Publications by authors named "Caughey W"

Article Synopsis
  • * This experiment produced 2.05 MJ of laser energy, resulting in 3.1 MJ of total fusion yield, which exceeds the Lawson criterion for ignition, demonstrating a key milestone in fusion research.
  • * The report details the advancements in target design, laser technology, and experimental methods that contributed to this historic achievement, validating over five decades of research in laboratory fusion.
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Background: The New Zealand Rotator Cuff Registry represents the largest prospective cohort of rotator cuff repairs. Despite this, there are limited medium- to long-term data of rotator cuff repair outcomes.

Purpose: To (1) analyze the pain and functional outcomes of a large cohort of primary rotator cuff repairs and (2) evaluate the effect of patient factors and tear characteristics on medium-term outcomes.

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Article Synopsis
  • * In inertially confined fusion, ignition allows the fusion process to spread into surrounding fuel, potentially leading to higher energy output.
  • * Recent experiments at the National Ignition Facility achieved capsule gains of 5.8 and approached ignition, even though "scientific breakeven" has not yet been fully realized.
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Background: This multicentre cohort study investigates the effect of smoking on the outcome of rotator cuff repair (RCR), with attention to age at presentation for surgery, pre-operative and post-operative pain and function and intra-operative findings.

Methods: Patient information was collected pre-operatively, including Flex Shoulder Function (Flex SF) and visual analogue scale pain, then at 6 months, 1, 2 and 5 years post-operatively. Intra-operative technical data were collected by the operating surgeon.

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Ageing of the skeleton is characterised by decreased bone mineral density, reduced strength, and increased risk of fracture. Although it is known that these changes are determined by the activities of bone cells through the processes of bone modelling and remodelling, details of the molecular mechanisms that underlie age-related changes in bone are still missing. Here, we analysed age-related changes in bone microarchitecture along with global gene expression in samples obtained from patients with osteoarthritis (OA).

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Background: Native joint septic arthritis (NJSA) is poorly studied. We describe the epidemiology, treatment, and outcomes of large joint NJSA (LNJSA) and small joint NJSA (SNJSA) in adults at Middlemore Hospital, Auckland, New Zealand.

Methods: This was a coding-based retrospective study of patients ≥16 years old admitted between 2009 and 2014.

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Introduction: Obstructive sleep apnea (OSA) is difficult to manage for those who are intolerant or noncompliant with standard facial mask treatment options. Current treatment options do not address the underlying cause of OSA. Exercise as a treatment option has been found to improve OSA indices.

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Hemin (iron protoporphyrin IX) is a crucial component of many physiological processes acting either as a prosthetic group or as an intracellular messenger. Some unnatural, synthetic porphyrins have potent anti-scrapie activity and can interact with normal prion protein (PrPC). These observations raised the possibility that hemin, as a natural porphyrin, is a physiological ligand for PrPC.

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Cyclic tetrapyrroles are among the most potent compounds with activity against transmissible spongiform encephalopathies (TSEs; or prion diseases). Here the effects of differential sulfonation and metal binding to cyclic tetrapyrroles were investigated. Their potencies in inhibiting disease-associated protease-resistant prion protein were compared in several types of TSE-infected cell cultures.

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No validated treatments exist for transmissible spongiform encephalopathies (TSEs or prion diseases) in humans or livestock. The search for TSE therapeutics is complicated by persistent uncertainties about the nature of mammalian prions and their pathogenic mechanisms. In pursuit of anti-TSE drugs, we and others have focused primarily on blocking conversion of normal prion protein, PrP(C), to the TSE-associated isoform, PrP(Sc).

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Prion diseases, including scrapie, are incurable neurodegenerative disorders. Some compounds can delay disease after a peripheral scrapie inoculation, but few are effective against advanced disease. Here, we tested multiple related porphyrins, but only Fe(III)meso-tetra(4-sulfonatophenyl)porphine injected into mouse brains after intracerebral scrapie inoculation substantially increased survival times.

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Chronic wasting disease (CWD) is an emerging transmissible spongiform encephalopathy (prion disease) of North American cervids, i.e., mule deer, white-tailed deer, and elk (wapiti).

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The transmissible spongiform encephalopathy (TSE) diseases are rare, neurodegenerative diseases that include scrapie in sheep, bovine spongiform encephalopathy, and Creutzfeldt-Jakob disease in humans. There are no effective treatments available for clinical use in humans. We now demonstrate that, in 2 different rodent models of scrapie, multiple pretreatments with the cyclic tetrapyrrole phthalocyanine tetrasulfonate (PcTS) were as effective at delaying disease as multiple treatments starting at the time of infection.

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Noncovalent bonding interactions of nitric oxide (NO) with human serum albumin (HSA), human hemoglobin A, bovine myoglobin, and bovine cytochrome c oxidase (CcO) have been explored. The anesthetic nitrous oxide (NNO) occupies multiple sites within each protein, but does not bind to heme iron. Infrared (IR) spectra of NNO molecules sequestered within albumin, with NO present, support the binding of NO and NNO to the same sites with comparable affinities.

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The transmissible spongiform encephalopathies (TSEs) are fatal, neurodegenerative diseases for which no effective treatments are available. The likelihood that a bovine form of TSE has crossed species barriers and infected humans underscores the urgent need to identify anti-TSE drugs. Certain cyclic tetrapyrroles (porphyrins and phthalocyanines) have recently been shown to inhibit the in vitro formation of PrP-res, a protease-resistant protein critical for TSE pathogenesis.

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The source(s) of reactive partially reduced oxygen species associated with myocardial ischemia/reperfusion injury remain unclear and controversial. Myoglobin has not been viewed as a participant but is present in relatively high concentrations in heart muscle and, even under normal conditions, undergoes reactions that generate met (Fe3+) species and also superoxide, hydrogen peroxide, and other oxidants, albeit slowly. The degree to which the decrease in pH and the freeing of copper ions, as well as the variations in pO2 associated with ischemia and reperfusion increase the rates of such myoglobin reactions has been investigated.

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A central aspect of pathogenesis in the transmissible spongiform encephalopathies or prion diseases is the conversion of normal protease-sensitive prion protein (PrP-sen) to the abnormal protease-resistant form, PrP-res. Here we identify porphyrins and phthalocyanines as inhibitors of PrP-res accumulation. The most potent of these tetrapyrroles had IC50 values of 0.

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Spectroelectrochemical titration studies involving the binding of the infrared-active probe ligand carbon monoxide (CO) to the heme alpha 3/CuB site of bovine heart cytochrome c oxidase (CcO) have been reexamined. The spectroelectrochemical cell employed was constructed to monitor both the infrared (IR) and visible/Soret spectra of the CcO-CO complex as a function of the overall oxidation state of the enzyme. A number of commonly used electron transfer mediators were employed to shuttle electrons between the redox active sites within the enzyme and the electrode surface.

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Reduction of nitric oxide (NO) to nitrous oxide (N2O) is catalyzed by bovine heart cytochrome c oxidase (CcO) in anaerobic solutions at pH 7.2 and 20 degrees C. Cyanide inhibits and forms Fea3(3+)CN.

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Redox-dependent conformational changes of bovine Cu,Zn superoxide dismutase in 20 mM phosphate buffer (pH 7.4) were studied at 20 degrees C using Fourier transform infrared spectroscopy. Amide I spectra provide evidence that conformational changes in the protein accompany a change in the oxidation state of copper at the active site.

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Effects of 10-30% (v/v) of dimethyl sulfoxide, glycerol, and ethylene glycol on the H-O-H bending vibration of water and the amide I bands of horse heart cytochrome c and chicken egg white lysozyme in 25 mM sodium phosphate buffer (pH 7.4) were examined at 20 degrees C by Fourier transform infrared spectroscopy. The H-O-H bending mode of water was strongly affected by these cryoprotectant solvents.

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A series of hydrophilic to hydrophobic surface mutations were prepared at the highly solvent-exposed lysine 73 of iso-1-cytochrome c to assess the ability of such mutants to affect the energetics of the denatured state. In this report, the aliphatic hydrophobics (leucine, isoleucine, valine, alanine, glycine) were studied. The thermodynamic stability of each of these mutants was determined by guanidine hydrochloride denaturation.

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Effects of changes in oxidation state at the other metal centers on oxidized heme a3 cyanide of bovine heart cytochrome c oxidase have been investigated. Only one CN- binds, giving Fe3+a3CN, in fully-oxidized cytochrome c oxidase and its 1-, 2-, and 3-electron reduction products. Soret/visible spectra for the heme a3 cyanide are independent of overall redox level, whereas distinct shifts in C-N infrared stretch band frequency occur upon reduction, reflecting changes in the polarity of the ligand (CN-) environment.

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