Comparison of Apoptosis Detection Markers Combined with Macrophage Immunostaining to Study Phagocytosis of Apoptotic Cells in Situ

Efficient phagocytosis of cells undergoing apoptosis by macrophages is important to prevent immunological responses and development of chronic inflammatory disorders such as systemic lupus erythematosus, cystic fibrosis and atherosclerosis. To study phagocytosis of apoptotic cells (AC) by macrophages in tissue, we validated different apoptosis markers (DNA fragmentation, caspase-3 activation and cleavage of its substrate poly(ADP-ribose)polymerase-1) in combination with macrophage immunostaining. Human tonsils were used as a model because they show a high apoptosis frequency under physiological conditions as well as efficient phagocytosis of AC by macrophages. On the other hand, advanced human atherosclerotic plaques were examined since plaques show severely impaired phagocytosis of AC. Our results demonstrate that the presence of non-phagocytized terminal deoxynucleotidyl transferase end labelling (TUNEL)-positive AC represents a suitable marker of poor phagocytosis by macrophages in situ. Other markers for apoptosis, such as cleavage of caspase-3 or PARP-1, should not be used to assess phagocytosis efficiency, because activation of the caspase cascade and cleavage of their substrates can occur in AC when they have not yet been phagocytized by macrophages

Measuring the mixing efficiency in a simple model of stirring:some analytical results and a quantitative study via Frequency Map Analysis

We prove the existence of invariant curves for a $T$--periodic Hamiltonian system which models a fluid stirring in a cylindrical tank, when $T$ is small and the assigned stirring protocol is piecewise constant. Furthermore, using the Numerical Analysis of the Fundamental Frequency of Laskar, we investigate numerically the break down of invariant curves as $T$ increases and we give a quantitative estimate of the efficiency of the mixing.Comment: 10 figure

Worms and the treatment of inflammatory bowel disease: are molecules the answer?

The lack of exposure to helminth infections, as a result of improved living standards and medical conditions, may have contributed to the increased incidence of IBD in the developed world. Epidemiological, experimental, and clinical data sustain the idea that helminths could provide protection against IBD. Studies investigating the underlying mechanisms by which helminths might induce such protection have revealed the importance of regulatory pathways, for example, regulatory T-cells. Further investigation on how helminths influence both innate and adaptive immune reactions will shed more light on the complex pathways used by helminths to regulate the hosts immune system. Although therapy with living helminths appears to be effective in several immunological diseases, the disadvantages of a treatment based on living parasites are explicit. Therefore, the identification and characterization of helminth-derived immunomodulatory molecules that contribute to the protective effect could lead to new therapeutic approaches in IBD and other immune diseases

Low-energy fusion caused by an interference

Fusion of two deuterons of room temperature energy is studied. The nuclei are in vacuum with no connection to any external source (electric or magnetic field, illumination, surrounding matter, traps, etc.) which may accelerate them. The energy of the two nuclei is conserved and remains small during the motion through the Coulomb barrier. The penetration through this barrier, which is the main obstacle for low-energy fusion, strongly depends on a form of the incident flux on the Coulomb center at large distances from it. In contrast to the usual scattering, the incident wave is not a single plane wave but the certain superposition of plane waves of the same energy and various directions, for example, a convergent conical wave. As a result of interference, the wave function close to the Coulomb center is determined by a cusp caustic which is probed by de Broglie waves. The particle flux gets away from the cusp and moves to the Coulomb center providing a not small probability of fusion (cusp driven tunneling). Getting away from a caustic cusp also occurs in optics and acoustics

Herman's Theory Revisited

We prove that a $C^{2+\alpha}$-smooth orientation-preserving circle diffeomorphism with rotation number in Diophantine class $D_\delta$, $0<\delta<\alpha\le1$, is $C^{1+\alpha-\delta}$-smoothly conjugate to a rigid rotation. We also derive the most precise version of Denjoy's inequality for such diffeomorphisms.Comment: 10 page

Bayesian Analysis of Instrumental Variable Models: Acceptance-Rejection within Direct Monte Carlo

We discuss Bayesian inferential procedures within the family of instrumental variables regression models and focus on two issues: existence conditions for posterior moments of the parameters of interest under a flat prior and the potential of Direct Monte Carlo (DMC) approaches for efficient evaluation of such possibly highly non-elliptical posteriors. We show that, for the general case of m endogenous variables under a flat prior, posterior moments of order r exist for the coefficients reflecting the endogenous regressors' effect on the dependent variable, if the number of instruments is greater than m +r, even though there is an issue of local non-identification that causes non-elliptical shapes of the posterior. This stresses the need for efficient Monte Carlo integration methods. We introduce an extension of DMC that incorporates an acceptance-rejection sampling step within DMC. This Acceptance-Rejection within Direct Monte Carlo (ARDMC) method has the attractive property that the generated random drawings are independent, which greatly helps the fast convergence of simulation results, and which facilitates the evaluation of the numerical accuracy. The speed of ARDMC can be easily further improved by making use of parallelized computation using multiple core machines or computer clusters. We note that ARDMC is an analogue to the well-known "Metropolis-Hastings within Gibbs" sampling in the sense that one 'more difficult' step is used within an 'easier' simulation method. We compare the ARDMC approach with the Gibbs sampler using simulated data and two empirical data sets, involving the settler mortality instrument of Acemoglu et al. (2001) and father's education's instrument used by Hoogerheide et al. (2012a). Even without making use of parallelized computation, an efficiency gain is observed both under strong and weak instruments, where the gain can be enormous in the latter case

Scaling law in the Standard Map critical function. Interpolating hamiltonian and frequency map analysis

We study the behaviour of the Standard map critical function in a neighbourhood of a fixed resonance, that is the scaling law at the fixed resonance. We prove that for the fundamental resonance the scaling law is linear. We show numerical evidence that for the other resonances $p/q$, $q \geq 2$, $p \neq 0$ and $p$ and $q$ relatively prime, the scaling law follows a power--law with exponent $1/q$.Comment: AMS-LaTeX2e, 29 pages with 8 figures, submitted to Nonlinearit

The Protein Synthesis Inhibitor Anisomycin Induces Macrophage Apoptosis in Rabbit Atherosclerotic Plaques through p38 Mitogen-Activated Protein Kinase

ABSTRACT Because macrophages play a major role in atherosclerotic plaque destabilization, selective removal of macrophages represents a promising approach to stabilize plaques. We showed recently that the protein synthesis inhibitor cycloheximide, in contrast to puromycin, selectively depleted macrophages in rabbit atherosclerotic plaques without affecting smooth muscle cells (SMCs). The mechanism of action of these two translation inhibitors is dissimilar and could account for the differential effects on SMC viability. It is not known whether selective depletion of macrophages is confined to cycloheximide or whether it can also be achieved with translation inhibitors that have a similar mechanism of action. Therefore, in the present study, we investigated the effect of anisomycin, a translation inhibitor with a mechanism of action similar to cycloheximide, on macrophage and SMC viability. In vitro, anisomycin induced apoptosis of macrophages in a concentration-dependent manner, whereas SMCs were only affected at higher concentrations. In vivo, anisomycin selectively decreased the macrophage content of rabbit atherosclerotic plaques through apoptosis. The p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190 [4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)-1H-imidazole] prevented anisomycin-induced macrophage death, without affecting SMC viability. SB202190 decreased anisomycin-induced p38 MAPK phosphorylation, did not alter c-Jun NH 2 -terminal kinase (JNK) phosphorylation, and increased extracellular signal-regulated kinase (ERK) 1/2 phosphorylation. The latter effect was abolished by the mitogenactivated protein kinase kinase 1/2 inhibitor U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene ethanolate], although the prevention of anisomycin-induced macrophage death by SB202190 remained unchanged. The JNK phosphorylation inhibitor SP600125 did not affect anisomycin-induced macrophage or SMC death. In conclusion, anisomycin selectively decreased the macrophage content in rabbit atherosclerotic plaques, indicating that this effect is not confined to cycloheximide. p38 MAPK, but not ERK1/2 or JNK, plays a major role in anisomycin-induced macrophage death

Theory of Circle Maps and the Problem of One-Dimensional Optical Resonator with a Periodically Moving Wall

We consider the electromagnetic field in a cavity with a periodically oscillating perfectly reflecting boundary and show that the mathematical theory of circle maps leads to several physical predictions. Notably, well-known results in the theory of circle maps (which we review briefly) imply that there are intervals of parameters where the waves in the cavity get concentrated in wave packets whose energy grows exponentially. Even if these intervals are dense for typical motions of the reflecting boundary, in the complement there is a positive measure set of parameters where the energy remains bounded.Comment: 34 pages LaTeX (revtex) with eps figures, PACS: 02.30.Jr, 42.15.-i, 42.60.Da, 42.65.Y