Cell organization in soft media due to active mechanosensing

Adhering cells actively probe the mechanical properties of their environment and use the resulting information to position and orient themselves. We show that a large body of experimental observations can be consistently explained from one unifying principle, namely that cells strengthen contacts and cytoskeleton in the direction of large effective stiffness. Using linear elasticity theory to model the extracellular environment, we calculate optimal cell organization for several situations of interest and find excellent agreement with experiments for fibroblasts, both on elastic substrates and in collagen gels: cells orient in the direction of external tensile strain, they orient parallel and normal to free and clamped surfaces, respectively, and they interact elastically to form strings. Our method can be applied for rational design of tissue equivalents. Moreover our results indicate that the concept of contact guidance has to be reevaluated. We also suggest that cell-matrix contacts are upregulated by large effective stiffness in the environment because in this way, build-up of force is more efficient.Comment: Revtex, 7 pages, 4 Postscript files include

Intravenous tPA therapy does not worsen acute intracerebral hemorrhage in mice

Tissue plasminogen activator (tPA) is the only FDA-approved treatment for reperfusing ischemic strokes. But widespread use of tPA is still limited by fears of inadvertently administering tPA in patients with intracerebral hemorrhage (ICH). Surprisingly, however, the assumption that tPA will worsen ICH has never been biologically tested. Here, we assessed the effects of tPA in two models of ICH. In a mouse model of collagenase-induced ICH, hemorrhage volumes and neurological deficits after 24 hrs were similar in saline controls and tPA-treated mice, whereas heparin-treated mice had 3-fold larger hematomas. In a model of laser-induced vessel rupture, tPA also did not worsen hemorrhage volumes, while heparin did. tPA is known to worsen neurovascular injury by amplifying matrix metalloproteinases during cerebral ischemia. In contrast, tPA did not upregulate matrix metalloproteinases in our mouse ICH models. In summary, our experimental data do not support the assumption that intravenous tPA has a deleterious effect in acute ICH. However, due to potential species differences and the inability of models to fully capture the dynamics of human ICH, caution is warranted when considering the implications of these findings for human therapy

A Measurement of the Interference Structure Function, R_LT, for the 12C(e,e'p) reaction in the Quasielastic Region

The coincidence cross-section and the interference structure function, R_LT, were measured for the 12C(e,e'p) 11B reaction at quasielastic kinematics and central momentum transfer of q=400 MeV/c. The measurement was at an opening angle of theta_pq=11 degrees, covering a range in missing energy of E_m = 0 to 65 MeV. The R_LT structure function is found to be consistent with zero for E_m > 50 MeV, confirming an earlier study which indicated that R_L vanishes in this region. The integrated strengths of the p- and s-shell are compared with a Distorted Wave Impulse Approximation calculation. The s-shell strength and shape are compared with a Hartree Fock-Random Phase Approximation calculation. The DWIA calculation overestimates the cross sections for p- and s-shell proton knockout as expected, but surprisingly agrees with the extracted R_LT value for both shells. The HF-RPA calculation describes the data more consistently, which may be due to the inclusion of 2-body currents in this calculation.Comment: 8 Pages LaTex, 5 postscript figures. Submitted to Phys. Rev.

The fables of pity: Rousseau, Mandeville and the animal-fable

Copyright @ 2012 Edinburgh University PressPrompted by Derrida’s work on the animal-fable in eighteenth-century debates about political power, this article examines the role played by the fiction of the animal in thinking of pity as either a natural virtue (in Rousseau’s Second Discourse) or as a natural passion (in Mandeville’s The Fable of the Bees). The war of fables between Rousseau and Mandeville – and their hostile reception by Samuel Johnson and Adam Smith – reinforce that the animal-fable illustrates not so much the proper of man as the possibilities and limitations of a moral philosophy that is unable to address the political realities of the state

Measurement of the Transverse-Longitudinal Cross Sections in the p (e,e'p)pi0 Reaction in the Delta Region

Accurate measurements of the p(e,e?p)pi0 reaction were performed at Q^2=0.127(GeV/c)^2 in the Delta resonance energy region. The experiments at the MIT-Bates Linear Accelerator used an 820 MeV polarized electron beam with the out of plane magnetic spectrometer system (OOPS). In this paper we report the first simultaneous determination of both the TL and TL? (``fifth" or polarized) cross sections at low Q^{2} where the pion cloud contribution dominates the quadrupole amplitudes (E2 and C2). The real and imaginary parts of the transverse-longitudinal cross section provide both a sensitive determination of the Coulomb quadrupole amplitude and a test of reaction calculations. Comparisons with model calculations are presented. The empirical MAID calculation gives the best overall agreement with this accurate data. The parameters of this model for the values of the resonant multipoles are |M_{1+}(I=3/2)|= (40.9 \pm 0.3)10^{-3}/m_pi, CMR= C2/M1= -6.5 \pm 0.3%, EMR=E2/M1=-2.2 \pm 0.9%, where the errors are due to the experimental uncertainties.Comment: 10 pages, 3 figures, minor corrections and addition

Quantifying the Microvascular Origin of BOLD-fMRI from First Principles with Two-Photon Microscopy and an Oxygen-Sensitive Nanoprobe

The blood oxygenation level-dependent (BOLD) contrast is widely used in functional magnetic resonance imaging (fMRI) studies aimed at investigating neuronal activity. However, the BOLD signal reflects changes in blood volume and oxygenation rather than neuronal activity per se. Therefore, understanding the transformation of microscopic vascular behavior into macroscopic BOLD signals is at the foundation of physiologically informed noninvasive neuroimaging. Here, we use oxygen-sensitive two-photon microscopy to measure the BOLD-relevant microvascular physiology occurring within a typical rodent fMRI voxel and predict the BOLD signal from first principles using those measurements. The predictive power of the approach is illustrated by quantifying variations in the BOLD signal induced by the morphological folding of the human cortex. This framework is then used to quantify the contribution of individual vascular compartments and other factors to the BOLD signal for different magnet strengths and pulse sequences.National Institutes of Health (U.S.) (Grant P41RR14075)National Institutes of Health (U.S.) (Grant R01NS067050)National Institutes of Health (U.S.) (Grant R01NS057198)National Institutes of Health (U.S.) (Grant R01EB000790)American Heart Association (Grant 11SDG7600037)Advanced Multimodal NeuroImaging Training Program (R90DA023427