The effect of two distinct fast time scales in the rotating, stratified Boussinesq equations: variations from quasi-geostrophy

This is the author accepted manuscript. The final version is available from Springer via the DOI in this record.Inspired by the use of fast singular limits in time-parallel numerical methods for a single fast frequency, we consider the limiting, nonlinear dynamics for a system of partial differential equations when two fast, distinct time scales are present. First order slow equations are derived via the method of multiple time scales when the two small parameters are related by a rational power. We find that the resultant system depends only on the relationship of the two fast time-scales, i.e. which fast time is fastest? Using the theory of cancellation of fast oscillations, we show that with the appropriate assumptions on the nonlinear operator of the full system, this reduced slow system is exactly that which the solution will converge to if each asymptotic limit is considered sequentially. The same result is also obtained via the method of renormalization. The specific example of the rotating, stratified Boussinesq equations is explored in detail, indicating that the most common distinguished limit of this system – quasi-geostrophy, is not the only limiting asymptotic system.We wish to thank the 2 anonymous referees whose comments significantly enhanced the presentation and scope of this article. J. P. W. would like to thank A.Larios, K. Julien, G. Chini, and A. Farhat for various discussions that prompted and motivated this work as well as generous support from the Mathematics Department of Brigham Young University. All of the authors wish to acknowledge the DOE LANL/LDRD program for support, as well as the hospitality of the Courant Institute of New York University where some of this work was completed. Wingate also wishes to thank the University of Exeter for support during the completion of this manuscript

High-affinity tamoxifen analogues retain extensive positional disorder when bound to calmodulin

Using a combination of NMR and fluorescence measurements, we have investigated the structure and dynamics of the complexes formed between calcium-loaded calmodulin (CaM) and the potent breast cancer inhibitor idoxifene, a derivative of tamoxifen. High-affinity binding (Kd∼300 nM) saturates with a 2:1 idoxifene:CaM complex. The complex is an ensemble where each idoxifene molecule is predominantly in the vicinity of one of the two hydrophobic patches of CaM but, in contrast with the lower-affinity antagonists TFP, J-8, and W-7, does not substantially occupy the hydrophobic pocket. At least four idoxifene orientations per domain of CaM are necessary to satisfy the intermolecular nuclear Overhauser effect (NOE) restraints, and this requires that the idoxifene molecules switch rapidly between positions. The CaM molecule is predominantly in the form where the N and C-terminal domains are in close proximity, allowing for the idoxifene molecules to contact both domains simultaneously. Hence, the 2:1 idoxifene:CaM complex illustrates how high-affinity binding occurs without the loss of extensive positional dynamics

Screening for coping style increases the power of gene expression studies

Background: Individuals of many vertebrate species show different stress coping styles and these have a striking influence on how gene expression shifts in response to a variety of challenges. Principal Findings: This is clearly illustrated by a study in which common carp displaying behavioural predictors of different coping styles (characterised by a proactive, adrenaline-based or a reactive, cortisol-based response) were subjected to inflammatory challenge and specific gene transcripts measured in individual brains. Proactive and reactive fish differed in baseline gene expression and also showed diametrically opposite responses to the challenge for 80% of the genes investigated. Significance: Incorporating coping style as an explanatory variable can account for some the unexplained variation that is common in gene expression studies, can uncover important effects that would otherwise have passed unnoticed and greatly enhances the interpretive value of gene expression data

Differential signaling to glycogen synthesis by the intracellular domain of the insulin versus the insulin-like growth factor-1 receptor

Insulin and insulin-like growth factor-1 (IGF-1) have similar cell-surface receptors yet subserve different physiological functions, To examine whether these differences relate to intrinsic signaling properties of the intracellular domains of their respective receptors, chimeric receptors were constructed using the extracellular domain of the neurotrophin-3 (NT-3) receptor, TrkC, and the intracellular domain of either the insulin receptor or the IGF-1 receptor, TrkC-IR (TIR) and TrkC-IGF-1R (TIGR) were stably expressed in 3T3-L1 cells, While TIR and TIGR cell lines expressing similar numbers of chimeric receptors showed a similar dose-response relationship in NT-3 stimulated DNA synthesis, NT-3 stimulated glycogen synthesis was greater in TIR than in TIGR cells (maximum TIGR response was 35% of maximum TIR response), Additionally, the concentration of NT-3 at which significant stimulation of glycogen synthesis was seen was 0.1 ng/ml in TIR and 1 ng/ml in TIGR cells, Basal levels of thymidine incorporation but not glycogen synthesis were consistently higher in TIR than in TIGR expressing cells, No detectable basal autophosphorylation of chimeric receptors was seen in any of the cell lines, However, exposure of cell lines to the phosphatase inhibitor bisperoxovanadate resulted in greater basal autophosphorylation of the TIR and endogenous murine IR than the TIGR and endogenous murine IGF-1R. Thus, in this system, the intracellular domain of the IR appears to couple more effectively to glycogen synthesis than that of the IGF-1R, whereas the intracellular domains of both receptors have a similar capacity to stimulate DNA synthesis

Carbon stable isotope analysis of cereal remains as a way to reconstruct water availability: preliminary results

Reconstructing past water availability, both as rainfall and irrigation, is important to answer questions about the way society reacts to climate and its changes and the role of irrigation in the development of social complexity. Carbon stable isotope analysis of archaeobotanical remains is a potentially valuable method for reconstructing water availability. To further define the relationship between water availability and plant carbon isotope composition and to set up baseline values for the Southern Levant, grains of experimentally grown barley and sorghum were studied. The cereal crops were grown at three stations under five different irrigation regimes in Jordan. Results indicate that a positive but weak relationship exists between irrigation regime and total water input of barley grains, but no relationship was found for sorghum. The relationship for barley is site-specific and inter-annual variation was present at Deir ‘Alla, but not at Ramtha and Khirbet as-Samra

An Integrated Approach Providing Scientific and Policy-Relevant Insights for South-West Bangladesh

Bangladesh is identified as an impact hotspot for sea-level rise in multiple studies. However, a range of other factors must be considered including catchment management, socio-economic development and governance quality, as well as delta plain biophysical processes. Taking an integrated assessment approach highlights that to 2050 future changes are more sensitive to human choice/policy intervention than climate change, ecosystem services diminish as a proportion of the economy with time, continuing historic trends and significant poverty persists for some households. Hence under favourable policy decisions, development could transform Bangladesh by 2050 making it less vulnerable to longer-term climate change and subsidence. Beyond 2050, the threats of climate change are much larger, requiring strategic adaptation responses and policy changes that must be initiated now

Technical Analysis of cDNA Microarrays

Background: There is extensive variation in gene expression among individuals within and between populations. Accurate measures of the variation in mRNA expression using microarrays can be confounded by technical variation, which includes variation in RNA isolation procedures, day of hybridization and methods used to amplify and dye label RNA for hybridization. Methodology/Principal Findings: In this manuscript we analyze the relationship between the amount of mRNA and the fluorescent signal from the microarray hybridizations demonstrating that for a wide-range of mRNA concentrations the fluorescent signal is a linear function of the amount of mRNA. Additionally, the separate isolation, labeling or hybridization of RNA does not add significant amounts of variation in microarray measures of gene expression. However, single or double rounds of amplification for labeling do have small but significant affects on 10 % of genes, but this source of technical variation is easy to avoid. To examine both technical and stochastic biological variation, mRNA expression was measured from the same five individuals over a six-week time course. Conclusion: There were few, if any, meaningful differences in gene expression among time points. Thus, microarray measures using standard laboratory procedures can be precise and quantitative and are not subject to significant rando

Differences in signaling properties of the cytoplasmic domains of the insulin receptor and insulin-like growth factor receptor in 3T3-L1 adipocytes

Insulin and insulin-like growth factors (IGFs) elicit distinct but overlapping biological effects in vivo. To investigate whether differences in intrinsic signaling capacity of receptors contribute to biological specificity, we constructed chimeric receptors containing the extracellular portion of the neurotrophin receptor TrkC fused to the intracellular portion of the insulin or IGF-I receptors, Chimeras were stably expressed in 3T3-L1 adipocytes at levels comparable to endogenous insulin receptors and were efficiently activated by neurotrophin-3. The wild-type insulin receptor chimera mediated approximately 2-fold greater phosphorylation of insulin receptor substrate 1 (IRS-1), association of IRS-1 with phosphoinositide 3-kinase, stimulation of glucose uptake, and GLUT4 translocation, compared with the IGF-I receptor chimera. In contrast, the IGF-I receptor chimera mediated more effective Shc phosphorylation, association of Shc with Grb2, and activation of mitogen-activated protein kinase compared with the insulin receptor chimera. The two receptors elicited similar activation of protein kinase B, p70S6 kinase, and glycogen synthesis. We conclude that the insulin receptor mediates some aspects of metabolic signaling in adipocytes more effectively than the IGF-I receptor, as a consequence of more efficient phosphorylation of IRS-1 and greater recruitment/activation of phosphoinositide 3-kinase

Who knows best? A Q methodology study to explore perspectives of professional stakeholders and community participants on health in low-income communities

Abstract Background Health inequalities in the UK have proved to be stubborn, and health gaps between best and worst-off are widening. While there is growing understanding of how the main causes of poor health are perceived among different stakeholders, similar insight is lacking regarding what solutions should be prioritised. Furthermore, we do not know the relationship between perceived causes and solutions to health inequalities, whether there is agreement between professional stakeholders and people living in low-income communities or agreement within these groups. Methods Q methodology was used to identify and describe the shared perspectives (‘subjectivities’) that exist on i) why health is worse in low-income communities (‘Causes’) and ii) the ways that health could be improved in these same communities (‘Solutions’). Purposively selected individuals (n = 53) from low-income communities (n = 25) and professional stakeholder groups (n = 28) ranked ordered sets of statements – 34 ‘Causes’ and 39 ‘Solutions’ – onto quasi-normal shaped grids according to their point of view. Factor analysis was used to identify shared points of view. ‘Causes’ and ‘Solutions’ were analysed independently, before examining correlations between perspectives on causes and perspectives on solutions. Results Analysis produced three factor solutions for both the ‘Causes’ and ‘Solutions’. Broadly summarised these accounts for ‘Causes’ are: i) ‘Unfair Society’, ii) ‘Dependent, workless and lazy’, iii) ‘Intergenerational hardships’ and for ‘Solutions’: i) ‘Empower communities’, ii) ‘Paternalism’, iii) ‘Redistribution’. No professionals defined (i.e. had a significant association with one factor only) the ‘Causes’ factor ‘Dependent, workless and lazy’ and the ‘Solutions’ factor ‘Paternalism’. No community participants defined the ‘Solutions’ factor ‘Redistribution’. The direction of correlations between the two sets of factor solutions – ‘Causes’ and ‘Solutions’ – appear to be intuitive, given the accounts identified. Conclusions Despite the plurality of views there was broad agreement across accounts about issues relating to money. This is important as it points a way forward for tackling health inequalities, highlighting areas for policy and future research to focus on