Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

Background: Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results: Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion: The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in this response.

A novel scheme for human-friendly and time-delays robust neuropredictive teleoperation

A novel Neuropredictive Teleoperation (NPT) Scheme is presented. The design results from two key ideas: the exploitation of the measured or estimated neural input to the human arm or its electromyograph (EMG) as the system input and the employment of a predictor of the arm movement, based on this neural signal and an arm model, to compensate for time delays in the system. Although a multitude of such models, as well as measuring devices for the neural signals and the EMG, have been proposed, current telemanipulator research has only been considering highly simplified arm models. In the present design, the bilateral constraint that the master and slave are simultaneously compliant to each other's state (equal positions and forces) is abandoned, thus obtaining a simple to analyzesuccession of only locally controlled modules, and a robustness to time delays of up to 500 ms. The proposed designs were inspired by well established physiological evidence that the brain, rather than controlling the movement on-line, programs the arm with an action plan of a complete movement, which is then executed largely in open loop, regulated only by local reflex loops. As a model of the human arm the well-established Stark model is employed, whose mathematical representation is modified to make it suitable for an engineering application. The proposed scheme is however valid for any arm model. BIBO-stability and passivity results for a variety of local control laws are reported. Simulation results and comparisons with traditional designs also highlight the advantages of the proposed design.

Temporal relations of column water vapor and tropical precipitation

Empirical studies using satellite data and radiosondes have shown that precipitation increases with column water vapor (CWV) in the tropics, and that this increase is much steeper above some critical CWV value. Here, eight years of 1-min-resolution microwave radiometer and optical gauge data at Nauru Island are analyzed to better understand the relationships among CWV, column liquid water (CLW), and precipitation at small time scales. CWV is found to have large autocorrelation times compared with CLW and precipitation. Before precipitation events, CWV increases on both a synoptic-scale time period and a subsequent shorter time period consistent with mesoscale convective activity; the latter period is associated with the highest CWV levels. Probabilities of precipitation increase greatly with CWV. Given initial high CWV, this increased probability of precipitation persists at least 10–12 h. Even in periods of high CWV, however, probabilities of initial precipitation in a 5-min period remain low enough that there tends to be a lag before the start of the next precipitation event. This is consistent with precipitation occurring stochastically within environments containing high CWV, with the latter being established by a combination of synoptic-scale and mesoscale forcing.

Spatial and temporal effects of free-air CO2 enrichment (POPFACE) on leaf growth, cell expansion and cell production in a closed canopy of poplar

Leaf expansion in the fast-growing tree,Populus × euramericana was stimulated by elevated [CO2] in a closed-canopy forest plantation, exposed using a free air CO2 enrichment technique enabling long-term experimentation in field conditions. The effects of elevated [CO2] over time were characterized and related to the leaf plastochron index (LPI), and showed that leaf expansion was stimulated at very early (LPI, 0–3) and late (LPI, 6–8) stages in development. Early and late effects of elevated [CO2] were largely the result of increased cell expansion and increased cell production, respectively. Spatial effects of elevated [CO2] were also marked and increased final leaf size resulted from an effect on leaf area, but not leaf length, demonstrating changed leaf shape in response to [CO2]. Leaves exhibited a basipetal gradient of leaf development, investigated by defining seven interveinal areas, with growth ceasing first at the leaf tip. Interestingly, and in contrast to other reports, no spatial differences in epidermal cell size were apparent across the lamina, whereas a clear basipetal gradient in cell production rate was found. These data suggest that the rate and timing of cell production was more important in determining leaf shape, given the constant cell size across the leaf lamina. The effect of elevated [CO2] imposed on this developmental gradient suggested that leaf cell production continued longer in elevated [CO2] and that basal increases in cell production rate were also more important than altered cell expansion for increased final leaf size and altered leaf shape in elevated [CO2].

Generic unified modelling process for developing semantically rich, dynamic and temporal models

Models play a vital role in supporting a range of activities in numerous domains. We rely on models to support the design, visualisation, analysis and representation of parts of the world around us, and as such significant research effort has been invested into numerous areas of modelling; including support for model semantics, dynamic states and behaviour, temporal data storage and visualisation. Whilst these efforts have increased our capabilities and allowed us to create increasingly powerful software-based models, the process of developing models, supporting tools and /or data structures remains difficult, expensive and error-prone. In this paper we define from literature the key factors in assessing a model’s quality and usefulness: semantic richness, support for dynamic states and object behaviour, temporal data storage and visualisation. We also identify a number of shortcomings in both existing modelling standards and model development processes and propose a unified generic process to guide users through the development of semantically rich, dynamic and temporal models.

Temporal-envelope constancy of speech in rooms and the perceptual weighting of frequency bands

Three experiments measured constancy in speech perception, using natural-speech messages or noise-band vocoder versions of them. The eight vocoder-bands had equally log-spaced center-frequencies and the shapes of corresponding “auditory” filters. Consequently, the bands had the temporal envelopes that arise in these auditory filters when the speech is played. The “sir” or “stir” test-words were distinguished by degrees of amplitude modulation, and played in the context; “next you’ll get _ to click on.” Listeners identified test-words appropriately, even in the vocoder conditions where the speech had a “noise-like” quality. Constancy was assessed by comparing the identification of test-words with low or high levels of room reflections across conditions where the context had either a low or a high level of reflections. Constancy was obtained with both the natural and the vocoded speech, indicating that the effect arises through temporal-envelope processing. Two further experiments assessed perceptual weighting of the different bands, both in the test word and in the context. The resulting weighting functions both increase monotonically with frequency, following the spectral characteristics of the test-word’s [s]. It is suggested that these two weighting functions are similar because they both come about through the perceptual grouping of the test-word’s bands.

Modeling data with structural and temporal correlation using lower level and higher level multilevel models

Novel imaging techniques are playing an increasingly important role in drug development, providing insight into the mechanism of action of new chemical entities. The data sets obtained by these methods can be large with complex inter-relationships, but the most appropriate statistical analysis for handling this data is often uncertain - precisely because of the exploratory nature of the way the data are collected. We present an example from a clinical trial using magnetic resonance imaging to assess changes in atherosclerotic plaques following treatment with a tool compound with established clinical benefit. We compared two specific approaches to handle the correlations due to physical location and repeated measurements: two-level and four-level multilevel models. The two methods identified similar structural variables, but higher level multilevel models had the advantage of explaining a greater proportion of variation, and the modeling assumptions appeared to be better satisfied.

Spatial and temporal modeling of community non-timber forest extraction

This paper examines the interaction of spatial and dynamic aspects of resource extraction from forests by local people. Highly cyclical and varied across space and time, the patterns of resource extraction resulting from the spatial–temporal model bear little resemblance to the patterns drawn from focusing either on spatial or temporal aspects of extraction alone. Ignoring this variability inaccurately depicts villagers’ dependence on different parts of the forest and could result in inappropriate policies. Similarly, the spatial links in extraction decisions imply that policies imposed in one area can have unintended consequences in other areas. Combining the spatial–temporal model with a measure of success in community forest management—the ability to avoid open-access resource degradation—characterizes the impact of incomplete property rights on patterns of resource extraction and stocks.