Measuring cell adhesion forces with the atomic force microscope at the molecular level

In the past 25 years many techniques have been developed to characterize cell adhesion and to quantify adhesion forces. Atomic force microscopy (AFM) has been used to measure forces in the pico-newton range, an experimental technique known as force spectroscopy. We modified such an AFM to measure adhesion forces between live cells or between cells and surfaces. This strategy required functionalizing the surface of the sensors for immobilizing the cell. We used Dictyostelium discoideum cells which respond to starvation by surface expression of the adhesion molecule csA and consequent aggregation to measure the adhesion force of a single csA-csA bond. Relevant experimental parameters include the duration of contact between the interacting surfaces, the force against which this contact is maintained, the number and specificity of interacting adhesion molecules and the constituents of the medium in which the interaction occurs. This technology also permits the measurement of the viscoelastic properties of single cells or cell layers. Copyright (C) 2002 S, Karger AG, Basel

Canard-like phenomena in piecewise-smooth Van der Pol systems

We show that a nonlinear, piecewise-smooth, planar dynamical system can exhibit canard phenomena. Canard solutions and explosion in nonlinear, piecewise-smooth systems can be qualitatively more similar to the phenomena in smooth systems than piecewise-linear systems, since the nonlinearity allows for canards to transition from small cycles to canards ``with heads." The canards are born of a bifurcation that occurs as the slow-nullcline coincides with the splitting manifold. However, there are conditions under which this bifurcation leads to a phenomenon called super-explosion, the instantaneous transition from a globally attracting periodic orbit to relaxations oscillations. Also, we demonstrate that the bifurcation---whether leading to canards or super-explosion---can be subcritical.Comment: 17 pages, 11 figure

Understanding of matrix embedding: a theoretical spectroscopic study of CO interacting with Ar clusters, surfaces and matrices

Through benchmark studies, we explore the performance of PBE density functional theory, with and without Grimme's dispersion correction (DFT-D3), in predicting spectroscopic properties for molecules interacting with rare gas matrices. Here, a periodic-dispersion corrected model of matrix embedding is used for the first time. We use PBE-D3 to determine the equilibrium structures and harmonic vibrational frequencies of carbon monoxide in interaction with small Ar clusters (CO–Arn, n = 1, 2, 3), with an Ar surface and embedded in an Ar matrix. Our results show a converging trend for both the vibrational frequencies and binding energies when going from the gas-phase to a fully periodic approach describing CO embedding in Ar. This trend is explained in terms of solvation effects, as CO is expected to alter the structure of the Ar matrix. Due to a competition between CO–Ar interactions and Ar–Ar interactions, perturbations caused by the presence of CO are found to extend over several Å in the matrix. Accordingly, it is mandatory to fully relax rare gas matrices when studying their interaction with embedded molecules. Moreover, we show that the binding energy per Ar is almost constant (∼−130 cm−1 atom−1) regardless of the environment of the CO molecule. Finally, we show that the concentration of the solute into the cold matrix influences the spectroscopic parameters of molecules embedded into cold matrices. We suggest hence that several cautions should be taken before comparing these parameters to gas phase measurements and to theoretical data of isolated species

A Sunyaev-Zel'dovich map of the massive core in the luminous X-ray cluster RXJ1347-1145

We have mapped the Sunyaev-Zel'dovich decrement (hereafter SZ) in the direction of the most luminous X-ray cluster known to date, RXJ1347-1145, at z=0.451. This has been achieved with an angular resolution of about 23'' using the Diabolo photometer running on the IRAM 30 meter radio telescope. We present here a map of the cluster central region at 2.1mm. The Comptonization parameter towards the cluster center, \yc=(12.7^{+2.9}_{-3.1})\times 10^{-4}, corresponds to the deepest SZ decrement ever observed. Using the gas density distribution derived from X-ray data, this measurement implies a gas temperature \te=16.2 \pm 3.8 keV. The resulting total mass of the cluster is, under hydrostatic equilibrium, $M(r<1 Mpc)=(1.0 \pm 0.3) \times 10^{15} M_\odot$ for a corresponding gas fraction $f_{gas}(r<1 Mpc)=(19.5 \pm 5.8)$.Comment: 16 pages, 2 figures, accepted for publication in ApJ Letter

Infinite Kinematic Self-Similarity and Perfect Fluid Spacetimes

Perfect fluid spacetimes admitting a kinematic self-similarity of infinite type are investigated. In the case of plane, spherically or hyperbolically symmetric space-times the field equations reduce to a system of autonomous ordinary differential equations. The qualitative properties of solutions of this system of equations, and in particular their asymptotic behavior, are studied. Special cases, including some of the invariant sets and the geodesic case, are examined in detail and the exact solutions are provided. The class of solutions exhibiting physical self-similarity are found to play an important role in describing the asymptotic behavior of the infinite kinematic self-similar models.Comment: 38 pages, 6 figures. Accepted for publication in General Relativity & Gravitatio

Characterisation of AMS H35 HV-CMOS monolithic active pixel sensor prototypes for HEP applications

Monolithic active pixel sensors produced in High Voltage CMOS (HV-CMOS) technology are being considered for High Energy Physics applications due to the ease of production and the reduced costs. Such technology is especially appealing when large areas to be covered and material budget are concerned. This is the case of the outermost pixel layers of the future ATLAS tracking detector for the HL-LHC. For experiments at hadron colliders, radiation hardness is a key requirement which is not fulfilled by standard CMOS sensor designs that collect charge by diffusion. This issue has been addressed by depleted active pixel sensors in which electronics are embedded into a large deep implantation ensuring uniform charge collection by drift. Very first small prototypes of hybrid depleted active pixel sensors have already shown a radiation hardness compatible with the ATLAS requirements. Nevertheless, to compete with the present hybrid solutions a further reduction in costs achievable by a fully monolithic design is desirable. The H35DEMO is a large electrode full reticle demonstrator chip produced in AMS 350 nm HV-CMOS technology by the collaboration of Karlsruher Institut f\"ur Technologie (KIT), Institut de F\'isica d'Altes Energies (IFAE), University of Liverpool and University of Geneva. It includes two large monolithic pixel matrices which can be operated standalone. One of these two matrices has been characterised at beam test before and after irradiation with protons and neutrons. Results demonstrated the feasibility of producing radiation hard large area fully monolithic pixel sensors in HV-CMOS technology. H35DEMO chips with a substrate resistivity of 200$\Omega$ cm irradiated with neutrons showed a radiation hardness up to a fluence of $10^{15}$n$_{eq}$cm$^{-2}$ with a hit efficiency of about 99% and a noise occupancy lower than $10^{-6}$ hits in a LHC bunch crossing of 25ns at 150V

On the Proof of Dark Matter, the Law of Gravity and the Mass of Neutrinos

We develop a new method to predict the density associated with weak lensing maps of (un)relaxed clusters in a range of theories interpolating between GR and MOND (General Relativity and Modified Newtonian Dynamics). We apply it to fit the lensing map of the bullet merging cluster 1E0657-56, in order to constrain more robustly the nature and amount of collisionless matter in clusters {\it beyond} the usual assumption of spherical equilibrium (Pointecouteau & Silk 2005) and the validity of GR on cluster scales (Clowe et al. 2006). Strengthening the proposal of previous authors we show that the bullet cluster is dominated by a collisionless -- most probably non-baryonic -- component in GR as well as in MOND, a result consistent with the dynamics of many X-ray clusters. Our findings add to the number of known pathologies for a purely baryonic MOND, including its inability to fit the latest data from the Wilkinson Microwave Anisotropy Probe. A plausible resolution of all these issues and standard issues of Cold Dark Matter with galaxy rotation curves is the "marriage" of MOND with ordinary hot neutrinos of 2eV. This prediction is just within the GR-independent maximum of neutrino mass from current $\beta$-decay experiments, and is falsifiable by the Karlsruhe Tritium Neutrino (KATRIN) experiment by 2009. Issues of consistency with strong lensing arcs and the large relative velocity of the two clusters comprising the bullet cluster are also addressed.Comment: 4 pages, 1 figure, accepted for publication in ApJL. Added a simple model of the bullet cluster's high velocity in TeVeS, and discussions of sterile neutrinos and of non-uniqueness of the lensing deprojectio

Horizon Profile Checkpoints For Low-Altitude Aircraft

A technique for utilizing on-board sensed horizon profiles and computer stored reference horizon profiles to provide navigation check points for low-altitude aircraft is described. The technique has been analyzed using digitized terrain data and computer simulations to select the best method of horizon profile comparison, to determine horizon data density requirements, and to provide performance comparisons, system error limitations, and tradeoffs. Results of these analyses are shown to support feasibility conclusions and system parameter tradeoffs. Copyright © 1976 by The Institute of Electrical and Electronics Engineers, Inc

Pricing High Growth Firms: Arbitrage Opportunities in the Inc. 100

The ability of the market to price high growth stocks is examined by analyzing the returns to simple investment portfolio strategies based on public information. The portfolios consist of shares in the firms listed in the Inc. 100 Ranking of the fastest growing public companies in America. The results indicate that significant abnormal returns are generated by these strategies, even after adjusting for risk. Although the tests could potentially be affected by a form of survivorship bias, supplementary analyses indicate that this is unlikely to be the case here. These results support the assumption that markets have difficulties pricing high-growth entities, leaving significant arbitrage opportunities in these stocks and validating the use of various market timing practices

LRP1 Has a Predominant Role in Production over Clearance of Aβ in a Mouse Model of Alzheimer's Disease.

The low-density lipoprotein receptor-related protein-1 (LRP1) has a dual role in the metabolism of the amyloid precursor protein (APP). In cellular models, LRP1 enhances amyloid-β (Aβ) generation via APP internalization and thus its amyloidogenic processing. However, conditional knock-out studies in mice define LRP1 as an important mediator for the clearance of extracellular Aβ from brain via cellular degradation or transcytosis across the blood-brain barrier (BBB). In order to analyze the net effect of LRP1 on production and clearance of Aβ in vivo, we crossed mice with impaired LRP1 function with a mouse model of Alzheimer's disease (AD). Analysis of Aβ metabolism showed that, despite reduced Aβ clearance due to LRP1 inactivation in vivo, less Aβ was found in cerebrospinal fluid (CSF) and brain interstitial fluid (ISF). Further analysis of APP metabolism revealed that impairment of LRP1 in vivo shifted APP processing from the Aβ-generating amyloidogenic cleavage by beta-secretase to the non-amyloidogenic processing by alpha-secretase as shown by a decrease in extracellular Aβ and an increase of soluble APP-α (sAPP-α). This shift in APP processing resulted in overall lower Aβ levels and a reduction in plaque burden. Here, we present for the first time clear in vivo evidence that global impairment of LRP1's endocytosis function favors non-amyloidogenic processing of APP due to its reduced internalization and subsequently, reduced amyloidogenic processing. By inactivation of LRP1, the inhibitory effect on Aβ generation overrules the simultaneous impaired Aβ clearance, resulting in less extracellular Aβ and reduced plaque deposition in a mouse model of AD