563 research outputs found
Fast adaptation of cooperative channels engenders Hopf bifurcations in auditory hair cells
Since the pioneering work of Thomas Gold, published in 1948, it has been known that we owe our sensitive sense of hearing to a process in the inner ear that can amplify incident sounds on a cycle-by-cycle basis. Called the active process, it uses energy to counteract the viscous dissipation associated with sound-evoked vibrations of the ear’s mechanotransduction apparatus. Despite its importance, the mechanism of the active process and the proximate source of energy that powers it have remained elusive, especially at the high frequencies characteristic of amniote hearing. This is partly due to our insufficient understanding of the mechanotransduction process in hair cells, the sensory receptors and amplifiers of the inner ear. It has been proposed previously that cyclical binding of Ca2+ ions to individual mechanotransduction channels could power the active process. That model, however, relied on tailored reaction rates that structurally forced the direction of the cycle. Here we ground our study on our previous model of hair-cell mechanotransduction, which relied on cooperative gating of pairs of channels, and incorporate into it the cyclical binding of Ca2+ ions. With a single binding site per channel and reaction rates drawn from thermodynamic principles, the current model shows that hair cells behave as nonlinear oscillators that exhibit Hopf bifurcations, dynamical instabilities long understood to be signatures of the active process. Using realistic parameter values, we find bifurcations at frequencies in the kilohertz range with physiological Ca2+ concentrations. The current model relies on the electrochemical gradient of Ca2+ as the only energy source for the active process and on the relative motion of cooperative channels within the stereociliary membrane as the sole mechanical driver. Equipped with these two mechanisms, a hair bundle proves capable of operating at frequencies in the kilohertz range, characteristic of amniote hearing
A Three-dimensional Printed Low-cost Anterior Shoulder Dislocation Model for Ultrasound-guided Injection Training.
Anterior shoulder dislocations are the most common, large joint dislocations that present to the emergency department (ED). Numerous studies support the use of intraarticular local anesthetic injections for the safe, effective, and time-saving reduction of these dislocations. Simulation training is an alternative and effective method for training compared to bedside learning. There are no commercially available ultrasound-compatible shoulder dislocation models. We utilized a three-dimensional (3D) printer to print a model that allows the visualization of the ultrasound anatomy (sonoanatomy) of an anterior shoulder dislocation. We utilized an open-source file of a shoulder, available from embodi3D® (Bellevue, WA, US). After approximating the relative orientation of the humerus to the glenoid fossa in an anterior dislocation, the humerus and scapula model was printed with an Ultimaker-2 Extended+ 3D® (Ultimaker, Cambridge, MA, US) printer using polylactic acid filaments. A 3D model of the external shoulder anatomy of a live human model was then created using Structure Sensor®(Occipital, San Francisco, CA, US), a 3D scanner. We aligned the printed dislocation model of the humerus and scapula within the resultant external shoulder mold. A pourable ballistics gel solution was used to create the final shoulder phantom. The use of simulation in medicine is widespread and growing, given the restrictions on work hours and a renewed focus on patient safety. The adage of see one, do one, teach one is being replaced by deliberate practice. Simulation allows such training to occur in a safe teaching environment. The ballistic gel and polylactic acid structure effectively reproduced the sonoanatomy of an anterior shoulder dislocation. The 3D printed model was effective for practicing an in-plane ultrasound-guided intraarticular joint injection. 3D printing is effective in producing a low-cost, ultrasound-capable model simulating an anterior shoulder dislocation. Future research will determine whether provider confidence and the use of intraarticular anesthesia for the management of shoulder dislocations will improve after utilizing this model
Undulation Instability of Epithelial Tissues
Treating the epithelium as an incompressible fluid adjacent to a viscoelastic
stroma, we find a novel hydrodynamic instability that leads to the formation of
protrusions of the epithelium into the stroma. This instability is a candidate
for epithelial fingering observed in vivo. It occurs for sufficiently large
viscosity, cell-division rate and thickness of the dividing region in the
epithelium. Our work provides physical insight into a potential mechanism by
which interfaces between epithelia and stromas undulate, and potentially by
which tissue dysplasia leads to cancerous invasion.Comment: 4 pages, 3 figure
Forces between clustered stereocilia minimize friction in the ear on a subnanometre scale
The detection of sound begins when energy derived from acoustic stimuli
deflects the hair bundles atop hair cells. As hair bundles move, the viscous
friction between stereocilia and the surrounding liquid poses a fundamental
challenge to the ear's high sensitivity and sharp frequency selectivity. Part
of the solution to this problem lies in the active process that uses energy for
frequency-selective sound amplification. Here we demonstrate that a
complementary part involves the fluid-structure interaction between the liquid
within the hair bundle and the stereocilia. Using force measurement on a
dynamically scaled model, finite-element analysis, analytical estimation of
hydrodynamic forces, stochastic simulation and high-resolution interferometric
measurement of hair bundles, we characterize the origin and magnitude of the
forces between individual stereocilia during small hair-bundle deflections. We
find that the close apposition of stereocilia effectively immobilizes the
liquid between them, which reduces the drag and suppresses the relative
squeezing but not the sliding mode of stereociliary motion. The obliquely
oriented tip links couple the mechanotransduction channels to this least
dissipative coherent mode, whereas the elastic horizontal top connectors
stabilize the structure, further reducing the drag. As measured from the
distortion products associated with channel gating at physiological stimulation
amplitudes of tens of nanometres, the balance of forces in a hair bundle
permits a relative mode of motion between adjacent stereocilia that encompasses
only a fraction of a nanometre. A combination of high-resolution experiments
and detailed numerical modelling of fluid-structure interactions reveals the
physical principles behind the basic structural features of hair bundles and
shows quantitatively how these organelles are adapted to the needs of sensitive
mechanotransduction.Comment: 21 pages, including 3 figures. For supplementary information, please
see the online version of the article at http://www.nature.com/natur
Homeostatic competition drives tumor growth and metastasis nucleation
We propose a mechanism for tumor growth emphasizing the role of homeostatic
regulation and tissue stability. We show that competition between surface and
bulk effects leads to the existence of a critical size that must be overcome by
metastases to reach macroscopic sizes. This property can qualitatively explain
the observed size distributions of metastases, while size-independent growth
rates cannot account for clinical and experimental data. In addition, it
potentially explains the observed preferential growth of metastases on tissue
surfaces and membranes such as the pleural and peritoneal layers, suggests a
mechanism underlying the seed and soil hypothesis introduced by Stephen Paget
in 1889 and yields realistic values for metastatic inefficiency. We propose a
number of key experiments to test these concepts. The homeostatic pressure as
introduced in this work could constitute a quantitative, experimentally
accessible measure for the metastatic potential of early malignant growths.Comment: 13 pages, 11 figures, to be published in the HFSP Journa
On the Milnor formula in arbitrary characteristic
The Milnor formula relates the Milnor number , the
double point number and the number of branches of a plane curve
singularity. It holds over the fields of characteristic zero. Melle and Wall
based on a result by Deligne proved the inequality in
arbitrary characteristic and showed that the equality
characterizes the singularities with no wild vanishing cycles. In this note we
give an account of results on the Milnor formula in characteristic . It
holds if the plane singularity is Newton non-degenerate (Boubakri et al. Rev.
Mat. Complut. (2010) 25) or if is greater than the intersection number of
the singularity with its generic polar (Nguyen H.D., Annales de l'Institut
Fourier, Tome 66 (5) (2016)). Then we improve our result on the Milnor number
of irreducible singularities (Bull. London Math. Soc. 48 (2016)). Our
considerations are based on the properties of polars of plane singularities in
characteristic .Comment: 18 page
Universal critical behavior of noisy coupled oscillators: A renormalization group study
We show that the synchronization transition of a large number of noisy
coupled oscillators is an example for a dynamic critical point far from
thermodynamic equilibrium. The universal behaviors of such critical
oscillators, arranged on a lattice in a -dimensional space and coupled by
nearest neighbors interactions, can be studied using field theoretical methods.
The field theory associated with the critical point of a homogeneous
oscillatory instability (or Hopf bifurcation of coupled oscillators) is the
complex Ginzburg-Landau equation with additive noise. We perform a perturbative
renormalization group (RG) study in a dimensional space. We
develop an RG scheme that eliminates the phase and frequency of the
oscillations using a scale-dependent oscillating reference frame. Within a
Callan-Symanzik RG scheme to two-loop order in perturbation theory, we find
that the RG fixed point is formally related to the one of the model
dynamics of the real Ginzburg-Landau theory with an O(2) symmetry of the order
parameter. Therefore, the dominant critical exponents for coupled oscillators
are the same as for this equilibrium field theory. This formal connection with
an equilibrium critical point imposes a relation between the correlation and
response functions of coupled oscillators in the critical regime. Since the
system operates far from thermodynamic equilibrium, a strong violation of the
fluctuation-dissipation relation occurs and is characterized by a universal
divergence of an effective temperature. The formal relation between critical
oscillators and equilibrium critical points suggests that long-range phase
order exists in critical oscillators above two dimensions.Comment: 24 pages, published in 200
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Experimental Transport Benchmarks for Physical Dosimetry to Support Development of Fast-Neutron Therapy with Neutron Capture Augmentation
The Idaho National Laboratory (INL), the University of Washington (UW) Neutron Therapy Center, the University of Essen (Germany) Neutron Therapy Clinic, and the Northern Illinois University(NIU) Institute for Neutron Therapy at Fermilab have been collaborating in the development of fast-neutron therapy (FNT) with concurrent neutron capture (NCT) augmentation [1,2]. As part of this effort, we have conducted measurements to produce suitable benchmark data as an aid in validation of advanced three-dimensional treatment planning methodologies required for successful administration of FNT/NCT. Free-beam spectral measurements as well as phantom measurements with Lucite{trademark} cylinders using thermal, resonance, and threshold activation foil techniques have now been completed at all three clinical accelerator facilities. The same protocol was used for all measurements to facilitate intercomparison of data. The results will be useful for further detailed characterization of the neutron beams of interest as well as for validation of various charged particle and neutron transport codes and methodologies for FNT/NCT computational dosimetry, such as MCNP [3], LAHET [4], and MINERVA [5]
Search for Doubly-Charged Higgs Boson Production at HERA
A search for the single production of doubly-charged Higgs bosons H^{\pm \pm}
in ep collisions is presented. The signal is searched for via the Higgs decays
into a high mass pair of same charge leptons, one of them being an electron.
The analysis uses up to 118 pb^{-1} of ep data collected by the H1 experiment
at HERA. No evidence for doubly-charged Higgs production is observed and mass
dependent upper limits are derived on the Yukawa couplings h_{el} of the Higgs
boson to an electron-lepton pair. Assuming that the doubly-charged Higgs only
decays into an electron and a muon via a coupling of electromagnetic strength
h_{e \mu} = \sqrt{4 \pi \alpha_{em}} = 0.3, a lower limit of 141 GeV on the
H^{\pm\pm} mass is obtained at the 95% confidence level. For a doubly-charged
Higgs decaying only into an electron and a tau and a coupling h_{e\tau} = 0.3,
masses below 112 GeV are ruled out.Comment: 15 pages, 3 figures, 1 tabl
Forward pi^0 Production and Associated Transverse Energy Flow in Deep-Inelastic Scattering at HERA
Deep-inelastic positron-proton interactions at low values of Bjorken-x down
to x \approx 4.10^-5 which give rise to high transverse momentum pi^0 mesons
are studied with the H1 experiment at HERA. The inclusive cross section for
pi^0 mesons produced at small angles with respect to the proton remnant (the
forward region) is presented as a function of the transverse momentum and
energy of the pi^0 and of the four-momentum transfer Q^2 and Bjorken-x.
Measurements are also presented of the transverse energy flow in events
containing a forward pi^0 meson. Hadronic final state calculations based on QCD
models implementing different parton evolution schemes are confronted with the
data.Comment: 27 pages, 8 figures and 3 table
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