Long-range morphogen gradient formation by cell-to-cell signal propagation

Morphogen gradients are a central concept in developmental biology. Their formation often involves the secretion of morphogens from a local source, that spread by diffusion in the cell field, where molecules eventually get degraded. This implies limits to both the time and length scales over which morphogen gradients can form which are set by diffusion coefficients and degradationrates. Towards the goal of identifying plausible mechanisms capable of extending the gradient range, we here use theory to explore properties of a cell-to-cell signaling relay. Inspired by the millimeter-scale wnt-expression and signaling gradients in flatworms, we consider morphogen-mediated morphogen production in the cell field. We show that such a relay cangenerate stable morphogen and signaling gradients that are oriented by a local,morphogen-independent source of morphogen at a boundary. This gradient formation can be related to an effective diffusion and an effective degradation that result from morphogen production due to signaling relay. If the secretion of morphogen produced in response to the relay is polarized, it further gives rise to an effective drift. We find that signaling relay can generate long-range gradients in relevant times without relying on extreme choices of diffusion coefficients or degradation rates, thus exceeding the limits set by physiological diffusion coefficients and degradation rates. A signaling relay is hence an attractive principle to conceptualize long-range gradient formation by slowly diffusing morphogens that are relevant for patterning in adult contexts such as regeneration and tissue turn-over

‘Antiflammins’: Two nonapeptide fragments of uteroglobin and lipocortin I have no phospholipase A2 -inhibitory and anti-inflammatory activity

AbstractThe ‘antiflammin’ nonapeptides P1 and P2 [(1988) Nature 335, 726-730] were synthesized and tested for inhibition of phospholipase A2 and release of prostaglandin E2, and leukotriene C4 in stimulated cells in vitro, and in vivo for anti-inflammatory activity in rats with carrageenan-induced paw oedema. Porcine pancreatic phospholipase A2, was not inhibited at concentrations of 0.5–50 μM. Prostaglandin E2, and leukotriene C4 release by mouse macrophages stimulated with zymosan or ATP was not affected up to a concentration of 10 μm, nor was prostaglandin release by interleukin 1β-stimulated mesangial cells and angiotensin II-stimulated smooth muscle cells. Both peptides exhibited no anti-inflammatory activity in carrageenan-induced rat paw oedema after topical (250 μg/paw) or systemic administration (1 or 4 mgkg s.c.). These results do not support the claim of potent phospholipase A2-inhibitory and anti-imflammatory activity of the ‘antiflammins’ P1 and P2 [1]

Essays on Inequality and Social Cohesion

This dissertation comprises three essays that explore determinants of inequality and social cohesion. The first essay explores the role of inheritance customs in spurring social equality. Using historical data on inheritance customs in Germany, I document that municipalities that historically fairly shared wealth among siblings see higher levels of social equality today. I point to two mechanisms that help explain the correlation: increased wealth equality and stronger pro-egalitarian preferences. Interestingly, I also find that equitably inheriting communities are associated with higher incomes and greater income inequality. I interpret this finding to mean that equitable inheritance levels the playing field by rewarding talent not hereditary status. The second essay analyzes how Protestant missions affect community cohesion. Exploiting variation in missionary activity in southeastern Peru, I document that villages exposed to missions have lower levels of community cohesion compared to non-exposed villages. I adjudicate between two mechanisms that may explain this finding - social networks and pro-social preferences - and find the latter to be more plausible. The third essay expands on this finding by implementing a field experiment with a missionary group in South Sudan in order to parse out the causal effect of Protestant evangelism on social capital. Using attitudinal and behavioral measures, I document that missionaries lower group-level social capital while increasing individual-level pro-social behavior. Taken together, my dissertation adds theoretical considerations and empirical evidence to a broad debate in the social sciences that tries to make sense of variation in social equality and cohesion

A Cantor set of tori with monodromy near a focus-focus singularity

We write down an asymptotic expression for action coordinates in an integrable Hamiltonian system with a focus-focus equilibrium. From the singularity in the actions we deduce that the Arnol'd determinant grows infinitely large near the pinched torus. Moreover, we prove that it is possible to globally parametrise the Liouville tori by their frequencies. If one perturbs this integrable system, then the KAM tori form a Whitney smooth family: they can be smoothly interpolated by a torus bundle that is diffeomorphic to the bundle of Liouville tori of the unperturbed integrable system. As is well-known, this bundle of Liouville tori is not trivial. Our result implies that the KAM tori have monodromy. In semi-classical quantum mechanics, quantisation rules select sequences of KAM tori that correspond to quantum levels. Hence a global labeling of quantum levels by two quantum numbers is not possible.Comment: 11 pages, 2 figure

Transverse sound in a magnetic field in UPt_3

We have propagated transverse sound in a magnetic field in the basal plane of UPt_3, with the polarization vector oriented both in the basal plane and perpendicular to it. We observe a strong anisotropy in the magnetic field dependence of the attenuation for the two polarizations. Using a simple phenomenological model, we can understand the low-temperature field dependence as a natural consequence of the anisotropy with temperature in zero field reported earlier [Phys. Rev. Lett. 56, 1078 (1986)]. However, for increasing temperatures there are significant deviations from this model. In no case do we find evidence for new superconducting phases in a magnetic field

Feedback effects and the self-consistent Thouless criterion of the attractive Hubbard model

We propose a fully microscopic theory of the anomalous normal state of the attractive Hubbard model in the low-density limit that accounts for propagator renormalization. Our analytical conclusions, which focus on the thermodynamic instabilities contained in the self-consistent equations associated with our formulation, have been verified by our comprehensive numerical study of the same equations. The resulting theory is found to contain no transitions at non-zero temperatures for all finite lattices, and we have confirmed, using our numerical studies, that this behaviour persists in the thermodynamic limit for low-dimensional systems.Comment: 6 pages, 2 eps format figure

Hole motion in the Ising antiferromagnet: an application of the recursion method

We study hole motion in the Ising antiferromagnet using the recursion method. Using the retraceable path approximation we find the hole's Green's function as well as its wavefunction for arbitrary values of $t/J_z$. The effect of small transverse interaction also is taken into account. Our results provide some additional insight into the self-consistent Born approximation.Comment: 8 pages, RevTex, no figures. Accepted for publication in Phys.Rev.