In vivo impact of a 4 bp deletion mutation in the DLX3 gene on bone development

AbstractDistal-less 3 (DLX3) gene mutations are etiologic for Tricho-Dento-Osseous syndrome. To investigate the in vivo impact of mutant DLX3 on bone development, we established transgenic (TG) mice expressing the c.571_574delGGGG DLX-3 gene mutation (MT-DLX3) driven by a mouse 2.3 Col1A1 promoter. Microcomputed tomographic analyses demonstrated markedly increased trabecular bone volume and bone mineral density in femora from TG mice. In ex vivo experiments, TG mice showed enhanced differentiation of bone marrow stromal cells to osteoblasts and increased expression levels of bone formation markers. However, TG mice did not show enhanced dynamic bone formation rates in in vivo fluorochrome double labeling experiments. Osteoclastic differentiation capacities of bone marrow monocytes were reduced in TG mice in the presence of osteoclastogenic factors and the numbers of TRAP(+) osteoclasts on distal metaphyseal trabecular bone surfaces were significantly decreased. TRACP 5b and CTX serum levels were significantly decreased in TG mice, while IFN-γ levels were significantly increased. These data demonstrate that increased levels of IFN-γ decrease osteoclast bone resorption activities, contributing to the enhanced trabecular bone volume and mineral density in these TG mice. These data suggest a novel role for this DLX-3 mutation in osteoclast differentiation and bone resorption

A Bayesian Approach to Calibrating Period-Luminosity Relations of RR Lyrae Stars in the Mid-Infrared

A Bayesian approach to calibrating period-luminosity (PL) relations has substantial benefits over generic least-squares fits. In particular, the Bayesian approach takes into account the full prior distribution of the model parameters, such as the a priori distances, and refits these parameters as part of the process of settling on the most highly-constrained final fit. Additionally, the Bayesian approach can naturally ingest data from multiple wavebands and simultaneously fit the parameters of PL relations for each waveband in a procedure that constrains the parameter posterior distributions so as to minimize the scatter of the final fits appropriately in all wavebands. Here we describe the generalized approach to Bayesian model fitting and then specialize to a detailed description of applying Bayesian linear model fitting to the mid-infrared PL relations of RR Lyrae variable stars. For this example application we quantify the improvement afforded by using a Bayesian model fit. We also compare distances previously predicted in our example application to recently published parallax distances measured with the Hubble Space Telescope and find their agreement to be a vindication of our methodology. Our intent with this article is to spread awareness of the benefits and applicability of this Bayesian approach and encourage future PL relation investigations to consider employing this powerful analysis method.Comment: 6 pages, 1 figure. Accepted for publication in Astrophysics & Space Science. Following a presentation at the conference The Fundamental Cosmic Distance Scale: State of the Art and the Gaia Perspective, Naples, May 201

Do we know the mass of a black hole? Mass of some cosmological black hole models

Using a cosmological black hole model proposed recently, we have calculated the quasi-local mass of a collapsing structure within a cosmological setting due to different definitions put forward in the last decades to see how similar or different they are. It has been shown that the mass within the horizon follows the familiar Brown-York behavior. It increases, however, outside the horizon again after a short decrease, in contrast to the Schwarzschild case. Further away, near the void, outside the collapsed region, and where the density reaches the background minimum, all the mass definitions roughly coincide. They differ, however, substantially far from it. Generically, we are faced with three different Brown-York mass maxima: near the horizon, around the void between the overdensity region and the background, and another at cosmological distances corresponding to the cosmological horizon. While the latter two maxima are always present, the horizon mass maxima is absent before the onset of the central singularity.Comment: 11 pages, 8 figures, revised version, accepted in General Relativity and Gravitatio

Kernel density classification and boosting: an L2 sub analysis

Kernel density estimation is a commonly used approach to classification. However, most of the theoretical results for kernel methods apply to estimation per se and not necessarily to classification. In this paper we show that when estimating the difference between two densities, the optimal smoothing parameters are increasing functions of the sample size of the complementary group, and we provide a small simluation study which examines the relative performance of kernel density methods when the final goal is classification. A relative newcomer to the classification portfolio is “boosting”, and this paper proposes an algorithm for boosting kernel density classifiers. We note that boosting is closely linked to a previously proposed method of bias reduction in kernel density estimation and indicate how it will enjoy similar properties for classification. We show that boosting kernel classifiers reduces the bias whilst only slightly increasing the variance, with an overall reduction in error. Numerical examples and simulations are used to illustrate the findings, and we also suggest further areas of research

Alternative soot detection strategies for application in aero-engine test-beds : assessment of the performance and uncertainties of time-integrated LII

We describe a laser induced incandescence (LII) measurement system for 2D mapping of non-volatile particulate matter (soot) in full-scale aero-engine exhausts. Simulation allows us to quantify the sensitivity of the measurement to variation in physical properties such as primary particle size, over a range of laser fluences and as a function of beam diameter. We discuss the implications of our results for optimisation and calibration of soot imaging in exhaust streams

Dapagliflozin: a sodium glucose cotransporter 2 inhibitor in development for type 2 diabetes

Type 2 diabetes mellitus (T2DM) is a growing worldwide epidemic. Patients face lifelong therapy to control hyperglycemia and prevent the associated complications. There are many medications, with varying mechanisms, available for the treatment of T2DM, but almost all target the declining insulin sensitivity and secretion that are associated with disease progression. Medications with such insulin-dependent mechanisms of action often lose efficacy over time, and there is increasing interest in the development of new antidiabetes medications that are not dependent upon insulin. One such approach is through the inhibition of renal glucose reuptake. Dapagliflozin, the first of a class of selective sodium glucose cotransporter 2 inhibitors, reduces renal glucose reabsorption and is currently under development for the treatment of T2DM. Here, we review the literature relating to the preclinical and clinical development of dapagliflozin

Magnetic Field Generation in Stars

Enormous progress has been made on observing stellar magnetism in stars from the main sequence through to compact objects. Recent data have thrown into sharper relief the vexed question of the origin of stellar magnetic fields, which remains one of the main unanswered questions in astrophysics. In this chapter we review recent work in this area of research. In particular, we look at the fossil field hypothesis which links magnetism in compact stars to magnetism in main sequence and pre-main sequence stars and we consider why its feasibility has now been questioned particularly in the context of highly magnetic white dwarfs. We also review the fossil versus dynamo debate in the context of neutron stars and the roles played by key physical processes such as buoyancy, helicity, and superfluid turbulence,in the generation and stability of neutron star fields. Independent information on the internal magnetic field of neutron stars will come from future gravitational wave detections. Thus we maybe at the dawn of a new era of exciting discoveries in compact star magnetism driven by the opening of a new, non-electromagnetic observational window. We also review recent advances in the theory and computation of magnetohydrodynamic turbulence as it applies to stellar magnetism and dynamo theory. These advances offer insight into the action of stellar dynamos as well as processes whichcontrol the diffusive magnetic flux transport in stars.Comment: 41 pages, 7 figures. Invited review chapter on on magnetic field generation in stars to appear in Space Science Reviews, Springe

Biodistribution of 64 Cu in Inflamed Rats Following Administration of Two Anti-Inflammatory Copper Complexes

64Cu was administered in two anti-inflammatory formulations to normal rats and to rats with 2 forms of local inflammation, namely (a) an acute paw oedema (elicited with carrageenan) or (b) a chronic granulomatous response to an implanted irritant (Mycobacterium tuberculosis in a polyurethane sponge). The copper formulations used were (i) a slow release one consisting of Cu(II) salicylate applied dermally with ethanol/DMSO and (ii) short acting hydrophilic complex (Cu(I)Cu(II)-penicillamine)5- given subcutaneously. Three types of changes in copper biodistribution with these forms of inflammation were discerned based on determination of 64Cu and copper content in the following organs: inflammatory locus (foot or sponge implant), kidney, liver, spleen, adrenals, brain, blood, thymus, heart, and skin (site of application). The most evident changes were in the kidneys, liver, spleen, adrenals, thymus and serum from animals with chronic granulomatous inflammation. In contrast, a short term acute inflammatory stress (carrageenan paw oedema) had little effect. While copper D-penicillamine (applied subcutaneously) appeared to move as a bolus through the animals, the results with the percutaneous copper salicylate formulation are consistent with it providing a slow release source of copper(II). Exogenous 64Cu from both formulations was sequestered at inflammatory sites (relative to serum). This may partly explain how applied copper complexes can be anti-inflammatory

Hypersurface-Invariant Approach to Cosmological Perturbations

Using Hamilton-Jacobi theory, we develop a formalism for solving semi-classical cosmological perturbations which does not require an explicit choice of time-hypersurface. The Hamilton-Jacobi equation for gravity interacting with matter (either a scalar or dust field) is solved by making an Ansatz which includes all terms quadratic in the spatial curvature. Gravitational radiation and scalar perturbations are treated on an equal footing. Our technique encompasses linear perturbation theory and it also describes some mild nonlinear effects. As a concrete example of the method, we compute the galaxy-galaxy correlation function as well as large-angle microwave background fluctuations for power-law inflation, and we compare with recent observations.Comment: 51 pages, Latex 2.09 ALBERTA THY/20-94, DAMTP R94/25 To appear in Phys. Rev.