On the buckling of an elastic holey column.

We report the results of a numerical and theoretical study of buckling in elastic columns containing a line of holes. Buckling is a common failure mode of elastic columns under compression, found over scales ranging from metres in buildings and aircraft to tens of nanometers in DNA. This failure usually occurs through lateral buckling, described for slender columns by Euler's theory. When the column is perforated with a regular line of holes, a new buckling mode arises, in which adjacent holes collapse in orthogonal directions. In this paper, we firstly elucidate how this alternate hole buckling mode coexists and interacts with classical Euler buckling modes, using finite-element numerical calculations with bifurcation tracking. We show how the preferred buckling mode is selected by the geometry, and discuss the roles of localized (hole-scale) and global (column-scale) buckling. Secondly, we develop a novel predictive model for the buckling of columns perforated with large holes. This model is derived without arbitrary fitting parameters, and quantitatively predicts the critical strain for buckling. We extend the model to sheets perforated with a regular array of circular holes and use it to provide quantitative predictions of their buckling.

Pharmaceuticals Licensing and Reimbursement in the European Union, United States, and Japan.

This article describes recent developments in licensing and reimbursement policies in the EU, US, and Japan, examines causes of changes and compares differences and projects trends. With respect to licensing, the European Medicines Agency (EMA), US Food and Drug Administration (FDA), and Japan's Pharmaceuticals and Medical Devices Agency (PMDA) are committed to rigorous evaluation of pharmaceuticals in advance of market access with feedback from postmarket experience. The EMA is exploring integrated adaptive pathways for licensing, with formal pilot tests to provide a practical proof of concept. The FDA is augmenting traditional licensing procedures through reforms including Breakthrough Product Designation. The PMDA is implementing reforms to foster innovation and earlier patient access through its Sakigake strategy and licensing reforms on regenerative medicines. With respect to reimbursement, several generalizations emerge. Relative to US counterparts, EU payers typically set higher standards for evidence of effectiveness as a condition of reimbursement, impose tougher limits on reimbursement by indication, and drive harder deals in negotiations over prices.

Buckling of a holey column.

We report the results from a combined experimental and numerical investigation of buckling in a novel variant of an elastic column under axial load. We find that including a regular line of centred holes in the column can prevent conventional, global, lateral buckling. Instead, the local microstructure introduced by the holes allows the column to buckle in an entirely different, internal, mode in which the holes are compressed in alternate directions, but the column maintains the lateral reflection symmetry about its centreline. The internal buckling mode can be accommodated within a smaller external space than the global one; and it is the preferred buckling mode over an intermediate range of column lengths for sufficiently large holes. For very short or sufficiently long columns a modification of the classical, global, lateral buckling is dominant.

Granular segregation driven by particle interactions.

We report the results of an experimental study of particle-particle interactions in a horizontally shaken granular layer that undergoes a second order phase transition from a binary gas to a segregation liquid as the packing fraction C is increased. By focusing on the behavior of individual particles, the effect of C is studied on (1) the process of cluster formation, (2) cluster dynamics, and (3) cluster destruction. The outcomes indicate that the segregation is driven by two mechanisms: attraction between particles with the same properties and random motion with a characteristic length that is inversely proportional to C. All clusters investigated are found to be transient and the probability distribution functions of the separation times display a power law tail, indicating that the splitting probability decreases with time.

Balancing a cylinder on a thin vertical layer of viscous fluid.

We analyze recent experiments that show that a cylinder can be suspended in a stable position by placing it on a vertically moving belt that is covered by a thin layer of very viscous oil. The weight of the cylinder is supported by viscous forces in the fluid layer, and the cylinder rotates with respect to its axis in the direction of the belt motion. We propose a simple model for stable suspension of the cylinder, based on lubrication ideas.

Folded edge of turbulence in a pipe.

The results of an experimental investigation into the threshold boundary between laminar and disordered pipe flow are presented. Complex features have been uncovered using a highly refined experimental approach where an intermediate periodic state forms an integral part of the transition sequence. In accord with the suggestions produced by a numerical investigation, the boundary is found to be folded with a complicated structure. This raises important questions about accepted definitions of threshold amplitudes in this long-standing problem.

Segregation pattern competition in a thin rotating drum.

Results are presented of an experimental investigation into patterned size segregation of binary granular mixtures in a thin rotating drum that is half full. It is observed that streaks of small particles are formed within regions of large ones where the integer number of streaks is fixed over a range of rotation rate of the drum. Different patterns form in adjacent parameter ranges and the dynamics associated with the exchange between neighboring states is analyzed using angular spatiotemporal diagrams. These help to reveal properties of the merging mechanism for streaks of small particles. We report experimental evidence that the merging of streaks is mediated by the movement of a surplus material in a direction opposite to that of the rotation of the drum. The excess material is distributed throughout the pattern and the extra streak eventually disappears.

Does limb angular motion raise limb arterial pressure?

AIM: Mechanical factors such as the muscle pump have been proposed to augment flow by several mechanisms. The potential for limb angular motion to augment local perfusion pressure (pressure = (1/2)rhor(2)omega(2), where rho is the fluid density, r the radius and omega the angular velocity) has been overlooked. We sought to test the hypothesis that limb angular motion augments limb arterial pressure. METHODS: Nine human subjects performed horizontal shoulder flexion ( approximately +/-90 degrees at 0.75 Hz for 30 s). We measured finger arterial pressure (photoplethysmography) in the moving (Trial 1) and non-moving arm (Trial 2) in separate trials along with the pressure (strain gauge) generated at the fingers within a length of water-filled tubing mounted on the moving arm in both trials. RESULTS: Arm swinging raised (P < 0.05) the mean pressure measured in the tubing by 11 +/- 2 and 14 +/- 2 mmHg (Trials 1 and 2 respectively). In response to exercise, the rise in mean finger arterial pressure in the swinging limb (18 +/- 3 mmHg, Trial 1) exceeded (P < 0.05) the rise in the resting limb (8 +/- 2 mmHg, Trial 2) by an amount similar to the 11 mmHg rise in pressure generated in the tubing in Trial 1. CONCLUSIONS: We conclude that the swinging of a limb creates centrifugal force (a biomechanical centrifuge) which imparts additional pressure to the arteries, but not the veins owing to the venous valves, which further widens the arterial-venous pressure difference.

Self-organized patterns in collections of chains.

Results are presented of an experimental investigation into patterned segregation in thin layers of poppy seeds and short lengths of metal chains subjected to vibration. Critical phenomena are uncovered and both continuous and discontinuous transitions are observed. A phase diagram for the behavior is mapped out and a tricritical point that separates hysteretic from continuous segregation is identified. Remarkable similarities are found between the observed behavior in this driven granular system and phase separation phenomena in mixtures where the dynamics of the constituent components are markedly different.

Stress dip under a two-dimensional semipile of grains.

The origin of stress dip under the apex of a standard sandpile has stimulated significant debate within the scientific community. On the other hand, it could be argued that a semipile built against a vertical wall is of more practical interest since it serves as a model of dams, dykes, and embankments. There is surprisingly little information available for the stress distribution in this case. Here we show clear experimental evidence that the presence of the wall enhances the dip under a granular pile significantly. Our investigation provides insight into the influence of walls on the orientation of force chains and this appears to be key in enhancing the dip. Moreover, numerical simulations and experiments with different kinds of particles show that the vertical wall induces an alignment of isotropic particles.

Experimental and theoretical progress in pipe flow transition.

There have been many investigations of the stability of Hagen-Poiseuille flow in the 125 years since Osborne Reynolds' famous experiments on the transition to turbulence in a pipe, and yet the pipe problem remains the focus of attention of much research. Here, we discuss recent results from experimental and numerical investigations obtained in this new century. Progress has been made on three fundamental issues: the threshold amplitude of disturbances required to trigger a transition to turbulence from the laminar state; the threshold Reynolds number flow below which a disturbance decays from turbulence to the laminar state, with quantitative agreement between experimental and numerical results; and understanding the relevance of recently discovered families of unstable travelling wave solutions to transitional and turbulent pipe flow.

Nonlinear vortex development in rotating flows.

We present the results of a combined experimental and numerical investigation into steady secondary vortex flows confined between two concentric right circular cylinders. When the flow is driven by the symmetric rotation of both end walls and the inner cylinder, toroidal vortex structures arise through the creation of stagnation points (in the meridional plane) at the inner bounding cylinder or on the mid-plane of symmetry. A detailed description of the flow regimes is presented, suggesting that a cascade of such vortices can be created. Experimental results are reported, which visualize some of the new states and confirm the prediction that they are stable to (mid-plane) symmetry-breaking perturbations. We also present some brief results for the flows driven by the rotation of a single end wall. Vortex structures may also be observed at low Reynolds numbers in this geometry. We show that standard flow visualization methods lead to some interesting non-axisymmetric particle paths in this case.

Pattern transformation triggered by deformation.

Periodic elastomeric cellular solids are subjected to uniaxial compression and novel transformations of the patterned structures are found upon reaching a critical value of applied load. The results of a numerical investigation reveal that the pattern switch is triggered by a reversible elastic instability. Excellent quantitative agreement between numerical and experimental results is found and the transformations are found to be remarkably uniform across the samples. It is proposed that the mechanism will also operate at much smaller scales opening the possibility for imprinting complex patterns at the nanoscale or switching photonic and phononic crystals in a controlled way.

Sensitive signal detection using a feed-forward oscillator network.

We present the results of an experimental investigation of a network of nonlinear coupled oscillators which are coupled in feed-forward mode. By exploiting the nonlinear response of each oscillator near its intrinsic Hopf bifurcation point, we have found remarkable amplification of small signals over a narrow bandwidth with a large dynamic range. The effect is exploited to extract a small amplitude periodic signal from an input time series which is dominated by noise. Specifically, we have used this relatively simple experimental system to measure responses with a bandwidth of approximately 1% of the central frequency, amplifications of approximately 60 dB, and a dynamic range of approximately 80 dB and can extract signals from a time series with a signal to noise ratio of approximately -50 dB.

Effect of particle shape on the stress dip under a sandpile.

The results of an experimental investigation into the effects of particle shape on the stress dip formed under a 2D sandpile is reported. We find good agreement with previous results of a small dip for mixtures of disks poured from a localized source. The new finding is that the dip is significantly enhanced when elliptical particles are used. We attribute the amplification of the effect to orientational ordering induced by the shape of the grains which removes the degeneracy of circular particles.

Pattern selection by a granular wave in a rotating drum.

The results of an experimental investigation of granular segregation in a thin rotating drum are presented. A mechanism based on the presence of an uphill wave of particles has been found to govern the observed pattern of petals. Specifically we develop a simple model that captures the essential physics of the segregation and yields an algebraic expression that predicts the number of petals in the pattern.

Decay of turbulence in pipe flow.

A novel experiment has been devised which provides direct evidence for critical point behavior in the longstanding problem of the transition to turbulence in a pipe. The novelty lies in the quenching of turbulence by reducing the Reynolds number and observing the decay of disordered motion. Divergence of the time scales implies underlying deterministic dynamics which are analogous to those found in boundary crises in dynamical systems. A modulated wave packet emerges from the long term transients and this coherent state provides evidence for connections with recent theoretical developments.

Phases of granular segregation in a binary mixture.

We present results from an extensive experimental investigation into granular segregation of a shallow binary mixture in which particles are driven by frictional interactions with the surface of a vibrating horizontal tray. Three distinct phases of the mixture are established viz. binary gas (unsegregated), segregation liquid, and segregation crystal. Their ranges of existence are mapped out as a function of the system's primary control parameters using a number of measures based on Voronoi tessellation. We study the associated transitions and show that segregation can be suppressed as the total filling fraction of the granular layer, C, is decreased below a critical value, Cc, or if the dimensionless acceleration of the driving, gamma, is increased above a value gammac.

Positive assortative mating with family size as a function of predicted parental breeding values.

While other investigations have described benefits of positive assortative mating (PAM) for forest tree breeding, the allocation of resources among mates in these studies was either equal or varied, using schemes corresponding only to parental rank (i.e., more resources invested in higher-ranking parents). In this simulation study, family sizes were proportional to predicted midparent BLUP values. The distribution of midparent BLUP values was standardized by a constant, which was varied to study the range of distributions of family size. Redistributing progenies from lower- to higher-ranking families to a point where an equal number of progenies were still selected out of each family to the next generation caused minimal change in group coancestry and inbreeding in the breeding population (BP), while the additive genetic response and variance in the BP were both greatly enhanced. This generated additional genetic gains for forest plantations by selecting more superior genotypes from the BP (compared to PAM with equal family sizes) for production of improved regeneration materials. These conclusions were verified for a range of heritability under a polygenic model and under a mixed-inheritance model with a QTL contributing to the trait variation.

Cavitation in a lubrication flow between a moving sphere and a boundary.

A heavy sphere is free to move inside a rotating horizontal cylinder filled with viscous liquid. The steady motion is essentially Stokesian, and the sphere rotates at a fixed location with a lubrication layer between the ball and the wall. The symmetry of the flow field suggests there will be no force to balance the normal component of the ball's weight. However, we show that a normal force can arise when a cavitation bubble is present. The bubble size was measured as a function of the cylinder rotation rate and agrees well with a model which uses the force and torque balances on the sphere.