196 resultados para Herbert S. Lowe


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PSA-RP2 is a variant transcript expressed from the PSA gene that is conserved in gorillas, chimpanzees and humans suggesting a particular relevance for this transcript in these primates. We demonstrated by qRT-PCR that PSA-RP2 is upregulated in prostate cancer compared with benign prostatic hyperplasia tissues. The PSA-RP2 protein was not detected in seminal fluid and was cytoplasmically localised but not secreted from LNCaP or transfected PC3 prostate cells, despite secretion from transfected Cos-7 and HEK293 kidney cell lines. PSA-RP2-transfected PC3 cells showed slightly decreased proliferation and increased migration towards PC3-conditioned medium that could suggest a functional role in prostate cancer.

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Alcohol use disorders (AUDs) impact millions of individuals and there remain few effective treatment strategies. Despite evidence that neuronal nicotinic acetylcholine receptors (nAChRs) have a role in AUDs, it has not been established which subtypes of the nAChR are involved. Recent human genetic association studies have implicated the gene cluster CHRNA3-CHRNA5-CHRNB4 encoding the α3, α5, and β4 subunits of the nAChR in susceptibility to develop nicotine and alcohol dependence; however, their role in ethanol-mediated behaviors is unknown due to the lack of suitable and selective research tools. To determine the role of the α3, and β4 subunits of the nAChR in ethanol self-administration, we developed and characterized high-affinity partial agonists at α3β4 nAChRs, CP-601932, and PF-4575180. Both CP-601932 and PF-4575180 selectively decrease ethanol but not sucrose consumption and operant self-administration following long-term exposure. We show that the functional potencies of CP-601932 and PF-4575180 at α3β4 nAChRs correlate with their unbound rat brain concentrations, suggesting that the effects on ethanol self-administration are mediated via interaction with α3β4 nAChRs. Also varenicline, an approved smoking cessation aid previously shown to decrease ethanol consumption and seeking in rats and mice, reduces ethanol intake at unbound brain concentrations that allow functional interactions with α3β4 nAChRs. Furthermore, the selective α4β2(*) nAChR antagonist, DHβE, did not reduce ethanol intake. Together, these data provide further support for the human genetic association studies, implicating CHRNA3 and CHRNB4 genes in ethanol-mediated behaviors. CP-601932 has been shown to be safe in humans and may represent a potential novel treatment for AUDs.

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Background Invasive species pose a significant threat to global economies, agriculture and biodiversity. Despite progress towards understanding the ecological factors associated with plant invasions, limited genomic resources have made it difficult to elucidate the evolutionary and genetic factors responsible for invasiveness. This study presents the first expressed sequence tag (EST) collection for Senecio madagascariensis, a globally invasive plant species. Methods We used pyrosequencing of one normalized and two subtractive libraries, derived from one native and one invasive population, to generate an EST collection. ESTs were assembled into contigs, annotated by BLAST comparison with the NCBI non-redundant protein database and assigned gene ontology (GO) terms from the Plant GO Slim ontologies. Key Results Assembly of the 221 746 sequence reads resulted in 12 442 contigs. Over 50 % (6183) of 12 442 contigs showed significant homology to proteins in the NCBI database, representing approx. 4800 independent transcripts. The molecular transducer GO term was significantly over-represented in the native (South African) subtractive library compared with the invasive (Australian) library. Based on NCBI BLAST hits and literature searches, 40 % of the molecular transducer genes identified in the South African subtractive library are likely to be involved in response to biotic stimuli, such as fungal, bacterial and viral pathogens. Conclusions This EST collection is the first representation of the S. madagascariensis transcriptome and provides an important resource for the discovery of candidate genes associated with plant invasiveness. The over-representation of molecular transducer genes associated with defence responses in the native subtractive library provides preliminary support for aspects of the enemy release and evolution of increased competitive ability hypotheses in this successful invasive. This study highlights the contribution of next-generation sequencing to better understanding the molecular mechanisms underlying ecological hypotheses that are important in successful plant invasions.

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Diesel engine fuel injector faults can lead to reduced power, increased fuel consumption and greater exhaust emission levels and if left unchecked, can eventually lead to premature engine failure. This paper provides an overview of the Diesel, or compression ignition combustion process, and of the two basic fuel injector nozzle designs used in Diesel engines, namely, the pintle-type and hole-type nozzles. Also described are some common faults associated with these two types of fuel injector nozzles and the techniques previously used to experimentally simulate these faults. This paper also presents a recent experimental campaign undertaken using two different diesel engines whereby various fuel injector nozzle faults were induced into the engines. The first series of tests was undertaken using a turbo-charged 5.9 litre; Cummins Diesel engine whist the second series of tests was undertaken using a naturally aspirated 4 cylinder, 2.216 litre, Perkins Diesel engine. Data corresponding to different injector fault conditions was captured using in-cylinder pressure, and acoustic emission transducers along with both crank-angle encoder and top-dead centre reference signals. Using averaged in-cylinder pressure signals, it was possible to qualify the severity of the faults whilst averaged acoustic emission signals were in turn, used as the basis for wavelets decomposition. Initial observations from this signal decomposition are also presented and discussed.

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Acoustic emission has been found effective in offering earlier fault detection and improving identification capabilities of faults. However, the sensors are inherently uncalibrated. This paper presents a source to sensor paths calibration technique which can lead to diagnosis of faults in a small size multi-cylinder diesel engine. Preliminary analysis of the acoustic emission (AE) signals is outlined, including time domain, time-frequency domain, and the root mean square (RMS) energy. The results reveal how the RMS energy of a source propagates to the adjacent sensors. The findings lead to allocate the source and estimate its inferences to the adjacent sensor, and finally help to diagnose the small size diesel engines by minimising the crosstalk from multiple cylinders.

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In the past, training in clinical psychology in Australia and overseas has been dominated by definitions of input— hours of classes or supervision and of specific components. While prospective practitioners have been required to demonstrate the acquisition of generic competencies, satisfaction of these input driven criteria has been required for both accreditation and registration. Ironically, for a discipline that prides itself on requiring empirical bases for practice and communicating those to students (Calhoun, Moras, Pilkonis, & Rehm, 1998), training criteria have been primarily derived from accepted wisdom, rather than from a sound body of data. The situation has been remarkably like that of a treatment establishing standards of fidelity before its effective components are known—an action our profession has correctly criticised in the past (Herbert & Mueser, 1992).

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You have chosen to enter a profession that can afford you a wonderfully rich career. It is a role that has many areas of speciality and many opportunities and challenges in communicating with a vast array of people including patients, families, peers, and management. Inherent in the role are all sorts of potential stressors such as not having the equipment you need at a time you think you crucially need it, working with people you find difficult, shift work, lack of staffing, overcrowding, and the list is sometimes seemingly endless. But there are also obvious advantages to your role such as meeting a large variety of people, helping people to recover, to feel comfortable in your care and supporting families, patients and colleagues. This brings me to the two primary points to this chapter. The first point of this chapter is to understand that sometimes the challenges you may face in the health arena overwhelm your initial understanding of your capacity to cope. That is to say, there will likely be times when you feel overwhelmed or even distraught in the face of a particular situation. The second point is that these same overwhelming experiences can provide a catalyst for you to grow as a human being; to develop beyond the person you perceived yourself to be beforehand. According to Aaron Antonovsky (1985), stress is inherent in the human condition, but further to that, in your role, there is a very high possibility of traumatic experiences as well.

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Safety culture is a concept that has long been accepted in high risk industries such as aviation, nuclear industries and mining, however, considerable research is now being undertaken within the construction sector, with varying levels of success. The current paper discusses three recent interlocked projects that have had some success in the Australian construction industry. The first project examined the development and implementation of a safety competency framework targeted at safety critical positions across first tier construction organisations. Combining qualitative and quantitative methods, the project: developed a matrix of safety critical positions (n=11) and safety managements tasks (SMTs; n=39); mapped the process steps for their acquisition and ongoing development; detailed the knowledge, skills and behaviours required for all SMTs; and outlined organisational cultural outcomes that could be anticipated in a successful implementation of the framework. The second project extended research on safety competency and leadership to develop behavioural guidelines for leaders to drive safety culture change down to second tier companies. This was designed to assist smaller construction companies to customise their own competency framework and develop implementation guidelines that match their aspirations and resources. The third interlocked project explored the use of safety effectiveness indicators (SEIs) as an industry-relevant assessment tool for reducing risk on construction sites. With direct linkages to safety competencies and safety management tasks, the SEIs are the next step towards an integrated safety cultural approach to safety and extend the concept of positive performance indicators (PPIs) by providing a valid, reliable, and user friendly measurement platform. Taken together, the results of the interlocked projects suggest that safety culture research has many potential benefits for the construction industry, particularly when research is conducted in partnership with industry stakeholders. Suggestions are made for future research, including further application and testing of the safety competency framework and aligning SEIs across construction projects of varying size, location and design.