Nonreciprocal Coupling Induced Self-Assembled Localized Structures.

Chains of coupled oscillators exhibit energy propagation by means of waves, pulses, and fronts. Nonreciprocal coupling radically modifies the wave dynamics of chains. Based on a prototype model of nonlinear chains with nonreciprocal coupling to nearest neighbors, we study nonlinear wave dynamics. Nonreciprocal coupling induces a convective instability between unstable and stable equilibrium. Increasing the coupling level, the chain presents a propagative pattern, a traveling wave. This emergent phenomenon corresponds to the self-assembly of localized structures. The pattern wavelength is characterized as a function of the coupling. Analytically, the phase diagram is determined and agrees with numerical simulations.

Contrarians Synchronize beyond the Limit of Pairwise Interactions.

We give evidence that a population of pure contrarian globally coupled D-dimensional Kuramoto oscillators reaches a collective synchronous state when the interplay between the units goes beyond the limit of pairwise interactions. Namely, we will show that the presence of higher-order interactions may induce the appearance of a coherent state even when the oscillators are coupled negatively to the mean field. An exact solution for the description of the microscopic dynamics for forward and backward transitions is provided, which entails imperfect symmetry breaking of the population into a frequency-locked state featuring two clusters of different instantaneous phases. Our results contribute to a better understanding of the powerful potential of group interactions entailing multidimensional choices and novel dynamical states in many circumstances, such as in social systems.

Pulse propagation in a 1D array of excitable semiconductor lasers.

Nonlinear pulse propagation is a major feature in continuously extended excitable systems. The persistence of this phenomenon in coupled excitable systems is expected. Here, we investigate theoretically the propagation of nonlinear pulses in a 1D array of evanescently coupled excitable semiconductor lasers. We show that the propagation of pulses is characterized by a hopping dynamics. The average pulse speed and bifurcation diagram are characterized as a function of the coupling strength between the lasers. Several instabilities are analyzed such as the onset and disappearance of pulse propagation and a spontaneous breaking of the translation symmetry. The pulse propagation modes evidenced are specific to the discrete nature of the 1D array of excitable lasers.

Front propagation steered by a high-wavenumber modulation: Theory and experiments.

Homogeneously driven dynamical systems exhibit multistability. Depending on the initial conditions, fronts present a rich dynamical behavior between equilibria. Qualitatively, this phenomenology is persistent under spatially modulated forcing. However, the understanding of equilibria and front dynamics organization is not fully established. Here, we investigate these phenomena in the high-wavenumber limit. Based on a model that describes the reorientation transition of a liquid crystal light valve with spatially modulated optical forcing and the homogenization method, equilibria and fronts as a function of forcing parameters are studied. The forcing induces patterns coexisting with the uniform state in regions where the system without forcing is monostable. The front dynamics is characterized theoretically and numerically. Experimental results verify these phenomena and the law describing bistability, showing quite good agreement.

Endowing networks with desired symmetries and modular behavior.

Symmetries in a network regulate its organization into functional clustered states. Given a generic ensemble of nodes and a desirable cluster (or group of clusters), we exploit the direct connection between the elements of the eigenvector centrality and the graph symmetries to generate a network equipped with the desired cluster(s), with such a synthetical structure being furthermore perfectly reflected in the modular organization of the network's functioning. Our results solve a relevant problem of designing a desired set of clusters and are of generic application in all cases where a desired parallel functioning needs to be blueprinted.

Multilayer representation of collaboration networks with higher-order interactions.

Collaboration patterns offer important insights into how scientific breakthroughs and innovations emerge in small and large research groups. However, links in traditional networks account only for pairwise interactions, thus making the framework best suited for the description of two-person collaborations, but not for collaborations in larger groups. We therefore study higher-order scientific collaboration networks where a single link can connect more than two individuals, which is a natural description of collaborations entailing three or more people. We also consider different layers of these networks depending on the total number of collaborators, from one upwards. By doing so, we obtain novel microscopic insights into the representativeness of researchers within different teams and their links with others. In particular, we can follow the maturation process of the main topological features of collaboration networks, as we consider the sequence of graphs obtained by progressively merging collaborations from smaller to bigger sizes starting from the single-author ones. We also perform the same analysis by using publications instead of researchers as network nodes, obtaining qualitatively the same insights and thus confirming their robustness. We use data from the arXiv to obtain results specific to the fields of physics, mathematics, and computer science, as well as to the entire coverage of research fields in the database.

Role of the subchondral vascular system in endochondral ossification: endothelial cell-derived proteinases derepress late cartilage differentiation in vitro.

Endochondral ossification in growth plates proceeds through several consecutive steps of late cartilage differentiation leading to chondrocyte hypertrophy, vascular invasion, and, eventually, to replacement of the tissue by bone. The subchondral vascular system is essential for this process and late chondrocyte differentiation is subject to negative control at several checkpoints. Endothelial cells of subchondral blood vessels not only are the source of vascular invasion accompanying the transition of hypertrophic cartilage to bone but also produce factors overruling autocrine barriers against late chondrocyte differentiation. Here, we have determined that the action of proteases secreted by endothelial cells were sufficient to derepress the production of the hypertrophy-markers collagen X and alkaline phosphatase in arrested populations of chicken chondrocytes. Signalling by thyroid hormones was also necessary but endothelial factors other than proteinases were not. Negative signalling by PTH/PTHrP- or TGF-beta-receptors remained unaffected by the endothelial proteases whereas signalling by FGF-2 did not suppress, but rather activated late chondrocyte differentiation under these conditions. A finely tuned balance between chondrocyte-derived signals repressing cartilage maturation and endothelial signals promoting late differentiation of chondrocytes is essential for normal endochondral ossification during development, growth, and repair of bone. A dysregulation of this balance in permanent joint cartilage also may be responsible for the initiation of pathological cartilage degeneration in joint diseases.

Terminal differentiation of chondrocytes is arrested at distinct stages identified by their expression repertoire of marker genes.

During endochondral bone formation, cells in the emerging cartilaginous model transit through a cascade of several chondrocyte differentiation stages, each characterized by a specific expression repertoire of matrix macromolecules, until, as a final step, the hypertrophic cartilage is replaced by bone. In many permanent cartilage tissues, however, late differentiation of chondrocytes does not occur, due to negative regulation by the environment of the cells. Here, addressing the reason for the difference between chondrocyte fates in the chicken embryo sternum, cells from the caudal and cranial part were cultured separately in serum-free agarose gels with complements defined earlier that either permit or prevent hypertrophic development. Total RNA was extracted using a novel protocol adapted to agarose cultures, and the temporal changes in developmental stage-specific mRNA expression were monitored by Northern hybridization and phosphor image analysis. Kinetic studies of the mRNA accumulation not only showed significant differences between the expression patterns of cranial and caudal cultures after recovery, but also revealed two checkpoints of chondrocyte differentiation in keeping with cartilage development in vivo. Terminal differentiation of caudal chondrocytes is blocked at the late proliferative stage (stage Ib), while the cranial cells can undergo hypertrophic development spontaneously. The differentiation of cranial chondrocytes is reversible, since they can re-assume an early proliferative (stage Ia) phenotype under the influence of insulin, fibroblast growth factor-2 and transforming growth factor-beta in combination. Thus, the expression pattern in the latter culture resembles that of articular chondrocytes. We also provide evidence that the capacities of caudal and sternal chondrocytes to progress from the late proliferative (stage Ib) to hypertrophic stage (stage II) correlate with their differing abilities to express the Indian hedgehog gene.

Latent inhibition of granulocyte function by cyclosporine A.

According to the literature, Cyclosporine A (CsA) is said to suppress specifically the activity of T and B cells. A significant influence on phagocyte function has been neglected. However, aggravated courses of bacterial and fungal infections have been frequently reported under the treatment with CsA, suggesting that a latent depression of phagocytic activity may possibly occur under clinical circumstances. Therefore, this study set out to assess whether CsA can also change granulocyte function under therapy conditions or not. Thirty-seven patients, 3 months-10 years after kidney transplantation being under immunosuppressive treatment with CsA + Prednisolone (n = 25), Azathioprine + Prednisolone (n = 6) and under Prednisolone alone (n = 6) underwent the study. 18 healthy persons served as a normal control group. Granulocyte function was tested ex vivo by chemiluminescence (CL) after stimulation with phorbolmyristate acetate (PMA) and with zymosan (zym) activated autologous or pool-serum. The obtained data were correlated to corresponding serum or plasma levels of CsA, human leukocyte elastase (HLE) and neopterin. Comparing the three therapy groups with the healthy control and with each other no differences could be seen in median CL values; but there was a significant (p = 0.05) negative correlation between CsA blood levels and maximum CL values of PMN. Such inhibition of CL could be calculated for zym but not for PMA stimulated PMN; suggesting that the CsA mediated inhibition of granulocyte function may be only partial and restricted to phagocytosis. In addition, a positive correlation between serum levels of human leukocyte elastase (HLE) and neopterin could be found. This indicates a simultaneous influence of CsA on both PMN and macrophages.

Fibrin glue as matrix for cultured autologous urothelial cells in urethral reconstruction.

In the present study, we have established a technique to create an artificial urethra in a rat animal model by transplantation of in vitro-expanded urothelial cells onto an in vivo-prefabricated tube formation using tissue engineering methods. Urothelial cells from isogenic rats were harvested for culture. A silicon catheter was used to induce a connective tissue capsule-tube formation underneath the abdominal skin. Two weeks later, the cultivated urothelial cells were seeded onto the lumen of this tube using fibrin glue as delivery matrix. The histomorphological and immunohistochemical studies revealed a viable multilayered urothelium, lining the inner surface of the prior formed connective tissue tube-formation 4 weeks after grafting the cells. We have shown that cultured and in vitro-expanded urothelial cells can be successfully reimplanted onto a prefabricated tube-like structure using fibrin glue as a delivery matrix and native cell expansion vehicle. The results suggest that the creation of an artificial urethra may be achieved in vivo using tissue engineering methods, showing potential for urethral reconstruction and providing autologous urothelium for reconstructive surgery in the genitourinary tract.

Plasmid gene delivery to human keratinocytes through a fibrin-mediated transfection system.

We have developed a matrix-mediated transfection system to deliver plasmids to human keratinocytes. The matrix is a soluble, self-hardening fibrin matrix (Tissucol), Baxter) that has been used clinically. Recently it has been shown that full thickness burn wounds can be successfully treated with a keratinocyte fibrin glue suspension. Further, it has been demonstrated that hEGF transfected cells accelerate wound healing. In this study, we inoculated the matrix with the hEGF expression plasmid and resuspended the matrix with either cultured or noncultured human keratinocytes. We obtained successful transfection rates of these cells (up to a 100-fold increase compared to controls containing no EGF expression plasmid) in vitro. After transplantation to full thickness wounds on athymic mice we were able to show a 180-fold increase in EGF concentration compared to controls, which persisted over the entire 7-day monitored period, decreasing from 180 to 20 pg/mL at day seven. This unique approach indicates the possible utility to combine a matrix for cell transplantation with a transfection system to release therapeutic proteins in vitro and in vivo.