Multi-dimensional transitional dynamics : a simple numerical procedure

We propose the relaxation algorithm as a simple and powerful method for simulating the transition process in growth models. This method has a number of important advantages: (1) It can easily deal with a wide range of dynamic systems including multi-dimensional systems with stable eigenvalues that di.er drastically in magnitude. (2) The application of the procedure is fairly user friendly. The only input required consists of the dynamic system. (3) The variant of the relaxation algorithm we propose exploits in a natural manner the in.nite time horizon, which usually underlies optimal control problems in economics. Overall, it seems that the relaxation procedure can easily cope with a large number of problems which arise frequently in the context of macroeconomic dynamic models. As an illustrative application, we simulate the transition process of the well-known Jones (1995) model.saddlepoint problems, transitional dynamics, economic growth, multidimensional stable manifolds

Rethinking the Concept of Long-Run Economic Growth

This paper argues that growth theory needs a more general “regularity” concept than that of exponential growth. This opens up for considering a richer set of parameter combinations than in standard growth models. Allowing zero population growth in the Jones (1995) model serves as our illustration of the usefulness of a general concept of “regular growth”.exponential growth; arithmetic growth; regular growth; semi-endogenous growth; knife-edge restrictions

When Economic Growth is Less than Exponential

This paper argues that growth theory needs a more general notion of “regularity” than that of exponential growth. We suggest that paths along which the rate of decline of the growth rate is proportional to the growth rate itself deserve attention. This opens up for considering a richer set of parameter combinations than in standard growth models. And it avoids the usual oversimplistic dichotomy of either exponential growth or stagnation. Allowing zero population growth in three different growth models (the Jones R&D-based model, a learning-by-doing model, and an embodied technical change model) serve as illustrations that a continuum of “regular” growth processes fill the whole range between exponential growth and complete stagnation.quasi-arithmetic growth; regular growth; semi-endogenous growth; knife-edge restrictions; learning by doing; embodied technical change

Differential Palmit(e)oylation of Wnt1 on C93 and S224 Residues Has Overlapping and Distinct Consequences

Though the mechanisms by which cytosolic/intracellular proteins are regulated by the post-translational addition of palmitate adducts is well understood, little is known about how this lipid modification affects secreted ligands, such as Wnts. Here we use mutational analysis to show that differential modification of the two known palmit(e)oylated residues of Wnt1, C93 and S224, has both overlapping and distinct consequences. Though the relative roles of each residue are similar with respect to stability and secretion, two distinct biological assays in L cells show that modification of C93 primarily modulates signaling via a ß-catenin independent pathway while S224 is crucial for ß-catenin dependent signaling. In addition, pharmacological inhibition of Porcupine (Porcn), an upstream regulator of Wnt, by IWP1, specifically inhibited ß-catenin dependent signaling. Consistent with these observations, mapping of amino acids in peptide domains containing C93 and S224 demonstrate that acylation of C93 is likely to be Porcn-independent while that of S224 is Porcn-dependent. Cumulatively, our data strongly suggest that C93 and S224 are modified by distinct enzymes and that the differential modification of these sites has the potential to influence Wnt signaling pathway choice

Krotov: A Python implementation of Krotov's method for quantum optimal control

We present a new open-source Python package, krotov, implementing the quantum optimal control method of that name. It allows to determine time-dependent external fields for a wide range of quantum control problems, including state-to-state transfer, quantum gate implementation and optimization towards an arbitrary perfect entangler. Krotov's method compares to other gradient-based optimization methods such as gradient-ascent and guarantees monotonic convergence for approximately time-continuous control fields. The user-friendly interface allows for combination with other Python packages, and thus high-level customization

Impaired endotoxin-induced interleukin-1β secretion, not total production, of mononuclear cells from ESRD patients

Impaired endotoxin-induced interleukin-1β secretion, not total production, of mononuclear cells from ESRD patients. Lipopolysaccharide (LPS)-induced interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNFα) production and secretion from peripheral blood mononuclear cells (PBMC) were determined in a longitudinal study with repeated measurements in PBMC from patients with chronic uremia not on hemodialysis (N = 8), end-stage renal disease (ESRD) patients (N = 8), and healthy controls (N = 7). ESRD patients were studied while using low-flux Cuprophan dialyzers and again using high-flux AN 69 dialyzers. Total (cell-associated plus secreted) LPS-induced IL-1β production was enhanced in uremic patients, but similar to controls in ESRD patients on Cuprophan. In contrast, LPS-induced IL-1β secretion (secreted amounts in % of total production) was similar to controls in uremic patients, but significantly reduced in ESRD patients on Cuprophan (P < 0.01). During AN 69 hemodialysis, LPS-induced total IL-1β production remained unchanged but IL-1β secretion increased significantly (P < 0.05) compared to Cuprophan dialysis. Increased IL-1β secretion coincided with a suppression in PGE2 synthesis (P < 0.02). Similarly, blockade of endogenous PGE2 by indomethacin increased LPS-induced IL-1β secretion (P < 0.01) but did not enhance total IL-1β production in PBMC from controls and patients on Cuprophan hemodialysis. Neither total production nor secretion of TNFα was different comparing the three study groups. We conclude that LPS-induced IL-1β secretion, but not total production, is impaired in PBMC from ESRD patients on long-term Cuprophan hemodialysis. This functional change in the PBMC response is specific for IL-1β, not due to uremia per se but hemodialysis-dependent and reversible. Hemodialysis with AN 69 suppresses endogenous PGE2 synthesis in PBMC which is associated with increased LPS-induced IL-1β secretion in the presence of unchanged total IL-1β production. We speculate that PGE2 could inactivate the IL-1β converting enzyme which is essential for processing and secretion of mature IL-1β

Microglia in the Mouse Retina Alter the Structure and Function of Retinal Pigmented Epithelial Cells: A Potential Cellular Interaction Relevant to AMD

BACKGROUND:Age-related macular degeneration (AMD) is a leading cause of legal blindness in the elderly in the industrialized word. While the immune system in the retina is likely to be important in AMD pathogenesis, the cell biology underlying the disease is incompletely understood. Clinical and basic science studies have implicated alterations in the retinal pigment epithelium (RPE) layer as a locus of early change. Also, retinal microglia, the resident immune cells of the retina, have been observed to translocate from their normal position in the inner retina to accumulate in the subretinal space close to the RPE layer in AMD eyes and in animal models of AMD. METHODOLOGY/PRINCIPAL FINDINGS:In this study, we examined the effects of retinal microglia on RPE cells using 1) an in vitro model where activated retinal microglia are co-cultured with primary RPE cells, and 2) an in vivo mouse model where retinal microglia are transplanted into the subretinal space. We found that retinal microglia induced in RPE cells 1) changes in RPE structure and distribution, 2) increased expression and secretion of pro-inflammatory, chemotactic, and pro-angiogenic molecules, and 3) increased extent of in vivo choroidal neovascularization in the subretinal space. CONCLUSIONS/SIGNIFICANCE:These findings share similarities with important pathological features found in AMD and suggest the relevance of microglia-RPE interactions in AMD pathogenesis. We speculate that the migration of retinal microglia into the subretinal space in early stages of the disease induces significant changes in RPE cells that perpetuate further microglial accumulation, increase inflammation in the outer retina, and fosters an environment conducive for the formation of neovascular changes responsible for much of vision loss in advanced AMD

Multidimensional transitional dynamics: A simple numerical procedure

We propose the relaxation algorithm as a simple and powerful method for determining the transition process in growth models numerically. This method has a number of important advantages: (1) It can easily deal with a wide range of dynamic systems including stiff differential equations and systems giving rise to a continuum of stationary equilibria. (2) The application of the procedure is fairly user-friendly. The only input required consists of the dynamic system. (3) The variant of the relaxation algorithm we propose exploits in a natural manner the infinite time horizon, which usually underlies optimal control problems in economics. As an illustrative application, we compute the transition process of the models of Jones [Jones, C.I. (1995) R&D-based models of economic growth. Journal of Political Economy 103 (3), 759784] and Lucas [Lucas, R.E., Jr. (1988) On the mechanics of economic development. Journal of Monetary Economics 22, 342]. © 2008 Cambridge University Press

GPR54 Regulates ERK1/2 Activity and Hypothalamic Gene Expression in a Gαq/11 and β-Arrestin-Dependent Manner

G protein-coupled receptor 54 (GPR54) is a Gq/11-coupled 7 transmembrane-spanning receptor (7TMR). Activation of GPR54 by kisspeptin (Kp) stimulates PIP2 hydrolysis, Ca2+ mobilization and ERK1/2 MAPK phosphorylation. Kp and GPR54 are established regulators of the hypothalamic-pituitary-gonadal (HPG) axis and loss-of-function mutations in GPR54 are associated with an absence of puberty and hypogonadotropic hypogonadism, thus defining an important role of the Kp/GPR54 signaling system in reproductive function. Given the tremendous physiological and clinical importance of the Kp/GPR54 signaling system, we explored the contributions of the GPR54-coupled Gq/11 and β-arrestin pathways on the activation of a major downstream signaling molecule, ERK, using Gq/11 and β-arrestin knockout mouse embryonic fibroblasts. Our study revealed that GPR54 employs the Gq/11 and β-arrestin-2 pathways in a co-dependent and temporally overlapping manner to positively regulate ERK activity and pERK nuclear localization. We also show that while β-arrestin-2 potentiates GPR54 signaling to ERK, β-arrestin-1 inhibits it. Our data also revealed that diminished β-arrestin-1 and -2 expression in the GT1-7 GnRH hypothalamic neuronal cell line triggered distinct patterns of gene expression following Kp-10 treatment. Thus, β-arrestin-1 and -2 also regulate distinct downstream responses in gene expression. Finally, we showed that GPR54, when uncoupled from the Gq/11 pathway, as is the case for several naturally occurring GPR54 mutants associated with hypogonadotropic hypogonadism, continues to regulate gene expression in a G protein-independent manner. These new and exciting findings add significantly to our mechanistic understanding of how this important receptor signals intracellularly in response to kisspeptin stimulation

Improved imaging of magnetically labeled cells using rotational magnetomotive optical coherence tomography

In this paper, we present a reliable and robust method for magnetomotive optical coherence tomography (MM-OCT) imaging of single cells labeled with iron oxide particles. This method employs modulated longitudinal and transverse magnetic fields to evoke alignment and rotation of anisotropic magnetic structures in the sample volume. Experimental evidence suggests that magnetic particles assemble themselves in elongated chains when exposed to a permanent magnetic field. Magnetomotion in the intracellular space was detected and visualized by means of 3D OCT as well as laser speckle reflectometry as a 2D reference imaging method. Our experiments on mesenchymal stem cells embedded in agar scaffolds show that the magnetomotive signal in rotational MM-OCT is significantly increased by a factor of ˜3 compared to previous pulsed MM-OCT, although the solenoid's power consumption was 16 times lower. Finally, we use our novel method to image ARPE-19 cells, a human retinal pigment epithelium cell line. Our results permit magnetomotive imaging with higher sensitivity and the use of low power magnetic fields or larger working distances for future three-dimensional cell tracking in target tissues and organs