701 resultados para Non-terminal alkyne
Resumo:
Improving the performance of a incident detection system was essential to minimize the effect of incidents. A new method of incident detection was brought forward in this paper based on an in-car terminal which consisted of GPS module, GSM module and control module as well as some optional parts such as airbag sensors, mobile phone positioning system (MPPS) module, etc. When a driver or vehicle discovered the freeway incident and initiated an alarm report the incident location information located by GPS, MPPS or both would be automatically send to a transport management center (TMC), then the TMC would confirm the accident with a closed-circuit television (CCTV) or other approaches. In this method, detection rate (DR), time to detect (TTD) and false alarm rate (FAR) were more important performance targets. Finally, some feasible means such as management mode, education mode and suitable accident confirming approaches had been put forward to improve these targets.
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Postconcussion symptoms are relatively common in the acute recovery period following mild traumatic brain injury (MTBI). However, for a small subset of patients, self reported postconcussion symptoms continue long after injury. Many factors have been proposed to account for the presence of persistent postconcussion symptoms. The influence of personality traits has been proposed as one explanation. The purpose of this study was to examine the relation between postconcussion-like symptom reporting and personality traits in a sample of 96 healthy participants. Participants completed the British Columbia Postconcussion Symptom Inventory (BC-PSI) and the Millon Clinical Multiaxial Inventory III (MCMI-III). There was a strong positive relation between the majority of MCMI-III scales and postconcussion-like symptom reporting. Approximately half of the sample met the International Classification of Diseases-10 Criterion C symptoms for Postconcussional Syndrome (PCS). Compared with those participants who did not meet this criterion, the PCS group had significant elevations on the negativistic, depression, major depression, dysthymia, anxiety, dependent, sadistic, somatic, and borderline scales of the MCMI-III. These findings support the hypothesis that personality traits can play a contributing role in self reported postconcussion-like symptoms.
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This article presents results from an exploratory study seeking to examine the role of sentencing in the continuing overrepresentation of Indigenous women in Western Australia’s prisons. Sentencing data from Western Australia’s higher courts indicate that Indigenous women were less likely than non-Indigenous women to be sentenced to a term of imprisonment when appearing before the court for comparable offending behaviour and histories.
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Over the last few decades, most large cities in the developing world have been experiencing rapid and imbalanced transport sector development resulting in severe congestion and poor levels of service. The most common response at a policy level under this circumstance has been to focus on private and public motorized transport modes, and especially on traffic control measures and mass transit systems. Despite their major role in the overall transport system in many developing cities in Asia & Latin America, relatively little attention is given to non-motorized transport (NMT) modes (walk, bicycle and cycle-rickshaw). In particular, this ideology is applicable to the paid category of non-motorized public transport (NMPT), notably three-wheeler cycle rickshaws that still have an important socio-economic, environmental and trip-making role in many developing cities. Despite, they are often seen as inefficient and backward; an impediment to progress; and inconsistent with modern urban image. Policy measures therefore, to restrict or eliminate non-motorized transport from urban arterials and other feeder networks have been implemented in cities as diverse as Dhaka, Delhi, Karachi, Bangkok, Jakarta, Manila, Surabaya and Beijing . This paper will primarily investigate the key contribution of NMPT in the sustainable transport system and urban fabric of developing cities, with Dhaka as case study. The paper will also highlight in detail the impediments towards NMPT development and provide introductory concept on possible role this mode is expected to play into the future of these cities
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Extended spectrum β-lactamases or ESBLs, which are derived from non-ESBL precursors by point mutation of β-lactamase genes (bla), are spreading rapidly all over the world and have caused considerable problems in the treatment of infections caused by bacteria which harbour them. The mechanism of this resistance is not fully understood and a better understanding of these mechanisms might significantly impact on choosing proper diagnostic and treatment strategies. Previous work on SHV β-lactamase gene, blaSHV, has shown that only Klebsiella pneumoniae strains which contain plasmid-borne blaSHV are able to mutate to phenotypically ESBL-positive strains and there was also evidence of an increase in blaSHV copy number. Therefore, it was hypothesised that although specific point mutation is essential for acquisition of ESBL activity, it is not yet enough, and blaSHV copy number amplification is also essential for an ESBL-positive phenotype, with homologous recombination being the likely mechanism of blaSHV copy number expansion. In this study, we investigated the mutation rate of non-ESBL expressing K. pneumoniae isolates to an ESBL-positive status by using the MSS-maximum likelihood method. Our data showed that blaSHV mutation rate of a non-ESBL expressing isolate is lower than the mutation rate of the other single base changes on the chromosome, even with a plasmid-borne blaSHV gene. On the other hand, mutation rate from a low MIC ESBL-positive (≤ 8 µg/mL for cefotaxime) to high MIC ESBL-positive (≥16 µg/mL for cefotaxime) is very high. This is because only gene copy number increase is needed which is probably mediated by homologous recombination that typically takes place at a much higher frequencies than point mutations. Using a subinhibitory concentration of novobiocin, as a homologous recombination inhibitor, revealed that this is the case.
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Practitioners and academics often assume that investments in innovation will lead to organizational improvements. However, previous research has often shown that implemented innovations fail to realise these potential improvements. On the other hand, organisation, perhaps, has been growing and productive because of the innovation, but traditional measurements have failed to capture that growth. In order to help organizations capture their innovation performance effectively, this study examined the organizations which employ different types of performance measurement and their perception of innovation effectiveness.
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Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.
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The purpose of this paper is to conduct a qualitative review of randomised controlled trials in relation to the treatment of adults with co-occurring mental health and substance use disorder (MH/SUD). In particular, integrated approaches are compared with non-integrated approaches to treatment. Ten articles were identified for inclusion in the review. The findings are equivocal with regard to the superior efficacy of integrated approaches to treatment, although the many limitations of the studies need to be considered in our understanding of this finding. Clearly, this is an extremely challenging client group to engage and maintain in intervention research, and the complexity and variability of the problems render control particularly difficult. The lack of available evidence to support the superiority of integration is discussed in relation to these challenges. Much remains to be investigated with regard to integrated management and care for people with co-occurring and MH/SUD, particularly for specific combinations of dual diagnosis and giving consideration to the level of inter-relatedness between the disorders.
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Increasingly, leadership is argued as a way forward to improve performance and practice in a variety of contexts. School leadership is no different. There is little doubt that in the current globalised world characterized by change and complexity, effective school leadership is a key requirement. The contribution of this chapter is framed around a synthesis of current research, writing and theoretical insights regarding leadership. It draws upon three bodies of writing, Firstly, it begins by distilling several key themes and trends regarding educational leadership from the current research and writing. Secondly, it reports on the findings of a current research project carried out by the authors that explored the leadership stories of ten outstanding leaders from non-educational settings in Australia. Finally, it concludes by referring to some of the paradoxes and tensions inherent in the work of school leaders. It is argued that understanding and endeavouring to reconcile these dilemmas is a pre-requisite for school leaders as they continue to operate in an environment fraught with change and complexity.
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This instrument was used in the project named Teachers Reporting Child Sexual Abuse: Towards Evidence-based Reform of Law, Policy and Practice (ARC DP0664847)
Ghrelin gene-related peptides : multifunctional endocrine/autocrine modulators in health and disease
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Ghrelin is a multi-functional peptide hormone which affects various processes including growth hormone and insulin release, appetite regulation, gut motility, metabolism and cancer cell proliferation. Ghrelin is produced in the stomach and in other normal and pathological cell types. It may act as an endocrine or autocrine/paracrine factor. The ghrelin gene encodes a precursor protein, preproghrelin, from which ghrelin and other potentially active peptides are derived by alternative mRNA splicing and/or proteolytic processing. The metabolic role of the peptide obestatin, derived from the preproghrelin C-terminal region, is controversial. However, it has direct effects on cancer cell proliferation. The regulation of ghrelin expression and the mechanisms through which the peptide products arise are unclear. We have recently re-examined the organisation of the ghrelin gene and identified several novel exons and transcripts. One transcript, which lacks the ghrelin-coding region of preproghrelin, contains the coding sequence of obestatin. Furthermore, we have identified an overlapping gene on the antisense strand of ghrelin, GHRLOS, which generates transcripts that may function as non-coding regulatory RNAs or code for novel, short bioactive peptides. The identification of these novel ghrelin-gene related transcripts and peptides raises critical questions regarding their physiological function and their role in obesity, diabetes and cancer.
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In this paper, we consider the following non-linear fractional reaction–subdiffusion process (NFR-SubDP): Formula where f(u, x, t) is a linear function of u, the function g(u, x, t) satisfies the Lipschitz condition and 0Dt1–{gamma} is the Riemann–Liouville time fractional partial derivative of order 1 – {gamma}. We propose a new computationally efficient numerical technique to simulate the process. Firstly, the NFR-SubDP is decoupled, which is equivalent to solving a non-linear fractional reaction–subdiffusion equation (NFR-SubDE). Secondly, we propose an implicit numerical method to approximate the NFR-SubDE. Thirdly, the stability and convergence of the method are discussed using a new energy method. Finally, some numerical examples are presented to show the application of the present technique. This method and supporting theoretical results can also be applied to fractional integrodifferential equations.
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In this paper, a two-dimensional non-continuous seepage flow with fractional derivatives (2D-NCSF-FD) in uniform media is considered, which has modified the well known Darcy law. Using the relationship between Riemann-Liouville and Grunwald-Letnikov fractional derivatives, two modified alternating direction methods: a modified alternating direction implicit Euler method and a modified Peaceman-Rachford method, are proposed for solving the 2D-NCSF-FD in uniform media. The stability and consistency, thus convergence of the two methods in a bounded domain are discussed. Finally, numerical results are given.
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This paper presents the design of self-tuning controllers for a two terminal HVDC link. The controllers are designed utilizing a novel discrete-time converter model based on multirate sampling. The nature of converter firing system necessitates the development of a two-step ahead self-tuning control strategy. A two terminal HVDC system study has been carried out to show the effectiveness of the control strategies proposed which include the design of minimum variance controller, pole assigned controller and PLQG controller. The coordinated control of a two terminal HVDC system has been established deriving the signal from inverter end current and voltage which has been estimated based on the measurements of rectifier end quantities only realized through the robust reduced order observer. A well known scaled down sample system data has been selected for studies and the controllers designed have been tested for worst conditions. The performance of self-tuning controllers has been evaluated through digital simulation.
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Established Monte Carlo user codes BEAMnrc and DOSXYZnrc permit the accurate and straightforward simulation of radiotherapy experiments and treatments delivered from multiple beam angles. However, when an electronic portal imaging detector (EPID) is included in these simulations, treatment delivery from non-zero beam angles becomes problematic. This study introduces CTCombine, a purpose-built code for rotating selected CT data volumes, converting CT numbers to mass densities, combining the results with model EPIDs and writing output in a form which can easily be read and used by the dose calculation code DOSXYZnrc. The geometric and dosimetric accuracy of CTCombine’s output has been assessed by simulating simple and complex treatments applied to a rotated planar phantom and a rotated humanoid phantom and comparing the resulting virtual EPID images with the images acquired using experimental measurements and independent simulations of equivalent phantoms. It is expected that CTCombine will be useful for Monte Carlo studies of EPID dosimetry as well as other EPID imaging applications.