878 research outputs found

    Phase separation in coupled chaotic maps on fractal networks

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    The phase ordering dynamics of coupled chaotic maps on fractal networks are investigated. The statistical properties of the systems are characterized by means of the persistence probability of equivalent spin variables that define the phases. The persistence saturates and phase domains freeze for all values of the coupling parameter as a consequence of the fractal structure of the networks, in contrast to the phase transition behavior previously observed in regular Euclidean lattices. Several discontinuities and other features found in the saturation persistence curve as a function of the coupling are explained in terms of changes of stability of local phase configurations on the fractals.Comment: (4 pages, 4 Figs, Submitted to PRE

    The therapeutic strategy of HDAC6 inhibitors in lymphoproliferative disease

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    Histone deacetylases (HDACs) are master regulators of chromatin remodeling, acting as epigenetic regulators of gene expression. In the last decade, inhibition of HDACs has become a target for specific epigenetic modifications related to cancer development. Overexpression of HDAC has been observed in several hematologic malignancies. Therefore, the observation that HDACs might play a role in various hematologic malignancies has brought to the development of HDAC inhibitors as potential antitumor agents. Recently, the class IIb, HDAC6, has emerged as one potential selective HDACi. This isoenzyme represents an important pharmacological target for selective inhibition. Its selectivity may reduce the toxicity related to the off-target effects of pan-HDAC inhibitors. HDAC6 has also been studied in cancer especially for its ability to coordinate a variety of cellular processes that are important for cancer pathogenesis. HDAC6 has been reported to be overexpressed in lymphoid cells and its inhibition has demonstrated activity in preclinical and clinical study of lymphoproliferative disease. Various studies of HDAC6 inhibitors alone and in combination with other agents provide strong scientific rationale for the evaluation of these new agents in the clinical setting of hematological malignancies. In this review, we describe the HDACs, their inhibitors, and the recent advances of HDAC6 inhibitors, their mechanisms of action and role in lymphoproliferative disorders

    Pattern Formation on Trees

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    Networks having the geometry and the connectivity of trees are considered as the spatial support of spatiotemporal dynamical processes. A tree is characterized by two parameters: its ramification and its depth. The local dynamics at the nodes of a tree is described by a nonlinear map, given rise to a coupled map lattice system. The coupling is expressed by a matrix whose eigenvectors constitute a basis on which spatial patterns on trees can be expressed by linear combination. The spectrum of eigenvalues of the coupling matrix exhibit a nonuniform distribution which manifest itself in the bifurcation structure of the spatially synchronized modes. These models may describe reaction-diffusion processes and several other phenomena occurring on heterogeneous media with hierarchical structure.Comment: Submitted to Phys. Rev. E, 15 pages, 9 fig

    Cytokine release syndrome associated with T-cell-based therapies for hematological malignancies: Pathophysiology, clinical presentation, and treatment

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    Cytokines are a broad group of small regulatory proteins with many biological functions involved in regulating the hematopoietic and immune systems. However, in pathological conditions, hyperactivation of the cytokine network constitutes the fundamental event in cytokine release syndrome (CRS). During the last few decades, the development of therapeutic monoclonal antibodies and T-cell therapies has rapidly evolved, and CRS can be a serious adverse event related to these treatments. CRS is a set of toxic adverse events that can be observed during infection or following the administration of antibodies for therapeutic purposes and, more recently, during T-cell-engaging therapies. CRS is triggered by on-target effects induced by binding of chimeric antigen receptor (CAR) T cells or bispecific antibody to its antigen and by subsequent activation of bystander immune and non-immune cells. CRS is associated with high circulating concentrations of several pro-inflammatory cytokines, including interleukins, interferons, tumor necrosis factors, colony-stimulating factors, and transforming growth factors. Recently, considerable developments have been achieved with regard to preventing and controlling CRS, but it remains an unmet clinical need. This review comprehensively summarizes the pathophysiology, clinical presentation, and treatment of CRS caused by T-cell-engaging therapies utilized in the treatment of hematological malignancies

    On Exact and Approximate Solutions for Hard Problems: An Alternative Look

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    We discuss in an informal, general audience style the da Costa-Doria conjecture about the independence of the P = NP hypothesis and try to briefly assess its impact on practical situations in economics. The paper concludes with a discussion of the Coppe-Cosenza procedure, which is an approximate, partly heuristic algorithm for allocation problems.P vs. NP , allocation problem, assignment problem, traveling salesman, exact solution for NP problems, approximate solutions for NP problems, undecidability, incompleteness

    Periodic Neural Activity Induced by Network Complexity

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    We study a model for neural activity on the small-world topology of Watts and Strogatz and on the scale-free topology of Barab\'asi and Albert. We find that the topology of the network connections may spontaneously induce periodic neural activity, contrasting with chaotic neural activities exhibited by regular topologies. Periodic activity exists only for relatively small networks and occurs with higher probability when the rewiring probability is larger. The average length of the periods increases with the square root of the network size.Comment: 4 pages, 5 figure

    Conteúdo de noradrenalina do hipotálamo e tronco-encefálico de ratos inoculados com Trypanosoma Cruzi

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    Noradrenaline was assayed fluorimetrically in the hypothalamus and brainstem of rats killed 20 and 32 days after inoculation with the Y strain of T. cruzi (300,000 trypomastigotes i.p.). In these animals and their normal controls the right atrial appendages were submitted to the glyoxilic acid fluorescence technique for the demonstration of noradrenergic nerves. The noradrenaline content of the brain-stem and hypothalamus of the infected animals was not significantly different from that of controls. In the atrial appendages, however, an almost complete noradrenergic denervation was observed. This result indicates that the mechanism involved in neuronal lesion in Chagas'disease discriminates between peripheral and central noradrenergic neurons.O conteúdo de noradrenalina do hipotálamo e do tronco encefálico de ratos controle e inoculados com a cepa Y (300.000 tripomastigotas, i.p.) de Trypanosoma cruzi foi medido pela técnica fluorimétrica de Anton e Sayre. Os animais foram sacrificados 20 e 32 dias depois da inoculação. Para avaliação do grau de desnervação simpática do coração dos animais infectados, a aurícula direita foi observada com microscópio de fluorescência após tratamento histoquímieo pela técnica do ácido glioxílico. O conteúdo de noradrenalina do hipotálamo e do tronco encefálico dos animais infectados não diferiu do medido nos animais controle. Contudo, um quase completo desaparecimento das fibras adrenérgicas foi observado no coração dos animais chagásicos, sugerindo que o mechanismo envolvido na lesão discrimina neurônios adrenérgicos centrais e periféricos
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