Optimization of a 3D dynamic culturing system for in vitro modeling of Frontotemporal Neurodegeneration-relevant pathologic features

Frontotemporal lobar degeneration (FTLD) is a severe neurodegenerative disorder that is diagnosed with increasing frequency in clinical setting. Currently, no therapy is available and in addition the molecular basis of the disease are far from being elucidated. Consequently, it is of pivotal importance to develop reliable and cost-effective in vitro models for basic research purposes and drug screening. To this respect, recent results in the field of Alzheimer’s disease have suggested that a tridimensional (3D) environment is an added value to better model key pathologic features of the disease. Here, we have tried to add complexity to the 3D cell culturing concept by using a microfluidic bioreactor, where cells are cultured under a continuous flow of medium, thus mimicking the interstitial fluid movement that actually perfuses the body tissues, including the brain. We have implemented this model using a neuronal-like cell line (SH-SY5Y), a widely exploited cell model for neurodegenerative disorders that shows some basic features relevant for FTLD modeling, such as the release of the FTLD-related protein progranulin (PRGN) in specific vesicles (exosomes). We have efficiently seeded the cells on 3D scaffolds, optimized a disease-relevant oxidative stress experiment (by targeting mitochondrial function that is one of the possible FTLD-involved pathological mechanisms) and evaluated cell metabolic activity in dynamic culture in comparison to static conditions, finding that SH-SY5Y cells cultured in 3D scaffold are susceptible to the oxidative damage triggered by a mitochondrial-targeting toxin (6-OHDA) and that the same cells cultured in dynamic conditions kept their basic capacity to secrete PRGN in exosomes once recovered from the bioreactor and plated in standard 2D conditions. We think that a further improvement of our microfluidic system may help in providing a full device where assessing basic FTLD-related features (including PRGN dynamic secretion) that may be useful for monitoring disease progression over time or evaluating therapeutic interventions

Star formation in disk galaxies driven by primordial H_2

We show that gaseous \HI disks of primordial composition irradiated by an external radiation field can develop a multiphase medium with temperatures between 10^2 and 10^4 K due to the formation of molecular hydrogen. For a given \HI column density there is a critical value of the radiation field below which only the cold \HI phase can exist. Due to a time decreasing quasar background, the gas starts cooling slowly after recombination until the lowest stable temperature in the warm phase is reached at a critical redshift $z=z_{cr}$. Below this redshift the formation of molecular hydrogen promotes a rapid transition towards the cold \HI phase. We find that disks of protogalaxies with 10^{20}\simlt N_{HI}\simlt 10^{21} cm^{-2} are gravitationally stable at $T\sim 10^4$ K and can start their star formation history only at z \simlt z_{cr}\sim 2, after the gas in the central portion of the disk has cooled to temperatures T\simlt 300 K. Such a delayed starbust phase in galaxies of low gas surface density and low dynamical mass can disrupt the disks and cause them to fade away. These objects could contribute significantly to the faint blue galaxy population.Comment: 16 pages (LaTeX), 2 Figures to be published in Astrophysical Journal Letter

A warped disk model for M33 and the 21-cm line width in spiral galaxies

To determine the actual HI distribution and the velocity field in the outermost disk of the spiral galaxy M33, a tilted-ring model is fitted to 21-cm line data taken with the Arecibo Telescope. Since M33 is one of the main calibrators for the extragalactic distance scale derived through the Tully-Fisher relation, the outer disk warping is of interest for a correct determination and deprojection of the galaxy's line width. Even though our best model predicts small effects on the observed line width of M33, we show that similar outer disk warping in galaxies oriented differently along our line of sight could affect the widths considerably. Therefore there may be systematic effects in the determination of the rotation velocities and dynamic masses of spiral galaxies, whose exact value depends also on which method is used for measuring the galaxy's total line width.Comment: 27 pages, ps files only, ApJ in pres

A Comprehensive Statistical Analysis of the Gas Distribution in Lyman-limit and Damped Lyman-alpha Absorption Systems

In this paper we show how to use data on Lyman-limit and Damped Lyman-alpha absorption systems to derive the hydrogen ionization fractions and the distribution of the face-on total gas column density. We consider axially symmetric, randomly oriented absorbers, ionized by an external background radiation field in order to relate the face-on total gas distribution to that of the neutral hydrogen observed along the line of sight. We devise a statistical procedure based on the Maximum Likelihood criterion, that is able to treat simultaneously data coming from different surveys and statistically recovers the "true" column densities in the presence of large uncertainties: this is especially important for Lyman-limit systems which leave an unmeasurable residual flux at wavelengths shorter than the Lyman break. We make use of simulated data to look for possible observational biases and extensively test our procedure. For a large statistical sample of real data in the redshift range [1.75,3.25] (collected from all published surveys) our Maximum Likelihood procedure gives a power-law slope for the total hydrogen distribution of -2.7. All together Lyman-limit systems therefore contain more gas than Damped Lyman-alpha systems. Analysis of data at other redshifts shows that more observations are needed to reach a compelling evidence for a cosmological evolution of the slope of the gas distribution.Comment: 30 pages with 7 eps figures, LaTeX accepted for publication in ApJ main journa

The effects of an ionizing background on the HI column density distribution in the local Universe

Using data on the HI column density distribution in the local Universe, f(N_{HI}), we show how to determine g(N_{H}), the distribution of the total gas (HI+HII) column density. A simple power law fit to f(N_{HI}) fails due to bendings in the distributions when N_{HI}<10^{20} cm^{-2} and H is no longer fully neutral. If an ultraviolet background is responsible for the gas ionization, and g(N_{H}) is proportional N_{H}^{-alpha}, we find the values of alpha and of the intensity of the background radiation which are compatible with the present data. These best fitting values, however, depend upon the scaling law of the the gas volume densities with N_{H} and cannot be determined unambiguously. We examine in detail two models: one in which the average gas volume density decreases steadily with N_H, while in the other it stays constant at low column densities. The former model leads to a steep power law fit for g(N_{H}), with alpha of order 3.3 +- 0.4 and requires an ultraviolet flux larger than what the QSOs alone produce at z=0. For the latter alpha is 1.5 +- 0.1 and a lower ionizing flux is required. The ambiguities about the modelling and the resulting steep or shallow N_{H} distribution can be resolved only if new 21-cm observations and QSOs Lyman limit absorbers searches will provide more data in the HI-HII transition region at low redshifts. Using the best fit obtained for higher redshift data we outline two possible scenarios for the evolution of gaseous structures, compatible with the available data at z=0.Comment: 12 pages, 2 figures, ApJ in press (2002, vol. 567

Very Luminous Carbon Stars in the Outer Disk of the Triangulum Spiral Galaxy

Stars with masses in the range from about 1.3 to 3.5 Mo pass through an evolutionary stage where they become carbon stars. In this stage, which lasts a few Myr, these stars are extremely luminous pulsating giants. They are so luminous in the near-infrared that just a few of them can double the integrated luminosity of intermediate-age (0.6 to 2 Gyr) Magellanic Cloud clusters at 2.2 microns. Astronomers routinely use such near-infrared observations to minimize the effects of dust extinction, but it is precisely in this band that carbon stars can contribute hugely. The actual contribution of carbon stars to the outer disk light of evolving spiral galaxies has not previously been morphologically investigated. Here we report new and very deep near-IR images of the Triangulum spiral galaxy M33=NGC 598, delineating spectacular arcs of carbon stars in its outer regions. It is these arcs which dominate the near-infrared m=2 Fourier spectra of M33. We present near-infrared photometry with the Hale 5-m reflector, and propose that the arcs are the signature of accretion of low metallicity gas in the outer disk of M33.Comment: 4 pages, 4 figures. Revised version submitted to A&A Letter

Radial HI Profiles at the Periphery of Galactic Disks: The Role of Ionizing Background Radiation

Observations of neutral hydrogen in spiral galaxies reveal a sharp cutoff in the radial density profile at some distance from the center. Using 22 galaxies with known HI distributions as an example, we discuss the question of whether this effect can be associated exclusively with external ionizing radiation, as is commonly assumed. We show that before the surface density reaches $\sigma_{\textrm{HI}}\le 0.5 {\cal M}_\odot/{\textrm {pc}}^2$(the same for galaxies of different types), it is hard to expect the gas to be fully ionized by background radiation. For two of 13 galaxies with a sharp drop in the HI profile, the "steepening" can actually be caused by ionization. At the same time, for the remaining galaxies, the observed cutoff in the radial HI profile is closer to the center than if it was a consequence of ionization by background radiation and, therefore, it should be caused by other factors.Comment: 15 pages, 6 figure

Kinematic modelling of disk galaxies I. A new method to fit tilted rings to data cubes

This is the first of a series of papers in which the kinematics of disk galaxies over a range of scales is scrutinised employing spectroscopy. A fundamental aspect of these studies is presented here: the new publicly available software tool TiRiFiC (http://www.astro.uni-bonn.de/~gjozsa/tirific.html) enables a direct fit of a ``tilted-ring model'' to spectroscopic data cubes. The algorithm generates model data cubes from the tilted-ring parametrisation of a rotating disk, which are automatically adjusted to reach an optimum fit via a chi-squared minimisation method to an observed data cube. The structure of the new software, the shortcomings of the previously available programs to produce a tilted-ring model, and the performance of TiRiFiC are discussed. Our method is less affected by the well-known problem of beam smearing that occurs when fitting to the velocity field. Since with our method we fit many data points in a data cube simultaneously, TiRiFiC is sensitive to very faint structures and can hence be used to derive tilted-ring models significantly extending in radius beyond those derived from a velocity field. The software is able to parametrise HI disks of galaxies that are intersected by the line-of-sight twice or more, i.e. if the disks are heavily warped, and/or with a significant shift of the projected centre of rotation, and/or if seen edge-on. Furthermore, our method delivers the surface-brightness profile of the examined galaxy in addition to the orientational parameters and the rotation curve. In order to derive kinematic and morphological models of disk galaxies, especially reliable rotation curves, a direct-fit method as implemented in our code should be the tool of choice.Comment: 37 pages, 24 figures. Accepted for publication in Astronomy and Astrophysic

Keck spectroscopy and Spitzer Space Telescope analysis of the outer disk of the Triangulum Spiral Galaxy M33

In an earlier study of the spiral galaxy M33, we photometrically identified arcs or outer spiral arms of intermediate age (0.6 Gyr - 2 Gyr) carbon stars precisely at the commencement of the HI-warp. Stars in the arcs were unresolved, but were likely thermally-pulsing asymptotic giant branch carbon stars. Here we present Keck I spectroscopy of seven intrinsically bright and red target stars in the outer, northern arc in M33. The target stars have estimated visual magnitudes as faint as V \sim 25 mag. Absorption bands of CN are seen in all seven spectra reported here, confirming their carbon star status. In addition, we present Keck II spectra of a small area 0.5 degree away from the centre of M33; the target stars there are also identified as carbon stars. We also study the non-stellar PAH dust morphology of M33 secured using IRAC on board the Spitzer Space Telescope. The Spitzer 8 micron image attests to a change of spiral phase at the start of the HI warp. The Keck spectra confirm that carbon stars may safely be identified on the basis of their red J-K_s colours in the outer, low metallicity disk of M33. We propose that the enhanced number of carbon stars in the outer arms are an indicator of recent star formation, fueled by gas accretion from the HI-warp reservoir.Comment: 9 pages, 5 figures, accepted in A&

the influence of nanoscale morphology on the resistivity of cluster assembled nanostructured metallic thin films

We have studied in situ the evolution of the electrical resistivity of Fe, Pd, Nb, W and Mo cluster-assembled films during their growth by supersonic cluster beam deposition. We observed resistivity of cluster-assembled films several orders of magnitude larger than the bulk, as well as an increase in resistivity by increasing the film thickness in contrast to what was observed for atom-assembled metallic films. This suggests that the nanoscale morphological features typical of ballistic films growth, such as the minimal cluster?cluster interconnection and the evolution of surface roughness with thickness, are responsible for the observed behaviour