Markov-modulated model for landing flow dynamics: An ordinal analysis validation.

Air transportation is a complex system characterized by a plethora of interactions at multiple temporal and spatial scales; as a consequence, even simple dynamics like sequencing aircraft for landing can lead to the appearance of emergent behaviors, which are both difficult to control and detrimental to operational efficiency. We propose a model, based on a modulated Markov jitter, to represent ordinal pattern properties of real landing operations in European airports. The parameters of the model are tuned by minimizing the distance between the probability distributions of ordinal patterns generated by the real and synthetic sequences, as estimated by the Permutation Jensen-Shannon Distance. We show that the correlation between consecutive hours in the landing flow changes between airports and that it can be interpreted as a metric of efficiency. We further compare the dynamics pre and post COVID-19, showing how this has changed beyond what can be attributed to a simple reduction of traffic. We finally draw some operational conclusions and discuss the applicability of these findings in a real operational environment.

Analyzing international events through the lens of statistical physics: The case of Ukraine.

During the last few years, statistical physics has received increasing attention as a framework for the analysis of real complex systems; yet, this is less clear in the case of international political events, partly due to the complexity in securing relevant quantitative data on them. Here, we analyze a detailed dataset of violent events that took place in Ukraine since January 2021 and analyze their temporal and spatial correlations through entropy and complexity metrics and functional networks. Results depict a complex scenario with events appearing in a non-random fashion but with eastern-most regions functionally disconnected from the remainder of the country-something opposing the widespread "two Ukraines" view. We further draw some lessons and venues for future analyses.

Contrasting chaotic with stochastic dynamics via ordinal transition networks.

We introduce a representation space to contrast chaotic with stochastic dynamics. Following the complex network representation of a time series through ordinal pattern transitions, we propose to assign each system a position in a two-dimensional plane defined by the permutation entropy of the network (global network quantifier) and the minimum value of the permutation entropy of the nodes (local network quantifier). The numerical analysis of representative chaotic maps and stochastic systems shows that the proposed approach is able to distinguish linear from non-linear dynamical systems by different planar locations. Additionally, we show that this characterization is robust when observational noise is considered. Experimental applications allow us to validate the numerical findings and to conclude that this approach is useful in practical contexts.

Development of a cell-based treatment for long-term neurotrophin expression and spiral ganglion neuron survival.

Spiral ganglion neurons (SGNs), the target cells of the cochlear implant, undergo gradual degeneration following loss of the sensory epithelium in deafness. The preservation of a viable population of SGNs in deafness can be achieved in animal models with exogenous application of neurotrophins such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3. For translation into clinical application, a suitable delivery strategy that provides ongoing neurotrophic support and promotes long-term SGN survival is required. Cell-based neurotrophin treatment has the potential to meet the specific requirements for clinical application, and we have previously reported that Schwann cells genetically modified to express BDNF can support SGN survival in deafness for 4 weeks. This study aimed to investigate various parameters important for the development of a long-term cell-based neurotrophin treatment to support SGN survival. Specifically, we investigated different (i) cell types, (ii) gene transfer methods and (iii) neurotrophins, in order to determine which variables may provide long-term neurotrophin expression and which, therefore, may be the most effective for supporting long-term SGN survival in vivo. We found that fibroblasts that were nucleofected to express BDNF provided the most sustained neurotrophin expression, with ongoing BDNF expression for at least 30 weeks. In addition, the secreted neurotrophin was biologically active and elicited survival effects on SGNs in vitro. Nucleofected fibroblasts may therefore represent a method for safe, long-term delivery of neurotrophins to the deafened cochlea to support SGN survival in deafness.

The structure and dynamics of multilayer networks.

In the past years, network theory has successfully characterized the interaction among the constituents of a variety of complex systems, ranging from biological to technological, and social systems. However, up until recently, attention was almost exclusively given to networks in which all components were treated on equivalent footing, while neglecting all the extra information about the temporal- or context-related properties of the interactions under study. Only in the last years, taking advantage of the enhanced resolution in real data sets, network scientists have directed their interest to the multiplex character of real-world systems, and explicitly considered the time-varying and multilayer nature of networks. We offer here a comprehensive review on both structural and dynamical organization of graphs made of diverse relationships (layers) between its constituents, and cover several relevant issues, from a full redefinition of the basic structural measures, to understanding how the multilayer nature of the network affects processes and dynamics.

Explosive transitions to synchronization in networks of phase oscillators.

The emergence of dynamical abrupt transitions in the macroscopic state of a system is currently a subject of the utmost interest. The occurrence of a first-order phase transition to synchronization of an ensemble of networked phase oscillators was reported, so far, for very particular network architectures. Here, we show how a sharp, discontinuous transition can occur, instead, as a generic feature of networks of phase oscillators. Precisely, we set conditions for the transition from unsynchronized to synchronized states to be first-order, and demonstrate how these conditions can be attained in a very wide spectrum of situations. We then show how the occurrence of such transitions is always accompanied by the spontaneous setting of frequency-degree correlation features. Third, we show that the conditions for abrupt transitions can be even softened in several cases. Finally, we discuss, as a possible application, the use of this phenomenon to express magnetic-like states of synchronization.

Topological measure locating the effective crossover between segregation and integration in a modular network.

We introduce an easily computable topological measure which locates the effective crossover between segregation and integration in a modular network. Segregation corresponds to the degree of network modularity, while integration is expressed in terms of the algebraic connectivity of an associated hypergraph. The rigorous treatment of the simplified case of cliques of equal size that are gradually rewired until they become completely merged, allows us to show that this topological crossover can be made to coincide with a dynamical crossover from cluster to global synchronization of a system of coupled phase oscillators. The dynamical crossover is signaled by a peak in the product of the measures of intracluster and global synchronization, which we propose as a dynamical measure of complexity. This quantity is much easier to compute than the entropy (of the average frequencies of the oscillators), and displays a behavior which closely mimics that of the dynamical complexity index based on the latter. The proposed topological measure simultaneously provides information on the dynamical behavior, sheds light on the interplay between modularity and total integration, and shows how this affects the capability of the network to perform both local and distributed dynamical tasks.

The development of encapsulated cell technologies as therapies for neurological and sensory diseases.

Cell encapsulation therapies involve the implantation of cells that secrete a therapeutic factor to provide clinical benefits. The transplanted cells are protected from immunorejection via encapsulation in a semipermeable membrane. This treatment strategy was originally investigated as a method for protecting pancreatic islets from immunorejection, thus allowing them to secrete insulin as a chronic treatment for diabetes. Since then a significant body of work has been conducted in developing cell encapsulation therapies to treat a variety of different diseases. Many of these conditions involve neurodegeneration, such as Alzheimer's and Parkinson's disease, as cell encapsulation therapies have proven to be particularly suitable for delivering therapeutics to the central nervous system. This is mainly because they offer chronic delivery of a therapeutic and can be implanted proximal to the affected tissue, bypassing the blood brain barrier, which is impermeable to many agents. Whilst these therapies are not yet widely available in the clinic, promising results have been obtained in several advanced clinical trials and further developmental work is currently underway. This review specifically examines the development of encapsulated cell therapies as treatments for neurological and sensory diseases and evaluates the challenges that are yet to be overcome before they can be made available for clinical use.

Complex networks analysis of obstructive nephropathy data.

Congenital obstructive nephropathy (ON) is one of the most frequent nephropathy observed among newborns and children, and the first cause of end-stage renal diseases treated by dialysis or transplantation. This pathology is characterized by the presence of an obstacle in the urinary tract, e.g., stenosis or abnormal implantation of the urethra in the kidney. In spite of important advances, pathological mechanisms are not yet fully understood. In this contribution, the topology of complex networks created upon vectors of features for control and ON subjects is related with the severity of the pathology. Nodes in these networks represent genetic and metabolic profiles, while connections between them indicate an abnormal relation between their expressions. Resulting topologies allow discriminating ON subjects and detecting which genetic or metabolic elements are responsible for the malfunction.

Computation as an emergent feature of adaptive synchronization.

We report on the spontaneous emergence of computation from adaptive synchronization of networked dynamical systems. The fundamentals are nonlinear elements, interacting in a directed graph via a coupling that adapts itself to the synchronization level between two input signals. These units can emulate different Boolean logics, and perform any computational task in a Turing sense, each specific operation being associated with a given network's motif. The resilience of the computation against noise is proven, and the general applicability is demonstrated with regard to periodic and chaotic oscillators, and excitable systems mimicking neural dynamics.

Bioequivalência de duas formulações de oxalato de escitalopram comprimidos em voluntários sadios administradas em jejum / Bioequivalence of two tablets formulations of escitalopram oxalate in healthy volunteers under fasting conditions

O estudo foi conduzido para verificar a bioequivalência entre duas formulações de oxalato de escitalopram 10 mg, comprimidos. Foram 32 voluntários sadios de ambos os sexos que participaram no estudo randomizado, cruzado, dois períodos, com washout mínimo de dez dias. Um comprimido de cada formulação foi administrado após jejum noturno de dez horas. Após administração, amostras seriadas de sangue foram coletadas por 144 horas. As amostras de plasma foram analisadas para determinação do escitalopram por método validado de cromatografia líquida acoplada à detecção por espectrometria de massas (LC-MS-MS). Os parâmetros farmacocinéticos área sob a curva de concentração plasmática do tempo zero a última concentração medida (ASC0-t) e concentração máxima observada (Cmax) foram os principais critérios para verificação da bioequivalência entre as formulações. Área sob a curva de zero a infinito (ASC0-inf), tempo em que ocorre Cmax (Tmax) e meia-vida (t1/2) também foram determinados. Os intervalos de confiança (IC) de 90% obtidos por análise de variância (ANOVA) não mostraram diferenças significativas entre as duas formulações e caíram dentro dos limites pre-estabelecidos (96,91-106,79 para ASC0-t e 89,40-102,39 para Cmax). A bioequivalência entre as duas formulações foi demonstrada tanto em termos de taxa quanto de extensão da absorção.

[Ureterorenoscopy with a flexible instrument].

Flexible ureterorenoscopy should be routinely used at the Urological Centers that deal with urinary stones. Flexible instruments should be used for both diagnostic and therapeutic purposes, allowing a safe exploration of the whole upper urinary tract. Thanks to their flexibility and to the active and passive deflection of their distal part, these instruments allowed to successfully treat several difficult situations, such as renal caliceal calculi in the lower calices or even in some middle/upper calices or in horseshoe kidneys. The therapeutic potential of this approach is enhanced by the large availability of ancillary instrumentation, such as baskets, grasps, holmium laser fibers, etc, which is continuously growing. On the other side, a steep learning curve of the technique is usually required for the surgeon. Furthermore, the intrinsic fragility of the instrument components and a potentially lower quality, when compared to that of the rigid and semi-rigid ureteroscopes, should be considered.

Study of barrier properties and chemical resistance of recycled PET coated with amorphous carbon through a plasma enhanced chemical vapour deposition (PECVD) process.

Many studies have been carried out in order to make bottle-to-bottle recycling feasible. The problem is that residual contaminants in recycled plastic intended for food packaging could be a risk to public health. One option is to use a layer of virgin material, named functional barrier, which prevents the contaminants migration process. This paper shows the feasibility of using polyethylene terephthalate (PET) recycled for food packaging employing a functional barrier made from hydrogen amorphous carbon film deposited by Plasma Enhanced Chemical Vapour Deposition (PECVD) process. PET samples were deliberately contaminated with a series of surrogates using a FDA protocol. After that, PET samples were coated with approximately 600 and 1200 Angstrons thickness of amorphous carbon film. Then, the migration tests using as food simulants: water, 10% ethanol, 3% acetic acid, and isooctane were applied to the sample in order to check the chemical resistance of the new coated material. After the tests, the liquid extracts were analysed using a solid-phase microextraction device (SPME) coupled to GC-MS.

Kinetics of TNF-alpha and IFN-gamma mRNA expression in islets and spleen of NOD mice.

Insulin-dependent diabetes mellitus is caused by autoimmune destruction of pancreatic beta cells. Non-obese diabetic (NOD) mice spontaneously develop diabetes similar to the human disease. Cytokines produced by islet-infiltrating mononuclear cells may be directly cytotoxic and can be involved in islet destruction coordinated by CD4+ and CD8+ cells. We utilized a semiquantitative RT-PCR assay to analyze in vitro the mRNA expression of TNF-alpha and IFN-gamma cytokine genes in isolated islets (N = 100) and spleen cells (5 x 10(5) cells) from female NOD mice during the development of diabetes and from female CBA-j mice as a related control strain that does not develop diabetes. Cytokine mRNAs were measured at 2, 4, 8, 14 and 28 weeks of age from the onset of insulitis to the development of overt diabetes. An increase in IFN-gamma expression in islets was observed for females aged 28 weeks (149 +/- 29 arbitrary units (AU), P<0.05, Student t-test) with advanced destructive insulitis when compared with CBA-j mice, while TNF-alpha was expressed in both NOD and CBA-j female islets at the same level at all ages studied. In contrast, TNF-alpha in spleen was expressed at higher levels in NOD females at 14 weeks (99 +/- 8 AU, P<0.05) and 28 weeks (144 +/- 17 AU, P<0.05) of age when compared to CBA-j mice. The data suggest that IFN-gamma and TNF-alpha expression in pancreatic islets of female NOD mice is associated with beta cell destruction and overt diabetes.

Kinetics of TNF-alpha and IFN-gamma mRNA expression in islets and spleen of NOD mice

Insulin-dependent diabetes mellitus is caused by autoimmune destruction of pancreatic ß cells. Non-obese diabetic (NOD) mice spontaneously develop diabetes similar to the human disease. Cytokines produced by islet-infiltrating mononuclear cells may be directly cytotoxic and can be involved in islet destruction coordinated by CD4+ and CD8+ cells. We utilized a semiquantitative RT-PCR assay to analyze in vitro the mRNA expression of TNF-alpha and IFN-gamma cytokine genes in isolated islets (N = 100) and spleen cells (5 x 10(5) cells) from female NOD mice during the development of diabetes and from female CBA-j mice as a related control strain that does not develop diabetes. Cytokine mRNAs were measured at 2, 4, 8, 14 and 28 weeks of age from the onset of insulitis to the development of overt diabetes. An increase in IFN-gamma expression in islets was observed for females aged 28 weeks (149 ± 29 arbitrary units (AU), P<0.05, Student t-test) with advanced destructive insulitis when compared with CBA-j mice, while TNF-alpha was expressed in both NOD and CBA-j female islets at the same level at all ages studied. In contrast, TNF-alpha in spleen was expressed at higher levels in NOD females at 14 weeks (99 ± 8 AU, P<0.05) and 28 weeks (144 ± 17 AU, P<0.05) of age when compared to CBA-j mice. The data suggest that IFN-gamma and TNF-alpha expression in pancreatic islets of female NOD mice is associated with ß cell destruction and overt diabetes

Distinct spatial and temporal distributions of aggrecan and versican in the embryonic chick heart.

Although chondroitin sulfate proteoglycans (CSPGs) are major components of the embryonic extracellular matrix, little attention has been paid to specific CSPGs in early heart development, in part because appropriate antibodies were not available. Therefore we prepared specific polyclonal antibodies against chicken aggrecan, versican, neurocan, and phosphacan. Western blotting and immunohistochemical studies revealed the presence of aggrecan and versican in stages 12-21 chicken embryo hearts in distinctive spatial and temporal patterns. Because this is the first demonstration of aggrecan in heart tissue, we further used RT-PCR to confirm that aggrecan is expressed in the heart and in situ hybridization to confirm the pattern of expression determined using antibodies. Versican is found in the myocardium and the myocardial basement membrane. In contrast, aggrecan is specifically colocalized with several groups of migrating cells including endocardial cushion tissue cells, epicardial cells, a mesenchymal cell population in the outflow tract that may be of neural crest origin, and a mesenchymal cell population in the inflow tract. The combined observations indicate that versican and aggrecan are expressed in unique patterns and suggest that they play very different roles in development.

Regulated binding of PTP1B-like phosphatase to N-cadherin: control of cadherin-mediated adhesion by dephosphorylation of beta-catenin.

Cadherins are a family of cell-cell adhesion molecules which play a central role in controlling morphogenetic movements during development. Cadherin function is regulated by its association with the actin containing cytoskeleton, an association mediated by a complex of cytoplasmic proteins, the catenins: alpha, beta, and gamma. Phosphorylated tyrosine residues on beta-catenin are correlated with loss of cadherin function. Consistent with this, we find that only nontyrosine phosphorylated beta-catenin is associated with N-cadherin in E10 chick retina tissue. Moreover, we demonstrate that a PTP1B-like tyrosine phosphatase associates with N-cadherin and may function as a regulatory switch controlling cadherin function by dephosphorylating beta-catenin, thereby maintaining cells in an adhesion-competent state. The PTP1B-like phosphatase is itself tyrosine phosphorylated. Moreover, both direct binding experiments performed with phosphorylated and dephosphorylated molecules, and treatment of cells with tyrosine kinase inhibitors indicate that the interaction of the PTP1B-like phosphatase with N-cadherin depends on its tyrosine phosphorylation. Concomitant with the tyrosine kinase inhibitor-induced loss of the PTP1B-like phosphatase from its association with N-cadherin, phosphorylated tyrosine residues are retained on beta-catenin, the association of N-cadherin with the actin containing cytoskeleton is lost and N-cadherin-mediated cell adhesion is prevented. Tyrosine phosphatase inhibitors also result in the accumulation of phosphorylated tyrosine residues on beta-catenin, loss of the association of N-cadherin with the actin-containing cytoskeleton, and prevent N-cadherin mediated adhesion, presumably by directly blocking the function of the PTP1B-like phosphatase. We previously showed that the binding of two ligands to the cell surface N-acetylgalactosaminylphosphotransferase (GalNAcPTase), the monoclonal antibody 1B11 and a proteoglycan with a 250-kD core protein, results in the accumulation of phosphorylated tyrosine residues on beta-catenin, uncoupling of N-cadherin from its association with the actin containing cytoskeleton, and loss of N-cadherin function. We now report that binding of these ligands to the GalNAcPTase results in the absence of the PTP1B-like phosphatase from its association with N-cadherin as well as the loss of the tyrosine kinase and tyrosine phosphatase activities that otherwise co-precipitate with N-cadherin. Control antibodies and proteoglycans have no such effect. This effect is similar to that observed with tyrosine kinase inhibitors, suggesting that the GalNAcPTase/proteoglycan interaction inhibits a tyrosine kinase, thereby preventing the phosphorylation of the PTP1B-like phosphatase, and its association with N-cadherin. Taken together these data indicate that a PTP1B-like tyrosine phosphatase can regulate N-cadherin function through its ability to dephosphorylate beta-catenin and that the association of the phosphatase with N-cadherin is regulated via the interaction of the GalNAcPTase with its proteoglycan ligand. In this manner the GalNAcPTase-proteoglycan interaction may play a major role in morphogenetic cell and tissue interactions during development.

Receptor-mediated adhesive and anti-adhesive functions of chondroitin sulfate proteoglycan preparations from embryonic chicken brain.

Chondroitin sulfate proteoglycans inhibit the adhesion of cells to extracellular matrix proteins that otherwise permit adhesion. Although proteoglycans are widely assumed to act by masking the other protein in a mixed substrate, recent studies suggest that proteoglycans inhibit adhesion through mechanisms initiated by their binding to specific cell surface receptors. To explore this issue, we developed a purification scheme to isolate proteoglycan aggregates, monomers, and core proteins. Two distinct adhesion assays were used to study the interaction of these proteoglycan preparations with human foreskin fibroblasts: the gravity assay in which cell attachment is stabilized by cell spreading, and the centrifugation assay in which spreading does not play a role. All proteoglycan preparations mediate adhesion in the centrifugation assay but not in the gravity assay. In the centrifugation assay, proteoglycan aggregates and monomers are considerably more active than other extracellular matrix proteins while proteoglycan core proteins are at least as active as other extracellular matrix proteins. Proteoglycan core proteins bind to cell-associated hyaluronic acid, but not to integrins. Using mixed substrates in the gravity assay, all proteoglycan preparations inhibited cell attachment to fibronectin and vitronectin but not to collagen I and laminin. Although proteoglycan aggregates and monomers are more active than core proteins in inhibiting adhesion in the gravity assay, core proteins are still clearly active. A variety of control experiments suggest that the inhibition of cell attachment by proteoglycans is mediated through the specific interactions of proteoglycans with cell surface receptors, resulting in the inhibition of cell spreading. These results suggest at least two molecular mechanisms for proteoglycan-fibroblast interactions, one involving the chondroitin sulfate on the proteoglycan and an as yet unidentified receptor, the other involving the proteoglycan core protein and cell-associated hyaluronic acid.