Postprandial total and HMW adiponectin following a high-fat meal in lean, obese and diabetic men

BACKGROUND/OBJECTIVES: Recent work suggests that macronutrients are pro-inflammatory and promote oxidative stress. Reports of postprandial regulation of total adiponectin have been mixed, and there is limited information regarding postprandial changes in high molecular weight (HMW) adiponectin. The aim of this study was to assess the effect of a standardised high-fat meal on metabolic variables, adiponectin (total and HMW), and markers of inflammation and oxidative stress in: (i) lean, (ii) obese non-diabetic and (iii) men with type 2 diabetes mellitus (T2DM). SUBJECTS/METHODS: Male subjects: lean (n=10), obese (n=10) and T2DM (n=10) were studied for 6 h following both a high-fat meal and water control. Metabolic variables (glucose, insulin, triglycerides), inflammatory markers (interleukin-6 (IL6), tumour necrosis factor (TNF)α, high-sensitivity C-reactive protein (hsCRP), nuclear factor (NF)κB expression in peripheral blood mononuclear cells (p65)), indicators of oxidative stress (oxidised low density lipoprotein (oxLDL), protein carbonyl) and adiponectin (total and HMW) were measured. RESULTS: No significant changes in TNFα, p65, oxLDL or protein carbonyl concentrations were observed. Overall, postprandial IL6 decreased in subjects with T2DM but increased in lean subjects, whereas hsCRP decreased in the lean cohort and increased in obese subjects. There was no overall postprandial change in total or HMW adiponectin in any group. Total adiponectin concentrations changed over time following the water control, and the response was significantly different in lean subjects compared with subjects with T2DM (P=0.04). CONCLUSIONS: No consistent significant postprandial inflammation, oxidative stress or regulation of adiponectin was observed in this study. Findings from the water control suggest differential basal regulation of total adiponectin in T2DM compared with lean controls.

A method of extracting switching loss from a high efficiency MOSFET based half bridge converter

The measurement of losses in high efficiency / high power converters is difficult. Measuring the losses directly from the difference between the input and output power results in large errors. Calorimetric methods are usually used to bypass this issue but introduce different problems, such as, long measurement times, limited power loss measurement range and/or large set up cost. In this paper the total losses of a converter are measured directly and switching losses are exacted. The measurements can be taken with only three multimeters and a current probe and a standard bench power supply. After acquiring two or three power loss versus output current sweeps, a series of curve fitting processes are applied and the switching losses extracted.

High efficiency auxiliary power converters

The auxiliary load DC-DC converters of the Sunshark solar car have never been examined. An analysis of the current design reveals it is complicated, and inefficient. Some simple measures to greatly improve the efficiency are present which will achieve an overall worthwhile power saving. Two switch-mode power supply DC-DC converter designs are presented. One is a constant current supply for the LED brake and turn indicators, which allows them to be powered directly from the main DC bus, and switched only as necessary. The second is a low power flyback converter, which employs synchronous rectification among other techniques to achieve good efficiency and regulation over a large range of output powers. Practical results from both converters, and an indication of the overall improvement in system efficiency will be offered.

Get real : the development, implementation and evaluation of an intervention for primary aged children with High Functioning Autism

Children with Autism Spectrum Disorder experience difficulty in communication and in understanding the social world which can have negative consequences for their relationships, in managing emotions, and generally dealing with the challenges of everyday life. This thesis examines the effectiveness of the Active and Reflective components of the Get REAL program through the assessment of the detailed coding of video-recorded observations and longitudinal quantitative analysis. The aim of Get REAL is to increase the social, emotional, and cognitive learning of children with High Functioning Autism (HFA). Get REAL is a group program designed specifically for use in inclusive primary school settings. The Get REAL program was designed in response to the mixed success of generalisation of learning to new contexts of existing social skills programs. The theoretical foundation of Get REAL is based upon pedagogical theory and learning theory to facilitate transfer of learning, combined with experiential, individualised, evaluative and organisational approaches. This thesis is by publication and consists of four refereed journal papers; 1 accepted for publication and 3 that are under review. Paper 1 describes the development and theoretical basis of the Get REAL program and provides detail of the program structure and learning cycle. The focus of Paper 1 reflects the first question of interest in the thesis which is about the extent to which learning derived from participation in the program can be generalised to other contexts. Participants are 16 children with HFA ranging in age from 8-13 years. Results provided support for the generalisability of learning from Get REAL to home and school evidenced by parent and teacher data collected pre and post participation in Get REAL. Following establishment of the generalisation of learning from Get REAL, Papers 2 and 3 focus on the Active and Reflective components of the program in order to examine how individual and group learning takes place. Participants (N = 12) in the program are video-taped during the Active and Reflective Sessions. Using identical coding protocols of video data, improvements in prosocial behaviour and diminishing of inappropriate behaviours were apparent with the exception of perspective taking. Data also revealed that 2 of the participants had atypical trajectories. An in-depth case study analysis was then conducted with these 2 participants in Paper 4. Data included reports from health care and education professionals within the school and externally (e.g., paediatrician) and identified the multi-faceted nature of care needed for children with comorbid diagnoses and extremely challenging family circumstances as a complex task to effect change. Results of this research support the effectiveness of the Get REAL program in promoting pro social behaviours such as improvements in engaging with others and emotional regulation, and in diminishing unwanted behaviours such as conduct problems. Further, the gains made by the participating children were found to be generalisable beyond Get REAL to home and other school settings. The research contained in the thesis adds to current knowledge about how learning can take place for children with HFA. Results show that an experiential learning framework with a focus on social cognition, together with explicit teaching, scaffolded with video feedback, are key ingredients for the generalisation of social learning to broader contexts.

Saliva-derived DNA performs well in large-scale, high-density single-nucleotide polymorphism microarray studies

As of June 2009, 361 genome-wide association studies (GWAS) had been referenced by the HuGE database. GWAS require DNA from many thousands of individuals, relying on suitable DNA collections. We recently performed a multiple sclerosis (MS) GWAS where a substantial component of the cases (24%) had DNA derived from saliva. Genotyping was done on the Illumina genotyping platform using the Infinium Hap370CNV DUO microarray. Additionally, we genotyped 10 individuals in duplicate using both saliva- and blood-derived DNA. The performance of blood- versus saliva-derived DNA was compared using genotyping call rate, which reflects both the quantity and quality of genotyping per sample and the “GCScore,” an Illumina genotyping quality score, which is a measure of DNA quality. We also compared genotype calls and GCScores for the 10 sample pairs. Call rates were assessed for each sample individually. For the GWAS samples, we compared data according to source of DNA and center of origin. We observed high concordance in genotyping quality and quantity between the paired samples and minimal loss of quality and quantity of DNA in the saliva samples in the large GWAS sample, with the blood samples showing greater variation between centers of origin. This large data set highlights the usefulness of saliva DNA for genotyping, especially in high-density single-nucleotide polymorphism microarray studies such as GWAS.

A high-throughput panel for identifying clinically relevant mutation profiles in melanoma

Success with molecular-based targeted drugs in the treatment of cancer has ignited extensive research efforts within the field of personalized therapeutics. However, successful application of such therapies is dependent on the presence or absence of mutations within the patient's tumor that can confer clinical efficacy or drug resistance. Building on these findings, we developed a high-throughput mutation panel for the identification of frequently occurring and clinically relevant mutations in melanoma. An extensive literature search and interrogation of the Catalogue of Somatic Mutations in Cancer database identified more than 1,000 melanoma mutations. Applying a filtering strategy to focus on mutations amenable to the development of targeted drugs, we initially screened 120 known mutations in 271 samples using the Sequenom MassARRAY system. A total of 252 mutations were detected in 17 genes, the highest frequency occurred in BRAF (n = 154, 57%), NRAS (n = 55, 20%), CDK4 (n = 8, 3%), PTK2B (n = 7, 2.5%), and ERBB4 (n = 5, 2%). Based on this initial discovery screen, a total of 46 assays interrogating 39 mutations in 20 genes were designed to develop a melanoma-specific panel. These assays were distributed in multiplexes over 8 wells using strict assay design parameters optimized for sensitive mutation detection. The final melanoma-specific mutation panel is a cost effective, sensitive, high-throughput approach for identifying mutations of clinical relevance to molecular-based therapeutics for the treatment of melanoma. When used in a clinical research setting, the panel may rapidly and accurately identify potentially effective treatment strategies using novel or existing molecularly targeted drugs

Controls on mid-Holocene fringing reef growth and termination in a high latitude, estuarine setting, Wellington Point, Southeast Queensland

Several fringing coral reefs in Moreton Bay, Southeast Queensland, some 300 km south of the Great Barrier Reef (GBR), are set in a relatively high latitude, estuarine environment that is considered marginal for coral growth. Previous work indicated that these marginal reefs, as with many fringing reefs of the inner GBR, ceased accreting in the mid-Holocene. This research presents for the first time data from the subsurface profile of the mid-Holocene fossil reef at Wellington Point comprising U/Th dates of in situ and framework corals, and trace element analysis from the age constrained carbonate fragments. Based on trace element proxies the palaeo-water quality during reef accretion was reconstructed. Results demonstrate that the reef initiated more than 7,000 yr BP during the post glacial transgression, and the initiation progressed to the west as sea level rose. In situ micro-atolls indicate that sea level was at least 1 m above present mean sea level by 6,680 years ago. The reef remained in "catch-up" mode, with a seaward sloping upper surface, until it stopped aggrading abruptly at ca 6,000 yr BP; no lateral progradation occurred. Changes in sediment composition encountered in the cores suggest that after the laterite substrate was covered by the reef, most of the sediment was produced by the carbonate factory with minimal terrigenous influence. Rare earth element, Y and Ba proxies indicate that water quality during reef accretion was similar to oceanic waters, considered suitable for coral growth. A slight decline in water quality on the basis of increased Ba in the later stages of growth may be related to increased riverine input and partial closing up of the bay due to either tidal delta progradation, climatic change and/or slight sea level fall. The age data suggest that termination of reef growth coincided with a slight lowering of sea level, activation of ENSO and consequent increase in seasonality, lowering of temperatures and the constrictions to oceanic flushing. At the cessation of reef accretion the environmental conditions in the western Moreton Bay were changing from open marine to estuarine. The living coral community appears to be similar to the fossil community, but without the branching Acropora spp. that were more common in the fossil reef. In this marginal setting coral growth periods do not always correspond to periods of reef accretion due to insufficient coral abundance. Due to several environmental constraints modern coral growth is insufficient for reef growth. Based on these findings Moreton Bay may be unsuitable as a long term coral refuge for most species currently living in the GBR.

High rates of muscle glycogen resynthesis after exhaustive exercise when carbohydrate is coingested with caffeine

We determined the effect of coingestion of caffeine (Caff) with carbohydrate (CHO) on rates of muscle glycogen resynthesis during recovery from exhaustive exercise in seven trained subjects who completed two experimental trials in a randomized, double-blind crossover design. The evening before an experiment subjects performed intermittent exhaustive cycling and then consumed a low-CHO meal. The next morning subjects rode until volitional fatigue. On completion of this ride subjects consumed either CHO [4 g/kg body mass (BM)] or the same amount of CHO + Caff (8 mg/kg BM) during 4 h of passive recovery. Muscle biopsies and blood samples were taken at regular intervals throughout recovery. Muscle glycogen levels were similar at exhaustion [?75 mmol/kg dry wt (dw)] and increased by a similar amount (?80%) after 1 h of recovery (133 ± 37.8 vs. 149 ± 48 mmol/kg dw for CHO and Caff, respectively). After 4 h of recovery Caff resulted in higher glycogen accumulation (313 ± 69 vs. 234 ± 50 mmol/kg dw, P < 0.001). Accordingly, the overall rate of resynthesis for the 4-h recovery period was 66% higher in Caff compared with CHO (57.7 ± 18.5 vs. 38.0 ± 7.7 mmol·kg dw-1·h-1, P < 0.05). After 1 h of recovery plasma Caff levels had increased to 31 ± 11 ?M (P < 0.001) and at the end of the recovery reached 77 ± 11 ?M (P < 0.001) with Caff. Phosphorylation of CaMKThr286 was similar after exercise and after 1 h of recovery, but after 4 h CaMKThr286 phosphorylation was higher in Caff than CHO (P < 0.05). Phosphorylation of AMP-activated protein kinase (AMPK)Thr172 and AktSer473 was similar for both treatments at all time points. We provide the first evidence that in trained subjects coingestion of large amounts of Caff (8 mg/kg BM) with CHO has an additive effect on rates of postexercise muscle glycogen accumulation compared with consumption of CHO alone.

Effect of high-frequency resistance exercise on adaptive responses in skeletal muscle

PURPOSE: Regulation of skeletal muscle mass is highly dependent on contractile loading. The purpose of this study was to examine changes in growth factor and inflammatory pathways following high-frequency resistance training. METHODS: Using a novel design in which male Sprague-Dawley rats undertook a "stacked" resistance training protocol designed to generate a summation of transient exercise-induced signaling responses (four bouts of three sets × 10 repetitions of squat exercise, separated by 3 h of recovery), we determined the effects of high training frequency on signaling pathways and transcriptional activity regulating muscle mass. RESULTS: The stacked training regimen resulted in acute suppression of insulin-like growth factor 1 mRNA abundance (P < 0.05) and Akt phosphorylation (P < 0.05), an effect that persisted 48 h after the final training bout. Conversely, stacked training elicited a coordinated increase in the expression of tumor necrosis factor alpha, inhibitor kappa B kinase alpha/beta activity (P < 0.05), and p38 mitogen-activated protein kinase phosphorylation (P < 0.05) at 3 h after each training bout. In addition, the stacked series of resistance exercise bouts induced an increase in p70 S6 kinase phosphorylation 3 h after bouts ×3 and ×4, independent of the phosphorylation state of Akt. CONCLUSIONS: Our results indicate that high resistance training frequency extends the transient activation of inflammatory signaling cascades, concomitant with persistent suppression of key mediators of anabolic responses. We provide novel insights into the effects of the timing of exercise-induced overload and recovery on signal transduction pathways and transcriptional activity regulating skeletal muscle mass in vivo.

Robust control algorithm for grid-interfaced three-phase inverters with high-bandwidth LCL filter

The paper introduces the design of robust current and voltage control algorithms for a grid-connected three-phase inverter which is interfaced to the grid through a high-bandwidth three-phase LCL filter. The algorithms are based on the state feedback control which have been designed in a systematic approach and improved by using oversampling to deal with the issues arising due to the high-bandwidth filter. An adaptive loop delay compensation method has also been adopted to minimize the adverse effects of loop delay in digital controller and to increase the robustness of the control algorithm in the presence of parameter variations. Simulation results are presented to validate the effectiveness of the proposed algorithm.

Behavioral evaluation of eight rat lines selected for high and low anxiety-related responses

Anxiety traits can be stable and permanent characteristics of an individual across time that is less susceptible of influences by a particular situation. One way to study trait anxiety in an experimental context is through the use of rat lines, selected according to contrasting phenotypes of fear and anxiety. It is not clear whether the behavioral differences between two contrasting rat lines in one given anxiety test are also present in others paradigms of state anxiety. Here, we examine the extent to which multiple anxiety traits generalize across selected animal lines originally selected for a single anxiety trait. We review the behavioral results available in the literature of eight rat genetic models of trait anxiety - namely Maudsley Reactive and Non-reactive rats, Floripa H and L rats, Tsukuba High and Low Emotional rats, High and Low Anxiety-related rats, High and Low Ultrasonic Vocalization rats, Roman High and Low Avoidance rats, Syracuse High and Low Avoidance rats, and Carioca High and Low Conditioned Freezing rats - across 11 behavioral paradigms of innate anxiety or aversive learning frequently used in the experimental setting. We observed both convergence and divergence of behavioral responses in these selected lines across the 11 paradigms. We find that predisposition for specific anxiety traits will usually be generalized to other anxiety provoking stimuli. However this generalization is not observed across all genetic models indicating some unique trait and state interactions. Genetic models of enhanced-anxiety related responses are beginning to help define how anxiety can manifest differently depending on the underlying traits and the current environmentally induced state.

Mice selectively bred for High and Low fear behavior show differences in the number of pMAPK (p44/42 ERK) expressing neurons in lateral amygdala following Pavlovian fear conditioning

Individual variability in the acquisition, consolidation and extinction of conditioned fear potentially contributes to the development of fear pathology including posttraumatic stress disorder (PTSD). Pavlovian fear conditioning is a key tool for the study of fundamental aspects of fear learning. Here, we used a selected mouse line of High and Low Pavlovian conditioned fear created from an advanced intercrossed line (AIL) in order to begin to identify the cellular basis of phenotypic divergence in Pavlovian fear conditioning. We investigated whether phosphorylated MAPK (p44/42 ERK/MAPK), a protein kinase required in the amygdala for the acquisition and consolidation of Pavlovian fear memory, is differentially expressed following Pavlovian fear learning in the High and Low fear lines. We found that following Pavlovian auditory fear conditioning, High and Low line mice differ in the number of pMAPK-expressing neurons in the dorsal sub nucleus of the lateral amygdala (LAd). In contrast, this difference was not detected in the ventral medial (LAvm) or ventral lateral (LAvl) amygdala sub nuclei or in control animals. We propose that this apparent increase in plasticity at a known locus of fear memory acquisition and consolidation relates to intrinsic differences between the two fear phenotypes. These data provide important insights into the micronetwork mechanisms encoding phenotypic differences in fear. Understanding the circuit level cellular and molecular mechanisms that underlie individual variability in fear learning is critical for the development of effective treatment of fear-related illnesses such as PTSD.