Development of a novel cell encapsulation system based on natural origin polymers for tissue engineering applications

Cells microencapsulated in biocompatible semi-permeable polymeric membranes are effective as cell delivery systems while protecting the host against immune responses. In this study, cell encapsulation membranes were prepared based on carrageenan and alginate, two natural cationic polymers. Different formulations/conditions were explored to optimize the microcapsules which were characterized with respect to their morphology, mechanical stability, and cytotoxicity. Spherical-shaped microcapsules were obtained from all the polymeric systems. The iota-carrageenan/sodium alginate microcapsules exhibited the best stability and permeability, and therefore, these were selected for the cell encapsulation. These capsules provided an environment that supported cell proliferation and have the potential for tissue engineering as well as other cell-based therapy applications.One of the authors (SML) acknowledges the support of the Programme Alssan-the European Union Programme of High Level Scholarships for Latin America (scholarship no. E04M041362CO). This work was partially supported by the European STREP HIPPOCRATES (NMP3-CT-2003-505758) and by the Fundacao para a Ciencia e Tecnologia (project PTDC/QUI/68804/2006) and carried out under the scope of European NoE EXPERTISSUES (NMP3-CT-2004-500283)

Simulation of Flow of Mixtures Through Anisotropic Porous Media using a Lattice Boltzmann Model

We propose a description for transient penetration simulations of miscible and immiscible fluid mixtures into anisotropic porous media, using the lattice Boltzmann (LB) method. Our model incorporates hydrodynamic flow, diffusion, surface tension, and the possibility for global and local viscosity variations to consider various types of hardening fluids. The miscible mixture consists of two fluids, one governed by the hydrodynamic equations and one by diffusion equations. We validate our model on standard problems like Poiseuille flow, the collision of a drop with an impermeable, hydrophobic interface and the deformation of the fluid due to surface tension forces. To demonstrate the applicability to complex geometries, we simulate the invasion process of mixtures into wood spruce samples.Comment: Submitted to EPJ

Structural Properties of Self-Attracting Walks

Self-attracting walks (SATW) with attractive interaction u > 0 display a swelling-collapse transition at a critical u_{\mathrm{c}} for dimensions d >= 2, analogous to the \Theta transition of polymers. We are interested in the structure of the clusters generated by SATW below u_{\mathrm{c}} (swollen walk), above u_{\mathrm{c}} (collapsed walk), and at u_{\mathrm{c}}, which can be characterized by the fractal dimensions of the clusters d_{\mathrm{f}} and their interface d_{\mathrm{I}}. Using scaling arguments and Monte Carlo simulations, we find that for u<u_{\mathrm{c}}, the structures are in the universality class of clusters generated by simple random walks. For u>u_{\mathrm{c}}, the clusters are compact, i.e. d_{\mathrm{f}}=d and d_{\mathrm{I}}=d-1. At u_{\mathrm{c}}, the SATW is in a new universality class. The clusters are compact in both d=2 and d=3, but their interface is fractal: d_{\mathrm{I}}=1.50\pm0.01 and 2.73\pm0.03 in d=2 and d=3, respectively. In d=1, where the walk is collapsed for all u and no swelling-collapse transition exists, we derive analytical expressions for the average number of visited sites and the mean time to visit S sites.Comment: 15 pages, 8 postscript figures, submitted to Phys. Rev.

Measuring Black Hole Spin using X-ray Reflection Spectroscopy

I review the current status of X-ray reflection (a.k.a. broad iron line) based black hole spin measurements. This is a powerful technique that allows us to measure robust black hole spins across the mass range, from the stellar-mass black holes in X-ray binaries to the supermassive black holes in active galactic nuclei. After describing the basic assumptions of this approach, I lay out the detailed methodology focusing on "best practices" that have been found necessary to obtain robust results. Reflecting my own biases, this review is slanted towards a discussion of supermassive black hole (SMBH) spin in active galactic nuclei (AGN). Pulling together all of the available XMM-Newton and Suzaku results from the literature that satisfy objective quality control criteria, it is clear that a large fraction of SMBHs are rapidly-spinning, although there are tentative hints of a more slowly spinning population at high (M>5*10^7Msun) and low (M<2*10^6Msun) mass. I also engage in a brief review of the spins of stellar-mass black holes in X-ray binaries. In general, reflection-based and continuum-fitting based spin measures are in agreement, although there remain two objects (GROJ1655-40 and 4U1543-475) for which that is not true. I end this review by discussing the exciting frontier of relativistic reverberation, particularly the discovery of broad iron line reverberation in XMM-Newton data for the Seyfert galaxies NGC4151, NGC7314 and MCG-5-23-16. As well as confirming the basic paradigm of relativistic disk reflection, this detection of reverberation demonstrates that future large-area X-ray observatories such as LOFT will make tremendous progress in studies of strong gravity using relativistic reverberation in AGN.Comment: 19 pages. To appear in proceedings of the ISSI-Bern workshop on "The Physics of Accretion onto Black Holes" (8-12 Oct 2012). Revised version adds a missing source to Table 1 and Fig.6 (IRAS13224-3809) and corrects the referencing of the discovery of soft lags in 1H0707-495 (which were in fact first reported in Fabian et al. 2009

MGMT-independent temozolomide resistance in pediatric glioblastoma cells associated with a PI3-kinase-mediated HOX/stem cell gene signature

Sensitivity to temozolomide is restricted to a subset of glioblastoma patients, with the major determinant of resistance being a lack of promoter methylation of the gene encoding the repair protein DNA methyltransferase MGMT, although other mechanisms are thought to be active. There are, however, limited preclinical data in model systems derived from pediatric glioma patients. We screened a series of cell lines for temozolomide efficacy in vitro, and investigated the differential mechanisms of resistance involved. In the majority of cell lines, a lack of MGMT promoter methylation and subsequent protein overexpression were linked to temozolomide resistance. An exception was the pediatric glioblastoma line KNS42. Expression profiling data revealed a coordinated upregulation of HOX gene expression in resistant lines, especially KNS42, which was reversed by phosphoinositide 3-kinase pathway inhibition. High levels of HOXA9/HOXA10 gene expression were associated with a shorter survival in pediatric high-grade glioma patient samples. Combination treatment in vitro of pathway inhibition and temozolomide resulted in a highly synergistic interaction in KNS42 cells. The resistance gene signature further included contiguous genes within the 12q13-q14 amplicon, including the Akt enhancer PIKE, significantly overexpressed in the KNS42 line. These cells were also highly enriched for CD133 and other stem cell markers. We have thus shown an in vitro link between phosphoinositide 3-kinase-mediated HOXA9/HOXA10 expression, and a drug-resistant, progenitor cell phenotype in MGMT-independent pediatric glioblastoma.Cancer Research UK (C1178/A10294, C309/A2187, C309/A8274), the Oak Foundation (L. Marshall), and La Fondation de France (N. Gaspar). We acknowledge NHS funding to the NIHR Biomedical Research Centre. P. Workman is a Cancer Research UK Life Fello

EGFRvIII deletion mutations in pediatric high-grade glioma and response to targeted therapy in pediatric glioma cell lines

Purpose: The epidermal growth factor receptor (EGFR) is amplified and overexpressed in adult glioblastoma, with response to targeted inhibition dependent on the underlying biology of the disease. EGFR has thus far been considered to play a less important role in pediatric glioma, although extensive data are lacking. We have sought to clarify the role of EGFR in pediatric high-grade glioma (HGG). Experimental Design: We retrospectively studied a total of 90 archival pediatric HGG specimens for EGFR protein overexpression, gene amplification, and mutation and assessed the in vitro sensitivity of pediatric glioma cell line models to the small-molecule EGFR inhibitor erlotinib. Results: Amplification was detected in 11% of cases, with corresponding overexpression of the receptor. No kinase or extracellular domain mutations were observed; however, 6 of 35 (17%) cases harbored the EGFRvIII deletion, including two anaplastic oligodendrogliomas and a gliosarcoma overexpressing EGFRvIII in the absence of gene amplification and coexpressing platelet-derived growth factor receptor α. Pediatric glioblastoma cells transduced with wild-type or deletion mutant EGFRvIII were not rendered more sensitive to erlotinib despite expressing wild-type PTEN. Phosphorylated receptor tyrosine kinase profiling showed a specific activation of platelet-derived growth factor receptor α/β in EGFRvIII-transduced pediatric glioblastoma cells, and targeted coinhibition with erlotinib and imatinib leads to enhanced efficacy in this model. Conclusions: These data identify an elevated frequency of EGFR gene amplification and EGFRvIII mutation in pediatric HGG than previously recognized and show the likely necessity of targeting multiple genetic alterations in the tumors of these children.Cancer Research UK grants C1178/A10294, C309/A2187, and C309/A8274; Oak Foundation (L. Marshall); La Fondation de France (N. Gaspar); and Breakthrough Breast Cancer (J.S. Reis-Filho). We acknowledge NHS funding to the National Institute for Health Research Biomedical Research Centre

Branching Fractions for D0 -> K+K- and D0 -> pi+pi-, and a Search for CP Violation in D0 Decays

Using the large hadroproduced charm sample collected in experiment E791 at Fermilab, we have measured ratios of branching fractions for the two-body singly-Cabibbo-suppressed charged decays of the D0: (D0 -> KK)/(D0 -> Kpi) = 0.109 +- 0.003 +- 0.003, (D0 -> pipi)/(D0 -> Kpi) = 0.040 +- 0.002 +- 0.003, and (D0 -> KK)/(D0 -> pipi) = 2.75 +- 0.15 +- 0.16. We have looked for differences in the decay rates of D0 and D0bar to the CP eigenstates K+K- and pi+pi-, and have measured the CP asymmetry parameters A_CP(K+K-) = -0.010 +- 0.049 +- 0.012 and A_CP(pi+pi-) = -0.049 +- 0.078 +- 0.030, both consistent with zero.Comment: 10 Postscript pages, including 2 figures. Submitted to Phys. Lett.

Asymmetries between the production of D+ and D- mesons from 500 GeV/c pi- nucleon interactions as a function of xF and pt**2

We present asymmetries between the production of D+ and D- mesons in Fermilab experiment E791 as a function of xF and pt**2. The data used here consist of 74,000 fully-reconstructed charmed mesons produced by a 500 GeV/c pi- beam on C and Pt foils. The measurements are compared to results of models which predict differences between the production of heavy-quark mesons that have a light quark in common with the beam (leading particles) and those that do not (non-leading particles). While the default models do not agree with our data, we can reach agreement with one of them, PYTHIA, by making a limited number of changes to parameters used

Search for CP Violation in Charged D Meson Decays

We report results of a search for CP violation in the singly Cabibbo-suppressed decays D+ -> K- K+ pi+, phi pi+, K*(892)0 K+, and pi- pi+ pi+ based on data from the charm hadroproduction experiment E791 at Fermilab. We search for a difference in the D+ and D- decay rates for each of the final states. No evidence for a difference is seen. The decay rate asymmetry parameters A(CP), defined as the difference in the D+ and D- decay rates divided by the sum of the decay rates, are measured to be: A(CP)(K K pi) = -0.014 +/- 0.029, A(CP)(phi pi) = -0.028 +/- 0.036, A(CP)(K*(892) K) = -0.010 +/- 0.050, and A(CP)(pi pi pi) = -0.017 +/- 0.042.Comment: 13 pages, 5 figures, 1 table; Elsevier LaTe

Search for Rare and Forbidden Dilepton Decays of the D+, Ds, and D0 Charmed Mesons

We report the results of a search for flavor-changing neutral current, lepton-flavor violating, and lepton-number violating decays of D+, Ds, and D0 mesons (and their antiparticles) into modes containing muons and electrons. Using data from Fermilab charm hadroproduction experiment E791, we examine the pi,l,l and K,l,l decay modes of D+ and Ds and the l+l- decay modes of D0. No evidence for any of these decays is found. Therefore, we present branching-fraction upper limits at 90% confidence level for the 24 decay modes examined. Eight of these modes have no previously reported limits, and fourteen are reported with significant improvements over previously published results.Comment: 12 pages, 3 figures, LaTeX, elsart.cls, epsf.sty, amsmath.sty Submitted to Physics Letters