Differential substrate behaviours of ethylene oxide and propylene oxide towards human glutathione transferase theta hGSTT1-1

The transformation of ethylene oxide (EO), propylene oxide (PO) and 1- butylene oxide (1-BuO) by human glutathione transferase theta (hGSTT1-1) was studied comparatively using 'conjugator' (GSTT1 + individuals) erythrocyte lysates. The relative sequence of velocity of enzymic transformation was PO > EO >> 1-BuO. The faster transformation of PO compared to EO was corroborated in studies with human and rat GSTT1-1 (hGSTT1-1 and rGSTT1-1, respectively) expressed by Salmonella typhimurium TA1535. This sequence of reactivities of homologous epoxides towards GSTT1-1 contrasts to the sequence observed in homologous alkyl halides (methyl bromide, MBr; ethyl bromide, EtBr; n-propyl bromide, PrBr) where the relative sequence MeBr >> EtBr > PrBr is observed. The higher reactivity towards GSTT1-1 of propylene oxide compared to ethylene oxide is consistent with a higher chemical reactivity. This is corroborated by experimental data of acid-catalysed hydrolysis of a number of aliphatic epoxides, including ethylene oxide and propylene oxide and consistent with semi-empirical molecular orbital modelings.

Differential effects of monotony versus fatigue on driving performance and the effectiveness of various detection methods : implications for road safety in the ACT

Background Situational driving factors, including fatigue, distraction, inattention and monotony, are recognised killers in Australia, contributing to an estimated 40% of fatal crashes and 34% of all crashes . More often than not the main contributing factor is identified as fatigue, yet poor driving performance has been found to emerge early in monotonous conditions, independent of fatigue symptoms and time on task. This early emergence suggests an important role for monotony. However, much road safety research suggests that monotony is solely a task characteristic that directly causes fatigue and associated symptoms and there remains an absence of consistent evidence explaining the relationship. Objectives We report an experimental study designed to disentangle the characteristics and effects of monotony from those associated with fatigue. Specifically, we examined whether poor driving performance associated with hypovigilance emerges as a consequence of monotony, independent of fatigue. We also examined whether monotony is a multidimensional construct, determined by environmental characteristics and/or task demands that independently moderate sustained attention and associated driving performance. Method Using a driving simulator, participants completed four, 40 minute driving scenarios. The scenarios varied in the degree of monotony as determined by the degree of variation in road design (e.g., straight roads vs. curves) and/or road side scenery. Fatigue, as well as a number of other factors known to moderate vigilance and driving performance, was controlled for. To track changes across time, driving performance was assessed in five minute time periods using a range of behavioural, subjective and physiological measures, including steering wheel movements, lane positioning, electroencephalograms, skin conductance, and oculomotor activity. Results Results indicate that driving performance is worse in monotonous driving conditions characterised by low variability in road design. Critically, performance decrements associated with monotony emerge very early, suggesting monotony effects operate independent of fatigue. Conclusion Monotony is a multi-dimensional construct where, in a driving context, roads containing low variability in design are monotonous and those high in variability are non-monotonous. Importantly, low variability in road side scenery does not appear to exacerbate monotony or associated poor performance. However, high variability in road side scenery can act as a distraction and impair sustained attention and poor performance when driving on monotonous roads. Furthermore, high sensation seekers seem to be more susceptible to distraction when driving on monotonous roads. Implications of our results for the relationship between monotony and fatigue, and the possible construct-specific detection methods in a road safety context, will be discussed.

Standard business reporting in Australia : efficiency, effectiveness, or both?

The benefits of using eXtensible Business Reporting Language (XBRL) as a business reporting standard have been widely canvassed in the extant literature, in particular, as the enabling technology for standard business reporting tools. One of the key benefits noted is the ability of standard business reporting to create significant efficiencies in the regulatory reporting process. Efficiency-driven cost reductions are highly desirable by data and report producers. However, they may not have the same potential to create long-term firm value as improved effectiveness of decision making. This study assesses the perceptions of Australian business stakeholders in relation to the benefits of the Australian standard business reporting instantiation (SBR) for financial reporting. These perceptions were drawn from interviews of persons knowledgeable in XBRL-based standard business reporting and submissions to Treasury relative to SBR reporting options. The combination of interviews and submissions permit insights into the views of various groups of stakeholders in relation to the potential benefits. In line with predictions based on a transaction-cost economics perspective, interviewees who primarily came from a data and report-producer background mentioned benefits that centre largely on asset specificity and efficiency. The interviewees who principally came from a data and report-consumer background mentioned benefits that centre on reducing decision-making uncertainty and decision-making effectiveness. The data and report consumers also took a broader view of the benefits of SBR to the financial reporting supply chain. Our research suggests that advocates of SBR have successfully promoted its efficiency benefits to potential users. However, the effectiveness benefits of SBR, for example, the decision-making benefits offered to investors via standardised reports, while becoming more broadly acknowledged, remain not a priority for all stakeholders.

Optimal HMM filtering and decision feedback equalisation for differential encoded transmission systems

In this paper conditional hidden Markov model (HMM) filters and conditional Kalman filters (KF) are coupled together to improve demodulation of differential encoded signals in noisy fading channels. We present an indicator matrix representation for differential encoded signals and the optimal HMM filter for demodulation. The filter requires O(N3) calculations per time iteration, where N is the number of message symbols. Decision feedback equalisation is investigated via coupling the optimal HMM filter for estimating the message, conditioned on estimates of the channel parameters, and a KF for estimating the channel states, conditioned on soft information message estimates. The particular differential encoding scheme examined in this paper is differential phase shift keying. However, the techniques developed can be extended to other forms of differential modulation. The channel model we use allows for multiplicative channel distortions and additive white Gaussian noise. Simulation studies are also presented.

Differential effects of refractive blur on day and night-time driving performance

Purpose To investigate the effect of different levels of refractive blur on real-world driving performance measured under day and nighttime conditions. Methods Participants included 12 visually normal, young adults (mean age = 25.8 ± 5.2 years) who drove an instrumented research vehicle around a 4 km closed road circuit with three different levels of binocular spherical refractive blur (+0.50 diopter sphere [DS], +1.00 DS, +2.00 DS) compared with a baseline condition. The subjects wore optimal spherocylinder correction and the additional blur lenses were mounted in modified full-field goggles; the order of testing of the blur conditions was randomized. Driving performance was assessed in two different sessions under day and nighttime conditions and included measures of road signs recognized, hazard detection and avoidance, gap detection, lane-keeping, sign recognition distance, speed, and time to complete the course. Results Refractive blur and time of day had significant effects on driving performance (P < 0.05), where increasing blur and nighttime driving reduced performance on all driving tasks except gap judgment and lane keeping. There was also a significant interaction between blur and time of day (P < 0.05), such that the effects of blur were exacerbated under nighttime driving conditions; performance differences were evident even for +0.50 DS blur relative to baseline for some measures. Conclusions The effects of blur were greatest under nighttime conditions, even for levels of binocular refractive blur as low as +0.50 DS. These results emphasize the importance of accurate and up-to-date refractive correction of even low levels of refractive error when driving at night.

The varied presentation of metastatic melanoma in fine needle aspiration cytology of the breast

Objective To identify cytomorphological patterns of metastatic melanoma (MM) in breast fine needle aspiration (FNA) specimens and highlight the differential diagnoses and features most useful in identifying MM. Methods The clinical, radiological and FNA findings of 16 cases were reviewed. Cytological features evaluated related to cell arrangement, size and shape of cells, nuclear and cytoplasmic features, and the presence or absence of necrosis. Results The series consisted of 14 females and two males, ranging in age from 24 to 83 years (mean = 50 years). A previous history of melanoma was available in 12/16 (75%) cases at the time of FNA reporting; however the clinical/radiological impression in 4/16 cases was of a breast cyst. The cases were classified into six morphological variants: classical (8/16), pseudopapillary (3/16), spindle-cell (1/16), melanin-rich (1/16), pleomorphic (2/16) and lymphoma-like (1/16). The varying patterns raised a wide range of differential diagnoses; however, discohesion, binucleation and granular cytoplasm were the major features seen in 94% of all cases. In 14/16 cases (88%), plasmacytoid cells, prominent nucleoli and cytoplasmic vacuolation were identified. Melanin and multinucleation were detected in 44% of cases and intranuclear cytoplasmic invaginations in 63%. Necrosis was present in more than half of the cases (56%). Conclusion MM should be considered in the differential diagnosis of breast FNA specimens when atypical cells are seen that present as plasmacytoid cells in a dispersed or pseudopapillary pattern, or as spindle, pleomorphic or pigmented cells. These features, combined with clinical history and immunocytochemistry, may assist in correctly identifying MM and directing optimal treatment.

Differential effects of tissue culture coating substrates on prostate cancer cell adherence, morphology and behavior

Weak cell-surface adhesion of cell lines to tissue culture surfaces is a common problem and presents technical limitations to the design of experiments. To overcome this problem, various surface coating protocols have been developed. However, a comparative and precise real-time measurement of their impact on cell behavior has not been conducted. The prostate cancer cell line LNCaP, derived from a patient lymph node metastasis, is a commonly used model system in prostate cancer research. However, the cells’ characteristically weak attachment to the surface of tissue culture vessels and cover slips has impeded their manipulation and analysis and use in high throughput screening. To improve the adherence of LNCaP cells to the culture surface, we compared different coating reagents (poly-L-lysine, poly-L-ornithine, collagen type IV, fibronectin, and laminin) and culturing conditions and analyzed their impact on cell proliferation, adhesion, morphology, mobility and gene expression using real-time technologies. The results showed that fibronectin, poly-L-lysine and poly-L-ornithine improved LNCaP cells adherence and provoked cell morphology alterations, such as increase of nuclear and cellular area. These coating reagents also induced a higher expression of F-actin and reduced cell mobility. In contrast, laminin and collagen type IV did not improve adherence but promoted cell aggregation and affected cell morphology. Cells cultured in the presence of laminin displayed higher mobility than control cells. All the coating conditions significantly affected cell viability; however, they did not affect the expression of androgen receptor-regulated genes. Our comparative findings provide important insight for the selection of the ideal coating reagent and culture conditions for the cancer cell lines with respect to their effect on proliferation rate, attachment, morphology, migration, transcriptional response and cellular cytoskeleton arrangement.

Characterization of acyl chain position in unsaturated phosphatidylcholines using differential mobility-mass spectrometry

Glycerophospholipids (GPs) that differ in the relative position of the two fatty acyl chains on the glycerol backbone (i.e., sn-positional isomers) can have distinct physicochemical properties. The unambiguous assignment of acyl chain position to an individual GP represents a significant analytical challenge. Here we describe a workflow where phosphatidylcholines (PCs) are subjected to ESI for characterization by a combination of differential mobility spectrometry and MS (DMS-MS). When infused as a mixture, ions formed from silver adduction of each phospholipid isomer {e.g., [PC (16:0/18:1) + Ag]+ and [PC (18:1/16:0) + Ag]+} are transmitted through the DMS device at discrete compensation voltages. Varying their relative amounts allows facile and unambiguous assignment of the sn-positions of the fatty acyl chains for each isomer. Integration of the well-resolved ion populations provides a rapid method (< 3 min) for relative quantification of these lipid isomers. The DMS-MS results show excellent agreement with established, but time-consuming, enzymatic approaches and also provide superior accuracy to methods that rely on MS alone. The advantages of this DMS-MS method in identification and quantification of GP isomer populations is demonstrated by direct analysis of complex biological extracts without any prior fractionation.