Barrier-protective effects of activated protein C in human alveolar epithelial cells

Acute lung injury (ALI) is a clinical manifestation of respiratory failure, caused by lung inflammation and the disruption of the alveolar-capillary barrier. Preservation of the physical integrity of the alveolar epithelial monolayer is of critical importance to prevent alveolar edema. Barrier integrity depends largely on the balance between physical forces on cell-cell and cell-matrix contacts, and this balance might be affected by alterations in the coagulation cascade in patients with ALI. We aimed to study the effects of activated protein C (APC) on mechanical tension and barrier integrity in human alveolar epithelial cells (A549) exposed to thrombin. Cells were pretreated for 3 h with APC (50 mg/ml) or vehicle (control). Subsequently, thrombin (50 nM) or medium was added to the cell culture. APC significantly reduced thrombin-induced cell monolayer permeability, cell stiffening, and cell contraction, measured by electrical impedance, optical magnetic twisting cytometry, and traction microscopy, respectively, suggesting a barrier-protective response. The dynamics of the barrier integrity was also assessed by western blotting and immunofluorescence analysis of the tight junction ZO-1. Thrombin resulted in more elongated ZO-1 aggregates at cell-cell interface areas and induced an increase in ZO-1 membrane protein content. APC attenuated the length of these ZO-1 aggregates and reduced the ZO-1 membrane protein levels induced by thrombin. In conclusion, pretreatment with APC reduced the disruption of barrier integrity induced by thrombin, thus contributing to alveolar epithelial barrier protection.

How tight should one's hands be tied? Fear of floating and credibility of exchange rate regimes

This paper analyzes the linkages between the credibility of a target zone regime, the volatility of the exchange rate, and the width of the band where the exchange rate is allowed to fluctuate. These three concepts should be related since the band width induces a trade-off between credibility and volatility. Narrower bands should give less scope for the exchange rate to fluctuate but may make agents perceive a larger probability of realignment which by itself should increase the volatility of the exchange rate. We build a model where this trade-off is made explicit. The model is used to understand the reduction in volatility experienced by most EMS countries after their target zones were widened on August 1993. As a natural extension, the model also rationalizes the existence of non-official, implicit target zones (or fear of floating), suggested by some authors.

The three strands of intercultural polities: a comprehensive view. A critical review of Bouchard and Cantle recent books on interculturalism

Within the emerging policy debate on interculturalism we critically review two recent books in 2012: Bouchard’s L’interculturalisme: un point de vue quebecois, and Cantle’s Interculturalism: The New Era of Cohesion and Diversity. In my view, both contribute very directly to open a foundational debate on interculturalism. In addressing the point of convergence and the dividing lines of these two contributions, I will claim that in spite of having one core concept of interculturalism, there are, however, at least two basic conceptions that have to be interpreted in complementary ways: Bouchard’s essay represents the contractual strand, Cantle’s book the cohesion strand. At the end I would also suggest that these two strands do not manage to express explicitly that diversity can also be seen as a resource of innovation and creativity, and so can drive individual and social development. This view is based on the diversity advantage literature already informing most of the diversity debate in Europe and elsewhere. This is what I will call the constructivist strand. My ultimate purpose is to defend a comprehensive view, grounded on the argument that no one can have the sole authority to define intercultural policy, since the three strands can be applied at different moments, according to different purposes and policy needs. The challenge now is that policy managers be able to achieve a balance between these three policy drivers.

Micropatterning of single endothelial cell shape reveals a tight coupling between nuclear volume in G1 and proliferation

Shape-dependent local differentials in cell proliferation are considered to be a major driving mechanism of structuring processes in vivo, such as embryogenesis, wound healing, and angiogenesis. However, the specific biophysical signaling by which changes in cell shape contribute to cell cycle regulation remains poorly understood. Here, we describe our study of the roles of nuclear volume and cytoskeletal mechanics in mediating shape control of proliferation in single endothelial cells. Micropatterned adhesive islands were used to independently control cell spreading and elongation. We show that, irrespective of elongation, nuclear volume and apparent chromatin decondensation of cells in G1 systematically increased with cell spreading and highly correlated with DNA synthesis (percent of cells in the S phase). In contrast, cell elongation dramatically affected the organization of the actin cytoskeleton, markedly reduced both cytoskeletal stiffness (measured dorsally with atomic force microscopy) and contractility (measured ventrally with traction microscopy), and increased mechanical anisotropy, without affecting either DNA synthesis or nuclear volume. Our results reveal that the nuclear volume in G1 is predictive of the proliferative status of single endothelial cells within a population, whereas cell stiffness and contractility are not. These findings show that the effects of cell mechanics in shape control of proliferation are far more complex than a linear or straightforward relationship. Our data are consistent with a mechanism by which spreading of cells in G1 partially enhances proliferation by inducing nuclear swelling and decreasing chromatin condensation, thereby rendering DNA more accessible to the replication machinery.

Interaction of a discrete breather with a lattice junction

We study the scattering of a moving discrete breather (DB) on a junction in a Fermi-Pasta-Ulam chain consisting of two segments with different masses of the particles. We consider four distinct cases: (i) a light-heavy (abrupt) junction in which the DB impinges on the junction from the segment with lighter mass, (ii) a heavy-light junction, (iii) an up mass ramp in which the mass in the heavier segment increases continuously as one moves away from the junction point, and (iv) a down mass ramp. Depending on the mass difference and DB characteristics (frequency and velocity), the DB can either reflect from, or transmit through, or get trapped at the junction or on the ramp. For the heavy-light junction, the DB can even split at the junction into a reflected and a transmitted DB. The latter is found to subsequently split into two or more DBs. For the down mass ramp the DB gets accelerated in several stages, with accompanying radiation (phonons). These results are rationalized by calculating the Peierls-Nabarro barrier for the various cases. We also point out implications of our results in realistic situations such as electron-phonon coupled chains.

Tight coupling in thermal Brownian motors

We study analytically a thermal Brownian motor model and calculate exactly the Onsager coefficients. We show how the reciprocity relation holds and that the determinant of the Onsager matrix vanishes. Such a condition implies that the device is built with tight coupling. This explains why Carnot¿s efficiency can be achieved in the limit of infinitely slow velocities. We also prove that the efficiency at maximum power has the maximum possible value, which corresponds to the Curzon-Alhborn bound. Finally, we discuss the model acting as a Brownian refrigerator.

Dyrk1A is dynamically expressed on subsets of motor neurons and in the neuromuscular junction: possible role in Down syndrome

Individuals with Down syndrome (DS) present important motor deficits that derive from altered motor development of infants and young children. DYRK1A, a candidate gene for DS abnormalities has been implicated in motor function due to its expression in motor nuclei in the adult brain, and its overexpression in DS mouse models leads to hyperactivity and altered motor learning. However, its precise role in the adult motor system, or its possible involvement in postnatal locomotor development has not yet been clarified. During the postnatal period we observed time-specific expression of Dyrk1A in discrete subsets of brainstem nuclei and spinal cord motor neurons. Interestingly, we describe for the first time the presence of Dyrk1A in the presynaptic terminal of the neuromuscular junctions and its axonal transport from the facial nucleus, suggesting a function for Dyrk1A in these structures. Relevant to DS, Dyrk1A overexpression in transgenic mice (TgDyrk1A) produces motor developmental alterations possibly contributing to DS motor phenotypes and modifies the numbers of motor cholinergic neurons, suggesting that the kinase may have a role in the development of the brainstem and spinal cord motor system.

An activator/repressor dual system allows tight tetracycline-regulated gene expression in budding yeast

We have developed an activator/repressor expression system for budding yeast in which tetracyclines control in opposite ways the ability of tetR-based activator and repressor molecules to bind tetO promoters. This combination allows tight expression of tetO-driven genes, both in a direct (tetracycline-repressible) and reverse (tetracycline-inducible) dual system. Ssn6 and Tup1, that are components of a general repressor complex in yeast, have been tested for their repressing properties in the dual system, using lacZ and CLN2 as reporter genes. Ssn6 gives better results and allows complete switching-off of the regulated genes, although increasing the levels of the Tup1-based repressor by expressing it from a stronger promoter improves repressing efficiency of the latter. Effector-mediated shifts between expression and non-expression conditions are rapid. The dual system here described may be useful for the functional analysis of essential genes whose conditional expression can be tightly controlled by tetracyclines.

Progress in single junction microcrystalline silicon solar cells deposited by Hot-Wire CVD

Hot-Wire Chemical Vapor Deposition has led to microcrystalline silicon solar cell efficiencies similar to those obtained with Plasma Enhanced CVD. The light-induced degradation behavior of microcrystalline silicon solar cells critically depends on the properties of their active layer. In the regime close to the transition to amorphous growth (around 60% of amorphous volume fraction), cells incorporating an intrinsic layer with slightly higher crystalline fraction and [220] preferential orientation are stable after more than 7000 h of AM1.5 light soaking. On the contrary, solar cells whose intrinsic layer has a slightly lower crystalline fraction and random or [111] preferential orientation exhibit clear light-induced degradation effects. A revision of the efficiencies of Hot-Wire deposited microcrystalline silicon solar cells is presented and the potential efficiency of this technology is also evaluated.

Extension of the impedance field method to the noise analysis of a semiconductor junction: Analytical approach

We present an analytical procedure to perform the local noise analysis of a semiconductor junction when both the drift and diffusive parts of the current are important. The method takes into account space-inhomogeneous and hot-carriers conditions in the framework of the drift-diffusion model, and it can be effectively applied to the local noise analysis of different devices: n+nn+ diodes, Schottky barrier diodes, field-effect transistors, etc., operating under strongly inhomogeneous distributions of the electric field and charge concentration

Extension of the impedance field method to the noise analysis of a semiconductor junction: Analytical approach

We present an analytical procedure to perform the local noise analysis of a semiconductor junction when both the drift and diffusive parts of the current are important. The method takes into account space-inhomogeneous and hot-carriers conditions in the framework of the drift-diffusion model, and it can be effectively applied to the local noise analysis of different devices: n+nn+ diodes, Schottky barrier diodes, field-effect transistors, etc., operating under strongly inhomogeneous distributions of the electric field and charge concentration

Sexual dimorphism of sonic apparatus and extreme intersexual variation of sounds in Ophidion rochei (Ophidiidae): first evidence of a tight relationship between morphology and sound characteristics in Ophidiidae

Many Ophidiidae are active in dark environments and display complex sonic apparatus morphologies. However, sound recordings are scarce and little is known about acoustic communication in this family. This paper focuses on Ophidion rochei which is known to display an important sexual dimorphism in swimbladder and anterior skeleton. The aims of this study were to compare the sound producing morphology, and the resulting sounds in juveniles, females and males of O. rochei.Results: Males, females, and juveniles possessed different morphotypes. Females and juveniles contrasted with males because they possessed dramatic differences in morphology of their sonic muscles, swimbladder, supraoccipital crest, and first vertebrae and associated ribs. Further, they lacked the ‘rocker bone’ typically found in males. Sounds from each morphotype were highly divergent. Males generally produced non harmonic, multiple-pulsed sounds that lasted for several seconds (3.5 ± 1.3 s) with a pulse period of ca. 100 ms. Juvenile and female sounds were recorded for the first time in ophidiids. Female sounds were harmonic, had shorter pulse period (±3.7 ms), and never exceeded a few dozen milliseconds (18 ± 11 ms). Moreover, unlike male sounds, female sounds did not have alternating long and short pulse periods. Juvenile sounds were weaker but appear to be similar to female sounds.Conclusions: Although it is not possible to distinguish externally male from female in O. rochei, they show a sonic apparatus and sounds that are dramatically different. This difference is likely due to their nocturnal habits that may have favored the evolution of internal secondary sexual characters that help to distinguish males from females and that could facilitate mate choice by females. Moreover, the comparison of different morphotypes in this study shows that these morphological differences result from a peramorphosis that takes place during the development of the gonads

Classical horizontal inequity and reranking: an integrated approach

The last 20 years have seen a significant evolution in the literature on horizontal inequity (HI) and have generated two major and "rival" methodological strands, namely, classical HI and reranking. We propose in this paper a class of ethically flexible tools that integrate these two strands. This is achieved using a measure of inequality that merges the well-known Gini coefficient and Atkinson indices, and that allows a decomposition of the total redistributive effect of taxes and transfers in a vertical equity effect and a loss of redistribution due to either classical HI or reranking. An inequality-change approach and a money-metric cost-of-inequality approach are developed. The latter approach makes aggregate classical HI decomposable across groups. As in recent work, equals are identified through a nonparametric estimation of the joint density of gross and net incomes. An illustration using Canadian data from 1981 to 1994 shows a substantial, and increasing, robust erosion of redistribution attributable both to classical HI and to reranking, but does not reveal which of reranking or classical HI is more important since this requires a judgement that is fundamentally normative in nature.

Analyzing aggregate real exchange rate persistence through the lens of sectoral data

In this paper we analyze the persistence of aggregate real exchange rates (RERs) for a group of EU-15 countries by using sectoral data. The tight relation between aggregate and sectoral persistence recently investigated by Mayoral (2008) allows us to decompose aggregate RER persistence into the persistence of its different subcomponents. We show that the distribution of sectoral persistence is highly heterogeneous and very skewed to the right, and that a limited number of sectors are responsible for the high levels of persistence observed at the aggregate level. We use quantile regression to investigate whether the traditional theories proposed to account for the slow reversion to parity (lack of arbitrage due to nontradibilities or imperfect competition and price stickiness) are able to explain the behavior of the upper quantiles of sectoral persistence. We conclude that pricing to market in the intermediate goods sector together with price stickiness have more explanatory power than variables related to the tradability of the goods or their inputs.