http://nova.newcastle.edu.au/vital/access/services/Feed ${session.getAttribute("locale")} 5 Autonomic control of bronchial circulation in awake sheep during rest and behaviour http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12828 1. We tested the hypothesis that the pattern and the intensity of autonomic mechanisms causing vasoconstriction in the resting bronchial circulation of awake dogs also exists in awake sheep. It was also postulated that sighing behaviour and the associated bron-chovascular dilatation induced by non-adrenergic, non-cholinergic (NANC) mechanisms observed in the dog exist in sheep. 2. Bronchial arterial blood flow to lower airways of both lungs of awake sheep was measured continuously using pulsed Doppler flow probes mounted on the bronchial artery at prio. thoracotomy. 3. Cumulative and factorial analysis of responses to randomized combinations of autonomi. α₁-, α₂-, β₁- and β₂-adrenoceptors and cholinoceptor autonomic blockade suggests that resting vasoconstrictor activity is less in sheep than in dogs. At normal aortic pressure, the autonomic activity of these receptor groups in the sheep lowers bronchial blood flow and conductance by 30%, whereas in the awake dog, the corresponding autonomic effect is 50%. 4. Tonic autonomic control of bronchial conductance can be partitioned in sheep to show significant and separat.α- and β-adrenoceptor vasoconstrictor activity at a ratio of 1.8:1, an effect normally offset by a weaker vasodilator α-/β-adrenoceptor interaction. In contrast to the situation in awake dogs, cholinoceptors do not play a role in awake sheep. 5. Nitric oxide (NO) synthase inhibition in sheep using NG-nitro-L-arginine following blockade of α- and β-adrenoceptors and cholinoceptors causes hypertension, but minor changes, if any, in pulmonary pressures or heart rate. Bronchial flow and conductance, however, fall from a higher resting conductance by approximately 50%, suggesting that, normally, resting bronchial flow conductance is dominated by strong tonic NO vasodilator effects that interact with weaker tonic autonomic vasoconstrictor effects.6. Superimposed (respiratory) behaviours of sighing, sneezing and coughing, which involve negative swings in intrathoracic pressure and the movement of inspired air, evoke large active bronchovascular dilator effects. These appear to be largely NANC in origin and appear to be dependent, in part, on mechanisms associated with NO release. It is postulated that the C-fibre axon reflex using substance P, calcitonin gene-related peptide and neurokinin A may be involved. Vocalization and eructation do not evoke bronchovascular effects. 2013-04-30T06:45:20.384Z ]]> Clustering nuclei using machine learning techniques http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10114 Cervical cancer is the second most common cancer among women. Meanwhile, cervical cancer could be largely preventable and curable with regular Pap tests. Nuclei changes in the cervix could be found by this test. Accurate nuclei detection is extremely critical as it is the previous step of analysing nuclei changes and diagnosis afterwards. Recently, computer-aided nuclei segmentation has increased dramatically. Although such algorithms could be utilised in the situation for sparse nuclei since they are intuitively detected, the segmentation for the complicated nuclei clusters is still challenging task. This paper presents a new methodology for the detection of cervical nuclei clusters. We first detect all the nuclei from the cervical microscopic image by an ellipse fitting algorithm. Second, we chose some high-relevant features from all the features we obtained in last step via F-score, which is based on to what extent one feature attributes to results. All the ellipses are then classified into single ones and cluster ones by C4.5 decision tree with selected features. We evaluated the performance of this method by the classification accuracy, sensitivity, and cluster predictive value. With the 9 selected features from the original 13 features, we came by the promising classification accuracy (97.8%). 2013-04-05T01:05:08.884Z ]]> Performance evaluation of a nine-phase synchronous reluctance drive http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:2891 This paper describes the performance of an experimental 5kW nine-phase synchronous reluctance motor (Syncrel) drive. Increasing the number of phases of the Syncrel above three allows the stator MMF’s to be shaped, producing significantly greater torque / RMS ampere in the same volume machine. Generalized d-q voltage and torque equations are derived for the nine-phase Syncrel. These demonstrate that harmonic direct and quadrature components of current contribute to torque production in the machine and can be controlled by applying appropriate stator voltages. A field-oriented controller is described and implemented using a TMS320C32 digital signal processor board. The controller designates portions of the stator winding as supplying either direct or quadrature excitation. A simple inverter switching strategy is used to control the phase currents to their reference values. Experimental current regulation, speed response and torque measurements are presented from the drive. These results validate the system model and demonstrate the drive capability. 2013-03-04T00:00:08.557Z ]]> BRIP1, PALB2, and RAD51C mutation analysis reveals their relative importance as genetic susceptibility factors for breast cancer http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12510 Mutations in the recognized breast cancer susceptibility genes BRCA1, BRCA2, TP53, ATM, and CHEK2 account for approximately 20% of hereditary breast cancer. This raises the possibility that mutations in other biologically relevant genes may be involved in genetic predisposition to breast cancer. In this study, BRIP1, PALB2, and RAD51C were sequenced for mutations as a result of previously being associated with breast cancer risk due to their role in the double-strand break repair pathway and their close association with BRCA1 and BRCA2. Two truncating mutations in PALB2 (Q66X and W1038X), one of which is has not been reported before, were detected in an independent Australian cohort of 70 individuals with breast or ovarian cancer, and have strong family histories of breast or breast/ovarian cancer. In addition, six missense variants predicted to be causative were detected, one in BRIP1 and five in PALB2. No causative variants were identified in RAD51C. This study supports recent observations that although rare, PALB2 mutations are present in a small but substantial proportion of inherited breast cancer cases, and indicates that RAD51C at a population level does not account for a substantial number of familial breast cancer cases. 2013-01-31T03:40:03.963Z ]]> Pharmacogenetics of cyclophosphamide and CYP2C19 polymorphism in Thai systemic lupus erythematosus http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12479 To assess whether the CYP2C19 polymorphism modified the effect of cyclophosphamide on ovarian toxicity in Thai patients with SLE. We performed a case–control study of female patients with SLE who were treated with cyclophosphamide at Ramathibodi Hospital, Bangkok, Thailand. Cases were patient who had ovarian toxicity (sustained amenorrhoea >12 months or lack of menstruation for >4 months). CYP2C19 polymorphism was genotyped using PCR–RFLP method. Logistic regression was applied to assess CYP2C19 polymorphism as an effect modifier of cyclophosphamide. Seventy-one patients with SLE were enrolled, of which 36 (59.7%) had ovarian toxicity. CYP2C19*2 allele frequencies were 27.8 and 21.4% in the ovarian and non-ovarian toxicity groups. Patients with CYP2C19*1/*1 genotype and higher cumulative dose of cyclophosphamide (>23.75 g) had the highest odds of ovarian toxicity, i.e. 11.0 (95% CI: 1.2–99.1) times higher than patients with the CYP2C19*1/*2 or *2/*2 genotypes who received less cyclophosphamide (<23.75 g). After adjusting for age at start of treatment, this risk increased to 13.6 (95% CI: 1.1–162.2). Our results suggest that a cumulative cyclophosphamide dose of 23.75 g or higher carries a twofold higher risk of ovarian toxicity and the CYP2C19*1/*1 genotype increases the risk of toxicity a further fivefold. 2013-01-24T01:20:04.137Z ]]> Factors affecting cytotrophoblast cell viability and differentiation: evidence of a link between syncytialisation and apoptosis http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12438 A relationship between cytotrophoblast differentiation (syncytialisation) and apoptosis is hypothesised to exist, but has not been clearly determined. To address this, we explored the effects of cAMP, an inducer of syncytialisation, on human choriocarcinoma cell differentiation and viability under three different culture conditions related to diverse survival status: no serum, 10% fetal calf serum or 10% charcoal-stripped fetal calf serum. 8-Br-cAMP increased BeWo cell viability in culture media without serum, but viability was decreased in a dose- and time-dependent manner when serum was present. The appearance of apoptotic nuclei fragments were only observed when BeWo cells were cultured in media containing serum combined with 8-Br-cAMP treatment. In addition, the ratio of FasL to Fas expression following treatment with 8-Br-cAMP increased by 20-fold in 10% charcoal-stripped fetal calf serum media and 65-fold 10% fetal calf serum media, and activation of caspase-3 also required media with serum. The markers of syncytialisation (syncytin 1 expression and human chorionic gonadotropin secretion) were induced significantly by 8-Br-cAMP, and were higher in 10% fetal calf serum media than in 10% charcoal-stripped fetal calf serum media, than in the absence of serum. Syncytia formation was stimulated by 8-Br-cAMP and this required serum in the media. We now show that factors contained within serum are necessary for cAMP-stimulated cytotrophoblast differentiation, that syncytialisation involves apoptotic events, and that a lack of serum based factors could switch the cellular program away from differentiation. 2013-01-16T05:20:03.781Z ]]> Heart-lung interactions: the sigh and autonomic control in the bronchial and coronary circulations http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:12191 1. The Darwin hypothesis that human and animal expressions of emotion are the product of evolution and are tied to patterns of autonomic activity specified to progress the emotion remains under challenge. 2. The sigh is a respiratory behaviour linked with emotional expression in animals and humans from birth to death. The aim of the present study was to explore Darwin’s hypothesis with respect to tied autonomic activity underlying sigh-induced changes in the bronchial and coronary circulations. 3. Awake dogs were prepared using pulsed ultrasonic flow probes on the right bronchial artery, parent intercostal artery and brachial artery, or on the right, circumflex and anterior descending coronary arteries. Central venous (CVP) and arterial pressures (AP) were measured; heart rate and flow conductances were derived. Three spontaneous sighs were monitored before and during random blockade of individual and combinations of cholinoceptors, -adrenoceptors and β-adrenoceptors using methscopolamine, phentolamine and propranolol infusions. The data were subject to a 2 3 factorial analysis. 4. A spontaneous sigh is marked by a transient fall and return (< 3 s) in CVP of 18 mmHg (from 4±1 to –14±2 mmHg), usually followed by apnoea lasting 23±2 s. There is an immediate tachycardia and small rise in AP (phase 1) then, during apnoea, bradycardia and a fall in AP (phase 2). During phase 2, bronchial and coronary blood flow and conductance rise two- to three-fold over 30 s (peak at 8 s). The vascular changes are absent in parent intercostal and brachial beds. 5. The phase 1 tachycardia is entirely cholino/adrenoceptor in origin and is due to cholinoceptor withdrawal and positive β-adrenoceptor plus β-adrenoceptor/cholinoceptor interaction activity, in the ratio 1.75 : 1. The phase 2 bradycardia is entirely cholinoceptor. However, only 17% of the peak rise in bronchial conductance is due to -/β-adrenoceptor interactions (sympathetic withdrawal); 83% is due to non-cholino/adrenoceptor mechanisms. In a separate four animals, the total sigh-induced conductance rise is virtually abolished by prior infusion of NG-nitro- L-arginine methyl ester. 6. Therefore, the mechanism of the sigh-induced bronchial and conductance effects may be an efferent nitrergic component of an arterial chemoreceptor reflex induction of sighing. An alternative hypothesis invokes local stretch-sensitive C-fibre sensory nerve endings releasing substance P–calcitonin gene-related peptide–neurokinin A in response to cardiovascular distortion secondary to the sudden transmural pressure rise when intrapleural pressure falls. Whatever the case, these effects and the cholino/adrenoceptor base for the heart rate and broncho/coronary changes support the Darwin hypothesis. 2012-12-12T23:57:01.713Z ]]> The chaperonin containing TCP1 complex (CCT/TRiC) involved in mediating sperm-oocyte interaction http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11888 Sperm-oocyte interactions are among the most remarkable processes in cell biology. These cellular recognition events are initiated by an exquisitely specific adhesion of free-swimming spermatozoa to the zona pellucida, an acellular matrix that surrounds the ovulated oocyte. Decades of research focusing on this interaction have led to the establishment of a widely held paradigm that the zona pellucida receptor is a single molecular entity that is constitutively expressed on the sperm cell surface. In contrast, we have employed the techniques of blue native-polyacrylamide gel electrophoresis, far Western blotting, and proximity ligation to secure the first direct evidence in support of a novel hypothesis that zona binding is mediated by multimeric sperm receptor complex(es). Furthermore, we show that one such multimeric association, comprising the chaperonin-containing TCP1 complex (CCT/TRiC) and a zona-binding protein, zona pellucida-binding protein 2, is present on the surface of capacitated spermatozoa and could account for the zona binding activity of these cells. Collectively, these data provide an important biochemical insight into the molecular basis of sperm-zona pellucida interaction and a plausible explanation for how spermatozoa gain their ability to fertilize. 2012-11-01T04:26:24.449Z ]]> Climate change, time-dependent corrosion damage and safety of deteriorating RC structures http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11727 The paper will assess how increases in atmospheric C0₂ levels will affect carbonation-induced corrosion damage and safety loss to reinforced concrete structures. Probabilistic methods are used as there is significant uncertainty and variability of atmospheric C0₂ levels, deterioration mechanisms, material properties, dimensions, strength and loading. The time-dependent structural reliability analysis will predict the probability of corrosion initiation, mean proportion of corrosion (cover) damage and the probability of failure (collapse) of typical reinforced concrete beams over the next 100 years. For the worst case emissions scenario the mean proportion of corrosion damage is up to 540% higher than the best C0₂ emission mitigation scenario. For the worst case scenario the probability of flexural failure is only 6% higher than that observed for the best mitigation scenario. If the worst emissions scenario is viewed as the most likely scenario then increasing design cover by approximately 3-18 mm may be needed to ameliorate corrosion damage. 2012-10-15T22:18:16.885Z ]]> A horizontal categorification of Gel'fand duality http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11531 In the setting of C*-categories, we provide a definition of spectrum of a commutative full C*-categories as a one-dimensional unital Fell bundle over a suitable groupoid (equivalence relation) and prove a categorical Gel'fand duality theorem generalizing the usual Gel'fand duality between the categories of commutative unital C*-algebras and compact Hausdorff spaces. Although many of the individual ingredients that appear along the way are well known, the somehow unconventional way we “glue” them together seems to shed some new light on the subject. 2012-09-20T05:50:59.204Z ]]> Histopathologic findings of autoimmunity in thyroid, pituitary, and adrenal diseases in chronic hepatitis C postmortem cases http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11187 Objective: To assess the histologic prevalence of immune-mediated thyroid, pituitary, and adrenal diseases in postmortem cases with hepatitis C. Methods: We reviewed 108 consecutive cases of chronic hepatitis C in patients in whom a complete postmortem examination was performed. All microscopic and histologic slides of the thyroid, pituitary, and adrenal reports were reviewed and assessed for evidence of autoimmune diseases. These were compared with a control group of 100 postmortem cases without hepatitis C. Results: In chronic hepatitis C infection, there is a heightened immune response resulting in many autoimmune diseases. The commonest endocrinopathy in association with this chronic infection is thyroid disease, a finding confirmed in our current study. Among the 108 postmortem cases of hepatitis C, there were 14 cases (13%) with evidence of thyroiditis. No cases of pituitary or adrenal disease were found. The mean age of the patients was 52 years (range, 29 to 68). This frequency compared with 7 cases of thyroid disease (7%) in the control group (no significant difference between the 2 groups). Conclusion: On the basis of our postmortem data, thyroid disease was the only major endocrinopathy associated with hepatitis C infection, with a prevalence of 13%. This was comparable with other serologic and nonhistologic antemortem findings. There was no evidence of pituitary or adrenal involvement. 2012-08-07T21:47:40.780Z ]]> The C282Y polymorphism of the hereditary hemochromatosis gene is associated with increased sex hormone-binding globulin and normal testosterone levels in men http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:11064 Background: Hereditary hemochromatosis resulting either from homozygosity for the C282Y polymorphism of the HFE gene, or compound heterozygosity for C282Y and H63D, manifests with liver disease and hypogonadism. However, it is unclear whether men who are heterozygotes for C282Y or H63D exhibit subtle abnormalities of sex hormone status. Aims: To evaluate whether heterozygosity for either of the HFE gene polymorphisms C282Y or H63D is associated with circulating testosterone and SHBG in men. Subjects and Methods: We performed a cross-sectional analysis of 388 community-dwelling men. Men were genotyped for C282Y and H63D. Sera were analysed for testosterone and SHBG, and insulin resistance was estimated using a homeostatic model (HOMA2-IR). Results: Mean age of men in the cohort was 56.9 yr. Men who were heterozygous for the C282Y polymorphism in the HFE gene had higher SHBG levels than men who did not carry this polymorphism (mean±SE, 38.2±1.64 vs 32.8±0.71 nmol/l, p=0.006). Total and free testosterone levels did not differ in the two groups. In multivariate analysis adjusting for potential confounders including age, waist circumference, testosterone, and HOMA2-IR, C282Y heterozygosity remained associated with SHBG levels (p<0.001). Conclusion: The C282Y polymorphism is associated with SHBG levels in men who do not manifest iron overload. Further studies are needed to clarify potential mechanisms and determine the clinical relevance of this finding. 2012-07-10T03:37:59.745Z ]]> A compactly generated group whose Hecke algebras admit no bounds on their representations http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:2409 We construct a compactly generated, totally disconnected, locally compact group whose Hecke algebra with respect to any compact open subgroup does not have a C*-enveloping algebra. 2012-06-28T03:05:57.910Z ]]> Comment on "Transformation of C-type defects on Si (1 0 0) - 2 x 1 surface at room temperature STM/STS study [Surf. Sci. 602 (2008) 2835]" http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10896 In a recent paper, Sobotík and Ošt’ádal report scanning tunneling microscopy/spectroscopy (STM/STS) experiments in which the common C-defect of the silicon (1 0 0) surface is seen to undergo several structural transformations. These transitions produce four types of surface features that the authors label C2, C′,C2′, and C3. Two of these features (C2 and C′) were previously described by Zhang et al. and Hata et al., while sequences of STM images showing the formation of all four features were also reported by us. Starting with the well-established inter-dimer H + OH model of the C-defect, Sobotík and Ošt’ádal propose that all four features arise from OH and H fragments undergoing site-to-site shift reactions. This interpretation is in sharp variance to our assignment of the C′,C2′, and C3 features to Si–O–Si species that form when OH fragments dissociate. In this comment we discuss why OH and H shift reactions, as advanced by Sobotík and Ošt’ádal cannot alone account for the reported C′,C2′, and C3 features. We provide three specific criticisms. 2012-06-13T01:24:01.686Z ]]> Disclosing hepatitis C infection within everyday contexts implications for accessing support and healthcare http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10503 In this paper the authors quantify hepatitis C disclosure outcomes across social contexts and identify the factors associated with widespread disclosure of infection. In a cross-sectional survey of people with hepatitis C (N = 504) more than half reported receiving a bad reaction from someone following disclosure. Unauthorized disclosure occurred, and many participants had been pressured into disclosing their infection. The factors associated with widespread disclosure were: education level; knowing other people with hepatitis C; feeling fatigued; receiving disclosure advice; and experiencing unauthorized disclosure. Bad reactions following disclosure are common and may impede health-seeking behaviour including uptake of hepatitis C treatment. 2012-03-22T04:10:04.233Z ]]> Identification and characterization of two novel JARID1C mutations: suggestion of an emerging genotype-phenotype correlation http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10419 Mental retardation (MR) is characterized by cognitive impairment with an IQ <70. Many of the major causes are genetically determined and the ~30% male excess suggests that mutations in genes carried on the X chromosome are disproportionably represented. One such gene, jumonji AT-rich interactive domain 1C (JARID1C) on Xp11.2, has been identified in families with X-linked MR (XLMR), with 18 different mutations reported to date. As part of a systematic resequencing of 720 genes in 208 XLMR families of the International Genetic of Learning Disability (IGOLD) consortium, two novel nucleotide changes in the JARID1C coding region were identified, with the nucleotide changes segregating with the disease phenotype in the two families. The first mutation is a single-nucleotide insertion in exon 21 (c.3258_3259insC p.K1087fs*43) causing a frameshift and resulting in a premature termination codon (PTC). Such PTC-containing mRNAs are generally degraded by nonsense-mediated mRNA decay (NMD) surveillance, but our results show that this is not the case with this mutation. The other change is a single-nucleotide substitution in exon 12 (c.1160C>A) in a published family with nonsyndromic MR, MRX13. This change occurs in a highly conserved amino acid, with proline (P) being substituted by threonine (T) (p.P544T). Functional analysis shows that this amino-acid substitution compromises both tri- and didemethylase activity of the JARID1C protein. We conclude that the two novel changes impair JARID1C protein function and are disease-causing mutations in these families. 2012-03-15T00:30:03.545Z ]]> The molecular basis of sperm - oocyte interactions http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10297 Research Doctorate - Doctor of Philosophy (PhD) 2012-03-12T07:51:33.087Z ]]> Demethylation by 5-aza-2'-deoxycytidine in colorectal cancer cells targets genomic DNA whilst promoter CpG island methylation persists http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10028 Background: DNA methylation and histone acetylation are epigenetic modifications that act as regulators of gene expression. Aberrant epigenetic gene silencing in tumours is a frequent event, yet the factors which dictate which genes are targeted for inactivation are unknown. DNA methylation and histone acetylation can be modified with the chemical agents 5-aza-2'-deoxycytidine (5-aza-dC) and Trichostatin A (TSA) respectively. The aim of this study was to analyse de-methylation and re-methylation and its affect on gene expression in colorectal cancer cell lines treated with 5-aza-dC alone and in combination with TSA. We also sought to identify methylation patterns associated with long term reactivation of previously silenced genes. Method: Colorectal cancer cell lines were treated with 5-aza-dC, with and without TSA, to analyse global methylation decreases by High Performance Liquid Chromatography (HPLC). Re-methylation was observed with removal of drug treatments. Expression arrays identified silenced genes with differing patterns of expression after treatment, such as short term reactivation or long term reactivation. Sodium bisulfite sequencing was performed on the CpG island associated with these genes and expression was verified with real time PCR. Results: Treatment with 5-aza-dC was found to affect genomic methylation and to a lesser extent gene specific methylation. Reactivated genes which remained expressed 10 days post 5-aza-dC treatment featured hypomethylated CpG sites adjacent to the transcription start site (TSS). In contrast, genes with uniformly hypermethylated CpG islands were only temporarily reactivated. Conclusion: These results imply that 5-aza-dC induces strong de-methylation of the genome and initiates reactivation of transcriptionally inactive genes, but this does not require gene associated CpG island de-methylation to occur. In addition, for three of our selected genes, hypomethylation at the TSS of an epigenetically silenced gene is associated with the long term reversion of gene expression level brought about by alterations in the epigenetic status following 5-aza-dC treatment. 2012-03-12T07:49:09.175Z ]]> Small molecules and targeted therapies in distant metastatic disease http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6916 Chemotherapy, biological agents or combinations of both have had little impact on survival of patients with metastatic melanoma. Advances in understanding the genetic changes associated with the development of melanoma resulted in availability of promising new agents that inhibit specific proteins up-regulated in signal cell pathways or inhibit anti-apoptotic proteins. Sorafenib, a multikinase inhibitor of the RAF/RAS/MEK pathway, elesclomol (STA-4783) and oblimersen (G3139), an antisense oligonucleotide targeting anti-apoptotic BCl-2, are in phase III clinical studies in combination with chemotherapy. Agents targeting mutant B-Raf (RAF265 and PLX4032), MEK (PD0325901, AZD6244), heat-shock protein 90 (tanespimycin), mTOR (everolimus, deforolimus, temsirolimus) and VEGFR (axitinib) showed some promise in earlier stages of clinical development. Receptor tyrosine-kinase inhibitors (imatinib, dasatinib, sunitinib) may have a role in treatment of patients with melanoma harbouring c-Kit mutations. Although often studied as single agents with disappointing results, new targeted drugs should be more thoroughly evaluated in combination therapies. The future of rational use of new targeted agents also depends on successful application of analytical techniques enabling molecular profiling of patients and leading to selection of likely therapy responders. 2012-03-12T07:47:38.311Z ]]> Folic acid: vitamin and panacea or genetic time bomb? http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:357 We live in a health-conscious age - many of us supplement our diet with essential micronutrients through the discretionary use of multivitamin pills or judicious selection of foods that have a health benefit beyond that conferred by the nutrient content alone - the so-called 'functional foods'. Indeed, the citizens of some nations have little choice, with a mandatory fortification policy in place for certain vitamins. But do we ever stop to consider the consequences of an increased exposure to micronutrients? We examine this issue in relation to the B-group vitamin folic acid, and ask whether supplementation with this vitamin could introduce a strong genetic selection pressure - one that has the side effect of increasing the prevalence of some of the most significant, human life-threatening diseases. Are we affecting our genetics - is this a case of human evolution in progress by altering our diet? 2012-03-01T01:35:08.701Z ]]> Implications for design and construct contractors operating in a public private partnership environment: an Australian perspective http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:10075 The term Design and Construct (D&C) is a well-established description of a procurement method in which the roles and responsibilities of the various stakeholders are clearly defined. The advent of Public Private Partnerships (PPPs) brings a new opportunity for design and construct contractors with the concomitant challenge of operating as a member of a private sector consortium with numerous stakeholders. This research investigated the implications for design and construct contractors bidding for social (as opposed to economic) PPP projects. The conventional wisdom has been to assume that there is little difference between bidding for a traditional design and construct contract as compared to submitting a design and construct bid as part of a total PPP bid, however the results of the study indicated that there were subtle, and in some instances, significant differences. The first phase of the research dealt with the direct costs of bidding. This paper describes Phase One of the research project together with a proposed research methodology for Phase Two of the research which, will examine not only direct bidding costs but also the indirect costs to the design and construct contractor during the bidding and the operational phase of the construction project. 2012-02-16T22:40:05.069Z ]]> Exel's crossed product and relative Cuntz-Pimsner algebras http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9929 We consider Exel’s new construction of a crossed product of a C*-algebra A by an endomorphism α. We prove that this crossed product is universal for an appropriate family of covariant representations, and we show that it can be realised as a relative Cuntz–Pimsner algbera. We describe a necessary and sufficient condition for the canonical map from A into the crossed product to be injective, and present several examples to demonstrate the scope of this result. We also prove a gauge-invariant uniqueness theorem for the crossed product. 2012-02-08T22:20:28.398Z ]]> Properties preserved under Morita equivalence of C*-algebras http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9935 We show that important structural properties of C*-algebras and the multiplicity numbers of representations are preserved under Morita equivalence. 2012-02-08T22:20:03.968Z ]]> Early gene expression programs accompanying trans-differentiation of epidermal cells of Vicia faba cotyledons into transfer cells http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6985 Transfer cells (TCs) trans-differentiate from differentiated cells by developing extensive wall ingrowths that enhance plasma membrane transport of nutrients. Here, we investigated transcriptional changes accompanying induction of TC development in adaxial epidermal cells of cultured Vicia faba cotyledons. Global changes in gene expression revealed by cDNA-AFLP were compared between adaxial epidermal cells during induction (3 h) and subsequent building (24 h) of wall ingrowths, and in cells of adjoining storage parenchyma tissue, which do not form wall ingrowths. A total of 5795 transcript-derived fragments (TDFs) were detected; of these, 264 TDFs showed epidermal-specific changes in gene expression and a further 207 TDFs were differentially expressed in both epidermal and storage parenchyma cells. Genes involved in signalling (auxin/ethylene), metabolism (mitochondrial; storage product hydrolysis), cell division, vesicle trafficking and cell wall biosynthesis were specifically induced in epidermal TCs. Blockers of auxin action and vesicle trafficking inhibited ingrowth formation and marked increases in cell division accompanied TC development. Auxin and possibly ethylene signalling cascades induce epidermal cells of V. faba cotyledons to trans-differentiate into TCs. Trans-differentiation is initiated by rapid de-differentiation to a mitotic state accompanied by mitochondrial biogenesis driving storage product hydrolysis to fuel wall ingrowth formation orchestrated by a modified vesicle trafficking mechanism. 2012-01-30T05:03:39.629Z ]]> Kinematic history of serpentinites in the faulted margins of the Hastings Block, New England Orogen, eastern Australia http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6989 Serpentinites along the boundaries of the Hastings Block, southern New England Orogen, eastern Australia, contain S, C and C' structures that provide information on the kinematic history of faults bounding the block. The serpentinite bodies at Yarras on the western boundary of the Hastings Block within the Ralfes Creek, Taylors Creek and Old Highway-Yarras Mountain Trail Faults display dominantly sinistral strike-slip or oblique-slip movement. Serpentinite bodies between these faults record dextralstrike-slip and oblique-slip movement histories as well as sinistral strike-slip or oblique-slip and rare normal, dip-slip movement. The Mt George Serpentinite consists of a northeast-oriented section folded and displaced by movement on a west-northwest section of the Peel–Manning Fault System. Serpentinite structures suggest the west-northwest section initially underwent dextral strike-slip, which reoriented the northeast-oriented section, and subsequently sinistral strike-slip movement. Preliminary studies of serpentinites elsewhere around the periphery of the Hastings Block indicate localised effects due to readjustment of the block during its interaction with the Nambucca Block on its northern margin. The structures observed in the serpentinites are thought to have occurred during and after the Hunter–Bowen Orogeny and prior to stitching of the accretionary–subduction and forearc by the 228 Ma Werrikimbe Caldera. 2012-01-30T05:03:36.549Z ]]> The methylenetetrahydrofolate reductase C677T mutation induces cell-specific changes in genomic DNA methylation and uracil misincorporation: a possible molecular basis for the site-specific cancer risk modification http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6984 The C677T polymorphism in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with a decreased risk of colon cancer although it may increase the risk of breast cancer. This polymorphism is associated with changes in intracellular folate cofactors, which may affect DNA methylation and synthesis via altered one-carbon transfer reactions. We investigated the effect of this mutation on DNA methylation and uracil misincorporation and its interaction with exogenous folate in further modulating these biomarkers of one-carbon transfer reactions in an in vitro model of the MTHFR 677T mutation in HCT116 colon and MDA-MB-435 breast adenocarcinoma cells. In HCT116 cells, the MTHFR 677T mutation was associated with significantly increased genomic DNA methylation when folate supply was adequate or high; however, in the setting of folate insufficiency, this mutation was associated with significantly decreased genomic DNA methylation. In contrast, in MDA-MB-435 cells, the MTHFR 677T mutation was associated with significantly decreased genomic DNA methylation when folate supply was adequate or high and with no effect when folate supply was low. The MTHFR 677T mutation was associated with a nonsignificant trend toward decreased and increased uracil misincorporation in HCT116 and MDA-MB-435 cells, respectively. Our data demonstrate for the first time a functional consequence of changes in intracellular folate cofactors resulting from the MTHFR 677T mutation in cells derived from the target organs of interest, thus providing a plausible cellular mechanism that may partly explain the site-specific modification of colon and breast cancer risks associated with the MTHFR C677T mutation. 2012-01-30T05:03:36.530Z ]]> Peginterferon and ribavirin for hepatitis C (letter) http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4549 To the Editor: In their review of peginterferon and ribavirin for the treatment of hepatitis C, Hoofnagle and Seeff (Dec. 7 issue) do not include data on the association between the consumption of alcohol and both treatment response and disease progression. Level-one evidence of the deleterious effects of alcohol on hepatitis C virus (HCV) RNA levels, on the response to treatment, and on disease progression led the National Institutes of Health and the American Gastroenterological Association to issue position statements advising that "abstinence should be recommended before and during antiviral treatment ... [since] even moderate alcohol consumption can have a deleterious effect on the progression of liver disease in patients with chronic hepatitis C." Alcohol consumption may explain the marked dichotomy in progression rates that cannot be explained by the HCV genotype. Knowledge of alcohol's effects on disease progression should provide reassurance to patients who want to alter the outcome of their disease, particularly since data for nondrinkers show a more benign course than the authors suggest. At a population level, targeting alcohol consumption may effectively reduce the excess deaths the authors anticipate. 2012-01-30T04:21:08.625Z ]]> A categorical approach to imprimitivity theorems for C*-dynamical systems http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9761 Imprimitivity theorems provide a fundamental tool for studying the representation theory and structure of crossed-product C*-algebras. In this work, we show that the Imprimitivity Theorem for induced algebras, Green's Imprimitivity Theorem for actions of groups, and Mansfield's Imprimitivity Theorem for coactions of groups can all be viewed as natural equivalences between various crossed-product functors among certain equivariant categories. The categories involved have C*-algebras with actions or coactions (or both) of a fixed locally compact group G as their objects, and equivariant equivalence classes of right-Hilbert bimodules as their morphisms. Composition is given by the balanced tensor product of bimodules. The functors involved arise from taking crossed products; restricting, inflating, and decomposing actions and coactions; inducing actions; and various combinations of these. Several applications of this categorical approach are also presented, including some intriguing relationships between the Green and Mansfield bimodules, and between restriction and induction of representations. 2012-01-10T02:20:05.510Z ]]> Semigroup C* crossed products and Toeplitz algebras http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4303 Research Doctorate - Doctor of Philosophy (PhD) 2011-12-19T05:20:02.177Z ]]> Regulation of the tumour suppressor PP2A by oncogenic tyrosine kinases http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6254 Research Doctorate - Doctor of Philosophy (PhD) 2011-12-07T22:10:02.794Z ]]> The categorical properties of higher rank graphs and applications to their C*-algebras http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7430 Research Doctorate - Doctor of Philosophy (PhD) 2011-12-07T05:30:35.552Z ]]> Facilitating needs-based care of people with progressive cancer: evaluation of a palliative care needs assessment intervention http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7726 Research Doctorate - Behavioural Science in Medicine 2011-12-07T05:30:18.251Z ]]> Climate change, deterioration and time-dependent reliability of concrete structures http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:9151 The paper will assess how increases in C0₂ levels will affect carbonation-induced damage and safety loss to prestressed concrete structures. Probabilistic methods are used as there is significant uncertainty and variability of deterioration mechanisms, material properties, dimensions, strength and load modelling and environments. The time-dependent structural reliability analysis will predict the probability of corrosion initiation and the probability of failure (collapse) of a typical prestressed concrete AASHTO bridge girder over the next 100 years. Results are presented for a range of future C0₂ emissions scenarios. For the worst case scenario the probability of corrosion initiation is 460% higher than the best mitigation scenario. There is thus a significant likelihood of corrosion damage that will need costly and disruptive repairs during the service life of many concrete structures. For the worst case scenario the probability of failure is 10% higher than that for the best mitigation scenario. 2011-10-12T01:40:09.898Z ]]> Application of multiobjective optimization methods for urban water management: a case study for Canberra water supply system http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8930 Planning and management of urban water supply headworks systems is a complex task which gives rise to a large number of infrastructure and operating policy options. This is often complicated by the existence of multiple competing objectives, whereby a gain in one particular objective may result in a loss in another objective. The solution to these problems requires simultaneous consideration of conflicting objectives. Multiobjective optimization deals with the process of simultaneously optimizing two or more conflicting objectives. In this study, the performance of two optimization methods, the ε-dominance genetic algorithm and ant colony optimization algorithm, is compared for the Canberra water supply headworks system. The case study employed two objectives, minimizing present worth cost and time spent in restrictions, and 13 decision variables associated with infrastructure and operating variables. While both methods produced comparable Pareto fronts, the genetic algorithm consistently produced better results and converged faster. This case study demonstrates the potential of multi-criterion optimization to solve realistic problems, thus freeing the systems planner from tedious and most likely inefficient exploration of the solution space. 2011-09-13T01:01:18.333Z ]]> Composition of sea urchin egg homogenate determines its potency to inositol trisphosphate and cyclic ADPRibose-induced Ca²⁺ release http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6555 Of the three intracellular Ca²⁺ signalling molecules (InsP₃, cADPR and NAADP)sea urchin egg homogenate has been used in the identification and characterisation of two, cADPR and NAADP. Homogenate is prepared in a Na⁺/Cl⁻ substitute of N-Methyl glucamine (NMG)/gluconate. To determine how media previous termcompositionnext term affects Ca²⁺ release we replaced NMG with various sugars or glycine and found a dramatic improvement in InsP₃ mediated Ca²⁺ release. Conversely the response to cADPR was diminished, whilst NAADP was unaffected. Therefore modifying media previous termcompositionnext term may be an important consideration in using homogenate to study Ca²⁺ release for future studies. 2011-08-30T06:10:01.736Z ]]> Calmodulin-dependent protein kinase II, and not protein kinase C, is sufficient for triggering cell-cycle resumption in mammalian eggs http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6543 Mouse eggs arrest at metaphase II following ovulation and are only triggered to complete meiosis when fertilized. Sperm break the cell-cycle arrest by a long-lasting series of Ca²⁺ spikes that lead to an activation of the anaphase-promoting complex/cyclosome. The signal transduction pathway is not fully resolved but both protein kinase C (PKC) and calmodulin-dependent protein kinase II (CamKII) activities increase at fertilization and previous pharmacological studies have implicated both in cell-cycle resumption. We have used a combination of pharmacological inhibitors and constitutively active cRNA constructs of PKCα and CamKIIα microinjected into mouse eggs to show that it is CamKII and not PKC that is the sufficient trigger for cell-cycle resumption from metaphase II arrest. Constitutively active PKC constructs had no effect on the resumption of meiosis but caused an immediate and persistent elevation in intracellular Ca²⁺ when store-operated Ca²⁺ entry was stimulated. With respect to resumption of meiosis, the effects of constitutively active CamKII on eggs were the same as sperm. Eggs underwent second polar body extrusion and pronucleus formation with normal timings; while both securin and cyclin B1 destruction, visualised by coupling to fluorescent protein tags, were complete by the time of polar body extrusion. Induction of a spindle checkpoint by overexpression of Mad2 or by spindle poisons blocked CamKII-induced resumption of meiosis, but the Ca²⁺ chelator BAPTA did not. Furthermore direct measurement of Ca²⁺ levels showed that CamKII did not induce exit from metaphase II arrest by raising Ca²⁺. Therefore, we conclude that PKCs may play an important role in maintaining Ca²⁺ spiking at fertilization by promoting store-operated Ca²⁺ entry, while CamKII transduces cell-cycle resumption, and lies downstream of sperm-induced Ca²⁺ release but upstream of a spindle checkpoint. These data, combined with the knowledge that CamKII activity increase at fertilization, suggest that mouse eggs undergo cell-cycle resumption through stimulation of CamKII. 2011-08-30T05:40:06.685Z ]]> Inhibition of dynamin mediated endocytosis by the dynoles-synthesis and functional activity of a family of indoles http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8338 Screening identified two bisindolylmaleimides as 100 μM inhibitors of the GTPase activity of dynamin I. Focused library approaches allowed development of indole-based dynamin inhibitors called dynoles. 100-Fold in vitro enhancement of potency was noted with the best inhibitor, 2-cyano-3-(1-(2-(dimethylamino)ethyl)-1H-indol-3-yl)-N-octylacrylamide (dynole 34−2), a 1.3 ± 0.3 μM dynamin I inhibitor. Dynole 34−2 potently inhibited receptor mediated endocytosis (RME) internalization of Texas red-transferrin. The rank order of potency for a variety of dynole analogues on RME in U2OS cells matched their rank order for dynamin inhibition, suggesting that the mechanism of inhibition is via dynamin. Dynoles are the most active dynamin I inhibitors reported for in vitro or RME evaluations. Dynole 34−2 is 15-fold more active than dynasore against dynamin I and 6-fold more active against dynamin mediated RME (IC50 15 μM; RME IC50 80 μM). The dynoles represent a new series of tools to better probe endocytosis and dynamin-mediated trafficking events in a variety of cells. 2011-07-19T06:00:03.759Z ]]> Development of thyroid diseases in the treatment of chronic hepatitis C with alpha-interferon may be a good prognosticator in achieving a sustained virological response: a meta-analysis http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8319 Background and Aim: Thyroid dysfunction is the most common endocrinopathy associated with hepatitis C and its interferon-based treatment. When undergoing treatment, interferon and ribavirin synergize to potently stimulate the immune system in order to eradicate the virus. One of the innocent bystanders in this accentuated response is the thyroid. The present study investigated whether thyroid dysfunction while undergoing combination treatment for hepatitis C is a favorable prognostic maker for a sustained virological response. Methods: We carried out a prospective clinical audit in 201 patients treated with combination ribavirin and -interferon and determined the prevalence of sustained virological response in patients in association with thyroid disease. A meta-analysis was also carried out pooling 741 patients from four previous studies on this topic. Results: There was positive and significant association between thyroid disease and viral clearance. This was not supported by the meta-analysis, however, and some plausible explanations are proffered for this inconsistency. Conclusion: Despite lacking supportive evidence from the meta-analysis, it is important that this information is confirmed (or refuted) in future studies. 2011-07-19T04:40:18.680Z ]]> Chronic hepatitis B and C infection in children in New South Wales http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8273 Objective: To characterise epidemiological, clinical and laboratory features of children in New South Wales with chronic hepatitis B (HBV) or C (HCV) infections. Design and setting: Retrospective record review of epidemiological, clinical, laboratory, liver biopsy and treatment data for children (aged < 18 years) referred to tertiary referral paediatric and refugee clinics in NSW with chronic HBV or HCV during 2000–2007; and comparison with NSW Health notification data for the same period. Main outcome measures: Numbers and characteristics of referred children with HBV and HCV, and notifications to NSW Health. Results: During 2000–2007, 79 children with chronic HBV and 29 with HCV infection were referred to specialist clinics, while 930 children with HBV and 777 with HCV infection were reported to NSW Health. Most of the referred children with HBV were born overseas, while most with HCV were born in Australia to mothers with a history of intravenous drug use. Of the 79 HBV-infected children, 56 were e-antigen positive. Most HCV-infected children (23/29) had alanine aminotransferase levels ≤ 2 times the upper limit of normal, and more than half of those who had genotype determined had type 2 or 3. Fibrosis was evident in liver biopsies performed for both HBV and HCV. Conclusions: Although advanced liver disease was uncommon in children referred with HBV or HCV infection, a large number of infected children in NSW were not referred for specialist medical care, indicating that opportunities to intervene early in the natural history of these infections, particularly HCV, are being missed. 2011-07-15T05:40:06.530Z ]]> An inverse relationship between plasma n-3 fatty acids and C-reactive protein in healthy individuals http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8243 High sensitivity C-reactive protein (hs-CRP) is a marker of low-grade sustained inflammation. Omega-3 (n-3) fatty acids have anti-inflammatory properties and are associated with reduced cardiovascular disease (CVD) risk. The aim of this study was to investigate whether plasma n-3 fatty acid concentration is related to hs-CRP concentration. A total of 124 free-living adults, were divided into tertiles of plasma hs-CRP (<1.0, 1.0–3.0 and >3.0 mg/l). Body composition and anthropometric measurements were recorded. Hs-CRP was analysed using immunoassays and fatty acids were measured by gas chromatography. Plasma hs-CRP concentration was negatively correlated with total n-3 fatty acids (P=0.05), eicosapentaenoic acid (EPA; P=0.002) and docosapentaenoic acid (DPA; P=0.01). The highest hs-CRP tertile (>3.0 mg/l) had significantly lower concentrations of total n-3 fatty acids, EPA and DPA, when compared with the other tertiles (P<0.05). This study provides evidence that in healthy individuals, plasma n-3 fatty acid concentration is inversely related to hs-CRP concentration, a surrogate marker of CVD risk. 2011-07-14T01:40:30.178Z ]]> Hecke algebras from groups acting on trees and HNN extensions http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:8055 We study Hecke algebras of groups acting on trees with respect to geometrically defined subgroups. In particular, we consider Hecke algebras of groups of automorphisms of locally finite trees with respect to vertex and edge stabilizers and the stabilizer of an end relative to a vertex stabilizer, assuming that the actions are sufficiently transitive. We focus on identifying the structure of the resulting Hecke algebras, give explicit multiplication tables of the canonical generators and determine whether the Hecke algebra has a universal C*-completion. The paper unifies algebraic and analytic approaches by focusing on the common geometric thread. The results have implications for the general theory of totally disconnected locally compact groups. 2011-07-04T06:30:06.487Z ]]> Phosphorylation and consequent stimulation of the tyrosine kinase c-Abl by PKA in mouse spermatozoa: its implications during capacitation http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7891 Upon ejaculation, spermatozoa undergo a series of post-translational modifications in a process known as capacitation in order to prepare for fertilization. In the absence of capacitation, fertilization cannot occur. Spermatozoa are unusual in that one of the hallmarks of capacitation is a global up-regulation in phosphotyrosine expression, which is known to be mediated upstream by PKA. Little is known about the signaling events downstream of PKA apart from the involvement of SRC, as a key mediator of PKA-induced tyrosine phosphorylation in the sperm tail. Here we describe the presence of c-Abl in mouse spermatozoa. In vitro analysis confirmed that PKA can up-regulate c-Abl kinase activity. In vivo, this tyrosine kinase was found to associate, and become threonine phosphorylated by PKA in the sperm flagellum. By treating spermatozoa with hemolysin we could demonstrate that a significant proportion of the tyrosine phosphorylation associated with capacitation could be suppressed by the c-Abl inhibitor, Gleevac. This is the first report of c-Abl being up-regulated by PKA for any cell type. We present a model, whereby these kinases may operate together with SRC to ensure optimal levels of tyrosine phosphorylation in the sperm flagellum during the attainment of a capacitated state. 2011-06-20T00:00:12.145Z ]]> Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7782 Objective: To examine associations of neonatal adiposity with maternal glucose levels and cord serum C-peptide in a multicenter multinational study, the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study, thereby assessing the Pederson hypothesis linking maternal glycemia and fetal hyperinsulinemia to neonatal adiposity. Research Design and Methods: Eligible pregnant women underwent a standard 75-g oral glucose tolerance test between 24 and 32 weeks gestation (as close to 28 weeks as possible). Neonatal anthropometrics and cord serum C-peptide were measured. Associations of maternal glucose and cord serum C-peptide with neonatal adiposity (sum of skinfolds >90th percentile or percent body fat >90th percentile) were assessed using multiple logistic regression analyses, with adjustment for potential confounders, including maternal age, parity, BMI, mean arterial pressure, height, gestational age at delivery, and the baby's sex. Results: Among 23,316 HAPO study participants with glucose levels blinded to caregivers, cord serum C-peptide results were available for 19,885 babies and skin fold measurements for 19,389. For measures of neonatal adiposity there were strong statistically significant gradients across increasing levels of maternal glucose and cord serum C-peptide, which persisted after adjustment for potential confounders. In fully adjusted continuous variable models, odds ratios ranged from 1.35 to 1.44 for the two measures of adiposity for fasting, 1-h, and 2-h plasma glucose higher by 1 SD. Conclusions: These findings confirm the link between maternal glucose and neonatal adiposity, and suggest that the relationship is mediated by fetal insulin production and that the Pedersen hypothesis describes a basic biologic relationship influencing fetal growth. 2011-05-27T06:00:23.366Z ]]> The natural history of interferon-2b-induced thyroiditis and its exclusivity in a cohort of patients with chronic hepatitis C infection http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7749 Background: Interferon-α2b (IFN-α2b) is well known to cause both hyper- and hypo-thyroidism. In the former, the commonest aetiology is thyroiditis. As there is no previous data to fully characterize the entity of IFN-related thyroiditis, the aim of this study is to document in detail its evolution in a cohort of hepatitis C patients treated with pegylated IFN-α2b and Ribavirin (RBV). Methods: A prospective observational study was conducted in patients who developed thyroid diseases whilst receiving combination of pegylated IFN-α2b and RBV for hepatitis C. The patients were followed with monthly thyrotropin (TSH). Where TSH was undetectable, free tetra- (fT4) and tri-iodothyronine (fT3) were added. Anti-thyroperoxidase (TPO), anti-thyroglobulin (Tg) and thyroid stimulating immunoglobulin (TSI) levels were also performed at diagnosis, during and at the end of IFN therapy. All patients were assessed and followed up closely with monthly TSH, fT4 and fT3 levels until the completion, after 6 and 12 months of treatment. Results: There were seven females and four males over a 30-month period. All patients were found to have thyroiditis. On average, the time to the development of thyroid disease was 10 weeks and duration of disease 9 weeks. All patients eventually recovered normal biochemical thyroid function although two required short-term supplementation. Conclusions: Thyroiditis was found exclusively in our patients. Both the hyper- and hypo-thyroid phase can be short lived, extreme and transient in nature which warrants strict monthly TSH monitoring. Careful follow-up of all patients is mandatory as complete recovery is expected. 2011-05-20T05:50:03.920Z ]]> On twisted Fourier analysis and convergence of Fourier series on discrete groups http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7693 We study norm convergence and summability of Fourier series in the setting of reduced twisted group C*-algebras of discrete groups. For amenable groups, Følner nets give the key to Fejér summation. We show that Abel-Poisson summation holds for a large class of groups, including e.g. all Coxeter groups and all Gromov hyperbolic groups. As a tool in our presentation, we introduce notions of polynomial and subexponential H-growth for countable groups w.r.t. proper scale functions, usually chosen as length functions. These coincide with the classical notions of growth in the case of amenable groups. 2011-05-10T01:50:16.856Z ]]> Src family kinases are involved in the differential signaling from two splice forms of c-Kit http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3455 In both mice and humans alternate splicing results in isoforms of c-Kit characterized by the presence or the absence of a tetrapeptide sequence, GNNK, in the juxtamembrane region of the extracellular domain. Dramatic differences in the kinetics and magnitude of activation of the intrinsic tyrosine kinase activity of c-Kit between the GNNK- and GNNK+ isoforms has previously been shown. Here we report the analysis of downstream targets of receptor signaling, which revealed that the signaling was differentially regulated in the two splice forms. The kinetics of phosphorylation of Shc, previously demonstrated to be phosphorylated by Src downstream of c-Kit, was stronger and more rapid in the GNNK- form, whereas it showed slower kinetics in the GNNK+ form. Inhibition of Src family kinases with the specific Src family kinase inhibitor SU6656 altered the kinetics of activation of the GNNK- form of c-Kit so that it resembled that of the GNNK+ form. In cells expressing the GNNK- form, SCF was rapidly degraded, whereas in cells expressing the GNNK+ form only showed a very slow rate of degradation of SCF. In the GNNK+ form the Src inhibitor SU6656 only had a weak effect on degradation, whereas in the GNNK- form it dramatically inhibited degradation. In summary, the two splice forms show, despite only a four-amino acid sequence difference, remarkable differences in their signaling capabilities. 2011-05-03T00:10:03.531Z ]]> Investigation of serum bactericidal activity in childhood and adolescence 3-6 years after vaccination with a single dose of serogroup C meningococcal conjugate vaccine http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:7296 Serogroup C meningococcal conjugate vaccines were introduced in Greece in 2001, and although no cases of serogroup C meningococcal disease were recorded in 2004, a steady increase was observed since 2005. In this study, serum bactericidal activity was assessed in sera of 269 vaccinated children at a mean time of about 5 years after vaccination. Non-protective antibody titers were observed in most children vaccinated at age <6 years (85.9%), followed by those between 6 and 10 years (62.2%). This percentage was considerably lower in adolescents vaccinated at an age >10 years (37.8%) (p < 0.01). Geometric mean concentrations of serum IgG antibodies against serogroup C showed a similar variation. The results indicate that serum bactericidal antibody titers significantly correlate with age of vaccination; most children do not have protective antibody titers few years after immunization in infancy and childhood whereas most adolescents maintain sustained protection. 2011-02-23T02:40:13.773Z ]]> Hepatitis C caseload and models of care for rural GPs working in northern New South Wales http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4290 Objective: To estimate the hepatitis C patient caseload of general practitioners and explore their preferences regarding hepatitis C models of care. Method: An anonymous reply paid postal questionnaire was sent to all GPs working in rural northern New South Wales in August 2000. Pretesting found including hepatitis C knowledge and attitude questions would detract from the focus on hepatitis C education and management. Results: Two hundred and ninety-two out of 634 GPs responded (response rate 46%). A few (22 GPs, 8%) saw 3566 (59%) of the 6048 hepatitis C patients in the previous 12 months. Eighty-eight percent of GPs preferred a multidisciplinary model with the GP as the principal coordinator of care. Discussion: Rural GPs see their role as important in hepatitis C care. 2010-09-27T01:50:01.613Z ]]> The end of architecture? http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4260 Steven Fleming interviews Arthur C. Danto (New York, April 2006) 2010-09-26T23:30:01.575Z ]]> Protein kinase C action at fertilization: overstated or undervalued? http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6595 At fertilization, the spermatozoon is generally held to generate two important second messengers, inositol trisphosphate and diacylglycerol. A similar situation arises when these signalling molecules are generated after a hormone binds to its plasma membrane receptor. This signalling mechanism releases intracellular Ca²⁺ which causes cortical granule release and initiates meiotic resumption. This review will examine the role played at fertilization by protein kinase C which is a primary target of diacylglycerol. The pharmacological agents phorbol esters, which mimic the action of diacylglycerol, when added to mammalian oocytes induce cortical granule release and may cause meiotic resumption. However, the originally accepted mechanism of fertilization is now questioned with the recent finding of a soluble sperm Ca²⁺-releasing factor expelled directly into the oocyte cytoplasm, bypassing any membrane receptor. Therefore, it is timely to re-evaluate the role played by protein kinase C at fertilization in light of a mechanism that may produce Ca²⁺ without producing diacylglycerol concomitantly. This article will examine the evidence implicating activation of protein kinase C in Ca²⁺ oscillations, cortical granule release and meiotic resumption. It will contend that pharmacological studies relying on the specificity of phorbol esters and other agonists, as well as inhibitors of protein kinase C, have produced conflicting interpretations of the role of this kinase at fertilization. 2010-07-29T22:20:12.296Z ]]> Unique protein kinase C profile in mouse oocytes: lack of calcium-dependent conventional isoforms suggested by rtPCR and Western blotting http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6586 rtPCR and Western blotting were used to determine which members of the PKC family are present in both immature and mature mouse oocytes. Using isoform-specific PCR primers and antibodies PKC-δ and -λ were detected while such techniques failed to observe the conventional isoforms of PKC-α, -β, -γ. This isoform profile was confirmed using an alternative PCR strategy, which allowed discrimination of PCR products derived from conventional and novel PKC isoforms. In addition PKC-ε, -η, -θ and -ζ were not detected by rtPCR. These results suggest that the predominant isoforms in oocytes are PKC-δ and -λ. 2010-07-29T02:10:05.054Z ]]> Mammalian sperm contain a Ca²⁺-sensitive phospholipase C activity that can generate InsP₃ from PIP₂ associated with intracellular organelles http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6583 We have previously described a phospholipase C (PLC) activity in mammalian sperm cytosolic extracts. Here we have examined the Ca²⁺ dependency of the enzyme, whether there is enough in a single sperm to account for Ca²⁺ release at fertilization, and finally where in the egg is the phosphatidyl 4,5-bisphosphate, the substrate for the enzyme. As for all PLCs examined so far in vitro, we found that the boar sperm PLC activity was Ca²⁺ dependent. Specific activity increased when free Ca²⁺ levels were micromolar. However, even at nanomolar free Ca²⁺ concentration the boar sperm PLC activity was considerable, being two orders of magnitude greater than PLC activities in other tissues. We calculated that PLC activity of a single boar sperm in a mammalian egg is enough to generate 400 nM inositol 1,4,5-trisphosphate (InsP₃) in 1 min, which may be sufficient to account for the observed Ca²⁺ changes in an egg at fertilization. We fractionated sea urchin egg homogenate and examined the ability of boar sperm extract to generate InsP₃ from these fractions. The sperm PLC activity triggered InsP₃ production from a PIP₂-enriched nonmicrosomal egg compartment that contained yolk platelets. We propose that this sperm PLC activity, which is active at nanomolar Ca²⁺ levels and hydrolyzes PIP₂ from intracellular membranes, could be involved in the Ca²⁺ changes observed at fertilization. 2010-07-28T06:10:02.818Z ]]> A mammalian sperm cytosolic phospholipase C activity generates inositol trisphosphate and causes Ca²⁺ release in sea urchin egg homogenates http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6582 Injection of sperm extracts triggers Ca²⁺ oscillations in mammalian eggs similar to those seen at fertilisation. Here, we show that addition of sperm extracts to sea urchin egg homogenates causes Ca²⁺ release and inositol 1,4,5-trisphosphate (InsP₃) production. Furthermore depleting homogenates of phosphatidylinositol lipids using a phosphatidylinositol-specific phospholipase C blocked the sperm extract from causing InsP₃ production and a Ca²⁺ rise. A response could be recovered by the addition of phosphatidylinositol 4,5-bisphosphate to either sperm extracts or egg homogenates. These data indicate that sperm extracts contain an InsP₃-generating phospholipase C which may play a role in Ca²⁺ release at fertilisation. 2010-07-28T06:00:02.990Z ]]> The soluble sperm factor that causes Ca²⁺ release from sea-urchin (Lytechinus pictus) egg homogenates also triggers Ca²⁺ oscillations after injection into mouse eggs http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6581 Cytosolic extracts of boar sperm contain a soluble phospholipase C (PLC) activity that induces Ca²⁺ release in sea-urchin (Lytechinus pictus) egg homogenates and an uncharacterized protein factor that causes Ca²⁺ oscillations when injected into mammalian eggs. In the present study we fractionated boar sperm extracts on three different FPLC chromatographic columns and found that the fractions that caused maximal Ca²⁺ release in sea-urchin egg homogenates were also the ones that triggered Ca²⁺ oscillations in mouse eggs. Our data suggests that the sperm factor which triggers Ca²⁺ oscillations in eggs contains a PLC and not the 33 kDa glucosamine deaminase previously suggested to be one its components. 2010-07-28T05:50:02.938Z ]]> A symmetric imprimitivity theorem for commuting proper actions http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:79 We prove a symmetric imprimitivity theorem for commuting proper actions of locally compact groups H and K on a C*-algebra. 2010-07-23T04:06:00.731Z ]]> A dual graph construction for higher-rank graphs, and K-theory for finite 2-graphs http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:62 Given a k-graph Lambda and an element p of N-k, we define the dual k-graph, p Lambda. We show that when Lambda is row-finite and has no sources, the C*-algebras C*(Lambda) and C*(p Lambda) coincide. We use this isomorphism to apply Robertson and Steger's results to calculate the K-theory of C*(Lambda) when Lambda is finite and strongly connected and satisfies the aperiodicity condition. 2010-07-23T03:30:03.124Z ]]> Graph algebras http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3803 Graph algebras are a family of operator algebras which are associated to directed graphs. These algebras have an attractive structure theory in which algebraic properties of the algebra are related to the behaviour of paths in the underlying graph. In the past few years there has been a great deal of activity in this area, and graph algebras have cropped up in a surprising variety of situations, including non-abelian duality, non-commutative geometry, and the classification of simple C-algebras. 2010-07-12T02:21:21.852Z ]]> Taxonomy of graphs of order 10 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6508 Extending earlier data summaries for graphs of order n ≤ 9, this paper describes structural characteristics and relationships for the 12005168 graphs of order 10. It summarises data for their degree sequences, their component structure, their cycle structure, and their poset structure under the subgraph partial order. A standardized listing of the order 10 graphs, along with related data, is provided on the website www.maths.uq.edu.au/~pa/research/poset10.html 2010-06-16T05:50:02.118Z ]]> Degree sequences and poset structure of order 9 graphs http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6509 The set G(n) of unlabelled simple graphs of order n is a poset with partial ordering G ≤ H whenever G is a spanning subgraph of H. On the website www.maths.uq.edu.au/~pa/research/poset9.html we have made available a tabulation of the Hasse diagram for G(9), a digraph of order 274668 and size 4147388, extending our recent tabulations for G(n) with 4 ≤ n ≤ 8. The present paper is a descriptive summary of features of G(9) derived from the tabulation, including: the maximum number of graphs in G(9) with the same degree sequence is 3020, corresponding to 2¹3²4³5²6¹; there are 36 self-complementary graphs in G(9), but 10794 graphs with self-complementary degree sequences; there are 49 graphs in G(9) that are edge-transitive, and 134996 that have no edge-symmetry; the maximum number of immediate successors of a graph in G(9) is 28, and 12 graphs attain this maximum; the number of immediate successors of a graph in G(9) is distributed unimodally, with peak at 16 attained by 25010 graphs. All underlying data are available on the website. 2010-06-16T05:50:01.344Z ]]> Graphs with a given degree sequence http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6510 The level set G(n,m) comprises all unlabelled simple graphs of order n and size m, and is partitioned into similarity classes, comprising all graphs with the same degree sequence. When graphs are ordered lexicographically by their signature, a unique numerical list of structural descriptors, the similarity classes of G(n,m) occur in contiguous blocks; the first graph in each similarity class is its sentinel. The sentinel of the first similarity class in each G(n,m) is determined, and shown to be the unique realization of its degree sequence. The degree sequence of the last similarity class in each G(n,m) is also determined, as are the exact size range for which it has more than one realization and the exact size range for which its sentinel has more than one component. 2010-06-16T05:50:01.339Z ]]> Product systems of graphs and the Toeplitz algebras of higher-rank graphs http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:424 There has recently been much interest in the C*-algebras of directed graphs. Here we consider product systems E of directed graphs over sernigroups and associated C*-algebras C* (E) and TC* (E) which generalise the higher-rank graph algebras of Kumjian-Pask and their Toeplitz analogues. We study these algebras by constructing from E a product system X(E) of Hilbert bimodules, and applying recent results of Fowler about the Toeplitz algebras of such systems. Fowler's hypotheses turn out to be very interesting graph-theoretically, and indicate new relations which will have to be added to the usual Cuntz-Krieger relations to obtain a satisfactory theory of Cuntz-Krieger algebras for product systems of graphs; our algebras C* (E) and TC* (E) are universal for families of partial isometries satisfying these relations. Our main result is a uniqueness theorem for TC*(E) which has particularly interesting implications for the C*-algebras of non-row-finite higher-rank graphs. This theorem is apparently beyond the reach of Fowler's theory, and our proof requires a detailed analysis of the expectation onto the diagonal in TC*(E). 2010-06-11T02:14:20.219Z ]]> Proper actions on imprimitivity bimodules and decompositions of Morita equivalences http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6439 We consider a class of proper actions of locally compact groups on imprimitivity bimodules over C*-algebras which behave like the proper actions on C*-algebras introduced by Rieffel in 1988. We prove that every such action gives rise to a Morita equivalence between a crossed product and a generalized fixed-point algebra, and in doing so make several innovations which improve the applicability of Rieffel’s theory. We then show how our construction can be used to obtain canonical tensor-product decompositions of important Morita equivalences. Our results show, for example, that the different proofs of the symmetric imprimitivity theorem for actions on graph algebras yield isomorphic equivalences, and this gives new information about the amenability of actions on graph algebras. 2010-06-10T03:30:03.276Z ]]> Rank-two graphs whose C*-algebras are direct limits of circle algebras http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:6394 We describe a class of rank-2 graphs whose C*-algebras are AT algebras. For a subclass which we call rank-2 Bratteli diagrams, we compute the K-theory of the C*-algebra.We identify rank-2 Bratteli diagrams whose C*-algebras are simple and have real-rank zero, and characterise the K-invariants achieved by such algebras. We give examples of rank-2 Bratteli diagrams whose C*-algebras contain as full corners the irrational rotation algebras and the Bunce–Deddens algebras. 2010-06-10T03:00:02.680Z ]]> Coverings of k-graphs http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:420 k-graphs are higher-rank analogues of directed graphs which were first developed to provide combinatorial models for operator algebras of Cuntz-Krieger type. Here we develop the theory of covering spaces for k-graphs, obtaining a satisfactory version of the usual topological classification in terms of subgroups of a fundamental group. We then use this classification to describe the C*-algebras of covering k-graphs as crossed products by coactions of homogeneous spaces, generalizing recent results on the C*-algebras of graphs. 2010-06-03T06:10:34.648Z ]]> Septin 3 (G-septin) is a developmentally regulated phosphoprotein enriched in presynaptic nerve terminals http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1956 The septins are GTPase enzymes with multiple roles in cytokinesis, cell polarity or exocytosis. The proteins from the mammalian septin genes are called Sept1–10. Most are expressed in multiple tissues, but the mRNA for Sept5 (CDCrel-1) and Sept3 (G-septin) appear to be primarily expressed in brain. Sept3 is phosphorylated by cGMP-dependent protein kinase I (PKG-I) and the cGMP/PKG pathway is involved in presynaptic plasticity. Therefore to determine whether Sept3 specifically associates with neurones and nerve terminals we investigated its distribution in rat brain and neuronal cultures. Sept3 protein was detected only in brain by immunoblot, but not in 12 other tissues examined. Levels were high in all adult brain regions, and reduced in those enriched in white matter. Expression was developmentally regulated, being absent in the early embryo, low in late embryonic rat brain and increasing after birth. Like dynamin I, Sept3 was specifically enriched in synaptosomes compared with whole brain, and was only found in a peripheral membrane extract and not in the soluble or membrane extracts. Sept3 was particularly abundant in mossy fibre nerve terminals in the hippocampus. In primary cultured hippocampal neurones Sept3 immunoreactivity was punctate in neurites and predominantly localized to presynaptic terminals, strongly colocalizing with synaptophysin and dynamin I. The specific nerve terminal localization was confirmed by immunogold electron microscopy. Together this shows that Sept3 is a neurone-specific protein highly enriched in nerve terminals which supports a secretory role in synaptic vesicle recycling. 2010-04-27T06:59:15.223Z ]]> Identification and characterization of a novel Mt-retrotransposon highly represented in the female mouse germline http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1294 The control of primordial follicle recruitment into the growing follicle population is a major limiting process in female reproduction. In order to gain insight into the molecular processes occurring at the time of primordial follicle activation, a subtractive hybridization analysis was performed between cDNAs prepared from temporally distinct mouse neonatal ovarian tissues that differed according to the state of primordial follicle activation. One highly represented clone associated with activation was an Mt retrotransposon-like sequence designated Mtfull, which was subsequently cloned and determined to be novel and restricted in expression to the ovary. The polyadenylated 1684-bp sequence has long terminal repeats, is predicted to be noncoding, and is the predominant Mti-related sequence present in the mouse ovary. In situ hybridization further localized Mtfull expression to the oocyte and confirmed that expression is concomitant with follicle activation. Together with in silico data, we predict Mtfull plays an essential role in folliculogenesis through regulation of gene expression. 2010-04-27T06:54:31.859Z ]]> Ontogeny of tyrosine phosphorylation-signaling pathways during spermatogenesis and epididymal maturation in the mouse http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3007 The objectives of this study were to map the ontogeny of tyrosine phosphorylation signal transduction pathways during germ cell development and to determine their association with the differentiation of a functional gamete. Until testicular germ cells differentiate into spermatozoa, cAMP-induced tyrosine phosphorylation is not detectable. Entry of these cells into the epididymis is accompanied by sudden activation of the tyrosine phosphorylation pathway, initially in the principal piece of the cell and subsequently in the midpiece. In the caput and corpus epididymides, the potential to express this pathway is inhibited by the presence of calcium in the extracellular medium. However, calcium has no effect on the expression of this pathway in caudal epididymal sperm. The competence of these cells to phosphorylate the entire sperm tail, from the neck to the tail-end piece, is accompanied by a capacity to exhibit hyperactivated motility on stimulation with cAMP. A distinctly different pattern of tyrosine phosphorylation, involving the acrosomal domain of the sperm head, is invoked as spermatozoa enter the caput epididymis, and phosphorylation remains high until these cells enter the distal corpus and cauda. The proportion of cells exhibiting this form of tyrosine phosphorylation is not affected by extracellular calcium or cAMP but is negatively correlated (R² = 0.99) with their ability to acrosome-react. However, this relationship is not causative. Our findings indicate that the development of functional spermatozoa is accompanied by carefully orchestrated changes in tyrosine phosphorylation, controlled by independent regulatory mechanisms in distinct subcellular compartments of these highly specialized cells. 2010-04-27T06:47:09.439Z ]]> Corticotropin-releasing hormone gene expresssion in primary placental cells is modulated by cyclic adenosine 3',5'-monophosphate http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:2844 CRH, the principal neuropeptide regulator of pituitary ACTH secretion, is also expressed in placenta. Placental CRH has been linked to the process of human parturition. However, the mechanisms regulating transcription of the CRH gene in placenta remain unclear. cAMP signaling pathways play important roles in regulating the expression of a diverse range of endocrine genes in the placenta. Therefore, we have explored the effect of cAMP on CRH promoter activity in primary cultures of human placental cells. Both forskolin and 8-bromo-cAMP, activators of protein kinase A, can increase CRH promoter activity 5-fold in transiently transfected human primary placental cells, in a manner that parallels the increase in endogenous CRH peptide. Maximal stimulation of CRH promoter activity occurs at 500 µmol/L 8-bromo-cAMP and 10 µmol/L forskolin. Electrophoretic mobility shift assay and mutation analysis combined with transient transfection demonstrate that in placental cells cAMP stimulates CRH gene expression through a cAMP regulatory element in the proximal CRH promoter region and involves a placental nuclear protein interacting specifically with the cAMP regulatory element. 2010-04-27T06:47:03.209Z ]]> An in vitro model for investigating intestinal adhesion of potential dairy propionibacteria probiotic strains using cell line C2BBe1 http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1825 Aims: The purposes of this study were to screen the adhesion properties of dairy propionibacteria strains and evaluate whether C2BBe1 could be used in the screening of potential probiotic strains. Methods and Results: Thirteen dairy propionibacteria strains and two control strains, Lactobacillus acidophilus MJLA1 and Bifidobacterium lactis BDBB2, were tested for adhesion to C2BBe1. Electron microscopic observations demonstrated that the control strains, L. acidophilus MJLA1 and B. lactis BDBB2, had similar adhesive ability to C2BBe1 as had been previously shown to Caco-2. Only one of the 13 strains of dairy propionibacteria, strain P. jensenii 702, demonstrated adhesion to C2BBe1. Conclusions: C2BBe1 can provide an alternative to Caco-2 for assessing in vitro adhesion properties of probiotic strains. Adhesion properties of dairy propionibacteria were strain-dependent. Significance and Impact of the Study:C2BBe1 is highly suitable for application in bacterial adhesion studies, and was used successfully to select a new potential probiotic. 2010-04-27T06:36:16.423Z ]]> The ideal structure of the C*-algebras of infinite graphs http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1853 We classify the gauge-invariant ideals in the C*-algebras of infinite directed graphs, and describe the quotients as graph algebras. We then use these results to identify the gauge-invariant primitave ideals in terms of the structural properties of the graph, and describe the K-theory of the C*-algebras of arbitrary infinite graphs. 2010-04-27T06:35:34.175Z ]]> Stable rank of graph algebras: type I graph algebras and their limits http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1837 For an arbitrary countable directed graph E we show that the only possible values of the stable rank of the associated Cuntz-Krieger algebra C*(E) are 1, 2 or ∞. Explicit criteria for each of these three cases are given. We characterize graph algebras of type I, and graph algebras which are inductive limits of C*-algebras of type I. We also show that a gauge-invariant ideal of a graph algebra is itself isomorphic to a graph algebra. 2010-04-27T06:35:14.980Z ]]> Catullus, C. 37 and the theme of magna bella http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:2853 Scholars have tended to focus on the obscenity of Catullus' C. 37 for obvious reasons. This infamous indictment of Lesbia and her sexual partners was, not surprisingly, placed among C. J. Fordyce's collection of scurrilous verse unfit for classicists' consumption. In more recent times it has received attention of a more enlightened and productive kind. Despite the insights offered in these later treatments, I aim here to explore further the interpretative possibilities of C. 37. 2010-04-27T06:14:06.744Z ]]> The Seal of Silence (poster) http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3047 By C. Watson Mill, first performed at the Grand, Croydon, in 1902. The stock character types of melodrama are readily identifiable. The physical attributes of the actors are quite true to melodramatic acting style, as they also are in the other posters. 2010-04-27T06:13:12.334Z ]]> Improved antioxidant and fatty acid status of patients with cystic-fibrosis after antioxidant supplementation is linked to improved lung function http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1803 Background: Oxidative stress, as measured by 8-iso-prostaglandin F₂α (8-iso-PGF₂α), and depleted antioxidant defenses were shown in stable cystic fibrosis (CF) patients. The plasma fatty acid status of CF patients was linked to oxidative stress after respiratory exacerbations.Objective: We examined changes in plasma 8-iso-PGF₂α, antioxidant defenses, plasma fatty acid status, and clinical markers resulting from short-term antioxidant supplementation. Design: Forty-six CF patients were randomly assigned to either group A [low dose of supplement (10 mg vitamin E and 500 µg vitamin A)] or group B [high dose of supplement (200 mg vitamin E, 300 mg vitamin C, 25 mg ß-carotene, 90 µg Se, and 500 µg vitamin A)]. Plasma concentrations of 8-iso-PGF2α, vitamins E and C, ß-carotene, zinc, selenium, and copper; plasma fatty acid composition; erythrocyte glutathione peroxidase (EC 1.11.1.9) and superoxide dismutase (EC 1.15.1.1) activities; lung function; and dietary intake were measured before and after 8 wk of supplementation. Results: Antioxidant defenses in group B improved, whereas those in group A did not: in groups B and A, the mean (± SEM) changes (Δ) in vitamin E were 10.6 ± 1.5 and -1.9 ± 0.9 µmol/L, respectively (P < 0.001), Δß-carotene were 0.1 ± 0.04 and -0.01 ± 0.02 µmol/L, respectively (P = 0.007), Δselenium were 0.51 ± 0.10 and -0.09 ± 0.04 µmol/L, respectively (P < 0.001), and Δglutathione peroxidase activity were 1.3 ± 0.3 and -0.3 ± 0.6 U/g hemoglobin, respectively (P = 0.016). There were no significant differences between the groups in Δ8-iso-PGF2α, Δvitamin C, Δfatty acid composition, Δsuperoxide dismutase activity, Δlung function, or Δwhite cell count. Within group B, Δß-carotene correlated with Δpercentage of forced vital capacity (r = 0.586, P = 0.005), Δselenium correlated with Δpercentage of forced expiratory volume in 1 s (r = 0.440, P = 0.046), and Δplasma fatty acid concentrations correlated with Δpercentage of forced expiratory volume in 1 s (r = 0.583, P = 0.006) and Δ8-iso-PGF2α (r = 0.538, P = 0.010). Conclusions: Whereas increased ß-carotene, selenium, and fatty acid concentrations are linked to improved lung function, increased plasma fatty acid concentrations are linked to oxidative stress. If oxidative stress is deemed to be important to the clinical outcome of CF patients, means of reducing oxidative stress while maintaining a high-fat, high-energy diet must be investigated. 2010-04-27T06:11:07.647Z ]]> Evoked expression of the glutamate transporter GLT-1c in retinal ganglion cells in human glaucoma and in a rat model http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1074 PURPOSE: Glaucoma is a common disease of the eye, a key characteristic consequence of which is the death of retinal ganglion cells. The cause of this loss is unknown, though glutamate-mediated toxicity has been implicated. Glutamate transporters are key regulators of glutamate; therefore, the purpose of the study was to determine whether unusual excitation is associated with unusual expression of one or more transporters. METHODS: The expression of a splice variant of the glutamate transporter GLT-1 (EAAT2) was examined in normal and glaucomatous retinas from humans and rats. RESULTS: In normal eyes of humans and rats, GLT-1c was expressed only in photoreceptors. In glaucoma, there was additional robust expression of GLT-1c in retinal ganglion cells, including occasional displaced ganglion cells. Conversely, cells such as displaced amacrine cells and amacrine cells were unlabeled. CONCLUSIONS: The induction of GLT-1c expression by retinal ganglion cells supports the notion that an anomaly or anomalies in glutamate homeostasis may be evident in glaucoma and that such anomalies selectively influence retinal ganglion cells. By analogy to in vitro experiments in which elevated glutamate levels induce expression of glutamate transporters, the authors hypothesize that expression of GLT-1c may represent an attempt by retinal ganglion cells to protect themselves against elevated levels of glutamate. Such anomalies in glutamate levels cannot be restricted to the ganglion cell layer, as this would not have affected displaced ganglion cells. GLT-1c may be a useful indicator of the extent of stress of the retinal ganglion cells and thus a tool for examining outcomes of potential therapeutic and experimental interventions. 2010-04-27T06:06:47.519Z ]]> Simplicity of Cuntz-Krieger algebras of infinite matrices http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:1144 We give necessary and sufficient conditions for simplicity of Cuntz-Krieger algebras corresponding to infinite 0–1 matrices and of C*-algebras corresponding to countable directed graphs. We show that simple algebras within these two classes are either purely infinite or AF. 2010-04-27T06:05:34.753Z ]]> Enhanced clearance of Candida albicans from the oral cavities of mice following oral administration of Lactobacillus acidophilus http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:132 Orally administered live Lactobacillus acidophilus was assessed for its capacity to enhance clearance from the oral cavity of DBA/2 mice shown previously to be 'infection prone'. L. acidophilus fed to DBA/2 mice significantly shortened the duration of colonization of the oral cavity compared to controls. Enhanced clearance of Candida albicans correlated with both early mRNA gene expression for interleukin (IL)-4 and interferon (IFN)-gamma and expression of their secreted products in cultures of cervical lymph nodes stimulated with Candida antigen. In addition rapid clearance correlated with higher levels of IFN-gamma and nitric oxide in saliva. Delayed clearance, less pronounced levels of the cytokine response, saliva IFN-gamma and nitric oxide, and later mRNA expression for IL-4 and IFN-gamma relative to feeding with the L. acidophilus isolate were noted in mice fed a different Lactobacillus isolate (L. fermentum). These observations indicate significant variations in individual isolates to activate the common mucosal system. 2010-04-27T06:01:53.279Z ]]> Regulation of skeletal ryanodine receptors by dihydropyridine receptor II-III loop C-region peptides: relief of Mg2+ inhibition http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:225 The aim of the present study was to explore interactions between surface-membrane DHPR (dihydropyridine receptor) Ca2+ channels and RyR (ryanodine receptor) Ca2+ channels in skeletal-muscle sarcoplasmic reticulum. The C region ((725)Phe-Pro(742)) of the linker between the 2nd and 3rd repeats (II-III loop) of the a, subunit of skeletal DHPRs is essential for skeletal excitation-contraction coupling, which requires a physical interaction between the DHPR and RyR and is independent of external Ca2+. Little is known about the regulatory processes that might take place when the two Ca2+ channels interact. Indeed, interactions between C fragments of the DHPR (C peptides) and RyR have different reported effects on Ca2+ release from the sarcoplasmic reticulum and on RyR channels in lipid bilayers. To gain insight into functional interactions between the proteins and to explore different reported effects, we examined the actions of C peptides on RyR 1 channels in lipid bilayers with three key RyR regulators, Ca2+, Mg2+ and ATP. We identified four discrete actions: two novel, low-affinity (> 10 mu M), rapidly reversible effects (fast inhibition and decreased sensitivity to Mg2+ inhibition) and two slowly reversible effects (high-affinity activation and a slow-onset, low-affinity inhibition). Fast inhibition and high-affinity activation were decreased by ATP. Therefore peptide activation in the presence of ATP and Mg2+, used with Ca2+ release assays, depends on a mechanism different from that seen when Ca2+ is the sole agonist. The relief of Mg2+ inhibition was particularly important since RyR activation during excitation-contraction coupling depends on a similar decrease in Mg2+ inhibition. 2010-04-27T06:00:45.900Z ]]> Signal transduction mechanisms involved in the proliferation of C6 glioma cells induced by lysophosphatidic acid http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:121 We studied pathways involved in the proliferation of rat C6 glioma cells induced by lysophosphatidic acid (LPA), a phospholipid with diverse biological functions. LPA induced a dose-responsive proliferation of C6 cells after 48 h. Proliferation was blocked by inhibitors of the sodium/proton exchanger type 1 (NHE1), Rho-associated kinase, the phosphatidylinositol 3-kinase/Akt pathway (PI3K/Akt), protein kinase C (PKC) and extracellular signal regulated kinase kinase (MEK). Phospho-specific antibodies were used to investigate the pathways involved. LPA induced transient (10 min) phosphorylations of ERK 1/2, Akt and the transcription factor CREB. The LPA-induced phosphorylation of ERK 1/2 and CREB was blocked by inhibition of PI3K, PKC and MEK, but that of Akt was only inhibited by wortmannin, the PI3K inhibitor. Inhibition of Rho kinase or NHE1 did not reduce the LPA-induced phosphorylation of ERK, Akt or CREB. The results were compared with the effects of LPA on transduction pathways in other cell types. 2010-04-27T05:58:22.855Z ]]> The medical complications of alcohol use: understanding mechanisms to improve management http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:163 The use of alcohol in a dependent or even a regular heavy pattern predisposes the drinker to a range of adverse consequences. These include a risk of direct harm from alcohol, including organ damage, mental health disorders and a range of social and legal problems associated with behaviours due to alcohol's effects. The range of organ damage associated with regular heavy alcohol consumption is well described. Much new information on the mechanisms by which damage occurs is available and is reviewed in this paper. New knowledge can assist in the development of more appropriate management strategies for those affected by the medical complications of alcohol use. Genetic susceptibility to tissue injury is explored and the reasons why many heavy drinkers do not appear to experience organ damage are considered. Approaches to the management of certain alcohol-related disorders are outlined. 2010-04-27T05:56:53.932Z ]]> Sensitization to morphine withdrawal in guinea-pigs http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:451 The aim of this study was to determine whether sensitization occurred to morphine withdrawal. Guinea-pigs were treated twice daily with increasing doses of morphine (10-100 mg/kg s.c.) for 3 days followed by injection of morphine 100 mg/kg on the fourth day. Sixty min after the last morphine injection, animals were withdrawn from morphine with naltrexone, 15 mg/kg s.c., and locomotor activity and all other behaviours scored over 90 min. Animals were then rested for 3 days. This procedure was repeated twice over the next 2 weeks. Control animals were treated with saline for the first two treatment cycles. Guinea-pigs subjected to three cycles of morphine withdrawal showed a significant increase in the total number of withdrawal behaviour counts over the 90-min observation period following the third cycle of withdrawal compared with the first and second withdrawal cycles. However, locomotor activity, a major sign of morphine withdrawal in guinea-pigs, was not significantly increased. Fos-LI was markedly increased in the repeatedly withdrawn animals in several brain regions, including amygdala, dorsal striatum, thalamus, ventral tegmental area, and ventrolateral periaqueductal gray area. It is concluded that sensitization to morphine withdrawal occurs in guinea-pigs. 2010-04-27T05:47:31.979Z ]]> Reaction kinetics in Ti3SiC2 synthesis studied by time-resolved neutron diffraction http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:612 The reactive sintering of 3Ti/SiC/C to form the ternary carbide Ti3SiC2, previously found to involve the intermediate phases TiCx and Ti5Si3Cx, was investigated by time-resolved neutron powder diffraction. The kinetics of Ti3SiC2 formation from the intermediate phases TiCx Ti5Si3Cx (x <= 1) and a small amount of free C was determined. The crystallization rate of the Ti3SiC2 phase was determined through quantitative analyses of the diffraction patterns collected at different temperatures and is initially well-described by the Mehl-Avrami-Johnson equation. The activation energy was found to be 380 +/- 10 kj/mol and the Avrami exponent 3.0 +/- 0.2. The Avrami exponent decreases to close to I when more than half of the crystallization process was completed. This indicates a change in the mechanism of Ti3SiC2 crystal growth from unrestricted two or three-dimensional growth in the a-b planes to one-dimensional growth only, due to interaction of the growing,disk-like crystals and cessation of growth in the preferred direction. 2010-04-27T05:42:42.315Z ]]> Holocene millennial/centennial-scale multiproxy cyclicity in temperate eastern Australian estuary sediments http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:516 We have undertaken a comparative study of down-core variation in multiproxy palaeoclimate data (magnetic susceptibility, calcium carbonate content and total organic carbon) from two coastal water bodies (Myall and Tuggerah Lakes) in temperate eastern Australia to identify local, regional and global-forcing factors within Holocene estuarine sediments. The two lakes lie within the same temperate climate zone adjacent to the Tasman Sea, but are not part of the same catchment and drain different geological provinces. One is essentially a freshwater coastal lake whereas the other is a brackish back-barrier lagoon. Despite these differences, data from two sites in each of the two lakes have allowed us to investigate and compare cyclicity in otherwise uniform, single facies sediments within the frequency range of 200-2000 years, limited by the sedimentation rate within the lakes and our sample requirements. We have auto- and cross-correlated strong periodicities at similar to 360 years, similar to 500-530 years, similar to 270-290 years, 420-450 years and similar to 210 years, and subordinate periods of similar to 650 years, 1200-1400 years and similar to 1800 years. Our thesis is that climate is the only regionally available mechanism available to control common millennial and centennial scale cyclicity in these sediments, given the geographical and other differences. However, regional climate may not be the dominant effect at any single time and either location. Within the range of frequency spectral peaks we have identified, several fall within known long-term periodical fluctuations of sun spot activity; however, feedback loops associated with short-term orbital variation, such as Dansgaard-Oeschger cycles, and the relationship between these and palaeo-ENSO variation, are also possible contributors. 2010-04-27T05:38:12.041Z ]]> Cognitive-behavioural integrated treatment (C-BIT): A treatment manual for substance misuse in people with severe mental health problems (book review) http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:14 2010-04-27T05:35:38.730Z ]]> Impact of radio frequency electromagnetic radiation on DNA integrity in the male germline http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4 Concern has arisen over human exposures to radio frequency electromagnetic radiation (PFEMR), including a recent report indicating that regular mobile phone use can negatively impact upon human semen quality. These effects would be particularly serious if the biological effects of RFEMR included the induction of DNA damage in male germ cells. In this study, mice were exposed to 900 MHz RFEMR at a specific absorption rate of approximately 90 mW/kg inside a waveguide for 7 days at 12 h per day. Following exposure, DNA damage to caudal epididymal spermatozoa was assessed by quantitative PCR (QPCR) as well as alkaline and pulsed-field gel electrophoresis. The treated mice were overtly normal and all assessment criteria, including sperm number, morphology and vitality were not significantly affected. Gel electrophoresis revealed no gross evidence of increased single- or double-DNA strand breakage in spermatozoa taken from treated animals. However, a detailed analysis of DNA integrity using QPCR revealed statistically significant damage to both the mitochondrial genome (p < 0.05) and the nuclear beta-globin locus (p < 0.01). This study suggests that while RFEMR does not have a dramatic impact on male germ cell development, a significant genotoxic effect on epididymal spermatozoa is evident and deserves further investigation. 2010-04-27T05:34:23.454Z ]]> Hepatitis C infection and thyrotoxic periodic paralysis: a novel use of an old drug http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4769 Hypokalaemic thyrotoxic periodic paralysis is an enigmatic and uncommon condition which occurs exclusively in males of Asian descent. The underlying causes of thyrotoxicosis may be any of the well-recognized etiologies including a toxic multinodular goiter, Graves’ disease or iodine excess. Beside thyrotoxicosis,a number of other hormonal factors have been hypothesized to contribute to hypokalaemic thyrotoxic periodic paralysis, particularly postprandial hyperinsulinaemia and testosterone. We hereby present a case of a 48-year-old hepatitis C positive gender-assigned man in whom all of these factors are proposed to interact,lending further support to these hypotheses. The patient presented with interferon-induced thyroiditis causing acute generalized weakness whilst undergoing combination interferon α2β and ribavirin therapy. As part of his hepatitis C infection, marked insulin resistance with hyperinsulinaemia was also present, exacerbating the paresis. Initial treatment with beta-blocker failed to normalize his serum potassium concentration,requiring the novel use of spironolactone, despite euthyroidism.This continued to be required until his testosterone supplement dissipated. 2010-04-27T05:33:29.298Z ]]> Noncommutative balls and their doubles http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3488 Quantum analogues ofn-dimensional balls are defined via suitable generators and relations. In the even case they correspond to the Twisted Canonical Commutation Relations of Pusz and Woronowicz. Then we construct quantum spheres as double manifolds of the noncommutative balls. 2010-04-27T05:30:37.317Z ]]> Pycnanthuquinone C, an unusual 6,6,5-tricyclic geranyltoluquinone from the Western Australian brown alga Cystophora harveyi http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3495 Chemical investigation of the Western Australian marine brown alga Cystophora harveyi resulted in the isolation of the new linearly fused 6,6,5-tricyclic compound pycnanthuquinone C (1), in addition to four previously reported geranyltoluquinol derivatives. Structures were elucidated by interpretation of spectrometric data. Compounds with the same cyclic skeleton as 1 have been reported to be useful drug leads for the treatment of type 2 diabetes, while compounds 4 and 7 are known constituents of Chinese medicinal herbs. A biosynthetic scheme encompassing all of the geranyltoluquinol derivatives isolated from C. harveyi is proposed. 2010-04-27T05:30:29.601Z ]]> Separation of bioactive prostaglandins and their metabolites by reversed-phase thin-layer chromatography http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3474 Prostaglandins are biological lipid mediators that control a variety of physiological and pathophysiological processes. They function as locally acting hormones and are continuously synthesized and inactivated in target tissues by respective biosynthetic and metabolic enzymes. The separation of prostaglandins and their metabolites is crucial for study of their roles in biological systems. In this article, we describe systematic studies of the retention and separation of prostaglandin E₂ (PGE₂) from its inactive metabolites 15-keto-PGE₂ and 13,14-dihydro-15-keto-PGE₂. We also describe the separation of a second prostaglandin species, PGF₂α , from its metabolites 15-keto-PGF₂α and 13,14-dihydro-15-keto-PGF₂α . Chromatography was performed on RP-18W high-performance thin-layer chromatographic plates with binary mobile phases comprising water and an organic modifier (methanol, ethanol, acetonitrile, acetone, or tetrahydrofuran). The experimental data revealed that at constant temperature, plots of the retention, RM , of the prostaglandins against the mole fraction of organic modifier in the water (XS) were nonlinear. By use of mobile phases of similar eluent strength the effect of temperature on the retention and separation of the solutes was examined. Thermodynamic data, calculated from linear Van’t Hoff plots, indicated that the mechanism of retention for each prostaglandin compound was consistent for the different mobile phases. The separation of PGE₂ and PGF₂α from each other and from their respective metabolites was rapid and robust in acetonitrile and in acetonitrile-water mobile phases. Interestingly, with 100% acetonitrile as the mobile phase the reversed-phase system apparently performed as a normal-phase system. The chromatographic system described here is applicable to the rapid processing of a large number of samples, which is a requirement for determining the biological metabolism of PGE₂ and PGF₂α and for studying the kinetics of prostaglandin-inactivating enzymes. The system is also suitable for the prepurification of complex biological samples for subsequent quantification of individual prostaglandins. 2010-04-27T05:30:00.904Z ]]> Comparative analysis of Ti₃SiC₂ and associated compounds using x-ray diffraction and x-ray photoelectron spectroscopy http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3332 Ti₃SiC₂ exhibits a unique combination of ceramic and metallic properties suitable for both electrical and mechanical application. With high-temperature stability, high electrical and thermal conductivity and resistance to oxidation, Ti₃SiC₂ has proven promising as a contact layer for high power SiC semiconductors. However, until recently, synthesis of this material has proven difficult without appreciable quantities (<2 vol{%}) of impurity phases, namely TiC₁₋x and Ti₅Si₃Cx. As such, many properties of this compound are as yet unknown. In this paper, a comparable analysis of Ti₃SiC₂ and associated compounds, TiC and Ti₅Si₃Cx has been performed using both x-ray diffraction (XRD) and x-ray photoelectron spectroscopy (XPS). Assessing impurity sensitivities for each technique, XRD was shown to readily identify impurities of TiC and Ti₅Si₃Cx within Ti₃SiC₂ at <2 wt{%}. Although XPS could not independently resolve these impurities, its use resulted in the detection of a complex oxide structure on Ti₃SiC₂. It was speculated that it was composed of mixed C-Ti-C-O and Si-Ti-C-O bond chemistries. In a comparison of TiC, Ti₅Si₃Cx and Ti₃SiC₂, differences in oxide states suggest that oxidation is chemically dissimilar for all the three compounds. However, upon etching, the binding energies of Ti₃SiC₂ and Ti₅Si₃Cx were shown to be very similar. It may be concluded that a concurrent analysis of both XRD and XPS was essential for identifying the overall surface chemistry of Ti₃SiC₂. 2010-04-27T05:26:08.257Z ]]> Understanding and improving solid-state polymer/C₇₀-fullerene bulk-heterojunction solar cells using ternary porphyrin blends http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3196 Solid-state heterojunction solar cells formed from binary blends of conjugated polymers and fullerenes provide a promising class of organic devices. We demonstrate that ternary blends incorporating porphyrins can be of similar morphology to the binary mixture and retain full device functionality. They allow, for the first time, the construction of efficient devices containing less than 10% polymer. By analyzing the absorption spectra as a function of concentration, we determine the proportion of light absorbed by each individual component in both binary and ternary mixtures. This analysis reveals that the majority of the light is absorbed by the fullerene in 1:4 polymer/C₆₀-fullerene blends, with over 50% of the photocurrent produced under AM 1.5 conditions occurring subsequent to C₆₀-fullerene absorption. This result provides for a consistent understanding of the origin of primary charge separation in general polymer/C₆₀-fullerene blends, polymer/C₇₀-fullerene blends, and polymer-fullerene dyad molecules. Porphyrins are demonstrated to add broad-band character to the device and may be used to tune for particular wavelengths; they also are shown to initiate primary charge separation through electron-transfer to the fullerene. Finally, addition of the porphyrin is shown to increase the internal quantum efficiency following polymer absorption from ca. 60 to 80%. 2010-04-27T05:24:54.308Z ]]> Rotational and ro-vibrational transitions of He₂C²⁺ http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3252 Ab initio calculations of transition frequencies and line strengths have been calculated for the "forbidden" rotational spectrum and ν₂ fundamental ro-vibrational of the ¹A₁ state of He₂C²⁺. For the "pure" rotational spectrum, the vibration ground state transitions are very weak, with the intensity of the strongest line, 3₃₁–4₄₀, being only 2.15 × 10⁻²² cm molecule⁻¹. A group of significant line strengths is attributed to ro-vibrational transitions between (<0,2,0>←<0,1,0>) and (<0,1,0>←<0,0,0>) bands. These band centers are calculated at 309.5 and 330.4 cm⁻¹ respectively. The strongest band is identified with the (<0,2,0>←<0,0,0>) transition with a band center of 625.1 cm⁻¹ and line strength of 2.58 × 10⁻¹⁹ cm molecule⁻¹ for the (4₄₀←4₄₁) transition. 2010-04-27T05:24:14.962Z ]]> Identification of aminopyrimidine regioisomers via line broadening effects in ¹H and ¹³C NMR spectroscopy http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:3267 Substituted mono- and diamino-pyrimidines were synthesized as part of our medicinal chemistry programmes. Primary amines substituted at the 4-position exhibited room-temperature line broadening effects in both ¹H and ¹³C NMR spectroscopy due to the presence of rotamers, but these effects were not observed for substituents in the 2-position. This provided a simple diagnostic tool for the identification of regioisomers, a determination which would otherwise have required two-dimensional experiments. 2010-04-27T05:24:03.280Z ]]> Resuscitating the author: implications of Danto's philosophy for historians of trend-defying architecture http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4025 The paper revisits the often-contested terrain of historiography that is reliant on meta-narratives with specific reference to the writings of philosopher Arthur C. Danto. Architectural historians of-ten position their subjects according overarching views of history (commonly known as meta-narratives), an approach that seems incongruous to the study of architects who defy historical trends in the pursuit of shocking or iconic works. The paper argues that historians of trend-defying architecture can simply index the facts (telling small, unconnected and potentially banal stories), or else follow the lead of an historian like Danto (who is also a philosopher of historiography), who has abandoned the poststructuralist catch-cry 'the author is dead' to pursue a sophisticated kind of indexing that seeks to penetrate the thoughts and words of artists and architects. His approach is a fitting response to an art world that, he argues, exhausted its meta-narratives. The paper discusses Danto's texts in this light, while referring to a recent interview between Danto and the present author, about the implications, for architectural historians, of this seminal work on the analytical philosophy of history. 2010-04-27T05:21:06.155Z ]]> Association of paediatric mastocytosis with a polymorphism resulting in an amino acid substitution (M541L) in the transmembrane domain of c-KIT http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4827 Background: The receptor tyrosine kinase c-KIT plays a key role in normal mast cell development. Point mutations in c-KIT have been associated with sporadic or familial mastocytosis. Objectives: Two unrelated pairs of apparently identical twins affected by cutaneous mastocytosis attending the Mastocytosis Clinic at the Royal Children’s Hospital, Melbourne, provided an opportunity to assess the possible contribution of c-KIT germline mutations or polymorphisms in this disease. Methods: Tissue biopsy, blood and/or buccal swab specimens were collected from 10 children with mastocytosis. To detect germline mutations/polymorphisms in c-KIT, we studied all coding exons by denaturing high pressure liquid chromatography. Exons showing mismatches were examined by direct sequencing. The influence of the substitution identified was further examined by expressing the variant form of c-KIT in factor-dependent FDC-P1 cells. Results: In both pairs of twins, a heterozygous ATG to CTG transition in codon 541 was observed, resulting in the substitution of a methionine residue in the transmembrane domain by leucine (M541L). In each case, one parent was also heterozygous for this allele. Expression of M541L KIT in FDC-P1 cells enabled them to grow in human KIT ligand (stem cell factor, SCF) but did not confer factor independence. Compared with cells expressing wild-type KIT at a similar level, M541L KIT-expressing cells displayed enhanced growth at low levels of SCF, and heightened sensitivity to the KIT inhibitor, imatinib mesylate. Conclusions: The data suggest that the single nucleotide polymorphism resulting in the substitution M541L may predispose to paediatric mastocytosis. 2010-04-27T05:00:01.532Z ]]> A gauge invariant uniqueness theorem for corners of higher rank graph algebras http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4492 For a finitely aligned k-graph Λ with X a set of vertices in Λ, we define a universal C*-algebra called C* (Λ, X) generated by partial isometries. We show that C* (Λ, X) is isomorphic to the corner PXC*(Λ) PX, where PX is the sum of vertex projections in X. We then prove a version of the Gauge Invariant Uniqueness theorem for C*(Λ, X) and then use the theorem to prove various results involving fullness, simplicity and Morita equivalence as well as results relating to application in symbolic dynamics. 2010-04-27T04:58:06.134Z ]]> A new solid state synthesis methodology for ternary and higher order compounds http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4516 A persistent problem in the synthesis of complex materials from three or more constituents is the retention of very stable intermediate phases with properties grossly different from the target phase. In our recently developed two-stage synthesis methodology, a binary precursor is prepared and then directly converted into the product phase, thereby avoiding intermediate phase formation. Crystallographic similarities between the precursor and product phases are manipulated such that the major structural elements remain chemically intact. Ordered structural vacancies are used to facilitate rapid and highly selective diffusion of the third element into the precursor. Since no crystallographic reconstruction is required, no extraneous phases can form. The method has been tested on the solid state synthesis of Ti₃SiC₂ and Ti₃AlC₂, producing synthesis temperature reductions of 400 – 600°C. It is postulated that similar crystal structural relationships in layered oxides, nitrides and intermetallic compounds will allow an extension to many other systems. 2010-04-27T04:57:27.875Z ]]> Groups acting on products of trees, tiling systems and analytic K-theory http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:4294 Let T₁ and T₂ be homogeneous trees of even degree ≥ 4. A BM group Γ is a torsion-free discrete subgroup of Aut(T₁)×Aut(T₂) which acts freely and transitively on the vertex set of T₁×T₂. This article studies dynamical systems associated with BM groups. A higher rank Cuntz-Krieger algebra A(Γ) is associated both with a 2-dimensional tiling system and with a boundary action of a BM group Γ. An explicit expression is given for the K-theory of A(Γ). In particular K₀=K₁. A complete enumeration of possible BM groups Γ is given for a product homogeneous trees of degree 4, and the K-groups are computed. 2010-04-27T04:57:07.805Z ]]> Self-propagating high-temperature synthesis of Ti₃SiC₂: II. Kinetics of ultra-high-speed reactions from in situ neutron diffraction http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5455 In situ neutron diffraction data at 0.9-s time resolution during the self-propagating high-temperature synthesis of Ti₃SiC₂ from stoichiometric 3Ti+SiC+C mixtures have been further analyzed to give the phase quantities during all five stages of the identified reaction [(i) preheating, (ii) α→β phase transformation in Ti, (iii) preignition reactions, (iv) intermediate phase formation, and (v) rapid nucleation and growth of Ti₃SiC₂]. The phase quantities thus determined have been used, in conjunction with temperatures estimated from lattice parameters and thermal expansion data, to determine the kinetic parameters for the nucleation and growth stage using a nonisothermal form of the Avrami kinetic equation. The analysis gave an Avrami exponent, n, close to 3 in agreement with nucleation and the observed two-dimensional growth of Ti₃SiC₂ crystals. An activation energy of ~45 kJ/mol was also estimated. 2010-04-27T04:48:11.579Z ]]> The Coombs: a house of memories (book review) http://nova.newcastle.edu.au/vital/access/manager/Repository/uon:5024 Review of: The Coombs: a house of memories. Edited by Brij V. Lal and Allison Ley. Canberra, Research School of Pacific and Asian Studies, Australian National University, 2006. xx+294 pp., ISBN 1-920942-88 (pb), ISBN 1-920942-89-0 (online). 2010-04-27T04:45:30.871Z ]]>