Agent-based computational modeling of wounded epithelial cell monolayers

Computational modeling of biological systems, or ‘in silico biology’ is an emerging tool for understanding structure and order in biological tissues. Computational models of the behavior of epithelial cells in monolayer cell culture have been developed and used to predict the healing characteristics of scratch wounds made to urothelial cell cultures maintained in low and physiological [Ca2+] environments. Both computational models and in vitro experiments demonstrated that in low exogenous [Ca2+], the closure of 500mm scratch wounds was achieved primarily by cell migration into the denuded area. The wound healing rate in low (0.09mM) [Ca2+] was approximately twice as rapid as in physiological (2mM) [Ca2+]. Computational modeling predicted that in cell cultures that are actively proliferating, no increase in the fraction of cells in S-phase would be expected, and this conclusion was supported experimentally in vitro by BrdU incorporation assay. We have demonstrated that a simple rule-based model of cell behavior, incorporating rules relating to contact inhibition of proliferation and migration, is sufficient to qualitatively predict the calcium-dependent pattern of wound closure observed in vitro. Differences between the in vitro and in silico models suggest a role for wound-induced signaling events in urothelial cell cultures

Flight Test Results from the NF-15B Intelligent Flight Control System (IFCS) Project with Adaptation to a Simulated Stabilator Failure

Adaptive flight control systems have the potential to be more resilient to extreme changes in airplane behavior. Extreme changes could be a result of a system failure or of damage to the airplane. A direct adaptive neural-network-based flight control system was developed for the National Aeronautics and Space Administration NF-15B Intelligent Flight Control System airplane and subjected to an inflight simulation of a failed (frozen) (unmovable) stabilator. Formation flight handling qualities evaluations were performed with and without neural network adaptation. The results of these flight tests are presented. Comparison with simulation predictions and analysis of the performance of the adaptation system are discussed. The performance of the adaptation system is assessed in terms of its ability to decouple the roll and pitch response and reestablish good onboard model tracking. Flight evaluation with the simulated stabilator failure and adaptation engaged showed that there was generally improvement in the pitch response; however, a tendency for roll pilot-induced oscillation was experienced. A detailed discussion of the cause of the mixed results is presented

The Epitheliome: agent-based modelling of the social behaviour of cells

We have developed a new computational modelling paradigm for predicting the emergent behaviour resulting from the interaction of cells in epithelial tissue. As proof-of-concept, an agent-based model, in which there is a one-to-one correspondence between biological cells and software agents, has been coupled to a simple physical model. Behaviour of the computational model is compared with the growth characteristics of epithelial cells in monolayer culture, using growth media with low and physiological calcium concentrations. Results show a qualitative fit between the growth characteristics produced by the simulation and the in vitro cell models

The role of corticosterone in human hypothalamic– pituitary–adrenal axis feedback

Objective  In humans, the glucocorticoid corticosterone circulates in blood at 10–20-fold lower levels than cortisol, but is found in higher relative amounts in postmortem brain samples. Access of cortisol and corticosterone to the central nervous system may not be equal. Additionally, the relative affinities for the glucocorticoid and mineralocorticoid receptors differ, such that corticosterone may play a significant role in human brain function. Design  We measured cortisol and corticosterone levels in paired plasma and cerebrospinal fluid (CSF) samples. To test the relative potency of cortisol vs. corticosterone on hypothalamic–pituitary–adrenal (HPA) feedback, subjects underwent a three-phase, single-blind, randomized study assessing the postmetyrapone ACTH response over 3 h to an intravenous bolus of vehicle, cortisol or corticosterone (0·15 mg/kg and 0·04 mg/kg). Participants  Outpatients undergoing diagnostic lumbar puncture who were subsequently deemed to be free of disease. Feedback was tested in healthy male volunteers. Measurements  Plasma and CSF corticosterone to cortisol ratio was calculated and the ACTH response over time after the bolus glucocorticoid measured. Results  Plasma corticosterone : cortisol was 0·069 ± 0·007; CSF corticosterone : cortisol was 0·387 ± 0·050 ( P <  0·001). Cortisol and corticosterone (0·15 mg/kg) suppressed ACTH vs. vehicle ( P =  0·002); there was no difference between corticosterone and cortisol. The 0·04 mg/kg dose had no effect on ACTH despite supraphysiological plasma corticosterone levels. Conclusions  Corticosterone contributes almost 40% of total active glucocorticoids (cortisol and corticosterone) in the CSF. Significant effects on HPA axis suppression were only seen with supraphysiological levels of corticosterone, suggesting that corticosterone is not important in this model of nonstress-induced ACTH hypersecretion, in which the effect of cortisol predominates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72329/1/j.1365-2265.2006.02540.x.pd

Solar Flares and Coronal Mass Ejections: A Statistically Determined Flare Flux-CME Mass Correlation

In an effort to examine the relationship between flare flux and corresponding CME mass, we temporally and spatially correlate all X-ray flares and CMEs in the LASCO and GOES archives from 1996 to 2006. We cross-reference 6,733 CMEs having well-measured masses against 12,050 X-ray flares having position information as determined from their optical counterparts. For a given flare, we search in time for CMEs which occur 10-80 minutes afterward, and we further require the flare and CME to occur within +/-45 degrees in position angle on the solar disk. There are 826 CME/flare pairs which fit these criteria. Comparing the flare fluxes with CME masses of these paired events, we find CME mass increases with flare flux, following an approximately log-linear, broken relationship: in the limit of lower flare fluxes, log(CME mass)~0.68*log(flare flux), and in the limit of higher flare fluxes, log(CME mass)~0.33*log(flare flux). We show that this broken power-law, and in particular the flatter slope at higher flare fluxes, may be due to an observational bias against CMEs associated with the most energetic flares: halo CMEs. Correcting for this bias yields a single power-law relationship of the form log(CME mass)~0.70*log(flare flux). This function describes the relationship between CME mass and flare flux over at least 3 dex in flare flux, from ~10^-7 to 10^-4 W m^-2.Comment: 28 pages, 16 figures, accepted to Solar Physic

How Many CMEs Have Flux Ropes? Deciphering the Signatures of Shocks, Flux Ropes, and Prominences in Coronagraph Observations of CMEs

We intend to provide a comprehensive answer to the question on whether all Coronal Mass Ejections (CMEs) have flux rope structure. To achieve this, we present a synthesis of the LASCO CME observations over the last sixteen years, assisted by 3D MHD simulations of the breakout model, EUV and coronagraphic observations from STEREO and SDO, and statistics from a revised LASCO CME database. We argue that the bright loop often seen as the CME leading edge is the result of pileup at the boundary of the erupting flux rope irrespective of whether a cavity or, more generally, a 3-part CME can be identified. Based on our previous work on white light shock detection and supported by the MHD simulations, we identify a new type of morphology, the `two-front' morphology. It consists of a faint front followed by diffuse emission and the bright loop-like CME leading edge. We show that the faint front is caused by density compression at a wave (or possibly shock) front driven by the CME. We also present high-detailed multi-wavelength EUV observations that clarify the relative positioning of the prominence at the bottom of a coronal cavity with clear flux rope structure. Finally, we visually check the full LASCO CME database for flux rope structures. In the process, we classify the events into two clear flux rope classes (`3-part', `Loop'), jets and outflows (no clear structure). We find that at least 40% of the observed CMEs have clear flux rope structures. We propose a new definition for flux rope CMEs (FR-CMEs) as a coherent magnetic, twist-carrying coronal structure with angular width of at least 40 deg and able to reach beyond 10 Rsun which erupts on a time scale of a few minutes to several hours. We conclude that flux ropes are a common occurrence in CMEs and pose a challenge for future studies to identify CMEs that are clearly not FR-CMEs.Comment: 26 pages, 9 figs, to be published in Solar Physics Topical Issue "Flux Rope Structure of CMEs

Is the evidence for dark energy secure?

Several kinds of astronomical observations, interpreted in the framework of the standard Friedmann-Robertson-Walker cosmology, have indicated that our universe is dominated by a Cosmological Constant. The dimming of distant Type Ia supernovae suggests that the expansion rate is accelerating, as if driven by vacuum energy, and this has been indirectly substantiated through studies of angular anisotropies in the cosmic microwave background (CMB) and of spatial correlations in the large-scale structure (LSS) of galaxies. However there is no compelling direct evidence yet for (the dynamical effects of) dark energy. The precision CMB data can be equally well fitted without dark energy if the spectrum of primordial density fluctuations is not quite scale-free and if the Hubble constant is lower globally than its locally measured value. The LSS data can also be satisfactorily fitted if there is a small component of hot dark matter, as would be provided by neutrinos of mass 0.5 eV. Although such an Einstein-de Sitter model cannot explain the SNe Ia Hubble diagram or the position of the `baryon acoustic oscillation' peak in the autocorrelation function of galaxies, it may be possible to do so e.g. in an inhomogeneous Lemaitre-Tolman-Bondi cosmology where we are located in a void which is expanding faster than the average. Such alternatives may seem contrived but this must be weighed against our lack of any fundamental understanding of the inferred tiny energy scale of the dark energy. It may well be an artifact of an oversimplified cosmological model, rather than having physical reality.Comment: 12 pages, 5 figures; to appear in a special issue of General Relativity and Gravitation, eds. G.F.R. Ellis et al; Changes: references reformatted in journal style - text unchange

The rate of colonization by macro-invertebrates on artificial substrate samplers

The influence of exposure time upon macro-invertebrate colonization on modified Hester-Dendy substrate samplers was investigated over a 60-day period. The duration of exposure affected the number of individuals, taxa and community diversity. The numbers of individuals colonizing the samplers reached a maximum after 39 days and then began to decrease, due to the emergence of adult insects. Coefficients of variation for the four replicate samples retrieved each sampling day fluctuated extensively throughout the study. No tendencies toward increasing or decreasing coefficients of variation were noted with increasing time of sampler exposure. The number of taxa colonizing the samplers increased throughout the study period. The community diversity index was calculated for each sampling day and this function tended to increase throughout the same period. This supports the hypothesis that an exposure period of 6 weeks, as recommended by the United States Environmental Protection Agency, may not always provide adequate opportunity for a truly representative community of macro-invertebrates to colonize multiplate samplers. Many of the taxa were collected in quite substantial proportions after periods of absence or extreme sparseness. This is attributed to the growth of periphyton and the collection of other materials that created food and new habitats suitable for the colonization of new taxa. Investigation of the relationship between ‘equitability’ and length of exposure revealed that equitability did not vary like diversity with increased time of exposure.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72073/1/j.1365-2427.1979.tb01522.x.pd

Life span and reproductive cost explain interspecific variation in the optimal onset of reproduction.

Fitness can be profoundly influenced by the age at first reproduction (AFR), but to date the AFR-fitness relationship only has been investigated intraspecifically. Here, we investigated the relationship between AFR and average lifetime reproductive success (LRS) across 34 bird species. We assessed differences in the deviation of the Optimal AFR (i.e., the species-specific AFR associated with the highest LRS) from the age at sexual maturity, considering potential effects of life history as well as social and ecological factors. Most individuals adopted the species-specific Optimal AFR and both the mean and Optimal AFR of species correlated positively with life span. Interspecific deviations of the Optimal AFR were associated with indices reflecting a change in LRS or survival as a function of AFR: a delayed AFR was beneficial in species where early AFR was associated with a decrease in subsequent survival or reproductive output. Overall, our results suggest that a delayed onset of reproduction beyond maturity is an optimal strategy explained by a long life span and costs of early reproduction. By providing the first empirical confirmations of key predictions of life-history theory across species, this study contributes to a better understanding of life-history evolution