Alx1, a member of the Cart1/Alx3/Alx4 subfamily of Paired-class homeodomain proteins, is an essential component of the gene network controlling skeletogenic fate specification in the sea urchin embryo

In the sea urchin embryo, the large micromeres and their progeny function as a critical signaling center and execute a complex morphogenetic program. We have identified a new and essential component of the gene network that controls large micromere specification, the homeodomain protein Alx1. Alx1 is expressed exclusively by cells of the large micromere lineage beginning in the first interphase after the large micromeres are born. Morpholino studies demonstrate that Alx1 is essential at an early stage of specification and controls downstream genes required for epithelial-mesenchymal transition and biomineralization. Expression of Alx1 is cell autonomous and regulated maternally through ß-catenin and its downstream effector, Pmar1. Alx1 expression can be activated in other cell lineages at much later stages of development, however, through a regulative pathway of skeletogenesis that is responsive to cell signaling. The Alx1 protein is highly conserved among euechinoid sea urchins and is closely related to the Cart1/Alx3/Alx4 family of vertebrate homeodomain proteins. In vertebrates, these proteins regulate the formation of skeletal elements of the limbs, face and neck. Our findings suggest that the ancestral deuterostome had a population of biomineral-forming mesenchyme cells that expressed an Alx1-like protein

Mutual Inductance Route to Paramagnetic Meissner Effect in 2D Josephson Junction Arrays

We simulate two-dimensional Josephson junction arrays, including full mutual- inductance effects, as they are cooled below the transition temperature in a magnetic field. We show numerical simulations of the array magnetization as a function of position, as detected by a scanning SQUID which is placed at a fixed height above the array. The calculated magnetization images show striking agreement with the experimental images obtained by A. Nielsen et al. The average array magnetization is found to be paramagnetic for many values of the applied field, confirming that paramagnetism can arise from magnetic screening in multiply-connected superconductors without the presence of d-wave superconductivity.Comment: REVTeX 3.1, 5 pages, 5 figure

GALNT2 as a novel modulator of adipogenesis and adipocyte insulin signaling

Background/objectives: A better understanding of adipose tissue biology is crucial to tackle insulin resistance and eventually coronary heart disease and diabetes, leading causes of morbidity and mortality worldwide. GALNT2, a GalNAc-transferase, positively modulates insulin signaling in human liver cells by down-regulating ENPP1, an insulin signaling inhibitor. GALNT2 expression is increased in adipose tissue of obese as compared to that of non-obese individuals. Whether this association is secondary to a GALNT2-insulin sensitizing effect exerted also in adipocytes is unknown. We then investigated in mouse 3T3-L1 adipocytes the GALNT2 effect on adipogenesis, insulin signaling and expression levels of both Enpp1 and 72 adipogenesis-related genes. Methods: Stable over-expressing GALNT2 and GFP preadipocytes (T 0 ) were generated. Adipogenesis was induced with (R+) or without (R−) rosiglitazone and investigated after 15 days (T 15 ). Lipid accumulation (by Oil Red-O staining) and intracellular triglycerides (by fluorimetric assay) were measured. Lipid droplets (LD) measures were analyzed at confocal microscope. Gene expression was assessed by RT-PCR and insulin-induced insulin receptor (IR), IRS1, JNK and AKT phosphorylation by Western blot. Results: Lipid accumulation, triglycerides and LD measures progressively increased from T 0 to T 15 R- and furthermore to T 15 R+. Such increases were significantly higher in GALNT2 than in GFP cells so that, as compared to T 15 R+GFP, T 15 R- GALNT2 cells showed similar (intracellular lipid and triglycerides accumulation) or even higher (LD measures, p < 0.01) values. In GALNT2 preadipocytes, insulin-induced IR, IRS1 and AKT activation was higher than that in GFP cells. GALNT2 effect was totally abolished during adipocyte maturation and completely reversed at late stage maturation. Such GALNT2 effect trajectory was paralleled by coordinated changes in the expression of Enpp1 and adipocyte-maturation key genes. Conclusions: GALNT2 is a novel modulator of adipogenesis and related cellular phenotypes, thus becoming a potential target for tackling the obesity epidemics and its devastating sequelae

Distributed Control of Micro-Storage Devices With Mean Field Games

This paper proposes a fully distributed control strategy for the management of micro-storage devices that perform energy arbitrage. For large storage populations, the problem can be approximated as a differential game with infinite players (mean field game). Through the resolution of coupled partial differential equations (PDEs), it is possible to determine, as a fixed point, the optimal feedback strategy for each player and the resulting price of energy if that strategy is applied. Once this price is calculated, it can be communicated to the devices, which are able to independently determine their optimal charge profile. Simulation results are provided, calculating the fixed point through numerical integration of the PDEs. The original model is then extended in order to consider additional elements, such as multiple population of devices and demand uncertainty

Convergence and optimality of a new iterative price-based scheme for distributed coordination of flexible loads in the electricity market

This paper proposes a novel distributed control strategy for large-scale deployment of flexible demand. The devices are modelled as competing players that respond to iterative broadcasts of price signals, scheduling their power consumption to operate at minimum cost. By describing their power update at each price broadcast through a multi-valued discrete-time dynamical system and by applying Lyapunov techniques, it is shown that the proposed control strategy always converges to a stable final configuration, characterized as a Wardrop (or aggregative) equilibrium. It is also proved that such equilibrium is socially efficient and optimizes some global performance index of the system (e.g. minimizes total generation costs). These results are achieved under very general assumptions on the electricity price and for any penetration level of flexible demand. Practical implementation of the proposed scheme is discussed and tested in simulation on a future scenario of the UK-grid with large numbers of flexible loads

Frequency support by scheduling of variable-speed wind turbines

© IFAC.This paper characterizes optimal control policies for wind farms operated as frequency response services in case of a fault of conventional generators. The frequency support is provided through temporary over-production: when frequency drops, the turbines move from the steady-state operating point and extra power is produced by slowing down the turbines and releasing part of their kinetic energy. The control task is formulated and solved as an optimal containment problem: the time during which an extra quantity of power can be produced, within the set speed constraints for each turbine, is maximized. The solutions are calculated and compared for different assumptions on the electric torque of the turbines

Light-cone fluctuations and the renormalized stress tensor of a massless scalar field

We investigate the effects of light-cone fluctuations over the renormalized vacuum expectation value of the stress-energy tensor of a real massless minimally coupled scalar field defined in a ($d+1$)-dimensional flat space-time with topology ${\cal R}\times {\cal S}^d$. For modeling the influence of light-cone fluctuations over the quantum field, we consider a random Klein-Gordon equation. We study the case of centered Gaussian processes. After taking into account all the realizations of the random processes, we present the correction caused by random fluctuations. The averaged renormalized vacuum expectation value of the stress-energy associated with the scalar field is presented

Nod2 Deficiency in mice is Associated with Microbiota Variation Favouring the Expansion of mucosal CD4+ LAP+ Regulatory Cells

Nucleotide-binding Oligomerization Domain-2 (NOD2) mutations are associated with an increased risk to develop Crohn's Disease. In previous studies, we have shown that Nod2-/- mice manifest increased proportion of Lamina Propria (LP) CD4+ LAP+ Foxp3- regulatory cells, when compared with Nod2+/+ mice, while CD4+ Foxp3 + regulatory cells were not affected. Here, we investigated the Nod2 gut microbiota, by 16S rRNA pyrosequencing, at steady state and after TNBS-colitis induction in mice reared separately or in cohousing, correlating the microbial profiles with LP regulatory T cells proportion and tissue cytokines content. We found that enrichment of Rikenella and Alistipes (Rikenellaceae) in Nod2-/- mice at 8 weeks of age reared separately was associated with increased proportion of CD4+ LAP+ Foxp3- cells and less severe TNBS-colitis. In co-housed mice the acquisition of Rickenellaceae by Nod2+/+ mice was associated with increased CD4+ LAP+ Foxp3- proportion and less severe colitis. Severe colitis was associated with enrichment of gram-negative pathobionts (Escherichia and Enterococcus), while less severe colitis with protective bacteria (Barnesiella, Odoribacter and Clostridium IV). Environmental factors acting on genetic background with different outcomes according to their impact on microbiota, predispose in different ways to inflammation. These results open a new scenario for therapeutic attempt to re-establish eubiosis in Inflammatory Bowel Disease patients with NOD2 polymorphisms