Polygenic Adaptation to an Environmental Shift: Temporal Dynamics of Variation Under Gaussian Stabilizing Selection and Additive Effects on a Single Trait.

Predictions about the effect of natural selection on patterns of linked neutral variation are largely based on models involving the rapid fixation of unconditionally beneficial mutations. However, when phenotypes adapt to a new optimum trait value, the strength of selection on individual mutations decreases as the population adapts. Here, I use explicit forward simulations of a single trait with additive-effect mutations adapting to an "optimum shift." Detectable "hitchhiking" patterns are only apparent if (i) the optimum shifts are large with respect to equilibrium variation for the trait, (ii) mutation rates to large-effect mutations are low, and (iii) large-effect mutations rapidly increase in frequency and eventually reach fixation, which typically occurs after the population reaches the new optimum. For the parameters simulated here, partial sweeps do not appreciably affect patterns of linked variation, even when the mutations are strongly selected. The contribution of new mutations vs. standing variation to fixation depends on the mutation rate affecting trait values. Given the fixation of a strongly selected variant, patterns of hitchhiking are similar on average for the two classes of sweeps because sweeps from standing variation involving large-effect mutations are rare when the optimum shifts. The distribution of effect sizes of new mutations has little effect on the time to reach the new optimum, but reducing the mutational variance increases the magnitude of hitchhiking patterns. In general, populations reach the new optimum prior to the completion of any sweeps, and the times to fixation are longer for this model than for standard models of directional selection. The long fixation times are due to a combination of declining selection pressures during adaptation and the possibility of interference among weakly selected sites for traits with high mutation rates

Safety of localizing epilepsy monitoring intracranial electroencephalograph electrodes using MRI: radiofrequency-induced heating

Purpose: To investigate heating during postimplantation localization of intracranial electroencephalograph (EEG) electrodes by MRI. Materials and Methods: A phantom patient with a realistic arrangement of electrodes was used to simulate tissue heating during MRI. Measurements were performed using 1.5 Tesla (T) and 3T MRI scanners, using head- and body-transmit RF-coils. Two electrode-lead configurations were assessed: a standard condition with external electrode-leads physically separated and a fault condition with all lead terminations electrically shorted. Results: Using a head-transmit-receive coil and a 2.4 W/kg head-average specific absorption rate (SAR) sequence, at 1.5T the maximum temperature change remained within safe limits (<1°C). Under standard conditions, we observed greater heating (2.0°C) at 3T on one system and similar heating (<1°C) on a second, compared with the 1.5T system. In all cases these temperature maxima occurred at the grid electrode. In the fault condition, larger temperature increases were observed at both field strengths, particularly for the depth electrodes. Conversely, with a body-transmit coil at 3T significant heating (+6.4°C) was observed (same sequence, 1.2/0.5 W/kg head/body-average) at the grid electrode under standard conditions, substantially exceeding safe limits. These temperature increases neglect perfusion, a major source of heat dissipation in vivo. Conclusion: MRI for intracranial electrode localization can be performed safely at both 1.5T and 3T provided a head-transmit coil is used, electrode leads are separated, and scanner-reported SARs are limited as determined in advance for specific scanner models, RF coils and implant arrangements. Neglecting these restrictions may result in tissue injury

Feasibility of simultaneous intracranial EEG-fMRI in humans: a safety study

In epilepsy patients who have electrodes implanted in their brains as part of their pre-surgical assessment, simultaneous intracranial EEG and fMRI (icEEG-fMRI) may provide important localising information and improve understanding of the underlying neuropathology. However, patient safety during icEEG-fMRI has not been addressed. Here the potential health hazards associated with icEEG-fMRI were evaluated theoretically and the main risks identified as: mechanical forces on electrodes from transient magnetic effects, tissue heating due to interaction with the pulsed RF fields and tissue stimulation due to interactions with the switched magnetic gradient fields. These potential hazards were examined experimentally in vitro on a Siemens 3 T Trio, 1.5 T Avanto and a GE 3 T Signa Excite scanner using a Brain Products MR compatible EEG system. No electrode flexion was observed. Temperature measurements demonstrated that heating well above guideline limits can occur. However heating could be kept within safe limits (< 1.0 °C) by using a head transmit RF coil, ensuring EEG cable placement to exit the RF coil along its central z-axis, using specific EEG cable lengths and limiting MRI sequence specific absorption rates (SARs). We found that the risk of tissue damage due to RF-induced heating is low provided implant and scanner specific SAR limits are observed with a safety margin used to account for uncertainties (e.g. in scanner-reported SAR). The observed scanner gradient switching induced current (0.08 mA) and charge density (0.2 μC/cm2) were well within safety limits (0.5 mA and 30 μC/cm2, respectively). Site-specific testing and a conservative approach to safety are required to avoid the risk of adverse events

Comparison of NASTRAN and MITAS nonlinear thermal analyses of a convectively cooled structure

Comparative steady state nonlinear thermal analyses of a scramjet fuel injection strut are presented. The analyses were performed using the NASTRAN finite element program and MITAS, a lumped-parameter thermal analyzer. The strut is subjected to aerodynamic heating on two sides and is internally cooled by hydrogen flowing from internal manifolds through heat exchangers bonded to the primary structure. Based on coolant temperatures determined by MITAS, NASTRAN predicted temperature distributions throughout the strut which were in close agreement with similar MITAS predictions

Mechanical properties of brittle materials

Brittle materials are difficult to tensile test because of gripping problems. They either crack in conventional grips or they are crushed. Furthermore, they may be difficult to make into tensile specimens having, for example, threated ends or donut shapes. To overcome the problem, simple rectangular shapes can be used in bending (i.e., a simple beam) in order to obtain the modulus of rupture and the elastic modulus. The equipment necessary consists of a fixture for supporting the specimens horizontally at two points, these points contact points being rollers which are free to rotate. The force necessary to bend the specimen is produced by a tup attached to the crosshead of an Instron machine. Here, the experimental procedure is explained

Supercomputer implementation of finite element algorithms for high speed compressible flows

Prediction of compressible flow phenomena using the finite element method is of recent origin and considerable interest. Two shock capturing finite element formulations for high speed compressible flows are described. A Taylor-Galerkin formulation uses a Taylor series expansion in time coupled with a Galerkin weighted residual statement. The Taylor-Galerkin algorithms use explicit artificial dissipation, and the performance of three dissipation models are compared. A Petrov-Galerkin algorithm has as its basis the concepts of streamline upwinding. Vectorization strategies are developed to implement the finite element formulations on the NASA Langley VPS-32. The vectorization scheme results in finite element programs that use vectors of length of the order of the number of nodes or elements. The use of the vectorization procedure speeds up processing rates by over two orders of magnitude. The Taylor-Galerkin and Petrov-Galerkin algorithms are evaluated for 2D inviscid flows on criteria such as solution accuracy, shock resolution, computational speed and storage requirements. The convergence rates for both algorithms are enhanced by local time-stepping schemes. Extension of the vectorization procedure for predicting 2D viscous and 3D inviscid flows are demonstrated. Conclusions are drawn regarding the applicability of the finite element procedures for realistic problems that require hundreds of thousands of nodes

Free Cooling Phase-Diagram of Hard-Spheres with Short- and Long-Range Interactions

We study the stability, the clustering and the phase-diagram of free cooling granular gases. The systems consist of mono-disperse particles with additional non-contact (long-range) interactions, and are simulated here by the event-driven molecular dynamics algorithm with discrete (short-range shoulders or wells) potentials (in both 2D and 3D). Astonishingly good agreement is found with a mean field theory, where only the energy dissipation term is modified to account for both repulsive or attractive non-contact interactions. Attractive potentials enhance cooling and structure formation (clustering), whereas repulsive potentials reduce it, as intuition suggests. The system evolution is controlled by a single parameter: the non-contact potential strength scaled by the fluctuation kinetic energy (granular temperature). When this is small, as expected, the classical homogeneous cooling state is found. However, if the effective dissipation is strong enough, structure formation proceeds, before (in the repulsive case) non-contact forces get strong enough to undo the clustering (due to the ongoing dissipation of granular temperature). For both repulsive and attractive potentials, in the homogeneous regime, the cooling shows a universal behaviour when the (inverse) control parameter is used as evolution variable instead of time. The transition to a non-homogeneous regime, as predicted by stability analysis, is affected by both dissipation and potential strength. This can be cast into a phase diagram where the system changes with time, which leaves open many challenges for future research.Comment: 22 pages, 15 figure

The link between M1 and the monetary base in the 198O's

Monetary policy ; Money supply

Alternative measures of the monetary base: what are the differences and are they important?

Monetary policy