248 resultados para Regulatory Elements, Transcriptional
Resumo:
This paper presents a capacitor-clamped three-level inverter-based supercapacitor direct integration scheme for wind energy conversion systems. The idea is to increase the capacitance of clamping capacitors with the use of supercapacitors and allow their voltage to vary within a defined range. Even though this unique approach eliminates the need of interfacing dc-dc converters for supercapacitors, the variable voltage operation brings about several challenges. The uneven distribution of space vectors is the major modulation challenge. A space vector modulation method is proposed in this paper to address this issue and to generate undistorted currents even in the presence of dynamic changes in supercapacitor voltages. A supercapacitor voltage equalization algorithm is also presented. Moreover, control strategies of the proposed system are discussed in detail. Simulation and experimental results are presented to verify the efficacy of the proposed system in suppressing short-term wind power fluctuations.
Resumo:
Vascular endothelial growth factor (VEGF) promotes growth of blood or lymphatic vessels. The aim of the current study is to identify relationships between VEGF-A and VEGF-C, and their impact in angiogenesis and metastases in thyroid cancers. VEGF-A and VEGF-C mRNA and protein expression was investigated in 136 thyroid cancers (123 papillary thyroid carcinomas and 13 undifferentiated thyroid carcinomas) and 40 matched lymph node metastases with papillary thyroid carcinoma using reverse transcription polymerase chain reaction and immunohistochemistry. VEGF-A and VEGF-C mRNA expression was significantly different between conventional papillary thyroid carcinoma, follicular variant of papillary thyroid carcinoma, and undifferentiated thyroid carcinomas (P = 1 x 10(-6) and 1 x 10(-5), respectively). In undifferentiated carcinoma, VEGF-A and VEGF-C protein overexpression was noted in all cases. VEGF-A and VEGF-C mRNA overexpression was noted in 51% (n = 62) and 27% (n = 33) of the papillary thyroid carcinomas, whereas VEGF-A and VEGF-C protein overexpression was also identified in 70% (n = 86) and 62% (n = 76) of the carcinomas. VEGF-A mRNA was significantly higher in cancers with lymph node metastases compared with nonmetastatic cancers (P = .001), whereas most metastatic cancers underexpressed VEGF-C (P = .0002), with a similar trend for protein. The expression of VEGF-A and VEGF-C correlated with each other at both mRNA and protein levels (P = .00004 and .003, respectively). In summary, VEGF-A and -C expressions correlate with the pathological parameters and metastatic status of thyroid carcinomas. The significant correlations between the expressions of these genes add weight to hypotheses concerning VEGF-A and -C interaction in cancer progression.
Resumo:
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.
Resumo:
From 2014, QUT will be adopting a life-cycle approach to Course Quality Assurance informed by a wider and richer range of historic, ‘live’ and ‘predictive’ course data. Key data elements continue to be grouped according to the three broad categories – Viability, Quality of Learning Environment and Outcomes – and are further supported with analytic data presented within tables and charts. Course Quality Assurance and this Consolidated Courses Performance Report illuminate aspects of courses from a data evidence base highlighting the strengths and weaknesses of our courses. It provides the framework and tools to achieve QUT's commitment to excellent graduate outcomes by drawing attention and focus to the quality of our courses and providing a structured approach for bringing about change. Our portfolio of courses forms a vital part of QUT, generating almost $600 million in 2013 alone. Real world courses are fundamental to the strength of the Institution; they are what our many thousands of current and future students are drawn to and invest their time and aspirations in. As we move through a period of some regulatory and deregulatory uncertainty, there is a greater need for QUT to monitor and respond to the needs and expectations of our students. The life-cycle approach, with its rich and predicative data, provides the best source of evidence we have had, to date, to assure the quality of our courses and their relevance in a rapidly changing higher education context.
Resumo:
This paper presents a new direct integration scheme for supercapacitors that are used to mitigate short term power fluctuations in wind power systems. The idea is to replace ordinary capacitors of a 3-level flying capacitor inverter by supercapacitors and operate them under variable voltage conditions. This approach eliminates the need of interfacing dc-dc converters for supercapacitor integration and thus considerably improves the overall efficiency. However, the major problem of this unique system is the change of supercapacitor voltages. An analysis on the effects of these voltage variations are presented. A space vector modulation method, built from the scratch, is proposed to generate undistorted current even in the presence of dynamic changes in supercapacitor voltages. A supercapacitor voltage equalisation algorithm is also proposed. Furthermore, resistive behavior of supercapacitors at high frequencies and the need for a low pass filter are highlighted. Simulation results are presented to verify the efficacy of the proposed system in suppressing short term wind power fluctuations.
Resumo:
In recent times significant change has occurred to the Australian health and safety regulatory context. In this paper we consider the potential response of smaller firms in general, and ethnic owned and/or operated smaller firms in particular. We draw on literature examining smaller firms' responses to regulation and apply this to what little we know about smaller ethnic firms in Australia in the context of the regulatory change. We highlight the challenges to owner managers and what could be done to engage and support smaller ethnic firms to realise the opportunities resulting from this regulatory change.
Resumo:
The Japanese electricity industry has experienced regulatory reforms since the mid-1990s. This article measures productivity in Japan's steam power-generation sector and examines the effect of reforms on the productivity of this industry over the period 1978-2003. We estimate the Luenberger productivity indicator, which is a generalization of the commonly used Malmquist productivity index, using a data envelopment analysis approach. Factors associated with productivity change are investigated through dynamic generalized method of moments (GMM) estimation of panel data. Our empirical analysis shows that the regulatory reforms have contributed to productivity growth in the steam power-generation sector in Japan.
Resumo:
Selumetinib (AZD6244, ARRY-142886) is a selective, non-ATP-competitive inhibitor of mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK)-1/2. The range of antitumor activity seen preclinically and in patients highlights the importance of identifying determinants of response to this drug. In large tumor cell panels of diverse lineage, we show that MEK inhibitor response does not have an absolute correlation with mutational or phospho-protein markers of BRAF/MEK, RAS, or phosphoinositide 3-kinase (PI3K) activity. We aimed to enhance predictivity by measuring pathway output through coregulated gene networks displaying differential mRNA expression exclusive to resistant cell subsets and correlated to mutational or dynamic pathway activity. We discovered an 18-gene signature enabling measurement of MEK functional output independent of tumor genotype. Where the MEK pathway is activated but the cells remain resistant to selumetinib, we identified a 13-gene signature that implicates the existence of compensatory signaling from RAS effectors other than PI3K. The ability of these signatures to stratify samples according to functional activation of MEK and/or selumetinib sensitivity was shown in multiple independent melanoma, colon, breast, and lung tumor cell lines and in xenograft models. Furthermore, we were able to measure these signatures in fixed archival melanoma tumor samples using a single RT-qPCR-based test and found intergene correlations and associations with genetic markers of pathway activity to be preserved. These signatures offer useful tools for the study of MEK biology and clinical application of MEK inhibitors, and the novel approaches taken may benefit other targeted therapies.
Resumo:
Oncogenic mutations in BRAF are common in melanoma and drive constitutive activation of the MEK/ERK pathway. To elucidate the transcriptional events downstream of V600EBRAF/MEK signalling we performed gene expression profiling of A375 melanoma cells treated with potent and selective inhibitors of V600EBRAF and MEK (PLX4720 and PD184352 respectively). Using a stringent Bayesian approach, we identified 69 transcripts that appear to be direct transcriptional targets of this pathway and whose expression changed after 6 h of pathway inhibition. We also identified several additional genes whose expression changed after 24 h of pathway inhibition and which are likely to be indirect transcriptional targets of the pathway. Several of these were confirmed by demonstrating their expression to be similarly regulated when BRAF was depleted using RNA interference, and by using qRT-PCR in other BRAF mutated melanoma lines. Many of these genes are transcription factors and feedback inhibitors of the ERK pathway and are also regulated by MEK signalling in NRAS mutant cells. This study provides a basis for understanding the molecular processes that are regulated by V600EBRAF/MEK signalling in melanoma cells.
Resumo:
Purpose: The paper seeks to investigate emerging knowledge precincts under the urban design lens in order to identify recurrent spatial patterns of urban forms and functions to gather an understanding of physical aspects that contribute to the creation of place quality. Scope: This paper focuses on the physical design and layout of specific precincts. Although socio-economic and other factors come into play imparting the distinctiveness; this paper only focuses on the spatial dimensions. Method: The research first develops a design typology framework through the lead of literature, and then utilizes it to identify recurrent elements in knowledge precinct design in order to develop taxonomy of patterns and layouts. Results: The research reported in this paper provides preliminary insights into the various form and functional factors playing role in the design of knowledge precincts and evaluates the elements that contribute to the success of these urban interventions. Recommendations: The paper recommends the use of particular design-based solutions in order to enhance the place making in knowledge precincts. Conclusions: The study concludes that despite the locational, regulatory and other contextual differences, the underlying driving principle of providing place quality to people leads to the emergence of identifiable spatial patterns across the knowledge precincts.
Resumo:
Pathogenic bacteria have a large repertoire of surface organelles involved in adherence, motility and protein export, but how individual bacteria co-ordinate surface organelle expression to prevent interference and excessive immune stimulation is unclear. Phase variation is a mechanism by which expression of surface factors is limited to a fraction of the bacterial population; however, the presence of multiple homologous surface structures controlled by related mechanisms and regulators antagonizes the independent expression achieved by phase variation. To investigate whether other mechanisms have evolved to sort out the bacterial cell surface, we examined regulatory cross-talk between multiple phase-variable pyelonephritis-associated pili (pap) operons in Escherichia coli isolates associated with urinary tract infections. Allelic variation identified in the regulatory regions and regulators acts synergistically to limit coexpression of homologous fimbrial operons. In particular, there is evidence that papI is under positive selection and PapI variants displayed differences in their capacity to activate related pap operons. Alleles of the high-affinity binding site for PapB were shown to contain a variable number of (T/A)3 repeats occurring every 9 bp that altered the sensitivity of pap operon activation. Taken together with other examples of surface organelle cross-talk, we illustrate how this regulation could promote sequential expression.
Resumo:
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.
Resumo:
Provenance studies of iron-age pottery specimens originating from the Mngeni river area in South Africa was carried out by applying XRF spectrometry. A total of sixteen major and trace elements were analysed in a batch of 107 potsherds, excavated from four different archaeological sites in the aforementioned area. A multivariate statistical programme Correspondence Analysis was used in this study to obtain the relevant clustering patterns according to the similarity of the elemental distributions. Differences and similarities in the clusters obtained for the majors and trace elements are discussed.