Fludarabine as a cost-effective adjuvant to enhance engraftment of human normal and malignant hematopoiesis in immunodeficient mice

There is still an unmet need for xenotransplantation models that efficiently recapitulate normal and malignant human hematopoiesis. Indeed, there are a number of strategies to generate humanized mice and specific protocols, including techniques to optimize the cytokine environment of recipient mice and drug alternatives or complementary to the standard conditioning regimens, that can be significantly modulated. Unfortunately, the high costs related to the use of sophisticated mouse models may limit the application of these models to studies that require an extensive experimental design. Here, using an affordable and convenient method, we demonstrate that the administration of fludarabine (FludaraTM) promotes the extensive and rapid engraftment of human normal hematopoiesis in immunodeficient mice. Quantification of human CD45+ cells in bone marrow revealed approximately a 102-fold increase in mice conditioned with irradiation plus fludarabine. Engrafted cells in the bone marrow included hematopoietic stem cells, as well as myeloid and lymphoid cells. Moreover, this model proved to be sufficient for robust reconstitution of malignant myeloid hematopoiesis, permitting primary acute myeloid leukemia cells to engraft as early as 8 weeks after the transplant. Overall, these results present a novel and affordable model for engraftment of human normal and malignant hematopoiesis in immunodeficient mice

Quasi-Normal Modes of Stars and Black Holes

Perturbations of stars and black holes have been one of the main topics of relativistic astrophysics for the last few decades. They are of particular importance today, because of their relevance to gravitational wave astronomy. In this review we present the theory of quasi-normal modes of compact objects from both the mathematical and astrophysical points of view. The discussion includes perturbations of black holes (Schwarzschild, Reissner-Nordstr\"om, Kerr and Kerr-Newman) and relativistic stars (non-rotating and slowly-rotating). The properties of the various families of quasi-normal modes are described, and numerical techniques for calculating quasi-normal modes reviewed. The successes, as well as the limits, of perturbation theory are presented, and its role in the emerging era of numerical relativity and supercomputers is discussed.Comment: 74 pages, 7 figures, Review article for "Living Reviews in Relativity

Spacelike Singularities and Hidden Symmetries of Gravity

We review the intimate connection between (super-)gravity close to a spacelike singularity (the "BKL-limit") and the theory of Lorentzian Kac-Moody algebras. We show that in this limit the gravitational theory can be reformulated in terms of billiard motion in a region of hyperbolic space, revealing that the dynamics is completely determined by a (possibly infinite) sequence of reflections, which are elements of a Lorentzian Coxeter group. Such Coxeter groups are the Weyl groups of infinite-dimensional Kac-Moody algebras, suggesting that these algebras yield symmetries of gravitational theories. Our presentation is aimed to be a self-contained and comprehensive treatment of the subject, with all the relevant mathematical background material introduced and explained in detail. We also review attempts at making the infinite-dimensional symmetries manifest, through the construction of a geodesic sigma model based on a Lorentzian Kac-Moody algebra. An explicit example is provided for the case of the hyperbolic algebra E10, which is conjectured to be an underlying symmetry of M-theory. Illustrations of this conjecture are also discussed in the context of cosmological solutions to eleven-dimensional supergravity.Comment: 228 pages. Typos corrected. References added. Subject index added. Published versio

Survival Rate, Fracture Strength and Failure Mode of Ceramic Implant Abutments After Chewing Simulation

The aim of this study was to compare titanium-reinforced ZrO2 and pure Al2O3 abutments regarding their outcome after chewing simulation and static loading. Forty-eight standard diameter implants with an external hexagon were divided into three groups of 16 implants each and restored with three different types of abutments (group A: ZrO2 abutments with titanium inserts; group B: densely sintered high-purity Al2O3 abutments; group C: titanium abutments). All abutments were fixated on the implants with gold-alloy screws at 32 Ncm torque, and metal crowns were adhesively cemented onto the abutments. The specimens were exposed to 1.2 million cycles in a chewing simulator. Surviving specimens were subsequently loaded until fracture in a static testing device. Fracture loads (N) and fracture modes were recorded. A Wilcoxon Rank test to compare fracture loads among the 3 groups and a Fisher exact test to detect group differences in fracture modes were used for statistical evaluation (

Quantum Gravity in 2+1 Dimensions: The Case of a Closed Universe

In three spacetime dimensions, general relativity drastically simplifies, becoming a ``topological'' theory with no propagating local degrees of freedom. Nevertheless, many of the difficult conceptual problems of quantizing gravity are still present. In this review, I summarize the rather large body of work that has gone towards quantizing (2+1)-dimensional vacuum gravity in the setting of a spatially closed universe.Comment: 61 pages, draft of review for Living Reviews; comments, criticisms, additions, missing references welcome; v2: minor changes, added reference

Stationary Black Holes: Uniqueness and Beyond

The spectrum of known black-hole solutions to the stationary Einstein equations has been steadily increasing, sometimes in unexpected ways. In particular, it has turned out that not all black-hole-equilibrium configurations are characterized by their mass, angular momentum and global charges. Moreover, the high degree of symmetry displayed by vacuum and electro-vacuum black-hole spacetimes ceases to exist in self-gravitating non-linear field theories. This text aims to review some developments in the subject and to discuss them in light of the uniqueness theorem for the Einstein-Maxwell system.Comment: Major update of the original version by Markus Heusler from 1998. Piotr T. Chru\'sciel and Jo\~ao Lopes Costa succeeded to this review's authorship. Significantly restructured and updated all sections; changes are too numerous to be usefully described here. The number of references increased from 186 to 32

Organism-sediment interactions govern post-hypoxia recovery of ecosystem functioning

Hypoxia represents one of the major causes of biodiversity and ecosystem functioning loss for coastal waters. Since eutrophication-induced hypoxic events are becoming increasingly frequent and intense, understanding the response of ecosystems to hypoxia is of primary importance to understand and predict the stability of ecosystem functioning. Such ecological stability may greatly depend on the recovery patterns of communities and the return time of the system properties associated to these patterns. Here, we have examined how the reassembly of a benthic community contributed to the recovery of ecosystem functioning following experimentally-induced hypoxia in a tidal flat. We demonstrate that organism-sediment interactions that depend on organism size and relate to mobility traits and sediment reworking capacities are generally more important than recovering species richness to set the return time of the measured sediment processes and properties. Specifically, increasing macrofauna bioturbation potential during community reassembly significantly contributed to the recovery of sediment processes and properties such as denitrification, bedload sediment transport, primary production and deep pore water ammonium concentration. Such bioturbation potential was due to the replacement of the small-sized organisms that recolonised at early stages by large-sized bioturbating organisms, which had a disproportionately stronger influence on sediment. This study suggests that the complete recovery of organism-sediment interactions is a necessary condition for ecosystem functioning recovery, and that such process requires long periods after disturbance due to the slow growth of juveniles into adult stages involved in these interactions. Consequently, repeated episodes of disturbance at intervals smaller than the time needed for the system to fully recover organism-sediment interactions may greatly impair the resilience of ecosystem functioning.

The impact of iodine supplementation and bread fortification on urinary iodine concentrations in a mildly iodine deficient population of pregnant women in South Australia

Mild iodine deficiency during pregnancy can have significant effects on fetal development and future cognitive function. The purpose of this study was to characterise the iodine status of South Australian women during pregnancy and relate it to the use of iodine-containing multivitamins. The impact of fortification of bread with iodized salt was also assessed. Women (n = 196) were recruited prospectively at the beginning of pregnancy and urine collected at 12, 18, 30, 36 weeks gestation and 6 months postpartum. The use of a multivitamin supplement was recorded at each visit. Spot urinary iodine concentrations (UIC) were assessed. Median UICs were within the mildly deficient range in women not taking supplements (<90 μg/L). Among the women taking iodine-containing multivitamins UICs were within WHO recommendations (150–249 μg/L) for sufficiency and showed an increasing trend through gestation. The fortification of bread with iodized salt increased the median UIC from 68 μg/L to 84 μg/L (p = .011) which was still in the deficient range. Pregnant women in this region of Australia were unlikely to reach recommended iodine levels without an iodine supplement, even after the mandatory iodine supplementation of bread was instituted in October 2009.Vicki L Clifton, Nicolette A Hodyl, Paul A Fogarty, David J Torpy, Rachel Roberts, Ted Nettelbeck, Gary Ma and Basil Hetze

Physics, Astrophysics and Cosmology with Gravitational Waves

Gravitational wave detectors are already operating at interesting sensitivity levels, and they have an upgrade path that should result in secure detections by 2014. We review the physics of gravitational waves, how they interact with detectors (bars and interferometers), and how these detectors operate. We study the most likely sources of gravitational waves and review the data analysis methods that are used to extract their signals from detector noise. Then we consider the consequences of gravitational wave detections and observations for physics, astrophysics, and cosmology.Comment: 137 pages, 16 figures, Published version <http://www.livingreviews.org/lrr-2009-2