Neuronal microRNA eeregulation in response to Alzheimer's disease Amyloid-β

Normal brain development and function depends on microRNA (miRNA) networks to fine tune the balance between the transcriptome and proteome of the cell. These small non-coding RNA regulators are highly enriched in brain where they play key roles in neuronal development, plasticity and disease. In neurodegenerative disorders such as Alzheimer's disease (AD), brain miRNA profiles are altered; thus miRNA dysfunction could be both a cause and a consequence of disease. Our study dissects the complexity of human AD pathology, and addresses the hypothesis that amyloid-beta (Abeta) itself, a known causative factor of AD, causes neuronal miRNA deregulation, which could contribute to the pathomechanisms of AD. We used sensitive TaqMan low density miRNA arrays (TLDA) on murine primary hippocampal cultures to show that about half of all miRNAs tested were down-regulated in response to Abeta peptides. Time-course assays of neuronal Abeta treatments show that Abeta is in fact a powerful regulator of miRNA levels as the response of certain mature miRNAs is extremely rapid. Bioinformatic analysis predicts that the deregulated miRNAs are likely to affect target genes present in prominent neuronal pathways known to be disrupted in AD. Remarkably, we also found that the miRNA deregulation in hippocampal cultures was paralleled in vivo by a deregulation in the hippocampus of Abeta42-depositing APP23 mice, at the onset of Abeta plaque formation. In addition, the miRNA deregulation in hippocampal cultures and APP23 hippocampus overlaps with those obtained in human AD studies. Taken together, our findings suggest that neuronal miRNA deregulation in response to an insult by Abeta may be an important factor contributing to the cascade of events leading to AD.N.S. is supported by the Human Frontier Science Program. L.I. is supported by the National Health and Medical Research Council (NHMRC) and the Australian Research Council (ARC), and J.G. is supported by grants from the University of Sydney, the National Health and Medical Research Council (NHMRC), the Australian Research Council (ARC), and the J.O. & J.R. Wicking Trust. Postgraduate scholarship support has been provided by the Wenkart Foundation, GlaxoSmithKline and Alzheimer’s Australia

Dual wavelength heterodyne interferometry for rough surface measurements

For interferometric topography measurements of optically rough surfaces dual wavelength heterodyne Interferometry (DWHI) is a powerful tool. A DWHI system based on a two-wavelength HeNe laser and a matched grating technique is described. This set-up improves system stability and simple heterodyne frequency generation

Two-wavelength double heterodyne interferometry using a matched grating technique

Two-wavelength double heterodyne interferometry is applied for topographic measurements on optically rough target surfaces. A two-wavelength He-Ne laser and a matched grating technique are used to improve system stability and to simplify heterodyne frequency generation

Dual wavelength heterodyne interferometry using a matched grating set-up

Two-wavelength double heterodyne interferometry is applied for topographic measurements on rough target surfaces. A two-wavelength HeNe laser and a matched grating technique are used to improve system stability and to simplify heterodyne frequency generation. Results obtained with an experimental set-up will be presented. The results obtained show that a dual wavelength heterodyne interferometer is appropriate for high precision ranging. Progressing developments for large distances will be discussed

Two wavelength heterodyne absolute ranging technique using suppressed carrier modulation

For interferometric distance measurements on rough surfaces multiple wavelength interferometry is a powerful tool. It allows to reduce the sensitivity and to extend the range of unambiguity for interferometric measurement. A new kind of a double wavelength heterodyne interferometer is presented which uses only one laser source which generates two wavelengths λ 1 and λ 2 simultaneously. The two different heterodyne frequency shifts of the double heterodyne interferometer (DHI) are achieved by combining an acousto-optical modulator (driven in suppressed carrier mode) with a fixed diffraction grating. In a first prototype a multi-wavelength HeNe laser was used as light source. The synthetic wavelength λ in this system is 55.5 μm and the resolution about 0.15 μm. Measurement results obtained with the setup described are presented

Exposure to ambient air pollutants and acute respiratory distress syndrome risk in sepsis.

PURPOSE: Exposures to ambient air pollutants may prime the lung enhancing risk of acute respiratory distress syndrome (ARDS) in sepsis. Our objective was to determine the association of short-, medium-, and long-term pollutant exposures and ARDS risk in critically ill sepsis patients. METHODS: We analyzed a prospective cohort of 1858 critically ill patients with sepsis, and estimated short- (3 days), medium- (6 weeks), and long- (5 years) term exposures to ozone, nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO), particulate matter < 2.5 μm (PM2.5), and PM < 10 μm (PM10) using weighted averages of daily levels from monitors within 50 km of subjects residences. Subjects were followed for 6 days for ARDS by the Berlin Criteria. The association between each pollutant and ARDS was determined using multivariable logistic regression adjusting for preselected confounders. In 764 subjects, we measured plasma concentrations of inflammatory proteins at presentation and tested for an association between pollutant exposure and protein concentration via linear regression. RESULTS: ARDS developed in 754 (41%) subjects. Short- and long-term exposures to SO2, NO2, and PM2.5 were associated with ARDS risk (SO2: odds ratio (OR) for the comparison of the 75-25th long-term exposure percentile 1.43 (95% confidence interval (CI) 1.16, 1.77); p < 0.01; NO2: 1.36 (1.06, 1.74); p = 0.04, PM2.5: 1.21 (1.04, 1.41); p = 0.03). Long-term exposures to these three pollutants were also associated with plasma interleukin-1 receptor antagonist and soluble tumor necrosis factor receptor-1 concentrations. CONCLUSION: Short and long-term exposures to ambient SO2, PM2.5, and NO2 are associated with increased ARDS risk in sepsis, representing potentially modifiable environmental risk factors for sepsis-associated ARDS

Colloquium on Solid State Devices

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A Knowledge Framework Underlying Process Management

Organizations are increasingly implementing process-improvement techniques like Six Sigma, total quality management, lean, and business process re-engineering to improve organizational performance. These techniques are part of a process management system that includes the organizational infrastructure to support the improvement techniques. The knowledge-based view of a firm argues that organizational knowledge is the source of competitive advantage. To the extent that the process management system enables knowledge creation it should be a source of competitive advantage. This study investigates the underlying framework and factors of a process management system that lead to organizational knowledge creation. Prior studies have considered knowledge creation in process improvement, but none have considered the role of the process management system. Specifically, the study uses the case study method to investigate multiple levels (organization level and project level) of two firms using Six Sigma as their chosen process management system. Analysis of the cases reveals that the leadership creates a supportive infrastructure enabling process- improvement techniques to effectively create organizational knowledge. Interestingly, focusing on decision-making tools and methods may not be effective without developing a supportive infrastructure. The proposed framework provides a basis for organizational leaders to think about how to design and implement a process management system to better enable knowledge creation in organizations

The future of interpretive accounting research:A Polyphonic Debate

In 1997-99 the three of us organised a series of European Commission funded conferences aimed at building a network of young researchers in the area of accounting. At the time “young” was defined by the Commission as researchers under 35 years of age (allowing for maternity leave or national service). Over the intervening years our network had grown and we wanted to try and take stock of the field in which we had now been working for a surprising number of years. To that Page 1 of 29 Accepted Manuscript 2 end we put together the above email and a broad invitation list of people who had been at those first meetings, and others of the same generation (or even younger) whom we had met since. About half of those originally contacted managed to make the meeting where we spent a stimulating couple of hours of debate on the topics raised below—so stimulating that we developed a collective desire to leave a trace of the discussion. Writing a traditional paper with so many, so widely dispersed authors was not going to work. Instead we came up with a different form of collective writing that mirrored the original debate, and that might contribute to ongoing debates in this journal concerning the nature and status of our research (e.g. Arrington, 2004; Inanga & Schneider, 2005; Macintosh, 2004). We agreed a process in which each of us in turn would have one week to add a target of 300 words to a rolling document, going through the contributors alphabetically. After two rounds we would see what we had got

The Influence of a Firms\u27 Business Strategy on the Downside Risk of Earnings, Accruals and Cash Flow

This study examines whether a firm\u27s business strategy is an underlying determinant of downside risk in accounting earnings and its components. Based on organizational theory we predict that firms following an innovative prospector strategy exhibit lower profitability tendencies than firms following a cost-oriented defender strategy. Further, we anticipate that these strategies are asymmetrically positioned towards environmental uncertainty, with defenders focusing their efforts to efficiency, cost control, and minimizing exposure to downside risk, whereas prospectors direct their resources to flexibility, innovation, and maximizing the growth potential through aggressive expansion to new product markets. We find that prospectors are indeed less profitable than defenders. We also demonstrate that prospectors have greater total and downside earnings risk. Finally, we decompose earnings into accruals and cash flow and show that the higher exposure of prospectors to earnings downside risk is driven by the cash flow component rather than the accrual component. Collectively, our results suggest that considering how strategy interacts with financial reporting attributes is a useful way for evaluating a firms\u27 risk profile