the South Island in 1996. Subsequently, the disease spread to other farms in mid and south Canterbury in 1997 and to Southland and Otago in the lower half of the South Island in 1998-2003. In 1999, the same strain was responsible for abortions in cattle and gastroenteritis in calves and adult cattle. The same strain of bacterium also caused disease in horses, goats, deer, pigs and humans. Spread of the disease on farms was strongly associated with aborting ewes, which resulted in considerable environmental contamination. During the abortion season, black-backed gulls appeared to spread the disease to other farms. Other potential sources of infection were carrier sheep, contaminated water sources and contaminated sheepyard dust. Damage to the reproductive tract may affect the ability of surviving ewes to conceive. CONCLUSION: Important features of this disease are its high morbidity and mortality within a flock or herd, rapid local spread and its role as an occupational, health and safety risk to farm workers and their families.

Journal Article↗
PubMed2003

Atomically precise placement of single dopants in si.

We demonstrate the controlled incorporation of P dopant atoms in Si(001), presenting a new path toward the creation of atomic-scale electronic devices. We present a detailed study of the interaction of PH3 with Si(001) and show that it is possible to thermally incorporate P atoms into Si(001) below the H-desorption temperature. Control over the precise spatial location at which P atoms are incorporated was achieved using STM H lithography. We demonstrate the positioning of single P atoms in Si with approximately 1 nm accuracy and the creation of nanometer wide lines of incorporated P atoms.

Journal Article↗
PubMed2003

Progress in silicon-based quantum computing.

We review progress at the Australian Centre for Quantum Computer Technology towards the fabrication and demonstration of spin qubits and charge qubits based on phosphorus donor atoms embedded in intrinsic silicon. Fabrication is being pursued via two complementary pathways: a 'top-down' approach for near-term production of few-qubit demonstration devices and a 'bottom-up' approach for large-scale qubit arrays with sub-nanometre precision. The 'top-down' approach employs a low-energy (keV) ion beam to implant the phosphorus atoms. Single-atom control during implantation is achieved by monitoring on-chip detector electrodes, integrated within the device structure. In contrast, the 'bottom-up' approach uses scanning tunnelling microscope lithography and epitaxial silicon overgrowth to construct devices at an atomic scale. In both cases, surface electrodes control the qubit using voltage pulses, and dual single-electron transistors operating near the quantum limit provide fast read-out with spurious-signal rejection.

Journal Article↗
PubMed2002

Density-dependent spin polarization in ultra-low-disorder quantum wires.

There is controversy as to whether a one-dimensional (1D) electron gas can spin polarize in the absence of a magnetic field. Together with a simple model, we present conductance measurements on ultra-low-disorder quantum wires supportive of a spin polarization at B=0. A spin energy gap is indicated by the presence of a feature in the range (0.5-0.7)x2e(2)/h in conductance data. Importantly, it appears that the spin gap is not constant but a function of the electron density. Data obtained using a bias spectroscopy technique are consistent with the spin gap widening further as the Fermi level is increased.

Journal Article↗
PubMed2001

Growth hormone as a neuronal rescue factor during recovery from CNS injury.

There is growing evidence to suggest that growth hormone plays a role in the growth and development of the CNS. Specifically, growth hormone has been implicated in promoting brain growth, myelination, neuronal arborisation, glial differentiation and cognitive function. Here we investigate if growth hormone has a role in the recovery from an unilateral hypoxic-ischaemic brain injury. Using moderate (15 min hypoxia) and severe (60 min hypoxia) models of hypoxic-ischaemia in juvenile rats and standard immunohistochemical techniques, we found intense growth hormone-like immunoreactivity present within regions of cell loss by 3 days (P<0.05). Growth hormone-like immunoreactivity was observed on injured neurones, myelinated axons, glial cells within and surrounding infarcted tissue and on the choroid plexus plus ependymal cells within the injured hemisphere. The pattern of immunoreactivity suggests that (a) growth hormone (or a growth hormone-like substance) is transported via the cerebrospinal fluid and (b) that growth hormone (or a growth hormone-like substance) is acting in a neurotrophic manner specifically targeted to injured neurones and glia. To test this hypothesis we treated a moderate hypoxic-ischaemic brain injury with 20 microg of rat growth hormone by intracerebroventricular infusion starting 2 h after injury (n=12/group). After 3 days the animals were killed and the extent of neuronal loss quantified. Growth hormone treatment reduced neuronal loss in the frontoparietal cortex (P<0.001), hippocampus (P<0.01) and dorsolateral thalamus (P<0.01) but not in the striatum. This spatial distribution of the neuroprotection conveyed by growth hormone correlates with the spatial distribution of the constitutive neural growth hormone receptor, but not with the neuroprotection offered by insulin-like growth factor-I treatment in this model. These results suggest that some of the neuroprotective effects of growth hormone are mediated directly through the growth hormone receptor and do not involve insulin-like growth factor-I induction.In summary, we have found that a growth hormone-like factor increased in the brain in the days after injury. In addition, treatment with growth hormone soon after an hypoxic-ischaemic injury reduced the extent of neuronal loss. These results further suggest that a neural growth hormone axis is activated during recovery from injury and that this may act to restrict the extent of neuronal death.

Animals↗
PubMed2001

The metabolic effects of endotoxin are differentially affected by the pattern of GH administration in the rat.

GH treatment can increase the mortality and morbidity of critically ill patients. The mechanisms of these harmful effects of GH are unknown but have been, in part, ascribed to interactions between GH and the immune system. Because GH has pattern-dependent actions we have now compared the dose-related effects of continuous and intermittent GH treatment given with or without an endotoxin (lipopolysaccharide; LPS) challenge. Male Wistar rats (n=6 per group) were treated for 5 days with recombinant human GH (0, 10, 100 or 1000 microg/kg per day) using either continuous s.c. infusion by osmotic minipump or intermittent twice daily s.c. injections. On day 4, endotoxin (5 mg/kg, i.p.) was injected and the animals monitored for a further 16 h. LPS administration alone led to neutrophilia and lymphopoenia, with increased plasma concentrations of urea, cholesterol, triglyceride, insulin and leptin, and decreased levels of IGF-I. High dose GH infusion (1000 microg/kg per day) followed by LPS caused greater increases in plasma urea, cholesterol, triglyceride, sodium and magnesium, but lower plasma glucose and insulin levels, than treatment with LPS alone. In contrast, twice daily injections of GH did not enhance these effects of endotoxin. In conclusion, the effects of endotoxin on plasma electrolytes, lipids, urea, glucose and insulin are differentially affected by the pattern of GH administration in the rat.

Animals↗
PubMed2000

Insulin-like growth factor binding protein (IGFBP) displacers: relevance to the treatment of renal disease.

Chronic renal failure (CRF) results in complex metabolic and hormonal derangements, particularly in the GH-IGF-IGFBP axis, which can be manifest in children as growth retardation. The decreased glomerular filtration rate (GFR) in CRF is associated with increased plasma IGFBP levels, which may have an important role in inhibiting the bioavailability of IGF-I. There is a large literature from both animal and human studies showing that the administration of IGF-I can affect structure and function of normal and compromised kidneys. We propose an alternative therapeutic approach: activating bound IGF by administering molecules that bind to the IGFBPs. In initial animal studies we used a mutant IGF, an IGF displacer, that binds to IGFBPs but not to IGF receptors. In the rat this molecule activated the IGF system and produced IGF-like effects in vivo, such as increased kidney size, reduced serum creatinine, increased bone growth and increased body weight. Novel synthetic peptides have also been discovered which bind to specific IGFBPs, and we believe such molecules hold promise as therapeutic agents in renal disease.

Animals↗
PubMed2000

Neuroprotective strategies for basal ganglia degeneration: Parkinson's and Huntington's diseases.

There are three main mechanisms of neuronal cell death which may act separately or cooperatively to cause neurodegeneration. This lethal triplet of metabolic compromise, excitotoxicity, and oxidative stress causes neuronal cell death that is both necrotic and apoptotic in nature. Aspects of each of these three mechanisms are believed to play a role in the neurodegeneration that occurs in both Parkinson's and Huntington's diseases. Strategies to rescue or protect injured neurons usually involve promoting neuronal growth and function or interfering with neurotoxic processes. Considerable research has been done on testing a large array of neuroprotective agents using animal models which mimic these disorders. Some of these approaches have progressed to the clinical arena. Here, we review neuroprotective strategies which have been found to successfully ameliorate the neurodegeneration associated with Parkinson's and Huntington's diseases. First, we will give an overview of the mechanisms of cell death and the background of Parkinson's and Huntington's diseases. Then we will elaborate on a range of neuroprotective strategies, including neurotrophic factors, anti-excitotoxins, antioxidants, bioenergetic supplements, anti-apoptotics, immunosuppressants, and cell transplantation techniques. Most of these approaches hold promise as potential therapies in the treatment of these disorders.

Animals↗
PubMed2000

Echocardiographic assessment of cardiac morphology and function in mutant dwarf rats.

Although the mutant dwarf rat has been proposed as a model of growth hormone (GH) deficiency, few studies have addressed its cardiovascular abnormalities. Therefore, the aim of the present study was to investigate cardiac structure and function in mutant dwarf rats in vivo before and after chronic GH administration, by means of transthoracic Doppler echocardiography. To this purpose, forty 90-day-old female dwarf rats were randomized to receive either GH treatment or placebo. Twenty age-and sex-matched Lewis rats (200-250 g) served as the control group. All rats underwent echocardiograms before receiving any drug and after 3 weeks of therapy. Echocardiographically detected left ventricular mass indexed to tibial length was reduced by 41% in dwarf rats compared to the control group. Such relative cardiac atrophy was also evident at the myocyte level, and was fully reversible after GH therapy. In contrast to the control group, dwarf rats also showed a reduction of left ventricular diastolic volumes normalized to tibial length and impaired cardiac performance as suggested by the reduction of cardiac index, abnormal stress-shortening relations, and a significant elevation of total peripheral vascular resistance. All these abnormalities were reversible upon GH therapy for 3 weeks. In conclusion, GH plays an important role in maintaining a normal cardiac structure and function. Since the observed changes are similar to those seen in GH-deficient men, the mutant dwarf rat represents a faithful animal model of GH deficiency.

Animals↗
PubMed1999

Progressive cardiac dysfunction and fibrosis in the cardiomyopathic hamster and effects of growth hormone and angiotensin-converting enzyme inhibition.

BACKGROUND: Growth hormone (GH) improves cardiac function in the rat with myocardial infarction, but its effects in a model of primary dilated cardiomyopathy have not been reported. GH effects were examined at early (4 months) and late (10 months) phases of disease in the cardiomyopathic (CM) hamster, and the combination of GH with chronic ACE inhibition was assessed in late-phase heart failure. METHODS AND RESULTS: CM hamsters (CHF 147 line) at 4 months showed severe systolic left ventricular (LV) dysfunction with normal LV filling pressure, and at 10 months there was more severe systolic as well as diastolic dysfunction with increasing myocardial fibrosis. Recombinant human GH alone for 3 weeks at age 4 months increased LV wall thickness and reduced systolic wall stress without altering diastolic wall stress, whereas at 10 months, wall stress and fractional shortening did not improve. The LV dP/dt(max) was enhanced at both ages by GH, which at 4 months reflected increased contractility, but at 10 months was most likely caused by elevation of the LV filling pressure. The increasing degree of fibrosis correlated inversely with LV function but was unaffected by GH. In other CM hamsters, high-dose ACE inhibition alone (quinapril), started at 8 months and continued for 11 weeks, improved LV function and inhibited unfavorable remodeling, but the addition of GH for 3 weeks at age 10 months produced increased wall thickness with little additional functional benefit and increased the LV filling pressure and diastolic wall stress. CONCLUSIONS: GH treatment alone improved LV dysfunction at 4 months of age in CM hamsters by increasing contractility and reducing wall stress but had few beneficial effects at 10 months in severe LV failure. After chronic ACE inhibition, addition of GH at 10 months had no additional beneficial effects and further increased LV diastolic pressure. These differing effects of GH may relate to the progressive increase of LV fibrosis in the CM hamster.

Angiotensin-Converting Enzyme Inhibitors↗