Dental pulp pluripotent-like stem cells (DPPSC), a new stem cell population with chromosomal stability and osteogenic capacity for biomaterials evaluation

Background: Biomaterials are widely used to regenerate or substitute bone tissue. In order to evaluate their potential use for clinical applications, these need to be tested and evaluated in vitro with cell culture models. Frequently, immortalized osteoblastic cell lines are used in these studies. However, their uncontrolled proliferation rate, phenotypic changes or aberrations in mitotic processes limits their use in long-term investigations. Recently, we described a new pluripotent-like subpopulation of dental pulp stem cells derived from the third molars (DPPSC) that shows genetic stability and shares some pluripotent characteristics with embryonic stem cells. In this study we aim to describe the use of DPPSC to test biomaterials, since we believe that the biomaterial cues will be more critical in order to enhance the differentiation of pluripotent stem cells. Methods: The capacity of DPPSC to differentiate into osteogenic lineage was compared with human sarcoma osteogenic cell line (SAOS-2). Collagen and titanium were used to assess the cell behavior in commonly used biomaterials. The analyses were performed by flow cytometry, alkaline phosphatase and mineralization stains, RT-PCR, immunohistochemistry, scanning electron microscopy, Western blot and enzymatic activity. Moreover, the genetic stability was evaluated and compared before and after differentiation by short-comparative genomic hybridization (sCGH). Results: DPPSC showed excellent differentiation into osteogenic lineages expressing bone-related markers similar to SAOS-2. When cells were cultured on biomaterials, DPPSC showed higher initial adhesion levels. Nevertheless, their osteogenic differentiation showed similar trend among both cell types. Interestingly, only DPPSC maintained a normal chromosomal dosage before and after differentiation on 2D monolayer and on biomaterials. Conclusions: Taken together, these results promote the use of DPPSC as a new pluripotent-like cell model to evaluate the biocompatibility and the differentiation capacity of biomaterials used in bone regeneration

The postulates of gravitational thermodynamics

The general principles and logical structure of a thermodynamic formalism that incorporates strongly self-gravitating systems are presented. This framework generalizes and simplifies the formulation of thermodynamics developed by Callen. The definition of extensive variables, the homogeneity properties of intensive parameters, and the fundamental problem of gravitational thermodynamics are discussed in detail. In particular, extensive parameters include quasilocal quantities and are naturally incorporated into a set of basic general postulates for thermodynamics. These include additivity of entropies (Massieu functions) and the generalized second law. Fundamental equations are no longer homogeneous first-order functions of their extensive variables. It is shown that the postulates lead to a formal resolution of the fundamental problem despite non-additivity of extensive parameters and thermodynamic potentials. Therefore, all the results of (gravitational) thermodynamics are an outgrowth of these postulates. The origin and nature of the differences with ordinary thermodynamics are analyzed. Consequences of the formalism include the (spatially) inhomogeneous character of thermodynamic equilibrium states, a reformulation of the Euler equation, and the absence of a Gibbs-Duhem relation.Comment: 28 pages, Revtex, no figures. An important sentence and several minor corrections included. To appear in Physical Review

Relativistic quantum mechanics of a Dirac oscillator

The Dirac oscillator is an exactly soluble model recently introduced in the context of many particle models in relativistic quantum mechanics. The model has been also considered as an interaction term for modelling quark confinement in quantum chromodynamics. These considerations should be enough for demonstrating that the Dirac oscillator can be an excellent example in relativistic quantum mechanics. In this paper we offer a solution to the problem and discuss some of its properties. We also discuss a physical picture for the Dirac oscillator's non-standard interaction, showing how it arises on describing the behaviour of a neutral particle carrying an anomalous magnetic moment and moving inside an uniformly charged sphere.Comment: 19 pages, 1 figur

The Large Aperture GRB Observatory

The Large Aperture GRB Observatory (LAGO) is aiming at the detection of the high energy (around 100 GeV) component of Gamma Ray Bursts, using the single particle technique in arrays of Water Cherenkov Detectors (WCD) in high mountain sites (Chacaltaya, Bolivia, 5300 m a.s.l., Pico Espejo, Venezuela, 4750 m a.s.l., Sierra Negra, Mexico, 4650 m a.s.l). WCD at high altitude offer a unique possibility of detecting low gamma fluxes in the 10 GeV - 1 TeV range. The status of the Observatory and data collected from 2007 to date will be presented.Comment: 4 pages, proceeding of 31st ICRC 200

Water Cherenkov Detectors response to a Gamma Ray Burst in the Large Aperture GRB Observatory

In order to characterise the behaviour of Water Cherenkov Detectors (WCD) under a sudden increase of 1 GeV - 1 TeV background photons from a Gamma Ray Burst (GRB), simulations were conducted and compared to data acquired by the WCD of the Large Aperture GRB Observatory (LAGO). The LAGO operates arrays of WCD at high altitude to detect GRBs using the single particle technique. The LAGO sensitivity to GRBs is derived from the reported simulations of the gamma initiated particle showers in the atmosphere and the WCD response to secondaries.Comment: 5 pages, proceeding of the 31st ICRC 200

An international network to monitor the structure, composition and dynamics of Amazonian forests (RAINFOR)

The Amazon basin is likely to be increasingly affected by environmental changes: higher temperatures, changes in precipitation, CO2 fertilization and habitat fragmentation. To examine the important ecological and biogeochemical consequences of these changes, we are developing an international network, RAINFOR, which aims to monitor forest biomass and dynamics across Amazonia in a co-ordinated fashion in order to understand their relationship to soil and climate. The network will focus on sample plots established by independent researchers, some providing data extending back several decades. We will also conduct rapid transect studies of poorly monitored regions. Field expeditions analysed local soil and plant properties in the first phase (2001–2002). Initial results suggest that the network has the potential to reveal much information on the continental-scale relations between forest and environment. The network will also serve as a forum for discussion between researchers, with the aim of standardising sampling techniques and methodologies that will enable Amazonian forests to be monitored in a coherent manner in the coming decades

Expectations for time-delay measurements in active galactic nuclei with the Vera Rubin Observatory

The Vera Rubin Observatory will provide an unprecedented set of time-dependent observations of the sky. The planned Legacy Survey of Space and Time (LSST) operating for 10 years will provide dense lightcurves for thousands of active galactic nuclei (AGN) in Deep Drilling Fields (DDFs) and less dense lightcurves for millions of AGN. We model the prospects for measuring time delays for emission lines with respect to the continuum, using these data. We model the artificial lightcurves using Timmer-Koenig algorithm, we use the exemplary cadence to sample them, we supplement lightcurves with the expected contamination by the strong emission lines (Hbeta, Mg II and CIV as well as with Fe II pseudo-continuum and the starlight). We choose the suitable photometric bands appropriate for the redshift and compare the assumed line time delay with the recovered time delay for 100 statistical realizations of the light curves. We show that time delays for emission lines can be well measured from the Main Survey for the bright tail of the quasar distribution (about 15% of all sources) with the accuracy within 1 sigma error, for DDFs results for fainter quasars are also reliable when all 10 years of data are used. There are also some prospects to measure the time delays for the faintest quasars at the smallest redshifts from the first two years of data, and eventually even from the first season. The entire quasar population will allow obtaining results of apparently high accuracy but in our simulations, we see a systematic offset between the assumed and recovered time delay depending on the redshift and source luminosity which will not disappear even in the case of large statistics. Such a problem might affect the slope of the radius-luminosity relation and cosmological applications of quasars if simulations correcting for such effects are not performed.Comment: Submitted to Astronomy & Astrophysics, comments wellcom

LAT-1 and GLUT-1 Carrier Expression and Its Prognostic Value in Gastroenteropancreatic Neuroendocrine Tumors

Cancer cells develop mechanisms that increase nutrient uptake, including key nutrient carriers, such as amino acid transporter 1 (LAT-1) and glucose transporter 1 (GLUT-1), regulated by the oxygen-sensing Von Hippel Lindau-hypoxia-inducible factor (VHL-HIF) transcriptional pathway. We aimed to analyze these metabolic players in gastroenteropancreatic neuroendocrine tumors (GEP-NET) and correlate them with tumor malignancy and progression. LAT-1, GLUT-1, and pVHL expression was analyzed in 116 GEP-NETs and 48 peritumoral tissue samples by immunohistochemistry. LAT-1 was stably silenced using specific shRNA in the human NET BON cell line. LAT-1 expression was significantly increased in tumor tissue compared to non-tumor tissue in both gastrointestinal (67% vs. 44%) and pancreatic NETs (54% vs. 31%). Similarly, GLUT-1 was substantially elevated in gastrointestinal (74% vs. 19%) and pancreatic (58% vs. 4%) NETs. In contrast, pVHL expression was decreased (85% vs. 58%) in pancreatic NETs. Tumors with metastases at diagnosis displayed increased LAT-1 and GLUT-1 and decreased pVHL expression (p < 0.001). In accordance with these data, silencing LAT-1 curtailed cell proliferation in BON cells. These findings suggest that specific mechanisms that increase nutrient uptake, such as LAT-1 and GLUT-1, are increased in GEP-NETs, whereas pVHL is decreased. These markers might be related to the proliferation and metastatic capacity of these tumors

Autophagy modulates endothelial junctions to restrain neutrophil diapedesis during inflammation

The migration of neutrophils from the blood circulation to sites of infection or injury is a key immune response and requires the breaching of endothelial cells (ECs) that line the inner aspect of blood vessels. Unregulated neutrophil transendothelial cell migration (TEM) is pathogenic, but the molecular basis of its physiological termination remains unknown. Here, we demonstrated that ECs of venules in inflamed tissues exhibited a robust autophagic response that was aligned temporally with the peak of neutrophil trafficking and was strictly localized to EC contacts. Genetic ablation of EC autophagy led to excessive neutrophil TEM and uncontrolled leukocyte migration in murine inflammatory models, while pharmacological induction of autophagy suppressed neutrophil infiltration into tissues. Mechanistically, autophagy regulated the remodeling of EC junctions and expression of key EC adhesion molecules, facilitating their intracellular trafficking and degradation. Collectively, we have identified autophagy as a modulator of EC leukocyte trafficking machinery aimed at terminating physiological inflammation