Controlling current and voltage type interfaces in power-hardware-in-the-loop simulations

The usual practice to study a large power system is through digital computer simulation. However, the impact of large scale use of small distributed generators on a power network cannot be evaluated strictly by simulation since many of these components cannot be accurately modelled. Moreover, the network complexity makes the task of practical testing on a physical network nearly impossible. This study discusses the paradigm of interfacing a real-time simulation of a power system to real-life hardware devices. This type of splitting a network into two parts and running a real-time simulation with a physical system in parallel is usually termed as power-hardware-in-the-loop (PHIL) simulation. The hardware part is driven by a voltage source converter that amplifies the signals of the simulator. In this paper, the effects of suitable control strategy on the performance of PHIL and the associated stability aspects are analysed in detail. The analyses are validated through several experimental tests using an real-time digital simulator.

Evaluation of resonant damping techniques for Z-source current-type inverter

For the renewable energy sources whose outputs vary continuously, a Z-source current-type inverter has been proposed as a possible buck-boost alternative for grid-interfacing. With a unique X-shaped LC network connected between its dc power source and inverter topology, Z-source current-type inverter is however expected to suffer from compounded resonant complications in addition to those associated with its second-order output filter. To improve its damping performance, this paper proposes the careful integration of Posicast or three-step compensators before the inverter pulse-width modulator for damping triggered resonant oscillations. In total, two compensators are needed for wave-shaping the inverter boost factor and modulation ratio, and they can conveniently be implemented using first-in first-out stacks and embedded timers of modern digital signal processors widely used in motion control applications. Both techniques are found to damp resonance of ac filter well, but for cases of transiting from current-buck to boost state, three-step technique is less effective due to the sudden intermediate discharging interval introduced by its non-monotonic stepping (unlike the monotonic stepping of Posicast damping). These findings have been confirmed both in simulations and experiments using an implemented laboratory prototype.

Development and evaluation of the Ontrack Diabetes Program : an automated, web-based type 2 diabetes self-management and dysphoria intervention

This research was conducted in the area of Clinical and Health Psychology. The study involved the development and evaluation of a novel, web-based program aimed to improve Type 2 diabetes self-management and mood. The program was developed as an original technological intervention aimed to improve access to support for rural and remote communities, and is currently being trialled across Australia with a larger sample size. The researcher aims to continue research into the field of clinical psychology, and in particular is interested in working on further interventions to support those with comorbid physical and mental health conditions.

Functional role for senataxin, defective in ataxia oculomotor apraxia type 2, in transcriptional regulation

Ataxia oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin, a putative DNA/RNA helicase which shares high homology to the yeast Sen1p protein and has been shown to play a role in the response to oxidative stress. To investigate further the function of senataxin, we identified novel senataxin-interacting proteins, the majority of which are involved in transcription and RNA processing, including RNA polymerase II. Binding of RNA polymerase II to candidate genes was significantly reduced in senataxin deficient cells and this was accompanied by decreased transcription of these genes, suggesting a role for senataxin in the regulation/modulation of transcription. RNA polymerase II-dependent transcription termination was defective in cells depleted of senataxin in keeping with the observed interaction of senataxin with poly(A) binding proteins 1 and 2. Splicing efficiency of specific mRNAs and alternate splice-site selection of both endogenous genes and artificial minigenes were altered in senataxin depleted cells. These data suggest that senataxin, similar to its yeast homolog Sen1p, plays a role in coordinating transcriptional events, in addition to its role in DNA repair.

The impact of diabetic ketoacidosis and age on behavior six months post-diagnosis in children with type 1 diabetes

Objectives: Children with type 1 diabetes mellitus (DM1) may be at increased risk of psychosocial and adjustment difficulties. We examined behavioral outcomes six months post-diagnosis in a group of children with newly diagnosed DM1. Methods: This study formed part of a larger longitudinal project examining pathophysiology and neuropsychological outcomes in diabetic patients with or without diabetic ketoacidosis (DKA). Participants were 61 children (mean age 11.8 years, SD 2.7 years) who presented with a new diagnosis of DM1 at the Royal Children’s Hospital, Melbourne. Twenty-three (11 female) presented in DKA and 38 (14 female) without DKA. Parents completed the behavior assessment system for children, second edition six months post-diagnosis. Results: There was a non-linear relationship between age and behavior. Internalising problems (i.e. anxiety depression, withdrawal) peaked in the transition from childhood to adolescence; children aged 10–13 years had elevated rates relative to the normal population (t = 2.55, P = 0.018). There was a non-significant trend for children under 10 to display internalising problems (P = 0.052), but rates were not elevated in children over 13 (P = 0.538). Externalising problems were not significantly elevated in any age group. Interestingly, children who presented in DKA were at lower risk of internalising problems than children without DKA (t = 3.83, P < 0.001). There was no effect of DKA on externalising behaviors. Conclusions: Children transitioning from childhood to adolescence are at significant risk for developing internalising problems such as anxiety and lowered mood after diagnosis of DM1. Somewhat counter-intuitively, parents of children presenting in DKA reported fewer internalising symptoms than parents of children without DKA. These results highlight the importance of monitoring and supporting psychosocial adjustment in newly diagnosed children even when they seem physically well.

No genetic bottleneck in Plasmodium falciparum wild-type Pfcrt alleles reemerging in Hainan Island, China, following high-level chloroquine resistance

Chloroquine-resistant Plasmodium falciparum was highly prevalent in Hainan, China, in the 1970s. Twenty-five years after cessation of chloroquine therapy, the prevalence of P. falciparum wild-type Pfcrt alleles has risen to 36% (95% confidence interval, 22.1 to 52.4%). The diverse origins of wild-type alleles indicate that there was no genetic bottleneck caused by high chloroquine resistance.

Band gap tunable N-type molecules for organic field effect transistors

A series of four novel n-type molecules has been synthesized. Unlike previous approaches, the end group of these molecules was fixed and the molecular core was varied. The resulting materials were thoroughly analyzed. Electronic properties were derived from photoemission spectroscopy, optical properties were derived with the help of optical spectroscopy, and the structure of thin films on Au(111) was derived by scanning tunneling microscopy (STM). In addition, prototypical organic field-effect transistors (OFETs) (forming n-channels in OFETs) have been fabricated and tested. The correlation between the device performance of the respective OFETs (i.e., electron mobility) and their electronic as well as structural properties was investigated. It turned out that a combination of beneficial electronic and structural properties provides the best results. These findings are important for the design of new materials for future device applications.

A high mobility P-type DPP-thieno[3,2-b]thiophene copolymer for organic thin-film transistors

A copolymer comprising 1,4-diketopyrrolo[3,4-c]pyrrole (DPP) and thieno[3,2-b]thiophene moieties, PDBT-co-TT, shows high hole mobility of up to 0.94 cm2 V-1 s-1 in organic thin-film transistors. The strong intermolecular interactions originated from π-π stacking and donor-acceptor interaction lead to the formation of interconnected polymer networks having an ordered lamellar structure, which have established highly efficient pathways for charge carrier transport.

Speckle-type POZ protein mutations interrupt tumor suppressor function of speckle-type POZ protein in prostate cancer by affecting androgen receptor degradation

Large scale exome sequencing studies have revealed regions of the genome, which contribute to the castrate resistant prostate cancer (CRPC) phenotype. [1],[2],[3] Such studies have identified mutations in genes, which may have diagnostic/prognostic potential, or which may be targeted therapeutically. Two of these genes include the androgen receptor (AR) and speckle-type POZ protein (SPOP) genes. However, the findings from these exome sequencing studies can only be translated therapeutically once the functional consequences of these mutations have been determined. Here, we highlight the recent study by An et al. [4] which investigated the functional effects of mutations in the SPOP gene that were identified in the aforementioned exome sequencing studies, particularly in the context of SPOP-mediated degradation of the AR.

Molecular phylogeny, biogeography, and habitat preference evolution of marsupials

Marsupials exhibit great diversity in ecology and morphology. However, compared to their sister group, the placental mammals, our understanding of many aspects of marsupial evolution remains limited. We use 101 mitochondrial genomes and data from 26 nuclear loci to reconstruct a dated phylogeny including 97% of extant genera and 58% of modern marsupial species. This tree allows us to analyze the evolution of habitat preference and geographic distributions of marsupial species through time. We found a pattern of mesic-adapted lineages evolving to use more arid and open habitats, which is broadly consistent with regional climate and environmental change. However, contrary to the general trend, several lineages subsequently appear to have reverted from drier to more mesic habitats. Biogeographic reconstructions suggest that current views on the connectivity between Australia and New Guinea/Wallacea during the Miocene and Pliocene need to be revised. The antiquity of several endemic New Guinean clades strongly suggests a substantially older period of connection stretching back to the Middle Miocene, and implies that New Guinea was colonized by multiple clades almost immediately after its principal formation.

Molecular analysis of type 3 fimbrial genes from Escherichia coli, Klebsiella and Citrobacter species

Background Catheter-associated urinary tract infection (CAUTI) is the most common nosocomial infection in the United States and is caused by a range of uropathogens. Biofilm formation by uropathogens that cause CAUTI is often mediated by cell surface structures such as fimbriae. In this study, we characterised the genes encoding type 3 fimbriae from CAUTI strains of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Citrobacter koseri and Citrobacter freundii. Results Phylogenetic analysis of the type 3 fimbrial genes (mrkABCD) from 39 strains revealed they clustered into five distinct clades (A-E) ranging from one to twenty-three members. The majority of sequences grouped in clade A, which was represented by the mrk gene cluster from the genome sequenced K. pneumoniae MGH78578. The E. coli and K. pneumoniae mrkABCD gene sequences clustered together in two distinct clades, supporting previous evidence for the occurrence of inter-genera lateral gene transfer. All of the strains examined caused type 3 fimbriae mediated agglutination of tannic acid treated human erythrocytes despite sequence variation in the mrkD-encoding adhesin gene. Type 3 fimbriae deletion mutants were constructed in 13 representative strains and were used to demonstrate a direct role for type 3 fimbriae in biofilm formation. Conclusions The expression of functional type 3 fimbriae is common to many Gram-negative pathogens that cause CAUTI and is strongly associated with biofilm growth. Our data provides additional evidence for the spread of type 3 fimbrial genes by lateral gene transfer. Further work is now required to substantiate the clade structure reported here by examining more strains as well as other bacterial genera that make type 3 fimbriae and cause CAUTI.

Demonstration of regulatory cross-talk between P fimbriae and type 1 fimbriae in uropathogenic Escherichia coli

The majority of Escherichia coli strains isolated from urinary tract infections have the potential to express multiple fimbriae. Two of the most common fimbrial adhesins are type 1 fimbriae and pyelonephritis-associated pili (Pap). Previous research has shown that induced, plasmid-based expression of a Pap regulator, papB, and its close homologues can prevent inversion of the fim switch controlling the expression of type 1 fimbriae. The aim of the present study was to determine if this cross-regulation occurs when PapB is expressed from its native promoter in the chromosome of E. coli K-12 and clinical isolates. The regulation was examined in three ways: (1) mutated alleles of the pap regulatory region, including papB and papI, that maintain the pap promoter in either the off or the on phase were exchanged into the chromosome of both E. coli K-12 and the clinical isolate E. coli CFT073, and the effect on type 1 fimbrial expression was measured; (2) type 1 fimbrial expression was determined using a novel fimS : : gfp+ reporter system in mutants of the clinical isolate E. coli 536 in which combinations of complete fimbrial clusters had been deleted; (3) type 1 fimbrial expression was determined in a range of clinical isolates and compared with both the number of P clusters and their expression. All three approaches demonstrated that P expression represses type 1 fimbrial expression. Using a number of novel genetic approaches, this work extends the initial finding that PapB inhibits FimB recombination to the impact of this regulation in clinical isolates.

A cost-effectiveness analysis of a telephone-linked care intervention for individuals with Type 2 diabetes

AIM: To assess the cost-effectiveness of an automated telephone-linked care intervention, Australian TLC Diabetes, delivered over 6 months to patients with established Type 2 diabetes mellitus and high glycated haemoglobin level, compared to usual care. METHODS: A Markov model was designed to synthesize data from a randomized controlled trial of TLC Diabetes (n=120) and other published evidence. The 5-year model consisted of three health states related to glycaemic control: 'sub-optimal' HbA1c ≥58mmol/mol (7.5%); 'average' ≥48-57mmol/mol (6.5-7.4%) and 'optimal' <48mmol/mol (6.5%) and a fourth state 'all-cause death'. Key outcomes of the model include discounted health system costs and quality-adjusted life years (QALYS) using SF-6D utility weights. Univariate and probabilistic sensitivity analyses were undertaken. RESULTS: Annual medication costs for the intervention group were lower than usual care [Intervention: £1076 (95%CI: £947, £1206) versus usual care £1271 (95%CI: £1115, £1428) p=0.052]. The estimated mean cost for intervention group participants over five years, including the intervention cost, was £17,152 versus £17,835 for the usual care group. The corresponding mean QALYs were 3.381 (SD 0.40) for the intervention group and 3.377 (SD 0.41) for the usual care group. Results were sensitive to the model duration, utility values and medication costs. CONCLUSION: The Australian TLC Diabetes intervention was a low-cost investment for individuals with established diabetes and may result in medication cost-savings to the health system. Although QALYs were similar between groups, other benefits arising from the intervention should also be considered when determining the overall value of this strategy.

Circulating fragments of N-Terminal Pro-B-Type Natriuretic Peptides in plasma of heart failure patients

BACKGROUND: The use of nonstandardized N-terminal pro-B-type natriuretic peptide (NT-proBNP) assays can contribute to the misdiagnosis of heart failure (HF). Moreover, there is yet to be established a common consensus regarding the circulating forms of NT-proBNP being used in current assays. We aimed to characterize and quantify the various forms of NT-proBNP in the circulation of HF patients. METHODS: Plasma samples were collected from HF patients (n = 20) at rest and stored at -80 degrees C. NT-proBNP was enriched from HF patient plasma by use of immunoprecipitation followed by mass spectrometric analysis. Customized homogeneous sandwich AlphaLISA (R) immunoassays were developed and validated to quantify 6 fragments of NT-proBNP. RESULTS: Mass spectrometry identified the presence of several N- and C-terminally processed forms of circulating NT-proBNP, with physiological proteolysis between Pro2-Leu3, Leu3-Gly4, Pro6-Gly7, and Pro75-Arg76. Consistent with this result, AlphaLISA immunoassays demonstrated that antibodies targeting the extreme N or C termini measured a low apparent concentration of circulating NT-proBNP. The apparent circulating NT-proBNP concentration was increased with antibodies targeting nonglycosylated and nonterminal epitopes (P < 0.05). CONCLUSIONS: In plasma collected from HF patients, immunoreactive NT-proBNP was present as multiple N- and C-terminally truncated fragments of the full length NT-proBNP molecule. Immunodetection of NT-proBNP was significantly improved with the use of antibodies that did not target these terminal regions. These findings support the development of a next generation NT-proBNP assay targeting nonterminal epitopes as well as avoiding the central glycosylated region of this molecule. (c) 2013 American Association for Clinical Chemistry

Canagliflozin : something new for type 2 diabetes, but is it safe and efficacious?

Evaluation of Inagaki N, Kondo K, Yoshinari T, et al. Efficacy and safety of canagliflozin in Japanese patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, 12-week study. Diabetes Obes Metab 2013. [Epub ahead of print] and Cefalu WT, Leiter LA, Yoon KH, et al. Efficacy and safety of canagliflozin versus glimepiride in patients with type 2 diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results from a randomized, double-blind, phase 3 non-inferiority trial. Lancet 2013;382:941-50 INTRODUCTION Inhibition of the sodium-glucose cotransporter 2 (SGLT2), to promote the excretion of glucose, is a new paradigm in the treatment of type 2 diabetes. AREAS COVERED Canagliflozin is an SGLT2 inhibitor, which has been the subject of two recent clinical trials, which are evaluated. EXPERT OPINION Studies with canagliflozin, in subjects with type 2 diabetes, have shown that its use is associated with reductions in HbA1c and body weight and small reductions in blood pressure and triglycerides, while increasing high-density lipoprotein cholesterol and low-density lipoprotein cholesterol. As monotherapy in Japanese subjects, or in comparison with glimepiride in CANTATA-SU (CANagliflozin Treatment and Trial Analysis versus SUlphonylurea), canagliflozin causes a low incidence of hypoglycemia, and this is an advantage over glimepiride. However, one of the disadvantages with canagliflozin, which was also highlighted in CANTATA-SU, is that canagliflozin can cause urogenital infections, which are not observed with other antidiabetic drugs. The Federal Drug Administration has recently approved canagliflozin for use in type 2 diabetes, while directing that a clinical outcome safety trial be undertaken. We are concerned that canagliflozin has been approved for use in type 2 diabetes prior to a clinical outcome study of efficacy being undertaken and without the outcome of further safety testing.