L-selectin mediated leukocyte tethering in shear flow is controlled by multiple contacts and cytoskeletal anchorage facilitating fast rebinding events

L-selectin mediated tethers result in leukocyte rolling only above a threshold in shear. Here we present biophysical modeling based on recently published data from flow chamber experiments (Dwir et al., J. Cell Biol. 163: 649-659, 2003) which supports the interpretation that L-selectin mediated tethers below the shear threshold correspond to single L-selectin carbohydrate bonds dissociating on the time scale of milliseconds, whereas L-selectin mediated tethers above the shear threshold are stabilized by multiple bonds and fast rebinding of broken bonds, resulting in tether lifetimes on the timescale of $10^{-1}$ seconds. Our calculations for cluster dissociation suggest that the single molecule rebinding rate is of the order of $10^4$ Hz. A similar estimate results if increased tether dissociation for tail-truncated L-selectin mutants above the shear threshold is modeled as diffusive escape of single receptors from the rebinding region due to increased mobility. Using computer simulations, we show that our model yields first order dissociation kinetics and exponential dependence of tether dissociation rates on shear stress. Our results suggest that multiple contacts, cytoskeletal anchorage of L-selectin and local rebinding of ligand play important roles in L-selectin tether stabilization and progression of tethers into persistent rolling on endothelial surfaces.Comment: 9 pages, Revtex, 4 Postscript figures include

Impacts of China’s Foreign Direct Investment in Sub-Saharan Africa

This paper examines the impacts of foreign direct investment, as well as China’s FDI on GDP growth of Sub-Saharan African countries from a macroeconomic perspective. By using the data from 44 Sub-Saharan African countries from 2003-2010, our GMM results show that neither China’s FDI nor FDI net inflow in SSA has significant effect on economic growth of SSA countries. The possible explanations about the insignificant results include crowding out effect of China’s FDI on domestic investment, the declining in outward FDI in traditional sectors and rising in service sector which ignored in the current model, and the types of sectors in which Chinese FDI has been concentrated. We also test other economic growth determinants of SSA countries based on growth accounting theory. Our results also show that capital stock per labor has persistent and significant positive impacts on SSA’s growth. In addition, capital per worker is another important determinant in growth

Cursed yet Satisfied Agents

In real life auctions, a widely observed phenomenon is the winner's curse -- the winner's high bid implies that the winner often over-estimates the value of the good for sale, resulting in an incurred negative utility. The seminal work of Eyster and Rabin [Econometrica'05] introduced a behavioral model aimed to explain this observed anomaly. We term agents who display this bias "cursed agents". We adopt their model in the interdependent value setting, and aim to devise mechanisms that prevent the cursed agents from obtaining negative utility. We design mechanisms that are cursed ex-post IC, that is, incentivize agents to bid their true signal even though they are cursed, while ensuring that the outcome is individually rational -- the price the agents pay is no more than the agents' true value. Since the agents might over-estimate the good's value, such mechanisms might require the seller to make positive transfers to the agents to prevent agents from over-paying. For revenue maximization, we give the optimal deterministic and anonymous mechanism. For welfare maximization, we require ex-post budget balance (EPBB), as positive transfers might lead to negative revenue. We propose a masking operation that takes any deterministic mechanism, and imposes that the seller would not make positive transfers, enforcing EPBB. We show that in typical settings, EPBB implies that the mechanism cannot make any positive transfers, implying that applying the masking operation on the fully efficient mechanism results in a socially optimal EPBB mechanism. This further implies that if the valuation function is the maximum of agents' signals, the optimal EPBB mechanism obtains zero welfare. In contrast, we show that for sum-concave valuations, which include weighted-sum valuations and l_p-norms, the welfare optimal EPBB mechanism obtains half of the optimal welfare as the number of agents grows large

Boolean versus continuous dynamics on simple two-gene modules

We investigate the dynamical behavior of simple modules composed of two genes with two or three regulating connections. Continuous dynamics for mRNA and protein concentrations is compared to a Boolean model for gene activity. Using a generalized method, we study within a single framework different continuous models and different types of regulatory functions, and establish conditions under which the system can display stable oscillations. These conditions concern the time scales, the degree of cooperativity of the regulating interactions, and the signs of the interactions. Not all models that show oscillations under Boolean dynamics can have oscillations under continuous dynamics, and vice versa.Comment: 8 pages, 10 figure

Sperner type theorems with excluded subposets

Let F be a family of subsets of an n-element set. Sperner's theorem says that if there is no inclusion among the members of F then the largest family under this condition is the one containing all ⌊ frac(n, 2) ⌋-element subsets. The present paper surveys certain generalizations of this theorem. The maximum size of F is to be found under the condition that a certain configuration is excluded. The configuration here is always described by inclusions. More formally, let P be a poset. The maximum size of a family F which does not contain P as a (not-necessarily induced) subposet is denoted by La (n, P). The paper is based on a lecture of the author at the Jubilee Conference on Discrete Mathematics [Banasthali University, January 11-13, 2009], but it was somewhat updated in December 2010. © 2011 Elsevier B.V. All rights reserved

Gut microbes contribute to variation in solid organ transplant outcomes in mice

© The Author(s), 2018. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Microbiome 6 (2018): 96, doi:10.1186/s40168-018-0474-8.Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics. We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival. These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes. The association between Alistipes and prolonged skin graft survival in mice suggests that members of this genus might affect host physiology, including at sites distal to the gastrointestinal tract. Overall, these findings allude to a potential therapeutic role for specific gut microbes to promote graft survival through the administration of probiotics, or FMT.This work was supported by NIH/NIAID R01 AI115716 to MLA