57 research outputs found
The Cosmology of Composite Inelastic Dark Matter
Composite dark matter is a natural setting for implementing inelastic dark
matter - the O(100 keV) mass splitting arises from spin-spin interactions of
constituent fermions. In models where the constituents are charged under an
axial U(1) gauge symmetry that also couples to the Standard Model quarks, dark
matter scatters inelastically off Standard Model nuclei and can explain the
DAMA/LIBRA annual modulation signal. This article describes the early Universe
cosmology of a minimal implementation of a composite inelastic dark matter
model where the dark matter is a meson composed of a light and a heavy quark.
The synthesis of the constituent quarks into dark mesons and baryons results in
several qualitatively different configurations of the resulting dark matter
hadrons depending on the relative mass scales in the system.Comment: 31 pages, 4 figures; references added, typos correcte
Black Hole Thermodynamics and Massive Gravity
We consider the generalized laws of thermodynamics in massive gravity. Making
use of explicit black hole solutions, we devise black hole merger processes in
which i) total entropy of the system decreases ii) the zero-temperature
extremal black hole is created. Thus, both second and third laws of
thermodynamics are violated. In both cases, the violation can be traced back to
the presence of negative-mass black holes, which, in turn, is related to the
violation of the null energy condition. The violation of the third law of
thermodynamics implies, in particular, that a naked singularity may be created
as a result of the evolution of a singularity-free state. This may signal a
problem in the model, unless the creation of the negative-mass black holes from
positive-mass states can be forbidden dynamically or the naked singularity may
somehow be resolved in a full quantum theory.Comment: 15 pages, 4 figures; v2:Style changed to JHEP. Discussion added in
the conclusions. Revised version to match published versio
11ÎČ-HSD1 plays a critical role in trabecular bone loss associated with systemic glucocorticoid therapy
Background: Despite their efficacy in the treatment of chronic inflammation, the prolonged application of therapeutic glucocorticoids (GCs) is limited by significant systemic side effects including glucocorticoid-induced osteoporosis (GIOP). 11ÎČ-Hydroxysteroid dehydrogenase type 1 (11ÎČ-HSD1) is a bi-directional enzyme that primarily activates GCs in vivo, regulating tissue-specific exposure to active GC. We aimed to determine the contribution of 11ÎČ-HSD1 to GIOP. Methods: Wild type (WT) and 11ÎČ-HSD1 knockout (KO) mice were treated with corticosterone (100âÎŒg/ml, 0.66% ethanol) or vehicle (0.66% ethanol) in drinking water over 4 weeks (six animals per group). Bone parameters were assessed by micro-CT, sub-micron absorption tomography and serum markers of bone metabolism. Osteoblast and osteoclast gene expression was assessed by quantitative RT-PCR. Results: Wild type mice receiving corticosterone developed marked trabecular bone loss with reduced bone volume to tissue volume (BV/TV), trabecular thickness (Tb.Th) and trabecular number (Tb.N). Histomorphometric analysis revealed a dramatic reduction in osteoblast numbers. This was matched by a significant reduction in the serum marker of osteoblast bone formation P1NP and gene expression of the osteoblast markers Alp and Bglap. In contrast, 11ÎČ-HSD1 KO mice receiving corticosterone demonstrated almost complete protection from trabecular bone loss, with partial protection from the decrease in osteoblast numbers and markers of bone formation relative to WT counterparts receiving corticosterone. Conclusions: This study demonstrates that 11ÎČ-HSD1 plays a critical role in GIOP, mediating GC suppression of anabolic bone formation and reduced bone volume secondary to a decrease in osteoblast numbers. This raises the intriguing possibility that therapeutic inhibitors of 11ÎČ-HSD1 may be effective in preventing GIOP in patients receiving therapeutic steroids
Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.
Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field
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