Molecular mechanisms of oestrogen action on growth of human breast cancer cells in culture

Growth responses to oestrogen can be reproducibly obtained using a selection of oestrogen-receptor-containing human breast cancer cell lines, and molecular mechanisms have been shown to include modulation to growth factor/receptor/signalling pathways, cell-cycle proteins, apoptosis, differentiation, adhesion, motility and migration. Considerable progress has been made in understanding the molecular basis of oestrogen action on gene expression through the ligand-activated transcription factors human oestrogen receptor α (ERα) and ERβ and the resulting effects on global gene expression patterns, but the full profile of coordination of the alterations, which brings about changes in cell growth through genomic and non-genomic mechanisms remain to be fully elucidated. Oestrogen regulation of cell growth involves a complex cross-talk between oestrogen receptor and growth factor signalling pathways such that inhibition of one pathway may lead to stimulation of another, which may explain the remarkable ability of human breast cancer cells to escape from any mode of imposed growth inhibition be it oestrogen deprivation or administration of antioestrogen. Although studies on cell growth have focused to date on the effects of physiological oestrogens, many hundreds of environmental chemicals with oestrogenic properties have now been measured in the human breast. Whether or not the weight of evidence eventually establishes any causal link of complex mixtures of environmental oestrogenic chemicals with breast cancer, the presence of so many oestrogenic chemicals in the breast must influence resulting oestrogenic responses, and the impact of this additional oestrogenic burden needs to be taken into account in future studies on growth regulation of human breast cancer cells.

Developing skin analogues for a robotic octopus

In order to fabricate a biomimetic skin for an octopus inspired robot, a new process was developed based on mechanical properties measured from real octopus skin. Various knitted nylon textiles were tested and the one of 10-denier nylon was chosen as reinforcement. A combination of Ecoflex 0030 and 0010 silicone rubbers was used as matrix of the composite to obtain the right stiffness for the skin-analogue system. The open mould fabrication process developed allows air bubble to escape easily and the artificial skin produced was thin and waterproof. Material properties of the biomimetic skin were characterised using static tensile and instrumented scissors cutting tests. The Young’s moduli of the artificial skin are 0.08 MPa and 0.13 MPa in the longitudinal and transverse directions, which are much lower than those of the octopus skin. The strength and fracture toughness of the artificial skin, on the other hand are higher than those of real octopus skins. Conically-shaped skin prototypes to be used to cover the robotic arm unit were manufactured and tested. The biomimetic skin prototype was stiff enough to maintain it conical shape when filled with water. The driving force for elongation was reduced significantly compared with previous prototypes.

Sensitivity of simulated climate to conservation of momentum in gravity wave drag parameterization

The Canadian Middle Atmosphere Model is used to examine the sensitivity of simulated climate to conservation of momentum in gravity wave drag parameterization. Momentum conservation requires that the parameterized gravity wave momentum flux at the top of the model be zero and corresponds to the physical boundary condition of no momentum flux at the top of the atmosphere. Allowing momentum flux to escape the model domain violates momentum conservation. Here the impact of momentum conservation in two sets of model simulations is investigated. In the first set, the simulation of present-day climate for two model-lid height configurations, 0.001 and 10 hPa, which are identical below 10 hPa, is considered. The impact of momentum conservation on the climate with the model lid at 0.001 hPa is minimal, which is expected because of the small amount of gravity wave momentum flux reaching 0.001 hPa. When the lid is lowered to 10 hPa and momentum is conserved, there is only a modest impact on the climate in the Northern Hemisphere; however, the Southern Hemisphere climate is more adversely affected by the deflection of resolved waves near the model lid. When momentum is not conserved in the 10-hPa model the climate is further degraded in both hemispheres, particularly in winter at high latitudes, and the impact of momentum conservation extends all the way to the surface. In the second set of simulations, the impact of momentum conservation and model-lid height on the modeled response to ozone depletion in the Southern Hemisphere is considered, and it is found that the response can display significant sensitivity to both factors. In particular, both the lower-stratospheric polar temperature and surface responses are significantly altered when the lid is lowered, with the effect being most severe when momentum is not conserved. The implications with regard to the current round of Intergovernmental Panel on Climate Change model projections are discussed.

Multi-vehicle planning using RRT-connect

The problem of planning multiple vehicles deals with the design of an effective algorithm that can cause multiple autonomous vehicles on the road to communicate and generate a collaborative optimal travel plan. Our modelling of the problem considers vehicles to vary greatly in terms of both size and speed, which makes it suboptimal to have a faster vehicle follow a slower vehicle or for vehicles to drive with predefined speed lanes. It is essential to have a fast planning algorithm whilst still being probabilistically complete. The Rapidly Exploring Random Trees (RRT) algorithm developed and reported on here uses a problem specific coordination axis, a local optimization algorithm, priority based coordination, and a module for deciding travel speeds. Vehicles are assumed to remain in their current relative position laterally on the road unless otherwise instructed. Experimental results presented here show regular driving behaviours, namely vehicle following, overtaking, and complex obstacle avoidance. The ability to showcase complex behaviours in the absence of speed lanes is characteristic of the solution developed.

Multi-level planning for semi-autonomous vehicles in traffic scenarios based on separation maximization

The planning of semi-autonomous vehicles in traffic scenarios is a relatively new problem that contributes towards the goal of making road travel by vehicles free of human drivers. An algorithm needs to ensure optimal real time planning of multiple vehicles (moving in either direction along a road), in the presence of a complex obstacle network. Unlike other approaches, here we assume that speed lanes are not present and that different lanes do not need to be maintained for inbound and outbound traffic. Our basic hypothesis is to carry forward the planning task to ensure that a sufficient distance is maintained by each vehicle from all other vehicles, obstacles and road boundaries. We present here a 4-layer planning algorithm that consists of road selection (for selecting the individual roads of traversal to reach the goal), pathway selection (a strategy to avoid and/or overtake obstacles, road diversions and other blockages), pathway distribution (to select the position of a vehicle at every instance of time in a pathway), and trajectory generation (for generating a curve, smooth enough, to allow for the maximum possible speed). Cooperation between vehicles is handled separately at the different levels, the aim being to maximize the separation between vehicles. Simulated results exhibit behaviours of smooth, efficient and safe driving of vehicles in multiple scenarios; along with typical vehicle behaviours including following and overtaking.

Electron trapping in shear Alfvén waves that power the aurora

Results from 1D Vlasov drift-kinetic plasma simulations reveal how and where auroral electrons are accelerated along Earth’s geomagnetic field. In the warm plasma sheet, electrons become trapped in shear Alfven waves, preventing immediate wave damping. As waves move to regions with larger vTe=vA, their parallel electric field decreases, and the trapped electrons escape their influence. The resulting electron distribution functions compare favorably with in situ observations, demonstrating for the first time a self-consistent link between Alfven waves and electrons that form aurora.

Perceived helplessness is associated with individual differences in the central motor output system

Learned helplessness is a maladaptive response to uncontrollable stress characterized by impaired motor escape responses, reduced motivation and learning deficits. There are important individual differences in the likelihood of becoming helpless following exposure to uncontrollable stress but little is known about the neural mechanisms underlying these individual differences. Here we used structural MRI to measure gray and white matter in individuals with chronic pain, a population at high risk for helplessness due to prolonged exposure to a poorly controlled stressor (pain). Given that self-reported helplessness is predictive of treatment outcomes in chronic pain, understanding such differences might provide valuable clinical insight. We found that the magnitude of self-reported helplessness correlated with cortical thickness in the supplementary motor area (SMA) and midcingulate cortex, regions implicated in cognitive aspects of motor behavior. We then examined the white matter connectivity of these regions and found that fractional anisotropy of connected white matter tracts along the corticospinal tract was associated with helplessness and mediated the relationship between SMA cortical thickness and helplessness. These data provide novel evidence that links individual differences in the motor output pathway with perceived helplessness over a chronic and poorly controlled stressor.

Adapting wheat in Europe for climate change

Increasing cereal yield is needed to meet the projected increased demand for world food supply of about 70% by 2050. Sirius, a process-based model for wheat, was used to estimate yield potential for wheat ideotypes optimized for future climatic projections (HadCM3 global climate model) for ten wheat growing areas of Europe. It was predicted that the detrimental effect of drought stress on yield would be decreased due to enhanced tailoring of phenology to future weather patterns, and due to genetic improvements in the response of photosynthesis and green leaf duration to water shortage. Yield advances could be made through extending maturation and thereby improve resource capture and partitioning. However the model predicted an increase in frequency of heat stress at meiosis and anthesis. Controlled environment experiments quantify the effects of heat and drought at booting and flowering on grain numbers and potential grain size. A current adaptation of wheat to areas of Europe with hotter and drier summers is a quicker maturation which helps to escape from excessive stress, but results in lower yields. To increase yield potential and to respond to climate change, increased tolerance to heat and drought stress should remain priorities for the genetic improvement of wheat.

Destructive behaviours and leadership: the source of the shift from a functional to dysfunctional workplace?

Destructive leadership behaviour often results in damage to the organisations that the individual is entrusted to lead. Although accurately pinpointing the type of destructive behaviour is difficult, this article seeks to offer suggestions as to why leaders spiral into such unattractive behaviour. After reviewing the literature, this paper highlights four drivers for destructive ways that people act based on detailed qualitative scenarios that involve how those who experienced such behaviour reacted and felt. The study reveals a noticeable human experience from which nobody can escape, and offers understanding of the study participants’ experiences. Out of respect to the participants, the authors keep their identity anonomous. We drew our subjects from a cross-section of organisations that function internationally within one area of the manufacturing industry. The article presents a model comprising two dimensions: 1) the leader’s attitude to the organisation he or she leads and 2) adequacy of his or her leadership capabilities. The models offer us understanding of the drivers of the destructive actions that the leader exhibits. Understanding allows us to provide managers with tactical methods to protect them against destructive behaviour and help them lessen the worst aspects of destructive behaviour in both their colleagues and themselves.

The population dynamics of disease on short and long time-scales

Observational evidence is scarce concerning the distribution of plant pathogen population sizes or densities as a function of time-scale or spatial scale. For wild pathosystems we can only get indirect evidence from evolutionary patterns and the consequences of biological invasions.We have little or no evidence bearing on extermination of hosts by pathogens, or successful escape of a host from a pathogen. Evidence over the last couple of centuries from crops suggest that the abundance of particular pathogens in the spectrum affecting a given host can vary hugely on decadal timescales. However, this may be an artefact of domestication and intensive cultivation. Host-pathogen dynamics can be formulated mathematically fairly easily–for example as SIR-type differential equation or difference equation models, and this has been the (successful) focus of recent work in crops. “Long-term” is then discussed in terms of the time taken to relax from a perturbation to the asymptotic state. However, both host and pathogen dynamics are driven by environmental factors as well as their mutual interactions, and both host and pathogen co-evolve, and evolve in response to external factors. We have virtually no information about the importance and natural role of higher trophic levels (hyperpathogens) and competitors, but they could also induce long-scale fluctuations in the abundance of pathogens on particular hosts. In wild pathosystems the host distribution cannot be modelled as either a uniform density or even a uniform distribution of fields (which could then be treated as individuals). Patterns of short term density-dependence and the detail of host distribution are therefore critical to long-term dynamics. Host density distributions are not usually scale-free, but are rarely uniform or clearly structured on a single scale. In a (multiply structured) metapopulation with coevolution and external disturbances it could well be the case that the time required to attain equilibrium (if it exists) based on conditions stable over a specified time-scale is longer than that time-scale. Alternatively, local equilibria may be reached fairly rapidly following perturbations but the meta-population equilibrium be attained very slowly. In either case, meta-stability on various time-scales is a more relevant than equilibrium concepts in explaining observed patterns.

Diversity for resilience : multi-scale application of agro-ecology

The integration of ecological principles into agricultural systems presents major opportunities for spreading risk at the crop and farm scale. This paper presents mechanisms by which diversity at several scales within the farming system can increase the stability of production. Diversity of above- and below-ground biota, but also genetic and phenotypic diversity within crops, has an essential role in safeguarding farm production. Novel mixtures of legume-grass leys have been shown to potentially provide significant benefits for pollinator and decomposer ecosystem services but to realise the greatest improvements carefully tailored farm management is needed such as mowing or grazing time, and the type and depth of cutivation. Complex farmland landscapes such as agroforestry systems have the potential to support pollinator abundance and diversity and spread risk across production enterprises. At the crop level, early results indicate that the vulnerability of pollen development, flowering and early grain set to abiotic stress can be ameliorated by managing flowering time through genotypic selection, and through the buffering effects of pollinators. Finally, the risk of sub-optimal quality in cereals can be mitigated through integration of near isogenic lines selected to escape specific abiotic stress events. We conclude that genotypic, phenotypic and community diversity can all be increased at multiple scales to enhance resilience in agricultural systems.

High night temperature induces contrasting responses for spikelet fertility, spikelet tissue temperature, flowering characteristics and grain quality in rice

Climate change is increasing night temperature (NT) more than day temperature (DT) in rice-growing areas. Effects of combinations of NT (24-35°C) from microsporogenesis to anthesis at one or more DT (30 or 35°C) at anthesis on rice spikelet fertility, temperature within spikelets, flowering pattern, grain weight per panicle, amylose content and gel consistency were investigated in contrasting rice cultivars under controlled environments. Cultivars differed in spikelet fertility response to high NT, with higher fertility associated with cooler spikelets (P < 0.01). Flowering dynamics were altered by high NT and a novel high temperature tolerance complementary mechanism, shorter flower open duration in cv. N22, was identified. High NT reduced spikelet fertility, grain weight per panicle, amylose content and gel consistency, whereas high DT reduced only gel consistency. Night temperature >27°C was estimated to reduce grain weight. Generally, high NT was more damaging to grain weight and selected grain quality traits than high DT, with little or no interaction between them. The critical tolerance and escape traits identified, i.e. spikelet cooling, relatively high spikelet fertility, earlier start and peak time of anthesis and shorter spikelet anthesis duration can aid plant breeding programs targeting resilience in warmer climates.

Field-perpendicular and field-aligned plasma flows observed by EISCAT during a prolonged period of northward IMF

The effect of a prolonged period of strongly northward Interplanetary Magnetic Field (IMF) on the high-latitude F-region is studied using data from the EISCAT Common Programme Zero mode of operation on 11–12 August 1982. The analysis of the raw autocorrelation functions is kept to the directly derived parameters Ne, Te, Ti and velocity, and limits are defined for the errors introduced by assumptions about ion composition and by changes in the transmitted power and system constant. Simple data-cleaning criteria are employed to eliminate problems due to coherent signals and large background noise levels. The observed variations in plasma densities, temperatures and velocities are interpreted in terms of supporting data from ISEE-3 and local riometers and magnetometers. Both field-aligned and field-perpendicular plasma flows at Tromsø showed effects of the northward IMF: convection was slow and irregular and field-aligned flow profiles were characteristic of steady-state polar wind outflow with flux of order 1012 m−2 s−1. This period followed a strongly southward IMF which had triggered a substorm. The substorm gave enhanced convection, with a swing to equatorward flow and large (5 × 1012 m−2 s−1), steady-state field-aligned fluxes, leading to the possibility of O+ escape into the magnetosphere. The apparent influence of the IMF over both field-perpendicular and field-aligned flows is explained in terms of the cross-cap potential difference and the location of the auroral oval.

Thermospheric Control of the Auroral Source of O+Ions for the Magnetosphere

Linear theory, model ion-density profiles and MSIS neutral thermospheric predictions are used to investigate the stability of the auroral, topside ionosphere to oxygen cyclotron waves: variations of the critical height, above which the plasma is unstable, with field-aligned current, thermal ion density and exospheric temperature are considered. In addition, probabilities are assessed that interactions with neutral atomic gases prevent O+ ions from escaping into the magnetosphere after they have been transversely accelerated by these waves. The two studies are combined to give a rough estimate of the total O+ escape flux as a function of the field-aligned current density for an assumed rise in the perpendicular ion temperature. Charge exchange with neutral oxygen, not hydrogen, is shown to be the principle limitation to the escape of O+ ions, which occurs when the waves are driven unstable down to low altitudes. It is found that the largest observed field-aligned current densities can heat a maximum of about 5×1014 O+ ions m−2 to a threshold above which they are subsequently able to escape into the magnetosphere in the following 500s. Averaged over this period, this would constitute a flux of 1012 m−2 s−1 and in steady-state the peak outflow would then be limited to about 1013 m−2 s−1 by frictional drag on thermal O+ at lower altitudes. Maximum escape is at low plasma density unless the O+ scale height is very large. The outflow decreases with decreasing field-aligned current density and, to a lesser extent, with increasing exospheric temperature. Upward flowing ion events are evaluated as a source of O+ ions for the magnetosphere and as an explanation of the observed solar cycle variation of ring current O+ abundance.

Thermal ion flows in the topside auroral ionosphere and the effects of low-altitude, transverse acceleration

Topside ionospheric profiles are used to study the upward field-aligned flow of thermal O+ at high latitudes. On the majority of the field lines outside the plasmasphere, the mean flux is approximately equal to the mean polar wind measured by spacecraft at greater altitudes. This is consistent with the theory of thermal light ion escape supported, via charge exchange, by upward O+ flow at lower heights. Events of larger O+ flow are detected at auroral latitudes and their occurrence is found to agree with that of transversely accelerated ions within the topside ionosphere and the magnetosphere. The effects of low altitude heating of O+ by oxygen cyclotron waves, driven by downward field-aligned currents, are considered as a possible common cause of these two types of event.