Part II: Fibroblasts preferentially migrate in the direction of principal strain

A growing body of evidence suggests that the sensory information from the cytoskeleton and integrins may be responsible for guiding migration during mechano- and haptotaxis. However, the dual function of these subcellular structures as mechano-sensors and -actuators is only partially understood. Using a new cell chamber described in the preceding companion paper (Ref to part I, Raeber etal. 2007a) we investigated the migration response of adhesion-dependent fibroblasts embedded 3-dimensionally within synthetic protease-sensitive poly(ethylene glycol) hydrogels to stepwise and cyclic mechanical loads. To that end, we developed a spatially and temporally resolved migration analysis technique capable of providing estimates of statistical cell migration parameters along and perpendicular to the main strain direction. Fibroblasts reoriented themselves in the direction of principal strain, increased their proteolytic migration activity and moved preferentially parallel to the principal strain axis. These results point to a possible correlation between planes of iso-strain and migration directio

Part I: A novel in-vitro system for simultaneous mechanical stimulation and time-lapse microscopy in 3D

To investigate the migration response of cells to changes in their biophysical environment, a novel uniaxial cell stimulation device (UCSD) has been designed and tested. The device is capable of applying very precise user-defined static or dynamic mechanical stimuli in a physiologically relevant strain window (up to 50%) and frequency bandwidth (up to 2Hz) to cells residing in a three-dimensional (3D) environment while single-cell migration is simultaneously measured by time-lapse microscopy. The system is an advancement over uniaxial loading devices reported to date in that it allows temporal and spatial quantification of migration as a function of the micromechanical environment. We make use of the favorable physical and biological properties of poly(ethylene glycol) hydrogels as model matrix and present a method for fabricating cell-containing hydrogel constructs. The 3D strain field within these constructs is modeled by finite element analysis. Fibroblasts reversibly altered their morphology and orientation in response to the strain field. In the succeeding companion paper we then exploit the system to analyze fibroblast motility induced by different stimulation regimes (refer to part II

Lunar base CELSS: A bioregenerative approach

During the twenty-first century, human habitation of a self-sustaining lunar base could become a reality. To achieve this goal, the occupants will have to have food, water, and an adequate atmosphere within a carefully designed environment. Advanced technology will be employed to support terrestrial life-sustaining processes on the Moon. One approach to a life support system based on food production, waste management and utilization, and product synthesis is outlined. Inputs include an atmosphere, water, plants, biodegradable substrates, and manufacutured materials such as fiberglass containment vessels from lunar resources. Outputs include purification of air and water, food, and hydrogen (H2) generated from methane (CH4). Important criteria are as follows: (1) minimize resupply from Earth; and (2) recycle as efficiently as possible

High-energy expansion of Coulomb corrections to the e+e- photoproduction cross section

First correction to the high-energy asymptotics of the total $e^+e^-$ photoproduction cross section in the electric field of a heavy atom is derived with the exact account of this field. The consideration is based on the use of the quasiclassical electron Green function in an external electric field. The next-to-leading correction to the cross section is discussed. The influence of screening on the Coulomb corrections is examined in the leading approximation. It turns out that the high-energy asymptotics of the corresponding correction is independent of the photon energy. In the region where both produced particles are relativistic, the corrections to the high-energy asymptotics of the electron (positron) spectrum are derived. Our results for the total cross section are in good agreement with experimental data for photon energies down to a few $MeV$. In addition, the corrections to the bremsstrahlung spectrum are obtained from the corresponding results for pair production.Comment: 22 pages, 7 figures, RevTeX.Typos are corrected. The numerical results, figures and conclusions remain unchanged as they were obtained using correct formula

Voter Model with Time dependent Flip-rates

We introduce time variation in the flip-rates of the Voter Model. This type of generalisation is relevant to models of ageing in language change, allowing the representation of changes in speakers' learning rates over their lifetime and may be applied to any other similar model in which interaction rates at the microscopic level change with time. The mean time taken to reach consensus varies in a nontrivial way with the rate of change of the flip-rates, varying between bounds given by the mean consensus times for static homogeneous (the original Voter Model) and static heterogeneous flip-rates. By considering the mean time between interactions for each agent, we derive excellent estimates of the mean consensus times and exit probabilities for any time scale of flip-rate variation. The scaling of consensus times with population size on complex networks is correctly predicted, and is as would be expected for the ordinary voter model. Heterogeneity in the initial distribution of opinions has a strong effect, considerably reducing the mean time to consensus, while increasing the probability of survival of the opinion which initially occupies the most slowly changing agents. The mean times to reach consensus for different states are very different. An opinion originally held by the fastest changing agents has a smaller chance to succeed, and takes much longer to do so than an evenly distributed opinion.Comment: 16 pages, 6 figure

Turning Research into Practice: Key Strategies for Developing a Shared Vision Approach for Health Education Advocacy

Public health studies thus far have not identified methods toward developing a shared vision to reduce health disparities in a unique area such as the U.S./Mexico border region. Purpose: To identify strategies to foster a shared vision among those in the media, the public, and policy arenas to help reduce health disparities in the U.S.- Mexico border. Methods: The Healthy Border 2010 research project included qualitative structured face-to-face interviews with ten individuals, each from Las Cruces, NM, El Paso, TX, and Cd. Juarez, Chih, Mexico, for a total of 30 interviewees from the media, the public and policy affiliations. Participants were identified and selected from the population of agenda-setters in the Paso Del Norte region. A snowball sample was used for studying the sometimes “hidden” population of border region agenda-setters. Data-analysis included extraction, coding, and quantifying of common themes from a transcription of interviews. Findings: Most participants (93%) suggested a systems level approach is required. The second most suggested strategy with 63% of participant support was sensitizing border leaders of the reality of issues in the area. Participants (46%) also suggested networking and media advocacy (40%) strategies as more important than the inclusion of priority audience (23%) or the proper allocation of resources (23%). Conclusion: In review of many current border health issues, there are significant gaps where a clear, shared vision is yet to emerge. When a common vision is well developed in a group or population, that is when genuine cooperative actions foster health policy development

Engineered binding to erythrocytes induces immunological tolerance to E. coli asparaginase.

Antigen-specific immune responses to protein drugs can hinder efficacy and compromise safety because of drug neutralization and secondary clinical complications. We report a tolerance induction strategy to prevent antigen-specific humoral immune responses to therapeutic proteins. Our modular, biomolecular approach involves engineering tolerizing variants of proteins such that they bind erythrocytes in vivo upon injection, on the basis of the premise that aged erythrocytes and the payloads they carry are cleared tolerogenically, driving the deletion of antigen-specific T cells. We demonstrate that binding the clinical therapeutic enzyme Escherichia coli l-asparaginase to erythrocytes in situ antigen-specifically abrogates development of antibody titers by >1000-fold and extends the pharmacodynamic effect of the drug 10-fold in mice. Additionally, a single pretreatment dose of erythrocyte-binding asparaginase tolerized mice to multiple subsequent doses of the wild-type enzyme. This strategy for reducing antigen-specific humoral responses may enable more effective and safer treatment with therapeutic proteins and drug candidates that are hampered by immunogenicity

Coherent and incoherent atomic scattering: Formalism and application to pionium interacting with matter

The experimental determination of the lifetime of pionium provides a very important test on chiral perturbation theory. This quantity is determined in the DIRAC experiment at CERN. In the analysis of this experiment, the breakup probabilities of of pionium in matter are needed to high accuracy as a theoretical input. We study in detail the influence of the target electrons. They contribute through screening and incoherent effects. We use Dirac-Hartree- Fock-Slater wavefunctions in order to determine the corresponding form factors. We find that the inner-shell electrons contribute less than the weakly bound outer electrons. Furthermore, we establish a more rigorous estimate for the magnitude of the contributions form the transverse current (magnetic terms thus far neglected in the calculations).Comment: Journal of Physics B: Atomic, Molecular and Optical Physics; (accepted; 22 pages, 6 figures, 26 references) Revised version: more detailed description of DIRAC experiment; failure of simplest models for incoherent scattering demonstrated by example

Non-neutral theory of biodiversity

We present a non-neutral stochastic model for the dynamics taking place in a meta-community ecosystems in presence of migration. The model provides a framework for describing the emergence of multiple ecological scenarios and behaves in two extreme limits either as the unified neutral theory of biodiversity or as the Bak-Sneppen model. Interestingly, the model shows a condensation phase transition where one species becomes the dominant one, the diversity in the ecosystems is strongly reduced and the ecosystem is non-stationary. This phase transition extend the principle of competitive exclusion to open ecosystems and might be relevant for the study of the impact of invasive species in native ecologies.Comment: 4 pages, 3 figur

Fixation and consensus times on a network: a unified approach

We investigate a set of stochastic models of biodiversity, population genetics, language evolution and opinion dynamics on a network within a common framework. Each node has a state, 0 < x_i < 1, with interactions specified by strengths m_{ij}. For any set of m_{ij} we derive an approximate expression for the mean time to reach fixation or consensus (all x_i=0 or 1). Remarkably in a case relevant to language change this time is independent of the network structure.Comment: 4+epsilon pages, two-column, RevTeX4, 3 eps figures; version accepted by Phys. Rev. Let