Differential pain-related behaviors and bone disease in immunocompetent mouse models of myeloma

Bone pain is a serious and debilitating symptom of multiple myeloma (MM) that impairs the quality of life of patients. The underlying mechanisms of the pain are unknown and understudied, and there is a need for immunocompetent preclinical models of myeloma‐induced bone pain. The aim of this study was to provide the first in‐depth behavioral characterization of an immunocompetent mouse model of MM presenting the clinical disease features: osteolytic bone disease and bone pain. We hypothesized that a widely used syngeneic model of MM, established by systemic inoculation of green fluorescent protein‐tagged myeloma cells (5TGM1‐GFP) in immunocompetent C57Bl/KaLwRijHsd (BKAL) mice, would present pain‐related behaviors. Disease phenotype was confirmed by splenomegaly, high serum paraprotein, and tumor infiltration in the bone marrow of the hind limbs; however, myeloma‐bearing mice did not present pain‐related behaviors or substantial bone disease. Thus, we investigated an alternative model in which 5TGM1‐GFP cells were directly inoculated into the intrafemoral medullary cavity. This localized myeloma model presented the hallmarks of the disease, including high serum paraprotein, tumor growth, and osteolytic bone lesions. Compared with control mice, myeloma‐bearing mice presented myeloma‐induced pain‐related behaviors, a phenotype that was reversed by systemic morphine treatment. Micro‐computed tomography analyses of the myeloma‐inoculated femurs showed bone disease in cortical and trabecular bone. Repeated systemic bisphosphonate treatment induced an amelioration of the nociceptive phenotype, but did not completely reverse it. Furthermore, intrafemorally injected mice presented a profound denervation of the myeloma‐bearing bones, a previously unknown feature of the disease. This study reports the intrafemoral inoculation of 5TGM1‐GFP cells as a robust immunocompetent model of myeloma‐induced bone pain, with consistent bone loss. Moreover, the data suggest that myeloma‐induced bone pain is caused by a combinatorial mechanism including osteolysis and bone marrow denervation. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research

Effect of green manure management on barley yields and N-recovery

Mulching of GM herbage can increase cereal yields compared to its removal. However, the same GM herbage removed for biogas production will provide biogas residue that can be used as spring fertilizer to cereals. This will improve N-recovery and reduce the risk for N pollution. Cooperation with existing biogas plants will be more efficient, as building small biogas plants are costly and challenging

The extended empirical process test for non-Gaussianity in the CMB, with an application to non-Gaussian inflationary models

In (Hansen et al. 2002) we presented a new approach for measuring non-Gaussianity of the Cosmic Microwave Background (CMB) anisotropy pattern, based on the multivariate empirical distribution function of the spherical harmonics a_lm of a CMB map. The present paper builds upon the same ideas and proposes several improvements and extensions. More precisely, we exploit the additional information on the random phases of the a_lm to provide further tests based on the empirical distribution function. Also we take advantage of the effect of rotations in improving the power of our procedures. The suggested tests are implemented on physically motivated models of non-Gaussian fields; Monte-Carlo simulations suggest that this approach may be very promising in the analysis of non-Gaussianity generated by non-standard models of inflation. We address also some experimentally meaningful situations, such as the presence of instrumental noise and a galactic cut in the map.Comment: 15 pages, 6 figures, submitted to Phys. Rev.

Spatiotemporal SNP analysis reveals pronounced biocomplexity at the northern range margin of Atlantic cod Gadus morhua

Accurate prediction of species distribution shifts in the face of climate change requires a sound understanding of population diversity and local adaptations. Previous modeling has suggested that global warming will lead to increased abundance of Atlantic cod (Gadus morhua) in the ocean around Greenland, but the dynamics of earlier abundance fluctuations are not well understood. We applied a retrospective spatiotemporal population genomics approach to examine the temporal stability of cod population structure in this region and to search for signatures of divergent selection over a 78-year period spanning major demographic changes. Analyzing >900 gene-associated single nucleotide polymorphisms in 847 individuals, we identified four genetically distinct groups that exhibited varying spatial distributions with considerable overlap and mixture. The genetic composition had remained stable over decades at some spawning grounds, whereas complete population replacement was evident at others. Observations of elevated differentiation in certain genomic regions are consistent with adaptive divergence between the groups, indicating that they may respond differently to environmental variation. Significantly increased temporal changes at a subset of loci also suggest that adaptation may be ongoing. These findings illustrate the power of spatiotemporal population genomics for revealing biocomplexity in both space and time and for informing future fisheries management and conservation efforts

Search for non-Gaussianity in pixel, harmonic and wavelet space: compared and combined

We present a comparison between three approaches to test non-Gaussianity of cosmic microwave background data. The Minkowski functionals, the empirical process method and the skewness of wavelet coefficients are applied to maps generated from non-standard inflationary models and to Gaussian maps with point sources included. We discuss the different power of the pixel, harmonic and wavelet space methods on these simulated almost full-sky data (with Planck like noise). We also suggest a new procedure consisting of a combination of statistics in pixel, harmonic and wavelet space.Comment: Accepted for publication in PR

Orientational order in dipolar fluids consisting of nonspherical hard particles

We investigate fluids of dipolar hard particles by a certain variant of density-functional theory. The proper treatment of the long range of the dipolar interactions yields a contribution to the free energy which favors ferromagnetic order. This corrects previous theoretical analyses. We determine phase diagrams for dipolar ellipsoids and spherocylinders as a function of the aspect ratio of the particles and their dipole moment. In the nonpolar limit the results for the phase boundary between the isotropic and nematic phase agree well with simulation data. Adding a longitudinal dipole moment favors the nematic phase. For oblate or slightly elongated particles we find a ferromagnetic liquid phase, which has also been detected in computer simulations of fluids consisting of spherical dipolar particles. The detailed structure of the phase diagram and its evolution upon changing the aspect ratio are discussed in detail.Comment: 35 pages LaTeX with epsf style, 11 figures in eps format, submitted to Phys. Rev.

Threshold criterion for wetting at the triple point

Grand canonical simulations are used to calculate adsorption isotherms of various classical gases on alkali metal and Mg surfaces. Ab initio adsorption potentials and Lennard-Jones gas-gas interactions are used. Depending on the system, the resulting behavior can be nonwetting for all temperatures studied, complete wetting, or (in the intermediate case) exhibit a wetting transition. An unusual variety of wetting transitions at the triple point is found in the case of a specific adsorption potential of intermediate strength. The general threshold for wetting near the triple point is found to be close to that predicted with a heuristic model of Cheng et al. This same conclusion was drawn in a recent experimental and simulation study of Ar on CO_2 by Mistura et al. These results imply that a dimensionless wetting parameter w is useful for predicting whether wetting behavior is present at and above the triple temperature. The nonwetting/wetting crossover value found here is w circa 3.3.Comment: 15 pages, 8 figure

Seismology of the Sun : Inference of Thermal, Dynamic and Magnetic Field Structures of the Interior

Recent overwhelming evidences show that the sun strongly influences the Earth's climate and environment. Moreover existence of life on this Earth mainly depends upon the sun's energy. Hence, understanding of physics of the sun, especially the thermal, dynamic and magnetic field structures of its interior, is very important. Recently, from the ground and space based observations, it is discovered that sun oscillates near 5 min periodicity in millions of modes. This discovery heralded a new era in solar physics and a separate branch called helioseismology or seismology of the sun has started. Before the advent of helioseismology, sun's thermal structure of the interior was understood from the evolutionary solution of stellar structure equations that mimicked the present age, mass and radius of the sun. Whereas solution of MHD equations yielded internal dynamics and magnetic field structure of the sun's interior. In this presentation, I review the thermal, dynamic and magnetic field structures of the sun's interior as inferred by the helioseismology.Comment: To be published in the proceedings of the meeting "3rd International Conference on Current Developments in Atomic, Molecular, Optical and Nano Physics with Applications", December 14-16, 2011, New Delhi, Indi

Challenges and Obstacles for a Bouncing Universe in Brane Models

A Brane evolving in the background of a charged AdS black-hole displays in general a bouncing behaviour with a smooth transition from a contracting to an expanding phase. We examine in detail the conditions and consequences of this behaviour in various cases. For a cosmological-constant-dominated Brane, we obtain a singularity-free, inflationary era which is shown to be compatible only with an intermediate-scale fundamental Planck mass. For a radiation-dominated Brane, the bouncing behaviour can occur only for background-charge values exceeding those allowed for non-extremal black holes. For a matter-dominated Brane, the black-hole mass affects the proper volume or the expansion rate of the Brane. We also consider the Brane evolving in an asymmetric background of two distinct charged AdS black hole spacetimes being bounded by the Brane and find that, in the case of an empty critical Brane, bouncing behaviour occurs only if the black-hole mass difference is smaller than a certain value. The effects of a Brane curvature term on the bounce at early and late times are also investigated.Comment: 23 pages, Latex file, comments and references added, version to appear in Phys. Rev.