Activation of neuronal ensembles via controlled synchronization

"In this contribution we present the activation of neuronal ensembles of Hindmarsh-Rose neurons by controlled synchronization. The main problem consists in to impose a particular spiking-bursting behavior in all the neurons of the network. We consider a network where the neurons are in its resting state, it is desired that the neurons change their resting state to a particular behavior of activation, dictated by a neuron called the reference neuron. The goal is reached by controlling some neurons in the network controlling only the membrane potential (electrical synapse). The key feature of the present contribution is that by controlling a small number of neurons in the network a desired behavior is induced in all the neurons in the network despite its network topology. The important parameters are the control gain and the coupling strength, thus the activation of the network lays down on a compromise between the control gain and the coupling strength.

On the emergence of chaos in dynamical networks

"We investigate how changes of specific topological features result on transitions among different bounded behaviours in dynamical networks. In particular, we focus on networks with identical dynamical systems, synchronised to a common equilibrium point, then a transition into chaotic behaviour is observed as the number of nodes and the strength of their coupling changes. We analyse the network's transverse Lyapunov exponents (tLes) to derive conditions for the emergence of bounded complex behaviour on different basic network models. We find that, for networks with a given number of nodes, chaotic behaviour emerges when the coupling strength is within a specific bounded interval; this interval is reduced as the number of nodes increases. Furthermore, the endpoints the emergence interval depend on the coupling structure of network. We also find that networks with homogeneous connectivity, such as regular lattices and small-world networks are more conducive to the emergence of chaos than networks with heterogeneous connectivity like scale-free and star-connected graphs. Our results are illustrated with numerical simulations of the chaotic benchmark Lorenz systems, and to underline their potential applicability to real-world systems, our results are used to establish conditions for the chaotic activation of a network of electrically coupled pancreatic β-cell models.

On the controllability of networks with nonidentical linear nodes

"The controllability of dynamical networks depends on both network structure and node dynamics. For networks of linearly coupled linear dynamical systems the controllability of the network can be determined using the well-known Kalman rank criterion. In the case of identical nodes the problem can be decomposed in local and structural contributions. However, for strictly different nodes an alternative approach is needed. We decomposed the controllability matrix into a structural component, which only depends on the networks structure and a dynamical component which includes the dynamical description of the nodes in the network. Using this approach we show that controllability of dynamical networks with strictly different linear nodes is dominated by the dynamical component. Therefore even a structurally uncontrollable network of different nn dimensional nodes becomes controllable if the dynamics of its nodes are properly chosen. Conversely, a structurally controllable network becomes uncontrollable for a given choice of the node’s dynamics. Furthermore, as nodes are not identical, we can have nodes that are uncontrollable in isolation, while the entire network is controllable, in this sense the node’s controllability is overwritten by the network even if the structure is uncontrollable. We illustrate our results using single-controller networks and extend our findings to conventional networks with large number of nodes.

Lie algebra on synchronization of different systems: a generalized function for Hodgkin-Huxley neurons

"In this contribution two results are taken: (1) The synchronization of noiseless Hodgkin- Huxley (HH) neurons is possible from robust feedback based on Lie algebra approaches and (2) the fact that, from Lie algebra of vector fields, the generalized synchronization of different (triangular form) chaotic systems can be used to derive an explicit synchronization function. Both results are extended to derive the synchronization function in HH neurons despite this systems are not in triangular form. Thus, the Lie algebra of vectors fields permits to establish a theoretical framework for finding the synchroniza- tion function in chaotic systems in face they have different model.

Conditions for synchronization and chaos in networks of β-cells

"The insulin producing and releasing pancreatic β-cells play a key role in glucose homeostasis. The proper function of these cells is characterized by a spiking-bursting activity in their membrane potential. It is known that these cells are coupled with each other and that this coupling can induce synchronization. This fact maybe relevant in the mechanisms of blood glucose regulation. However, not much is known about conditions of synchronization, nor about the topology of real-world β-cell network. Also about the conditions for the emergence of chaotic bursting in networks of β-cells not much is known. We investigate these phenomena in terms of complex network theory as model of β-cells networks, in which synchronization and emergence of chaotic bursting occurs.

Recombinant Listeria promotes tumor rejection by CD8+ T cell-dependent remodeling of the tumor microenvironment.

Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1+PD1loCD62L- CD8+ T cells. These IFNγ-producing effector CD8+ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to an inflamed microenvironment that was characterized by a decrease in regulatory T cells (Treg) levels, a proinflammatory cytokine milieu, and the shift of M2 macrophages to an inducible nitric oxide synthase (iNOS)+CD206- M1 phenotype. Remarkably, these LADD-Ag-induced tumor-specific T cells persisted for more than 2 months after primary tumor challenge and rapidly controlled secondary tumor challenge. Our results indicate that the striking antitumor efficacy observed in mice with LADD-based immunotherapy stems from TME remodeling which is a direct consequence of eliciting potent, systemic tumor-specific CD8+ T cells

Sincronización generalizada entre sistemas Rössler y Lorenz con dinámica Interna

"Se investiga la sincronización generalizada (SG) entre los osciladores caóticos Rössler y Lorenz en una configuración maestro-esclavo. Para lograr la sincronización se diseña un controlador escalar por retroalimentación obtenido a partir de una transformación de coordenadas basada enAlgebra de Lie. La SG se logra en términos de los cambios de coordenadas al estabilizar el error de sincronización en las variables transformadas. En particular, se muestra la existencia de una SG parcial entre Rössler y Lorenz cuando el grado relativo de los sistemas es menor a su dimensión.

Evolución clínica de pacientes en hemodiálisis en tratamiento con oxihidróxido sucroférrico

Introduction: Hyperphosphatemia is a common complication of CKD and progressively worsens as renal function decreases. Currently we have several pharmaceutical molecules for its treatment. Among them, there are chelators that contain iron, as is the case of sucroferric oxyhydroxide. Its use has been extended mainly among those on hemodialysis, replacing other chelators. Objective: Describe the tolerability, the appearance of side effects, therapeutic adherence and serum phosphorus levels in patients undergoing treatment with sucroferric oxyhydroxide in our center. Materials and methods: Five patients were analyzed from the hemodialysis unit of the Nephrology Service of the University Hospital of Burgos, from January 2017 to May 2018, all of them under treatment with sucroferric oxyhydroxide. Plasma concentrations of phosphorus, calcium and parathyroid hormone were evaluated during treatment with sucroferric oxyhydroxide, in addition to side effects and causes of abandonment. For the analysis of the data, they were processed using the IBM SPSS 22 statistical software with a confidence interval of 95%. Possible differences were evaluated with the t-Student analysis. Results: There was an average reduction of 12.27% in hyperphosphataemia and a reduction in the number of daily tablets of 15.79%, with good tolerance of the drug in all cases. There was no statistically significant reduction in plasma levels of calcium or parathyroid hormone (PTH). Conclusions: Sucroferric oxyhydroxide is a well-tolerated drug, which generated a decrease in serum phosphorus levels in the population studied. However, given the low number of cases analyzed, it is not possible to recommend the therapeutic use of this drug as the first line of treatment for hyperphosphatemia.Introducción: la hiperfosfatemia es una complicación común de la enfermedad renal crónica (ERC) y empeora progresivamente a medida que disminuye la función renal. Actualmente disponemos de diversas moléculas farmacéuticas para su tratamiento. Dentro de ellas, existen quelantes que contienen hierro, como es el caso del oxihidróxido sucroférrico. Su uso se ha extendido fundamental- mente entre pacientes en hemodiálisis, en sustitución de otros quelantes. Objetivo: describir la tolerabilidad, la aparición de efectos secundarios, la adherencia terapéutica y las cifras de fósforo sérico en pacientes en tratamiento con oxihidróxido sucroférrico en nuestro centro. Materiales y métodos: se analizaron 5 pacientes de la unidad de hemodiálisis del Servicio de Nefrología del Hospital Universitario de Burgos, España, en el periodo comprendido entre enero de 2017 a mayo de 2018, todos ellos en tratamiento con oxihidróxido sucroférrico. Se evaluaron las concentraciones plasmáticas de fósforo, calcio y hormona paratiroidea durante el tratamiento con oxihidróxido sucroférrico, además de los efectos secundarios y las causas de abandono. El análisis de los datos se realizó mediante el software estadístico IBM SPSS 22 con un intervalo de confianza del 95 %. Se evaluaron las posibles diferencias con el análisis de la t-Student. Resultados: se evidenció una reducción media del 12,27 % de la hiperfosforemia y una reducción en el número de comprimidos diarios del 15,79 %, con buena tolerancia del fármaco en todos los casos. No se evidenció reducción estadísticamente significativa en los niveles plasmáticos de calcio, ni de hormona paratiroidea (PTH). Conclusiones: el oxihidróxido sucroférrico es un fármaco bien tolerado, que generó una disminución de los niveles séricos de fósforo en la población estudiada. Sin embargo, dado el bajo número de casos analizados, no es posible recomendar el uso terapéutico de este fármaco como primera línea de tratamiento de la hiperfosforemia

Financial development and economic growth in an oil-rich economy: The case of Saudi Arabia

© 2014 Elsevier B.V.We investigate the effect of financial development on economic growth in the context of Saudi Arabia, an oil-rich economy. In doing so, we distinguish between the effects of financial development on the oil and non-oil sectors of the economy. Using the Autoregressive Distributed Lag (ARDL) Bounds test technique, we find that financial development has a positive impact on the growth of the non-oil sector. In contrast, its impact on the oil-sector growth and total GDP growth is either negative or insignificant. This suggests that the relationship between financial development and growth may be fundamentally different in resource-dominated economies

Gallstones, Body Mass Index, C-Reactive Protein, and Gallbladder Cancer: Mendelian Randomization Analysis of Chilean and European Genotype Data

BACKGROUND AND AIMS: Gallbladder cancer (GBC) is a neglected disease with substantial geographical variability: Chile shows the highest incidence worldwide, while GBC is relatively rare in Europe. Here, we investigate the causal effects of risk factors considered in current GBC prevention programs as well as C-reactive protein (CRP) level as a marker of chronic inflammation. APPROACH AND RESULTS: We applied two-sample Mendelian randomization (MR) using publicly available data and our own data from a retrospective Chilean and a prospective European study. Causality was assessed by inverse variance weighted (IVW), MR-Egger regression, and weighted median estimates complemented with sensitivity analyses on potential heterogeneity and pleiotropy, two-step MR, and mediation analysis. We found evidence for a causal effect of gallstone disease on GBC risk in Chileans (P = 9 × 10−5) and Europeans (P = 9 × 10−5). A genetically elevated body mass index (BMI) increased GBC risk in Chileans (P = 0.03), while higher CRP concentrations increased GBC risk in Europeans (P = 4.1 × 10−6). European results suggest causal effects of BMI on gallstone disease (P = 0.008); public Chilean data were not, however, available to enable assessment of the mediation effects among causal GBC risk factors. CONCLUSIONS: Two risk factors considered in the current Chilean program for GBC prevention are causally linked to GBC risk: gallstones and BMI. For Europeans, BMI showed a causal effect on gallstone risk, which was itself causally linked to GBC risk. (Hepatology 2021;73:1783-1796).Fil: Barahona Ponce, Carol. Ruprecht Karls Universitat Heidelberg; Alemania. Universidad de Chile; ChileFil: Scherer, Dominique. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Brinster, Regina. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Boekstegers, Felix. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Marcelain, Katherine. Universidad de Chile; ChileFil: Gárate Calderón, Valentina. Ruprecht Karls Universitat Heidelberg; Alemania. Universidad de Chile; ChileFil: Müller, Bettina. Instituto Nacional del Cáncer; ChileFil: de Toro, Gonzalo. Hospital Puerto Montt; Chile. Universidad Austral de Chile; ChileFil: Retamales, Javier. Instituto Nacional del Cáncer; ChileFil: Barajas, Olga. Universidad de Chile; ChileFil: Ahumada, Monica. Universidad de Chile; ChileFil: Morales, Erik. Hospital Regional de Talca; Chile. Universidad Católica del Maule; ChileFil: Rojas, Armando. Universidad Católica del Maule; ChileFil: Sanhueza, Verónica. Hospital Padre Hurtado; ChileFil: Loader, Denisse. Hospital Padre Hurtado; ChileFil: Rivera, María Teresa. Hospital del Salvador; ChileFil: Gutiérrez, Lorena. Hospital San Juan de Dios; ChileFil: Bernal, Giuliano. Universidad Católica del Norte; ChileFil: Ortega, Alejandro. Hospital Regional; ChileFil: Montalvo, Domingo. Hospital Regional Juan Noé Crevani; ChileFil: Portiño, Sergio. Universidad de Chile; ChileFil: Bertrán, Maria Enriqueta. Ministerio de Salud; ChileFil: Gabler, Fernando. Universidad de Santiago de Chile. Hospital Clinico San Borja Arriaran; ChileFil: Spencer, Loreto. Hospital Regional Guillermo Grant Benavente; ChileFil: Olloquequi, Jordi. Universidad Autónoma de Chile; ChileFil: Fischer, Christine. Ruprecht Karls Universitat Heidelberg; AlemaniaFil: Jenab, Mazda. International Agency For Research On Cancer; AlemaniaFil: Aleksandrova, Krasimira. German Institute Of Human Nutrition; AlemaniaFil: Katzke, Verena. German Cancer Research Center; AlemaniaFil: Gonzalez-Jose, Rolando. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Instituto Patagónico de Ciencias Sociales y Humanas; Argentin