G. Allen

Predictions for the Rates of Compact Binary Coalescences Observable by Ground-based Gravitational-wave Detectors

We present an up-to-date, comprehensive summary of the rates for all types of compact binary coalescence sources detectable by the initial and advanced versions of the ground-based gravitational-wave detectors LIGO and Virgo. Astrophysical estimates for compact-binary coalescence rates depend on a number of assumptions and unknown model parameters and are still uncertain. The most confident among these estimates are the rate predictions for coalescing binary neutron stars which are based on extrapolations from observed binary pulsars in our galaxy. These yield a likely coalescence rate of 100 Myr−1 per Milky Way Equivalent Galaxy (MWEG), although the rate could plausibly range from 1 Myr−1 MWEG−1 to 1000 Myr−1 MWEG−1 (Kalogera et al 2004 Astrophys. J. 601 L179; Kalogera et al 2004 Astrophys. J. 614 L137 (erratum)). We convert coalescence rates into detection rates based on data from the LIGO S5 and Virgo VSR2 science runs and projected sensitivities for our advanced detectors. Using the detector sensitivities derived from these data, we find a likely detection rate of 0.02 per year for Initial LIGO–Virgo interferometers, with a plausible range between 2 × 10−4 and 0.2 per year. The likely binary neutron–star detection rate for the Advanced LIGO–Virgo network increases to 40 events per year, with a range between 0.4 and 400 per year.

Mechanism of shape determination in motile cells

The shape of motile cells is determined by many dynamic processes spanning several orders of magnitude in space and time, from local polymerization of actin monomers at subsecond timescales to global, cell-scale geometry that may persist for hours. Understanding the mechanism of shape determination in cells has proved to be extremely challenging due to the numerous components involved and the complexity of their interactions. Here we harness the natural phenotypic variability in a large population of motile epithelial keratocytes from fish (Hypsophrys nicaraguensis) to reveal mechanisms of shape determination. We find that the cells inhabit a low-dimensional, highly correlated spectrum of possible functional states. We further show that a model of actin network treadmilling in an inextensible membrane bag can quantitatively recapitulate this spectrum and predict both cell shape and speed. Our model provides a simple biochemical and biophysical basis for the observed morphology and behaviour of motile cells.

Myosin II contributes to cell-scale actin network treadmilling through network disassembly

Crawling locomotion of eukaryotic cells is achieved by a process dependent on the actin cytoskeleton: protrusion of the leading edge requires assembly of a network of actin filaments, which must be disassembled at the cell rear for sustained motility. Although ADF/cofilin proteins have been shown to contribute to actin disassembly, it is not clear how activity of these locally acting proteins could be coordinated over the distance scale of the whole cell. Here we show that non-muscle myosin II has a direct role in actin network disassembly in crawling cells. In fish keratocytes undergoing motility, myosin II is concentrated in regions at the rear with high rates of network disassembly. Activation of myosin II by ATP in detergent-extracted cytoskeletons results in rear-localized disassembly of the actin network. Inhibition of myosin II activity and stabilization of actin filaments synergistically impede cell motility, suggesting the existence of two disassembly pathways, one of which requires myosin II activity. Our results establish the importance of myosin II as an enzyme for actin network disassembly; we propose that gradual formation and reorganization of an actomyosin network provides an intrinsic destruction timer, enabling long-range coordination of actin network treadmilling in motile cells.

Search for gravitational-wave bursts associated with gamma-ray bursts using data from LIGO science run 5 and VIRGO science run 1.

We present the results of a search for gravitational-wave bursts associated with 137 gamma-ray bursts (GRBs) that were detected by satellite-based gamma-ray experiments during the fifth LIGO science run and first Virgo science run. The data used in this analysis were collected from 2005 November 4 to 2007 October 1, and most of the GRB triggers were from the Swift satellite. The search uses a coherent network analysis method that takes into account the different locations and orientations of the interferometers at the three LIGO-Virgo sites. We find no evidence for gravitational-wave burst signals associated with this sample of GRBs. Using simulated short-duration (<1 s) waveforms, we set upper limits on the amplitude of gravitational waves associated with each GRB. We also place lower bounds on the distance to each GRB under the assumption of a fixed energy emission in gravitational waves, with typical limits of D ~ 15 Mpc (E_GW^iso / 0.01 M_o c^2)^1/2 for emission at frequencies around 150 Hz, where the LIGO-Virgo detector network has best sensitivity. We present astrophysical interpretations and implications of these results, and prospects for corresponding searches during future LIGO-Virgo runs.

Bipedal Locomotion in Crawling Cells

Many complex cellular processes from mitosis to cell motility depend on the ability of the cytoskeleton to generate force. Force-generating systems that act on elastic cytoskeletal elements are prone to oscillating instabilities. In this work, we have measured spontaneous shape and movement oscillations in motile fish epithelial keratocytes. In persistently polarized, fan-shaped cells, retraction of the trailing edge on one side of the cell body is out of phase with retraction on the other side, resulting in periodic lateral oscillation of the cell body. We present a physical description of keratocyte oscillation in which periodic retraction of the trailing edge is the result of elastic coupling with the leading edge. Consistent with the predictions of this model, the observed frequency of oscillation correlates with cell speed. In addition, decreasing the strength of adhesion to the substrate reduces the elastic force required for retraction, causing cells to oscillate with higher frequency at relatively lower speeds. These results demonstrate that simple elastic coupling between movement at the front of the cell and movement at the rear can generate large-scale mechanical integration of cell behavior.

Electrophoresis of Cellular Membrane Components Creates the Directional Cue Guiding Keratocyte Galvanotaxis

BACKGROUND Motile cells exposed to an external direct current electric field will reorient and migrate along the direction of the electric potential in a process known as galvanotaxis. The underlying physical mechanism that allows a cell to sense an electric field is unknown, although several plausible hypotheses have been proposed. In this work we evaluate the validity of each of these mechanisms. RESULTS We find that the directional motile response of fish epidermal cells to the cathode in an electric field does not require extracellular sodium or potassium, is insensitive to membrane potential, and is also insensitive to perturbation of calcium, sodium, hydrogen, or chloride ion transport across the plasma membrane. Cells migrate in the direction of applied forces from laminar fluid flow, but reversal of electro-osmotic flow did not affect the galvanotactic response. Galvanotaxis fails when extracellular pH is below 6, suggesting that the effective charge of membrane components might be a crucial factor. Slowing the migration of membrane components with an increase in aqueous viscosity slows the kinetics of the galvanotactic response. In addition, inhibition of PI3K reverses the cells response to the anode, suggesting the existence of multiple signaling pathways downstream of the galvanotactic signal. CONCLUSIONS Our results are most consistent with the hypothesis that electrophoretic redistribution of membrane components of the motile cell is the primary physical mechanism for motile cells to sense an electric field. This chemical polarization of the cellular membrane is then transduced by intracellular signaling pathways canonical to chemotaxis to dictate the cells direction of travel.

First search for gravitational waves from the youngest known neutron star

We present a search for periodic gravitational waves from the neutron star in the supernova remnant Cassiopeia A. The search coherently analyzes data in a 12 day interval taken from the fifth science run of the Laser Interferometer Gravitational-Wave Observatory. It searches gravitational-wave frequencies from 100 to 300 Hz and covers a wide range of first and second frequency derivatives appropriate for the age of the remnant and for different spin-down mechanisms. No gravitational-wave signal was detected. Within the range of search frequencies, we set 95% confidence upper limits of (0.7-1.2) × 10–24 on the intrinsic gravitational-wave strain, (0.4-4) × 10–4 on the equatorial ellipticity of the neutron star, and 0.005-0.14 on the amplitude of r-mode oscillations of the neutron star. These direct upper limits beat indirect limits derived from energy conservation and enter the range of theoretical predictions involving crystalline exotic matter or runaway r-modes. This paper is also the first gravitational-wave search to present upper limits on the r-mode amplitude.

Computational Simulations of Airflow in an In Vitro Model of the Pediatric Upper Airways

In order to understand mechanisms of gas and aerosol transport in the human respiratory system airflow in the upper airways of a pediatric subject (male aged 5) was calculated using Computational Fluid Dynamic techniques. An in vitro reconstruction of the subjects anatomy was produced from MRI images. Flow fields were solved for steady inhalation at 6.4 and 8 LPM. For validation of the numerical solution, airflow in an adult cadaver based trachea was solved using identical numerical methods. Comparisons were made between experimental results and computational data of the adult model to determine solution validity. It was found that numerical simulations can provide an accurate representation of axial velocities and turbulence intensity. Data on flow resistance, axial velocities, secondary velocity vectors, and turbulent kinetic energy are presented for the pediatric case. Turbulent kinetic energy and axial velocities were heavily dependant on flow rate, whereas turbulence intensity varied less over the flow rates studied. The laryngeal jet from an adult model was compared to the laryngeal jet in the pediatric model based on Tracheal Reynolds number. The pediatric case indicated that children show axial velocities in the laryngeal jet comparable to adults, who have much higher tracheal Reynolds numbers than children due to larger characteristic dimensions. The intensity of turbulence follows a similar trend, with higher turbulent kinetic energy levels in the pediatric model than would be expected from measurements in adults at similar tracheal Reynolds numbers. There was reasonable agreement between the location of flow structures between adults and children, suggesting that an unknown length scale correlation factor could exist that would produce acceptable predictions of pediatric velocimetry based off of adult data sets. A combined scale for turbulent intensity as well may not exist due to the complex nature of turbulence production and dissipation.

Balance between cell−substrate adhesion and myosin contraction determines the frequency of motility initiation in fish keratocytes

Significance Symmetry breaking and motility initiation are required for many physiological and pathological processes, but the mechanical mechanisms that drive symmetry breaking are not well understood. Fish keratocytes break symmetry spontaneously, in the absence of external cues, with myosin-driven actin flow preceding rear retraction. Here we combine experimental manipulations and mathematical modeling to show that the critical event for symmetry breaking is a flow-dependent, nonlinear switch in adhesion strength. Moreover, our results suggest that mechanical feedback among actin network flow, myosin, and adhesion is sufficient to amplify stochastic fluctuations in actin flow and trigger symmetry breaking. Our mechanical model for symmetry breaking in the relatively simple keratocyte provides a framework for understanding motility initiation in more complex cell types. Cells are dynamic systems capable of spontaneously switching among stable states. One striking example of this is spontaneous symmetry breaking and motility initiation in fish epithelial keratocytes. Although the biochemical and mechanical mechanisms that control steady-state migration in these cells have been well characterized, the mechanisms underlying symmetry breaking are less well understood. In this work, we have combined experimental manipulations of cell−substrate adhesion strength and myosin activity, traction force measurements, and mathematical modeling to develop a comprehensive mechanical model for symmetry breaking and motility initiation in fish epithelial keratocytes. Our results suggest that stochastic fluctuations in adhesion strength and myosin localization drive actin network flow rates in the prospective cell rear above a critical threshold. Above this threshold, high actin flow rates induce a nonlinear switch in adhesion strength, locally switching adhesions from gripping to slipping and further accelerating actin flow in the prospective cell rear, resulting in rear retraction and motility initiation. We further show, both experimentally and with model simulations, that the global levels of adhesion strength and myosin activity control the stability of the stationary state: The frequency of symmetry breaking decreases with increasing adhesion strength and increases with increasing myosin contraction. Thus, the relative strengths of two opposing mechanical forces—contractility and cell−substrate adhesion—determine the likelihood of spontaneous symmetry breaking and motility initiation.

A CFD study of the throat during aerosol drug delivery using heliox and air

Abstract Deposition of a series of monodisperse aerosol injections in 70/30 helium/oxygen (Heliox) and air for the larynx and trachea was numerically analyzed with Computational Fluid Dynamics (CFD) software. The CFD mesh was prepared from a cadaver-based throat (female, aged 84). Monosize droplets ranging between 0.25 and 10 μm in droplet radius were used for both Heliox and air simulations. The coupled simulation was performed with the KIVA-3V software for a flow rate of 18 l / min , an approximate adult breathing condition. Flow measurements were validated against previous experimental simulations of this cadaver model. It was found that Heliox and air had highly similar flow structures in the simulated region. Flow measurements such as turbulent kinetic energy and velocity magnitude typically differed by less than 5%. Particle deposition was shown to be affected by these small differences in the carrier gas. The use of Heliox led to less particle deposition for all droplet sizes indicating that Heliox will lead to a reduction of in vivo extrathoracic deposition due to the intrinsic properties of the gas phase. This numerical simulation suggests that a continuous Heliox phase provides a stronger steering force to the discrete phase.