Regulation of zygotic gene activation in the preimplantation mouse embryo: Global activation and repression of gene expression

Superimposed on the activation of the embryonic genome in the preimplantation mouse embryo is the formation of a transcriptionally repressive state during the two-cell stage. This repression appears mediated at the level of chromatin structure, because it is reversed by inducing histone hyperacetylation or inhibiting the second round of DNA replication. We report that of more than 200 amplicons analyzed by mRNA differential display, about 45% of them are repressed between the two-cell and four-cell stages. This repression is scored as either a decrease in amplicon expression that occurs between the two-cell and four-cell stages or on the ability of either trichostatin A tan inhibitor of histone deacetylases) or aphidicolin tan inhibitor of replicative DNA polymerases) to increase the level of amplicon expression. Results of this study also indicate that about 16% of the amplicons analyzed likely are novel genes whose sequence doesn't correspond to sequences in the current databases, whereas about 20% of the sequences expressed during this transition likely are repetitive sequences. Lastly, inducing histone hyperacetylation in the two-cell embryos inhibits cleavage to the four-cell stage. These results suggest that genome activation is global and relatively promiscuous and that a function of the transcriptionally repressive state is to dictate the appropriate profile of gene expression that is compatible with further development.

Oscillatory sensitivity patterns for global modes in wakes

Globally unstable wakes with co-flow at intermediate Reynolds numbers are studied, to quantify important spatial regions for the development and control of the global instability. One region of high structural sensitivity is found close to the inlet for all wakes, in agreement with previous findings for cylinder wakes. A second, elongated region of high structural sensitivity is seen downstream of the first one for unconfined wakes at Re = 400. When base flow modifications are considered, a spatially oscillating sensitivity pattern is found inside the downstream high structural sensitivity region. This implies that the same change in the base flow can either destabilize or stabilize the flow, depending on the exact position where it is applied. It is shown that the sensitivity pattern remains unchanged for different choices of streamwise boundary conditions and numerical resolution. Actual base flow modifications are applied in selected configurations, and the linear global modes recomputed. It is confirmed that the linear global eigenvalues move according to the predicted sensitivity pattern for small amplitude base flow modifications, for which the theory applies. We also look at the implications of a small control cylinder on the flow. Only the upstream high sensitivity region proves to be robust in terms of control, but one should be careful not to disturb the flow in the downstream high sensitivity region, in order to achieve control. The findings can have direct implications on the numerical resolution requirements for wakes at higher Reynolds numbers. Furthermore, they provide one more possible explanation to why confined wakes have a more narrow frequency spectrum than unconfined wakes.

Global nonlinear dynamics of thin aerofoil wakes

In the present investigation of thin aerofoil wakes we compare the global nonlinear dynamics, obtained by direct numerical simulations, to the associated local instability features, derived from linear stability analyses. A given configuration depends on two control parameters: the Reynolds number Re and the adverse pressure gradient m (with m < 0) prevailing at the aerofoil trailing edge. Global instability is found to occur for large enough Re and |m|; the naturally selected frequency is determined by the local absolute frequency prevailing at the trailing edge. © 2010 Springer Science+Business Media B.V.

Deformation measurement of a human chest experiencing global motion

Current state-of-the-art techniques for determination of the change in volume of human chests, used in lung-function measurement, calculate the volume bounded by a reconstructed chest surface and its projection on to an approximately parallel static plane over a series of time instants. This method works well so long as the subject does not move globally relative to the reconstructed surface's co-ordinate system. In practice this means the subject has to be braced, which restricts the technique's use. We present here a method to compensate for global motion of the subject, allowing accurate measurement while free-standing, and also while undergoing intentional motion. © 2012 Springer-Verlag.

Global solutions

As manufacturing enterprises become increasingly globalised, the supply chain is becoming more fragmented, with multiple players engaged in key aspects of the value chain. This has seen the emergence of suppliers offering specialised operations (research, design, production, service) which are capable of serving widely dispersed markets. It is generally assumed that managing these increasingly complex international supply chains requires sophisticated management techniques. Many companies have installed advanced planning systems for just this reason - systems that require skilled staff to implement the complex processes involved.

Surface tension-induced global instability of planar jets and wakes

The effect of surface tension on global stability of co-flow jets and wakes at a moderate Reynolds number is studied. The linear temporal two-dimensional global modes are computed without approximations. All but one of the flow cases under study are globally stable without surface tension. It is found that surface tension can cause the flow to be globally unstable if the inlet shear (or equivalently, the inlet velocity ratio) is strong enough. For even stronger surface tension, the flow is re-stabilized. As long as there is no change of the most unstable mode, increasing surface tension decreases the oscillation frequency. Short waves appear in the high-shear region close to the nozzle, and their wavelength increases with increasing surface tension. The critical shear (the weakest inlet shear at which a global instability is found) gives rise to antisymmetric disturbances for the wakes and symmetric disturbances for the jets. However, at stronger shear, the opposite symmetry can be the most unstable one, in particular for wakes at high surface tension. The results show strong effects of surface tension that should be possible to reproduce experimentally as well as numerically.

Mapping the global flow of steel: from steelmaking to end-use goods.

Our society is addicted to steel. Global demand for steel has risen to 1.4 billion tonnes a year and is set to at least double by 2050, while the steel industry generates nearly a 10th of the world's energy related CO₂ emissions. Meeting our 2050 climate change targets would require a 75% reduction in CO₂ emissions for every tonne of steel produced and finding credible solutions is proving a challenge. The starting point for understanding the environmental impacts of steel production is to accurately map the global steel supply chain and identify the biggest steel flows where actions can be directed to deliver the largest impact. In this paper we present a map of global steel, which for the first time traces steel flows from steelmaking, through casting, forming, and rolling, to the fabrication of final goods. The diagram reveals the relative scale of steel flows and shows where efforts to improve energy and material efficiency should be focused.

Self-excited circumferential instabilities in a model annular gas turbine combustor: Global flame dynamics

In this paper the global flame dynamics of a model annular gas turbine combustor undergoing strong self-excited circumferential instabilities is presented. The combustor consisted of either 12, 15 or 18 turbulent premixed bluff-body flames arranged around an annulus of fixed circumference so that the effect of flame separation distance, S, on the global heat release dynamics could be investigated. Reducing S was found to produce both an increase in the resonant frequency and the limit-cycle amplitudes of pressure and heat release for the same equivalence ratio. The phase-averaged global heat release, obtained from high-speed OH- chemiluminescence imaging from above, showed that these changes are caused by large-scale modifications to the flame structure around the annulus. For the largest S studied (12 flame configuration) the azimuthal instability produced a helical-like global heat release structure for each flame. When S was decreased, large-scale merging or linking between adjacent flames occurred spanning approximately half of the annulus with the peak heat release concentrated at the outer annular wall. The circumferential nature of the instability was evident from both the pressure measurements and the phase-averaged OH- chemiluminescence showing the phase of the heat release on either side of the annulus to be ≈180°apart and spinning in the counter clockwise direction. Both spinning and standing modes were found but only spinning modes are considered in this paper. To the best of the authors knowledge, these are the first experiments to provide a phase-averaged picture of self-excited azimuthal instabilities in a laboratory-scale annular combustor relevant to gas turbines. © 2012 The Combustion Institute. Published by Elsevier Inc. All rights reserved.

Mapping the global flow of aluminum: from liquid aluminum to end-use goods.

Demand for aluminum in final products has increased 30-fold since 1950 to 45 million tonnes per year, with forecasts predicting this exceptional growth to continue so that demand will reach 2-3 times today's levels by 2050. Aluminum production uses 3.5% of global electricity and causes 1% of global CO2 emissions, while meeting a 50% cut in emissions by 2050 against growing demand would require at least a 75% reduction in CO2 emissions per tonne of aluminum produced--a challenging prospect. In this paper we trace the global flows of aluminum from liquid metal to final products, revealing for the first time a complete map of the aluminum system and providing a basis for future study of the emissions abatement potential of material efficiency. The resulting Sankey diagram also draws attention to two key issues. First, around half of all liquid aluminum (~39 Mt) produced each year never reaches a final product, and a detailed discussion of these high yield losses shows significant opportunities for improvement. Second, aluminum recycling, which avoids the high energy costs and emissions of electrolysis, requires signification "dilution" (~ 8 Mt) and "cascade" (~ 6 Mt) flows of higher aluminum grades to make up for the shortfall in scrap supply and to obtain the desired alloy mix, increasing the energy required for recycling.

A global model for effective use and evaluation of e-learning in health.

Healthcare systems worldwide face a wide range of challenges, including demographic change, rising drug and medical technology costs, and persistent and widening health inequalities both within and between countries. Simultaneously, issues such as professional silos, static medical curricula, and perceptions of "information overload" have made it difficult for medical training and continued professional development (CPD) to adapt to the changing needs of healthcare professionals in increasingly patient-centered, collaborative, and/or remote delivery contexts. In response to these challenges, increasing numbers of medical education and CPD programs have adopted e-learning approaches, which have been shown to provide flexible, low-cost, user-centered, and easily updated learning. The effectiveness of e-learning varies from context to context, however, and has also been shown to make considerable demands on users' motivation and "digital literacy" and on providing institutions. Consequently, there is a need to evaluate the effectiveness of e-learning in healthcare as part of ongoing quality improvement efforts. This article outlines the key issues for developing successful models for analyzing e-health learning.

Prediction of FRP debonding using the global-energy-balance approach

A major research program was carried out to analyze the mechanism of FRP debonding from concrete beams using global-energy-balance approach (GEBA). The key findings are that the fracture process zone is small so there is no R-curve to consider, failure is dominated by Mode I behavior, and the theory agrees well with tests. The analyses developed in the study provide an essential tool that will enable fracture mechanics to be used to determine the load at which FRP plates will debond from concrete beams. This obviates the need for finite element (FE) analyses in situations where reliable details of the interface geometry and crack-tip stress fields are not attainable for an accurate analysis. This paper presents an overview of the GEBA analyses that is described in detail elsewhere, and explains the slightly unconventional assumptions made in the analyses, such as the revised moment-curvature model, the location of an effective centroid, the separate consideration of the FRP and the RC beam for the purposes of the analysis, the use of Mode I fracture energies and the absence of an R-curve in the fracture mechanics analysis.

Global analysis of dynamical decision-making models through local computation around the hidden saddle

Bistable dynamical switches are frequently encountered in mathematical modeling of biological systems because binary decisions are at the core of many cellular processes. Bistable switches present two stable steady-states, each of them corresponding to a distinct decision. In response to a transient signal, the system can flip back and forth between these two stable steady-states, switching between both decisions. Understanding which parameters and states affect this switch between stable states may shed light on the mechanisms underlying the decision-making process. Yet, answering such a question involves analyzing the global dynamical (i.e., transient) behavior of a nonlinear, possibly high dimensional model. In this paper, we show how a local analysis at a particular equilibrium point of bistable systems is highly relevant to understand the global properties of the switching system. The local analysis is performed at the saddle point, an often disregarded equilibrium point of bistable models but which is shown to be a key ruler of the decision-making process. Results are illustrated on three previously published models of biological switches: two models of apoptosis, the programmed cell death and one model of long-term potentiation, a phenomenon underlying synaptic plasticity. © 2012 Trotta et al.

Feedback mechanisms for global oscillations in Lure systems

The paper presents two mechanisms for global oscillations in feedback systems, based on bifurcations in absolutely stable systems. The external characterization of the oscillators provides the basis for a (energy-based) dissipativity theory for oscillators, thereby opening new possibilities for rigorous stability analysis of high-dimensional systems and interconnected oscillators. © 2004 Elsevier B.V. All rights reserved.