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.

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.

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.

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.

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.

The interaction of the retina cell surface N-acetylgalactosaminylphosphotransferase with an endogenous proteoglycan ligand results in inhibition of cadherin-mediated adhesion.

We have previously shown that the binding to cells of a monoclonal antibody directed against the chick neural retina N-acetylgalactosaminylphosphotransferase (GalNAcPTase) results in inhibition of cadherin-mediated adhesion and neurite outgrowth. We hypothesized that the antibody mimics the action of an endogenous ligand. Chondroitin sulfate proteoglycans (CSPGs) are potential ligands because they inhibit adhesion and neurite outgrowth and are present in situ at barriers to neuronal growth. We therefore assayed purified CSPGs for their ability to inhibit homophilic cadherin-mediated adhesion and neurite outgrowth, as well as their ability to bind directly to the GalNAcPTase. A proteoglycan with a 250-kD core protein following removal of chondroitin sulfate chains (250-kD PG) inhibits cadherin-mediated adhesion and neurite outgrowth whether presented as the core protein or as a proteoglycan monomer bearing chondroitin sulfate. A proteoglycan with a 400-kD core protein is not inhibitory in either core protein or monomer form. Treatment of cells with phosphatidylinositol-specific phospholipase C, which removes cell surface GalNAcPTase, abolishes this inhibitory effect. Binding of the 250-kD core protein to cells is competed by the anti-GalNAcPTase antibody 1B11, suggesting that 1B11 and the 250-kD core protein bind to the same site or in close proximity. Moreover, soluble GalNAcPTase binds to the immobilized 250-kD core protein but not to the immobilized 400-kD core protein. Concomitant with inhibition of cadherin mediated adhesion, binding of the 250-kD core protein to the GalNAcPTase on cells results in the enhanced tyrosine phosphorylation of beta-catenin and the uncoupling of N-cadherin from its association with the cytoskeleton. Moreover, the 250-kD PG is present in embryonic chick retina and brain and is associated with the GalNAcPTase in situ. We conclude that the 250-kD PG is an endogenous ligand for the GalNAcPTase. Binding of the 250-kD PG to the GalNAcPTase initiates a signal cascade, involving the tyrosine phosphorylation of beta-catenin, which alters the association of cadherin with the actin-containing cytoskeleton and thereby inhibits adhesion and neurite outgrowth. Regulation of the temporal and spatial expression patterns of each member of the GalNacPTase/250-kD PG interactive pair may create opportunities for interaction that influence the course of development through effects on cadherin-based morphogenetic processes.

Sex difference in sensitization to the locomotor effects of mazindol in rats.

Male and female rats were treated daily for 7 days with mazindol (5, 10, and 20 mg/kg), an anorectic drug, and tested in the open field. Mazindol developed sensitization to its locomotor stimulatory effect in both sexes on day 7 with a nondose-dependent pattern of response. However, the locomotor activity appeared to be sex dependent, female rats being more sensitive. Following a challenge dose of mazindol (10 and 20 mg/kg) on day 10, a marked enhancement of locomotion was seen in female rats. These findings indicate that repeated administration of mazindol produces sex-dependent sensitization to its effect on locomotor behavior.

Effects of age on behavioral and physiological responses to carbaryl in rats.

Motor, sensory and thermoregulatory functions were examined in young (3 months) and mature (12 months) rats following PO administration of single low doses (10 and 50 mg/kg) of carbaryl, a carbamate insecticide, and these effects were related to blood cholinesterase activity. Carbaryl 50 mg/kg decreased the frequency of ambulation in the open-field arena within 30 min while it enhanced the duration of haloperidol-induced catalepsy in both young and mature rats. Administration of carbaryl also resulted in an increased nociceptive threshold to thermic stimuli mainly in mature rats. An age-related reduction in body temperature was observed at 30, 60 and 90 min after injection. Activity of blood cholinesterase was reduced in young and mature rats at 30 and 60 min following carbaryl exposure. These results indicate that carbaryl can induce an age-related impairment on some behavioral and autonomic functions in rats correlated to the inhibition of cholinesterase activity.

Behavioral and biochemical changes following repeated administration of carbaryl to aging rats.

Motor, sensory and thermoregulatory functions were examined in aging rats (12 months) following two schedules of repeated po administration of the carbamate insecticide carbaryl and these effects were assessed in terms of blood cholinesterase activity. Administration of carbaryl (50 mg/kg) by gavage daily for 30 days resulted in a reduction of locomotor activity in the open-field and in an inhibition of cholinesterase activity within 30 min after the last treatment. Twenty-four h later, only the locomotor effect was evident. After 90 days of exposure to carbaryl in drinking water, no significant effects were observed. These findings suggest that repeated administration of carbaryl to aging rats can induce an impairment of motor function and a reduction of cholinesterase activity, while tolerance develops in some other parameters.

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.

Preliminary pharmacologic evaluation of crude whole plant extracts of Elephantopus scaber. Part I: In vivo studies.

Elephantopus scaber has been used in Brazil as a traditional remedy to cause diuresis, antipyresis and to eliminate bladder stones. In the current study, aqueous and hydroalcoholic extracts of whole plants were tested for acute toxicity, analgesic, antipyretic, antiinflammatory, cardiovascular, diuretic and constipating activities. Both extracts (0.3-6 g/kg i.p.) induced writhing, loss of muscle tone, ataxia, prostration and death in mice. No analgesic effects of these extracts were detected using mouse hot-plate and acetic acid-induced writhing tests. Both extracts failed to modify diuresis or carrageenan-induced rat paw edema. In contrast, given intraperitoneally, both reduced brewer's yeast-induced hyperthermia in rats, but when given orally did not affect it. Moreover, the aqueous extract decreased the intestinal transit time in mice while the hydroalcoholic extract increased it. Finally, these extracts, given intravenously, reduced blood pressure and heart rate in rats; these effects could be blocked by atropine but not by co-administration of pyrilamine and cimetidine.

Clinical features and treatment of Elapidae bites: report of three cases.

This report describes two accidents, involving snakes of the Micrurus corallinus species, where compromising respiratory function was not observed and the specific anti-elapidic serum was the single therapy used, and a third incident, probably involving Micrurus frontalis, where neostigmine was used to remedy respiratory failure.

[The pharmacologic action of extracts of Polygonum punctatum Elliot (= P. acre HBK)]. / Mise en évidence des actions pharmacologiques d'extraits de Polygonum punctatum Elliot (= P. acre H.B.K.).

In vivo pharmacological studies were carried out with the aqueous and hydroalcoholic extracts of P. punctatum Elliot. Previously we have made a phytochemical screening and a essay of acute toxicity. The extracts exhibited an inhibition of the carrageenan-induced rat paw oedema, at doses of 300 and 600 mg.kg-1 p.o. and the hydroalcoholic extract at a dose range of 100-600 mg.kg-1 p.o. reduced significantly the increase of the vascular permeability induced by histamine. The extracts showed antipyretic activity only by i.p. administration. The gastrointestinal propulsion of a charcoal suspension was affected by both extracts, but significantly only by the aqueous extract. They elicited bradycardia and lowered the arterial blood pressure, but they do not demonstrate analgesic and diuretic activities. The pharmacological effects assayed are discussed in relation to the chemical composition of this plant and also to its popular use.

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.

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.

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.

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.

[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.