Learning and generation of long-range correlated sequences

We study the capability to learn and to generate long-range, power-law correlated sequences by a fully connected asymmetric network. The focus is set on the ability of neural networks to extract statistical features from a sequence. We demonstrate that the average power-law behavior is learnable, namely, the sequence generated by the trained network obeys the same statistical behavior. The interplay between a correlated weight matrix and the sequence generated by such a network is explored. A weight matrix with a power-law correlation function along the vertical direction, gives rise to a sequence with a similar statistical behavior.Comment: 5 pages, 3 figures, accepted for publication in Physical Review

Correlated patterns in non-monotonic graded-response perceptrons

The optimal capacity of graded-response perceptrons storing biased and spatially correlated patterns with non-monotonic input-output relations is studied. It is shown that only the structure of the output patterns is important for the overall performance of the perceptrons.Comment: 4 pages, 4 figure

A toy model of the five-dimensional universe with the cosmological constant

A value of the cosmological constant in a toy model of the five-dimensional universe is calculated in such a manner that it remains in agreement with both astronomical observations and the quantum field theory concerning the zero-point fluctuations of the vacuum. The (negative) cosmological constant is equal to the inverse of the Planck length squared, which means that in the toy model the vanishing of the observed value of the cosmological constant is a consequence of the existence of an energy cutoff exactly at the level of the Planck scale. In turn, a model for both a virtual and a real particle-antiparticle pair is proposed which describes properly some energetic properties of both the vacuum fluctuations and created particles, as well as it allows one to calculate the discrete "bare" values of an elementary-particle mass, electric charge and intrinsic angular momentum (spin) at the energy cutoff. The relationships between the discussed model and some phenomena such as the Zitterbewegung and the Unruh-Davies effect are briefly analyzed, too. The proposed model also allows one to derive the Lorentz transformation and the Maxwell equations while considering the properties of the vacuum filled with the sea of virtual particles and their antiparticles. Finally, the existence of a finite value of the vacuum-energy density resulting from the toy model leads us to the formulation of dimensionless Einstein field equations which can be derived from the Lagrangian with a dimensionless (naively renormalized) coupling constant.Comment: 52 pages, 1 figure; a post-final, rewritten version with a number of new remarks and conclusion

Generalizing with perceptrons in case of structured phase- and pattern-spaces

We investigate the influence of different kinds of structure on the learning behaviour of a perceptron performing a classification task defined by a teacher rule. The underlying pattern distribution is permitted to have spatial correlations. The prior distribution for the teacher coupling vectors itself is assumed to be nonuniform. Thus classification tasks of quite different difficulty are included. As learning algorithms we discuss Hebbian learning, Gibbs learning, and Bayesian learning with different priors, using methods from statistics and the replica formalism. We find that the Hebb rule is quite sensitive to the structure of the actual learning problem, failing asymptotically in most cases. Contrarily, the behaviour of the more sophisticated methods of Gibbs and Bayes learning is influenced by the spatial correlations only in an intermediate regime of $\alpha$, where $\alpha$ specifies the size of the training set. Concerning the Bayesian case we show, how enhanced prior knowledge improves the performance.Comment: LaTeX, 32 pages with eps-figs, accepted by J Phys

Macrophage-derived human resistin is induced in multiple helminth infections and promotes inflammatory monocytes and increased parasite burden.

Parasitic helminth infections can be associated with lifelong morbidity such as immune-mediated organ failure. A better understanding of the host immune response to helminths could provide new avenues to promote parasite clearance and/or alleviate infection-associated morbidity. Murine resistin-like molecules (RELM) exhibit pleiotropic functions following helminth infection including modulating the host immune response; however, the relevance of human RELM proteins in helminth infection is unknown. To examine the function of human resistin (hResistin), we utilized transgenic mice expressing the human resistin gene (hRetnTg+). Following infection with the helminth Nippostrongylus brasiliensis (Nb), hResistin expression was significantly upregulated in infected tissue. Compared to control hRetnTg- mice, hRetnTg+ mice suffered from exacerbated Nb-induced inflammation characterized by weight loss and increased infiltration of inflammatory monocytes in the lung, along with elevated Nb egg burdens and delayed parasite expulsion. Genome-wide transcriptional profiling of the infected tissue revealed that hResistin promoted expression of proinflammatory cytokines and genes downstream of toll-like receptor signaling. Moreover, hResistin preferentially bound lung monocytes, and exogenous treatment of mice with recombinant hResistin promoted monocyte recruitment and proinflammatory cytokine expression. In human studies, increased serum resistin was associated with higher parasite load in individuals infected with soil-transmitted helminths or filarial nematode Wuchereria bancrofti, and was positively correlated with proinflammatory cytokines. Together, these studies identify human resistin as a detrimental factor induced by multiple helminth infections, where it promotes proinflammatory cytokines and impedes parasite clearance. Targeting the resistin/proinflammatory cytokine immune axis may provide new diagnostic or treatment strategies for helminth infection and associated immune-mediated pathology

Psychoneuroimmunologia : nowe spojrzenie na funkcjonowanie układu odpornościowego=Psychoneuroimmunology : a new approach to the function of immunological system

The most recent evidence suggests that the immune system responses are not regulated only by the presence of antigens but they are also influenced by the brain and behavior. It has been known for some time that stressful conditions alter the functioning of the immune system. Despite methodological difficulties in the quantitation of stress, and its association with the onset of illness, the concept of the stress impact on susceptibility to several diseases is widely acknowledged. This paper reviews the effects of stress on the endocrine and central nervous systems and presents the interactions between these systems and the immune response after exposure to stress signals

Polimorfizm genetyczny s-transferaz glutationowych jako czynnik predysponujacy do wystapienia alergii skórnej=Genetic polymorphism of glutathione s-transferase as a factor predisposing to allergic dermatitis

In the inductive phase of contact allergic dermatitis, simple chemical compounds (haptens) produce together with epidermic proteins adducts presented by Langerhans cells to T lymphocytes. Binding to protein carrier is a necessary condition of transforming a low-molecular allergen into immunogenic one and evoking immunological reaction. The production of allergen adducts with proteins is conditioned by the presence of electrophilic groups in their molecules, or their acquiring during biotransformation phase I. Active allergen metabolites undergo further alterations during biotransformation phase II which leads most frequently to the decline in their chemical activity and more rapid excretion from the body. The number of reactive metabolites (reactive allergens) available for producing adducts with proteins keeps the balance between activation and deactivation reactions. Glutathione S-transferases play a particular role in the allergens (or their metabolites) deactivation process in biotransformation phase II. These enzymes catalyse reactions responsible for the declined electrophilic potential of allergens (or their metabolites), and thus for the decrease in the number of allergen molecules able to produce protein covalent bindings (adducts). Glutathione S-transferases, occurring in the human cellular cytoplasm belong to five classes: alpha(GST A), mu(GST M), theta(GST P), pi(GST T) and Z(GST Z), as well as to one class present in microsomes. The study indicated the presence of isoenzymes GST T1 and GST M1 in the skin. Both isoforms participate in the process of low-molecular allergen biotransformation. Carriers of defective genes GST T1 and/or GST M1 are more vulnerable to allergenic effect of some allergens, e.g. thimerosal, which is associated with the absence of or decrease in the activity of isoenzymes GST T1 and GST M1

Potential role of fibroblast-like synoviocytes in joint damage induced by Brucella abortus infection through production and induction of matrix metalloproteinases

Arthritis is one of the most common complications of human brucellosis, but its pathogenic mechanisms have not been elucidated. Fibroblast-like synoviocytes (FLS) are known to be central mediators of joint damage in inflammatory arthritides through the production of matrix metalloproteinases (MMPs) that degrade collagen and of cytokines and chemokines that mediate the recruitment and activation of leukocytes. In this study we show that Brucella abortus infects and replicates in human FLS (SW982 cell line) in vitro and that infection results in the production of MMP-2 and proinflammatory mediators (interleukin-6 [IL-6], IL-8, monocyte chemotactic protein 1 [MCP-1], and granulocyte-macrophage colony-stimulating factor [GM-CSF]). Culture supernatants from Brucella-infected FLS induced the migration of monocytes and neutrophils in vitro and also induced these cells to secrete MMP-9 in a GM-CSF- and IL-6-dependent fashion, respectively. Reciprocally, culture supernatants from Brucella-infected monocytes and neutrophils induced FLS to produce MMP-2 in a tumor necrosis factor alpha (TNF-α)-dependent fashion. The secretion of proinflammatory mediators and MMP-2 by FLS did not depend on bacterial viability, since it was also induced by heat-killed B. abortus (HKBA) and by a model Brucella lipoprotein (L-Omp19). These responses were mediated by the recognition of B. abortus antigens through Toll-like receptor 2. The intra-articular injection of HKBA or L-Omp19 into the knee joint of mice resulted in the local induction of the proinflammatory mediators MMP-2 and MMP-9 and in the generation of a mixed inflammatory infiltrate. These results suggest that FLS, and phagocytes recruited by them to the infection focus, may be involved in joint damage during brucellar arthritis through the production of MMPs and proinflammatory mediators.Fil: Scian, Romina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Barrionuevo, Paula. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Giambartolomei, Guillermo Hernan. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: de Simone, Emilio Adrian. Universidad de Buenos Aires. Facultad de Cs.veterinarias. Catedra de Fisiologia Animal; Argentina. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; ArgentinaFil: Vanzulli, Silvia I.. Academia Nacional de Medicina de Buenos Aires; ArgentinaFil: Fossati, Carlos Alberto. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Baldi, Pablo Cesar. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; ArgentinaFil: Delpino, María Victoria. Consejo Nacional de Investigaciones Cientificas y Tecnicas. Oficina de Coordinacion Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral "Profesor R. A. Margni"; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica; Argentin

Dual TNFα-induced effects on NRF2 mediated antioxidant defence in astrocyte-rich cultures: role of protein kinase activation

Tumor necrosis factor-α (TNFα) is a pleiotropic molecule that can have both protective and detrimental effects in neurodegeneration. Here we have investigated the temporal effects of TNFα on the inducible Nrf2 system in astrocyte-rich cultures by determination of glutathione (GSH) levels, γglutamylcysteine ligase (γGCL) activity, the protein levels of Nrf2, Keap1, the catalytic and modulatory subunit of γGCL (γGCL-C and γGCL-M respectively). Astrocyte-rich cultures were exposed for 24 or 72 h to different concentrations of TNFα. Acute exposure (24 h) of astrocyte-rich cultures to 10 ng/mL of TNFα increased GSH, γGCL activity, the protein levels of γGCL-M, γGCL-C and Nrf2 in parallel with decreased levels of Keap1. Antioxidant responsive element (ARE)-mediated transcription was blocked by inhibitors of ERK1/2, JNK and Akt whereas inactivation of p38 and GSK3β further enhanced transcription. In contrast treatment with TNFα for 72 h decreased components of the Nrf2 system in parallel with an increase of Keap1. Stimulation of the Nrf2 system by tBHQ was intact after 24 h but blocked after 72 h treatment with TNFα. This down-regulation after 72 h correlated with activation of p38 MAPK and GSK3β, since inhibition of these signalling pathways reversed this effect. The upregulation of the Nrf2 system by TNFα (24 h treatment) protected the cells from oxidative stress through elevated γGCL activity whereas the down-regulation (72 h treatment) caused pronounced oxidative toxicity. One of the important implications of the results is that in a situation where Nrf2 is decreased, such as in Alzheimer’s disease, the effect of TNFα is detrimental.Fil: Correa, Fernando Gabriel. University Goteborg; Suecia. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Mallard, Carina. University Goteborg; SueciaFil: Nilsson, Michael. University Goteborg; SueciaFil: Sandberg, Mats. University Goteborg; Sueci

The Immune System in Stroke

Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome. Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infection - similar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches