97 research outputs found
Research Update on Extreme-Mass-Ratio Inspirals
The inspirals of stellar-mass mass compact objects into massive black holes
in the centres of galaxies are one of the most important sources of
gravitational radiation for space-based detectors like LISA or eLISA. These
extreme-mass-ratio inspirals (EMRIs) will enable an ambitious research program
with implications for astrophysics, cosmology, and fundamental physics. This
article is a summary of the talks delivered at the plenary session on EMRIs at
the 10th International LISA Symposium. It contains research updates on the
following topics: astrophysics of EMRIs; EMRI science potential; and EMRI
modeling.Comment: 17 pages, no figures. Proceedings of the LISA Symposium X, to be
published at the Journal of Physic
Self-force: Computational Strategies
Building on substantial foundational progress in understanding the effect of
a small body's self-field on its own motion, the past 15 years has seen the
emergence of several strategies for explicitly computing self-field corrections
to the equations of motion of a small, point-like charge. These approaches
broadly fall into three categories: (i) mode-sum regularization, (ii) effective
source approaches and (iii) worldline convolution methods. This paper reviews
the various approaches and gives details of how each one is implemented in
practice, highlighting some of the key features in each case.Comment: Synchronized with final published version. Review to appear in
"Equations of Motion in Relativistic Gravity", published as part of the
Springer "Fundamental Theories of Physics" series. D. Puetzfeld et al.
(eds.), Equations of Motion in Relativistic Gravity, Fundamental Theories of
Physics 179, Springer, 201
Carbon Monoxide Induced Erythroid Differentiation of K562 Cells Mimics the Central Macrophage Milieu in Erythroblastic Islands
Growing evidence supports the role of erythroblastic islands (EI) as microenvironmental niches within bone marrow (BM), where cell-cell attachments are suggested as crucial for erythroid maturation. The inducible form of the enzyme heme oxygenase, HO-1, which conducts heme degradation, is absent in erythroblasts where hemoglobin (Hb) is synthesized. Yet, the central macrophage, which retains high HO-1 activity, might be suitable to take over degradation of extra, harmful, Hb heme. Of these enzymatic products, only the hydrophobic gas molecule - CO can transfer from the macrophage to surrounding erythroblasts directly via their tightly attached membranes in the terminal differentiation stage
Incomplete Inhibition of Sphingosine 1-Phosphate Lyase Modulates Immune System Function yet Prevents Early Lethality and Non-Lymphoid Lesions
BACKGROUND: S1PL is an aldehyde-lyase that irreversibly cleaves sphingosine 1-phosphate (S1P) in the terminal step of sphingolipid catabolism. Because S1P modulates a wide range of physiological processes, its concentration must be tightly regulated within both intracellular and extracellular environments. METHODOLOGY: In order to better understand the function of S1PL in this regulatory pathway, we assessed the in vivo effects of different levels of S1PL activity using knockout (KO) and humanized mouse models. PRINCIPAL FINDINGS: Our analysis showed that all S1PL-deficient genetic models in this study displayed lymphopenia, with sequestration of mature T cells in the thymus and lymph nodes. In addition to the lymphoid phenotypes, S1PL KO mice (S1PL(-/-)) also developed myeloid cell hyperplasia and significant lesions in the lung, heart, urinary tract, and bone, and had a markedly reduced life span. The humanized knock-in mice harboring one allele (S1PL(H/-)) or two alleles (S1PL(H/H)) of human S1PL expressed less than 10 and 20% of normal S1PL activity, respectively. This partial restoration of S1PL activity was sufficient to fully protect both humanized mouse lines from the lethal non-lymphoid lesions that developed in S1PL(-/-) mice, but failed to restore normal T-cell development and trafficking. Detailed analysis of T-cell compartments indicated that complete absence of S1PL affected both maturation/development and egress of mature T cells from the thymus, whereas low level S1PL activity affected T-cell egress more than differentiation. SIGNIFICANCE: These findings demonstrate that lymphocyte trafficking is particularly sensitive to variations in S1PL activity and suggest that there is a window in which partial inhibition of S1PL could produce therapeutic levels of immunosuppression without causing clinically significant S1P-related lesions in non-lymphoid target organs
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