Transcriptional regulation of the human ALDH1A1 promoter by the oncogenic homeoprotein TLX1/HOX11

The homeoprotein TLX1, which is essential to spleen organogenesis and oncogenic when aberrantly expressed in immature T cells, functions as a bifunctional transcriptional regulator, being capable of activation or repression depending on cell type and/or promoter context. However, the detailed mechanisms by which it regulates the transcription of target genes such as ALDH1A1 remains to be elucidated. We therefore functionally assessed the ability of TLX1 to regulate ALDH1A1 expression in two hematopoietic cell lines, PER-117 T-leukemic cells and human erythroleukemic (HEL) cells, by use of luciferase reporter and mobility shift assays. We showed that TLX1 physically interacts with the general transcription factor TFIIB via its homeodomain, and identified two activities in respect to TLX1-mediated regulation of the CCAAT box-containing ALDH1A1 promoter. The first involved CCAAT-dependent transcriptional repression via perturbation of GATA factor-containing protein complexes assembled at a non-canonical TATA (GATA) box. A structurally intact homeodomain was essential for repression by TLX1 although direct DNA binding was not required. The second activity, which involved CCAAT-independent transcriptional activation did not require an intact homeodomain, indicating that the activation and repression functions of TLX1 are distinct. These findings confirm ALDH1A1 gene regulation by TLX1 and support an indirect model for TLX1 function, in which protein-protein interactions, rather than DNA binding at specific sites, are crucial for its transcriptional activity

Mechanical behaviour and environmental stability of continuous fibre-reinforced glass-ceramic matrix composites

The mechanical behaviour of three continuous Silicon carbide fibre-reinforced glass-ceramic matrix composites has been investigated at room and high temperatures. Commercially available composites with magnesium aluminosilicate, calcium aluminosilicate and barium magnesium aluminosilicate glass-ceramic matrices were considered. The materials were tested in the as-received and aged (heat-treated in a n oxidizing environment) condition. Four-point bend static tests and fiexural creep, fatigue and creep-fatigue tests were carried out a s well as a small quantity of tensile tests of aged composites. The experimental results have highlighted the importance of the carbon-rich layer at the fibre/matrix interface for obtaining "graceful" failures. At temperatures of 700 to 800 °C oxidative degradation of the interface results in significant strength reduction and a transition to brittle fracture mode. By rapid heat treatment of the materials at 1100°C for 1 h it is possible to seal the fibre ends by forming a silica "plug" which prevents oxygen ingress, retaining the carbon-rich interphase and composite behaviour. The results of the creep and creep-fatigue tests indicate low-cycle loading has a strong influence on the life of components at high temperatures

Transcriptional regulation of the human ALDH1A1 promoter by the oncogenic homeoprotein TLX1/HOX11

The homeoprotein TLX1, which is essential to spleen organogenesis and oncogenic when aberrantly expressed in immature T cells, functions as a bifunctional transcriptional regulator, being capable of activation or repression depending on cell type and/or promoter context. However, the detailed mechanisms by which it regulates the transcription of target genes such as ALDH1A1 remains to be elucidated. We therefore functionally assessed the ability of TLX1 to regulate ALDH1A1 expression in two hematopoietic cell lines, PER-117 T-leukemic cells and human erythroleukemic (HEL) cells, by use of luciferase reporter and mobility shift assays. We showed that TLX1 physically interacts with the general transcription factor TFIIB via its homeodomain, and identified two activities in respect to TLX1-mediated regulation of the CCAAT box-containing ALDH1A1 promoter. The first involved CCAAT-dependent transcriptional repression via perturbation of GATA factor-containing protein complexes assembled at a non-canonical TATA (GATA) box. A structurally intact homeodomain was essential for repression by TLX1 although direct DNA binding was not required. The second activity, which involved CCAAT-independent transcriptional activation did not require an intact homeodomain, indicating that the activation and repression functions of TLX1 are distinct. These findings confirm ALDH1A1 gene regulation by TLX1 and support an indirect model for TLX1 function, in which protein-protein interactions, rather than DNA binding at specific sites, are crucial for its transcriptional activity

Channelled spectrum liquid refractometer

We describe an experimental demonstration of a novel technique for liquid refractometry. A channeled spectrum is produced from an optical beam generated by a diode laser operating below threshold by intercepting half of the beam with a liquid cell. The spectrum is analyzed using a grating and a linear CCD array and provides information on the refractive index of the liquid. The experimental results show that accuracies of better than 0.3% in the index may be obtained with the present method

DESIGNING AND TESTING A PARK-BASED VISITOR SURVEY

This technical report is part of a broader national project ‘Systematic and strategic collection and use of visitor information in protected area management’, funded by Sustainable Tourism Cooperative Research Centre (STCRC), and conducted in partnership with protected area agencies across Australia. The aim of this report is to provide a systematic approach to using a set of core variables to collect data in a way that can be consistently applied across Australian protected areas. This information is most relevant to park-level management, but is also of central interest for corporate reporting. An associated aim was to develop and test a questionnaire for collecting these data. The questionnaire was developed and tested in collaboration with the WA Department of Environment and Conservation (WA DEC) and Parks Australia (PA). Surveys were conducted in Yanchep National Park, a moderately sized peri-urban park managed by WA DEC, in April 2008 and in Booderee National Park, NSW, which encompasses marine features and a botanic garden, and is managed by Parks Australia (PA), in January 2009. In WA following the survey, a focus group was held with staff to obtain their feedback on the efficacy of the questionnaire. The following recommendations are based on statistical analyses of the results, feedback from the focus group, and the observations of the researchers conducting the surveys

Selection for androgen receptor mutations in prostate cancers treated with androgen antagonist

The role of androgen receptor (AR) mutations in androgen-independent prostate cancer (PCa) was determined by examining AR transcripts and genes from a large series of bone marrow metastases. Mutations were found in 5 of 16 patients who received combined androgen blockade with the AR antagonist flutamide, and these mutant ARs were strongly stimulated by flutamide. In contrast, the single mutant AR found among 17 patients treated with androgen ablation monotherapy was not flutamide stimulated. Patients with flutamide-stimulated AR mutations responded to subsequent treatment with bicalutamide, an AR antagonist that blocks the mutant ARs. These findings demonstrate that AR mutations occur in response to strong selective pressure from flutamide treatment

CAD in mammography: lesion-level versus case-level analysis of the effects of prompts on human decisions

Object: To understand decision processes in CAD-supported breast screening by analysing how prompts affect readers’ judgements of individual mammographic features (lesions). To this end we analysed hitherto unexamined details of reports completed by mammogram readers in an earlier evaluation of a CAD tool. Material and methods: Assessments of lesions were extracted from 5,839 reports for 59 cancer cases. Statistical analyses of these data focused on what features readers considered when recalling a cancer case and how readers reacted to CAD prompts. Results: About 13.5% of recall decisions were found to be caused by responses to features other than those indicating actual cancer. Effects of CAD: lesions were more likely to be examined if prompted; the presence of a prompt on a cancer increased the probability of both detection and recall especially for less accurate readers in subtler cases; lack of prompts made cancer features less likely to be detected; false prompts made non-cancer features more likely to be classified as cancer. Conclusion: The apparent lack of impact reported for CAD in some studies is plausibly due to CAD systematically affecting readers’ identification of individual features, in a beneficial way for certain combinations of readers and features and a damaging way for others. Mammogram readers do not ignore prompts. Methodologically, assessing CAD by numbers of recalled cancer cases may be misleading

Mammography Facility Characteristics Associated With Interpretive Accuracy of Screening Mammography

BackgroundAlthough interpretive performance varies substantially among radiologists, such variation has not been examined among mammography facilities. Understanding sources of facility variation could become a foundation for improving interpretive performance.MethodsIn this cross-sectional study conducted between 1996 and 2002, we surveyed 53 facilities to evaluate associations between facility structure, interpretive process characteristics, and interpretive performance of screening mammography (ie, sensitivity, specificity, positive predictive value [PPV1], and the likelihood of cancer among women who were referred for biopsy [PPV2]). Measures of interpretive performance were ascertained prospectively from mammography interpretations and cancer data collected by the Breast Cancer Surveillance Consortium. Logistic regression and receiver operating characteristic (ROC) curve analyses estimated the association between facility characteristics and mammography interpretive performance or accuracy (area under the ROC curve [AUC]). All P values were two-sided.ResultsOf the 53 eligible facilities, data on 44 could be analyzed. These 44 facilities accounted for 484 463 screening mammograms performed on 237 669 women, of whom 2686 were diagnosed with breast cancer during follow-up. Among the 44 facilities, mean sensitivity was 79.6% (95% confidence interval [CI] = 74.3% to 84.9%), mean specificity was 90.2% (95% CI = 88.3% to 92.0%), mean PPV1 was 4.1% (95% CI = 3.5% to 4.7%), and mean PPV2 was 38.8% (95% CI = 32.6% to 45.0%). The facilities varied statistically significantly in specificity (P < .001), PPV1 (P < .001), and PPV2 (P = .002) but not in sensitivity (P = .99). AUC was higher among facilities that offered screening mammograms alone vs those that offered screening and diagnostic mammograms (0.943 vs 0.911, P = .006), had a breast imaging specialist interpreting mammograms vs not (0.932 vs 0.905, P = .004), did not perform double reading vs independent double reading vs consensus double reading (0.925 vs 0.915 vs 0.887, P = .034), or conducted audit reviews two or more times per year vs annually vs at an unknown frequency (0.929 vs 0.904 vs 0.900, P = .018).ConclusionMammography interpretive performance varies statistically significantly by facility

Pressing ahead: developing and testing of new measures in implementation science

Measurement forms the foundation of any scientific field; yet, systematic reviews reveal that many available measures of implementation context, process, and outcomes lack reliability or validity. An urgent need exists for psychometrically strong measures in implementation science; without them, the field cannot produce cumulative knowledge about implementation barriers, facilitators, processes, or generate sound evidence about which implementation strategies work best, when, and for whom. In this panel session, three researchers reported on their efforts to develop and test new measures of constructs featured in the Consolidated Framework for Implementation Research (CFIR). Maria Fernandez described the work of the CDC/NCI-funded Cancer Prevention and Control Research Network to create measures for seven constructs in the inner-setting domain of CFIR and assess the psychometric properties of those measures using data from a multi-state sample of community health centers. Shuting Liang reported on the Network’s effort to develop and assess measures of selected constructs in other CFIR domains and discussed the inter-relationships of these constructs at both the individual and clinic level of analysis. Sara Jacobs explored in two different study contexts the psychometric properties of, and measurement issues associated with, a new theory-based measure of implementation climate. Building on the presentations, Stephen Taplin moderated a discussion between panelists and participants about the role of theory in measurement, the challenges of adapting existing measures, the implications of item-wording choices, the effects of context on measurement properties, and the measurement of organization-level constructs using individual-level data. Participants learned about new measures they could use in their own research; in addition, they engaged in dialogue about needs, opportunities, challenges, and recommended practices in measurement in implementation scienc

Observations of red-giant variable stars by Aboriginal Australians

Aboriginal Australians carefully observe the properties and positions of stars, including both overt and subtle changes in their brightness, for subsistence and social application. These observations are encoded in oral tradition. I examine two Aboriginal oral traditions from South Australia that describe the periodic changing brightness in three pulsating, red-giant variable stars: Betelgeuse (Alpha Orionis), Aldebaran (Alpha Tauri), and Antares (Alpha Scorpii). The Australian Aboriginal accounts stand as the only known descriptions of pulsating variable stars in any Indigenous oral tradition in the world. Researchers examining these oral traditions over the last century, including anthropologists and astronomers, missed the description of these stars as being variable in nature as the ethnographic record contained several misidentifications of stars and celestial objects. Arguably, ethnographers working on Indigenous Knowledge Systems should have academic training in both the natural and social sciences.Comment: The Australian Journal of Anthropology (2018