A modelling approach towards Epidermal homoeostasis control

In order to grasp the features arising from cellular discreteness and individuality, in large parts of cell tissue modelling agent-based models are favoured. The subclass of off-lattice models allows for a physical motivation of the intercellular interaction rules. We apply an improved version of a previously introduced off-lattice agent-based model to the steady-state flow equilibrium of skin. The dynamics of cells is determined by conservative and drag forces,supplemented with delta-correlated random forces. Cellular adjacency is detected by a weighted Delaunay triangulation. The cell cycle time of keratinocytes is controlled by a diffusible substance provided by the dermis. Its concentration is calculated from a diffusion equation with time-dependent boundary conditions and varying diffusion coefficients. The dynamics of a nutrient is also taken into account by a reaction-diffusion equation. It turns out that the analysed control mechanism suffices to explain several characteristics of epidermal homoeostasis formation. In addition, we examine the question of how {\em in silico} melanoma with decreased basal adhesion manage to persist within the steady-state flow-equilibrium of the skin.Interestingly, even for melanocyte cell cycle times being substantially shorter than for keratinocytes, tiny stochastic effects can lead to completely different outcomes. The results demonstrate that the understanding of initial states of tumour growth can profit significantly from the application of off-lattice agent-based models in computer simulations.Comment: 23 pages, 7 figures, 1 table; version that is to appear in Journal of Theoretical Biolog

miR-579-3p Controls Hepatocellular Carcinoma Formation by Regulating the Phosphoinositide 3-Kinase-Protein Kinase B Pathway in Chronically Inflamed Liver

Chronic liver inflammation causes continuous liver damage with progressive liver fibrosis and cirrhosis, which may eventually lead to hepatocellular carcinoma (HCC). Whereas the 10-year incidence for HCC in patients with cirrhosis is approximately 20%, many of these patients remain tumor free for their entire lives. Clarifying the mechanisms that define the various outcomes of chronic liver inflammation is a key aspect in HCC research. In addition to a wide variety of contributing factors, microRNAs (miRNAs) have also been shown to be engaged in promoting liver cancer. Therefore, we wanted to characterize miRNAs that are involved in the development of HCC, and we designed a longitudinal study with formalin-fixed and paraffin-embedded liver biopsy samples from several pathology institutes from Switzerland. We examined the miRNA expression by nCounterNanostring technology in matched nontumoral liver tissue from patients developing HCC (n = 23) before and after HCC formation in the same patient. Patients with cirrhosis (n = 26) remaining tumor free within a similar time frame served as a control cohort. Comparison of the two cohorts revealed that liver tissue from patients developing HCC displayed a down-regulation of miR-579-3p as an early step in HCC development, which was further confirmed in a validation cohort. Correlation with messenger RNA expression profiles further revealed that miR-579-3p directly attenuated phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) expression and consequently protein kinase B (AKT) and phosphorylated AKT. In vitro experiments and the use of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 technology confirmed that miR-579-3p controlled cell proliferation and cell migration of liver cancer cell lines. Conclusion: Liver tissues from patients developing HCC revealed changes in miRNA expression. miR-579-3p was identified as a novel tumor suppressor regulating phosphoinositide 3-kinase-AKT signaling at the early stages of HCC development

The origin of short-lived radionuclides and the astrophysical environment of solar system formation

Based on early solar system abundances of short-lived radionuclides (SRs), such as $^{26}$Al (T$_{1/2} = 0.74$ Myr) and $^{60}$Fe (T$_{1/2} = 1.5$ Myr), it is often asserted that the Sun was born in a large stellar cluster, where a massive star contaminated the protoplanetary disk with freshly nucleosynthesized isotopes from its supernova (SN) explosion. To account for the inferred initial solar system abundances of short-lived radionuclides, this supernova had to be close ($\sim$ 0.3 pc) to the young ($\leqslant$ 1 Myr) protoplanetary disk. Here we show that massive star evolution timescales are too long, compared to typical timescales of star formation in embedded clusters, for them to explode as supernovae within the lifetimes of nearby disks. This is especially true in an Orion Nebular Cluster (ONC)-type of setting, where the most massive star will explode as a supernova $\sim$ 5 Myr after the onset of star formation, when nearby disks will have already suffered substantial photoevaporation and/or formed large planetesimals. We quantify the probability for {\it any} protoplanetary disk to receive SRs from a nearby supernova at the level observed in the early solar system. Key constraints on our estimate are: (1) SRs have to be injected into a newly formed ($\leqslant$ 1 Myr) disk, (2) the disk has to survive UV photoevaporation, and (3) the protoplanetary disk must be situated in an enrichment zone permitting SR injection at the solar system level without disk disruption. The probability of protoplanetary disk contamination by a supernova ejecta is, in the most favorable case, 3 $\times$ 10$^{-3}$

Supernova Propagation And Cloud Enrichment: A new model for the origin of 60^{60}Fe in the early solar system

The radioactive isotope $^{60}$Fe ($T_{1/2} = 1.5$ Myr) was present in the early solar system. It is unlikely that it was injected directly into the nascent solar system by a single, nearby supernova. It is proposed instead that it was inherited during the molecular cloud stage from several supernovae belonging to previous episodes of star formation. The expected abundance of $^{60}$Fe in star forming regions is estimated taking into account the stochasticity of the star-forming process, and it is showed that many molecular clouds are expected to contain $^{60}$Fe (and possibly $^{26}$Al [$T_{1/2} = 0.74$ Myr]) at a level compatible with that of the nascent solar system. Therefore, no special explanation is needed to account for our solar system's formation.Comment: 15 pages, 3 figure

Evolution of Massive Stars Up to the End of Central Oxygen Burning

We present a detailed study of the evolution of massive stars of masses 15, 20, 25 and 30 \msun assuming solar-like initial chemical composition. The stellar sequences were evolved through the advanced burning phases up to the end of core oxygen burning. We present a careful analysis of the physical characteristics of the stellar models. In particular, we investigate the effect of the still unsettled reaction $^{12}$C($\alpha$,$\gamma$)$^{16}$O on the advanced evolution by using recent compilations of this rate. We find that this rate has a significant impact on the evolution not only during the core helium burning phase, but also during the late burning phases, especially the shell carbon-burning. We have also considered the effect of different treatment of convective instability based on the Ledoux criterion in regions of varying molecular weight gradient during the hydrogen and helium burning phases. We compare our results with other investigations whenever available. Finally, our present study constitutes the basis of analyzing the nucleosynthesis processes in massive stars. In particular we will present a detail analysis of the {\it s}-process in a forthcoming paper.Comment: 46 pages, 15 figures. To be published in ApJ vol 611, August 10, 200

On the nature of the Be star HR 7409 (7 Vul)

HR 7409 (7 Vul) is a newly identified Be star possibly part of the Gould Belt and is the massive component of a 69-day spectroscopic binary. The binary parameters and properties of the Be star measured using high-dispersion spectra obtained at Ondrejov Observatory and at Rozhen Observatory imply the presence of a low mass companion (~ 0.5-0.8 M_sun). If the pair is relatively young (<50-80 Myr), then the companion is a K V star, but, following another, older evolutionary scenario, the companion is a horizontal-branch star or possibly a white dwarf star. In the latter scenario, a past episode of mass transfer from an evolved star onto a less massive dwarf star would be responsible for the peculiar nature of the present-day, fast-rotating Be star.Comment: Accepted for publication in MNRA

The Case for Case C Mass Transfer in the Galactic Evolution of Black Hole Binaries

Earlier works, which we review, have shown that if the Fe core in a presupernova star is to be sufficiently massive to collapse into a black hole, earlier in the evolution of the star the He core must be covered (clothed) by a hydrogen envelope during He core burning and removed only following this, in, e.g. common envelope evolution. This is classified as Case C mass transfer. These previous arguments were based chiefly on stellar evolution, especially depending on the way in which 12C burned. In this work we argue for Case C mass transfer on the basis of binary evolution. The giant progenitor of the black hole will have a large radius 1000 Rsun at the end of its supergiant stage. Its lifetime at that point will be short, about 1000 yrs, so it will not expand much further. Thus, the initial giant radius for Case C mass transfer will be constrained to a narrow band about 1000 Rsun. This has the consequence that the final separation a_f following common envelope evolution will depend nearly linearly on the mass of the companion m_d which becomes the donor after the He core of the giant has collapsed into the black hole. The separation at which this collapse takes place is essentially a_f, because of the rapid evolution of the giant. (In at least two binaries the black hole donor separation has been substantially increased because of mass loss in the black hole formation. These can be reconstructed from the amount of mass deposited on the donor in this mass loss.) We show that the reconstructed preexplosion separations of the black hole binaries fit well the linear relationship.Comment: 20 pages, 5 figures, accepted for the publication in New Astronom

The structure of the nuclear stellar cluster of the Milky Way

We present high-resolution seeing limited and AO NIR imaging observations of the stellar cluster within about one parsec of Sgr A*, the massive black hole at the centre of the Milky Way. Stellar number counts and the diffuse background light density were extracted from these observations in order to examine the structure of the nuclear stellar cluster.Our findings are as follows: (a) A broken-power law provides an excellent fit to the overall structure of the GC nuclear cluster. The power-law slope of the cusp is $\Gamma=0.19\pm0.05$, the break radius is $R_{\rm break} = 6.0'' \pm 1.0''$ or $0.22\pm0.04$ pc, and the cluster density decreases with a power-law index of $\Gamma=0.75\pm0.1$ outside of $R_{\rm break}$. (b) Using the best velocity dispersion measurements from the literature, we derive higher mass estimates for the central parsec than assumed until now. The inferred density of the cluster at the break radius is $2.8\pm1.3\times 10^{6} {\rm M_{\odot} pc^{-3}}$. This high density agrees well with the small extent and flat slope of the cusp. Possibly, the mass of the stars makes up only about 50% of the total cluster mass. (c) Possible indications of mass segregation in the cusp are found (d) The cluster appears not entirely homogeneous. Several density clumps are detected that are concentrated at projected distances of $R=3''$ and $R=7''$ from Sgr A*.(e) There appears to exist an under-density of horizontal branch/red clump stars near $R=5''$, or an over-density of stars of similar brightness at $R=3''$ and $R=7''$. (f) The extinction map in combination with cometary-like features in an L'-band image may provide support for the assumption of an outflow from Sgr A*.Comment: accepted for publication by A&A; please contact first author for higher quality figure

On the maximum value of the cosmic abundance of oxygen and the oxygen yield

We search for the maximum oxygen abundance in spiral galaxies. Because this maximum value is expected to occur in the centers of the most luminous galaxies, we have constructed the luminosity - central metallicity diagram for spiral galaxies, based on a large compilation of existing data on oxygen abundances of HII regions in spiral galaxies. We found that this diagram shows a plateau at high luminosities (-22.3 < M_B < -20.3), with a constant maximum value of the gas-phase oxygen abundance 12+log(O/H) ~ 8.87. This provides strong evidence that the oxygen abundance in the centers of the most luminous metal-rich galaxies reaches the maximum attainable value of oxygen abundance. Since some fraction of the oxygen (about 0.08 dex) is expected to be locked into dust grains, the maximum value of the true gas+dust oxygen abundance in spiral galaxies is 12+log(O/H) ~ 8.95. This value is a factor of ~ 2 higher than the recently estimated solar value. Based on the derived maximum oxygen abundance in galaxies, we found the oxygen yield to be about 0.0035, depending on the fraction of oxygen incorporated into dust grains.Comment: 8 pages, 5 figures, accepted for publication in MNRA