STRATEGY MANAGEMENT IN A MULTI-AGENT SYSTEM USING NEURAL NETWORKS FOR INDUCTIVE AND EXPERIENCE-BASED LEARNING

Intelligent agents and multi-agent systems prove to be a promising paradigm for solving problems in a distributed, cooperative way. Neural networks are a classical solution for ensuring the learning ability of agents. In this paper, we analyse a multi-agent system where agents use different training algorithms and different topologies for their neural networks, which they use to solve classification and regression problems provided by a user. Out of the three training algorithms under investigation, Backpropagation, Quickprop and Rprop, the first demonstrates inferior performance to the other two when considered in isolation. However, by optimizing the strategy of accepting or rejecting tasks, Backpropagation agents succeed in outperforming the other types of agents in terms of the total utility gained. This strategy is learned also with a neural network, by processing the results of past experiences. Therefore, we show a way in which agents can use neural network models for both external purposes and internal ones.agents, learning, neural networks, strategy management multi-agent system.

The Fusion Loops of the Initial Prefusion Conformation of Herpes Simplex Virus 1 Fusion Protein Point Toward the Membrane

All enveloped viruses, including herpesviruses, must fuse their envelope with the host membrane to deliver their genomes into target cells, making this essential step subject to interference by antibodies and drugs. Viral fusion is mediated by a viral surface protein that transits from an initial prefusion conformation to a final postfusion conformation. Strikingly, the prefusion conformation of the herpesvirus fusion protein, gB, is poorly understood. Herpes simplex virus (HSV), a model system for herpesviruses, causes diseases ranging from mild skin lesions to serious encephalitis and neonatal infections. Using cryo-electron tomography and subtomogram averaging, we have characterized the structure of the prefusion conformation and fusion intermediates of HSV-1 gB. To this end, we have set up a system that generates microvesicles displaying full-length gB on their envelope. We confirmed proper folding of gB by nondenaturing electrophoresis-Western blotting with a panel of monoclonal antibodies (MAbs) covering all gB domains. To elucidate the arrangement of gB domains, we labeled them by using (i) mutagenesis to insert fluorescent proteins at specific positions, (ii) coexpression of gB with Fabs for a neutralizing MAb with known binding sites, and (iii) incubation of gB with an antibody directed against the fusion loops. Our results show that gB starts in a compact prefusion conformation with the fusion loops pointing toward the viral membrane and suggest, for the first time, a model for gB’s conformational rearrangements during fusion. These experiments further illustrate how neutralizing antibodies can interfere with the essential gB structural transitions that mediate viral entry and therefore infectivity

Mechanism of Neutralization of Herpes Simplex Virus by Antibodies Directed at the Fusion Domain of Glycoprotein B

Glycoprotein B (gB), the fusogen of herpes simplex virus (HSV), is a class III fusion protein with a trimeric ectodomain of known structure for the postfusion state. Seen by negative-staining electron microscopy, it presents as a rod with three lobes (base, middle, and crown). gB has four functional regions (FR), defined by the physical location of epitopes recognized by anti-gB neutralizing monoclonal antibodies (MAbs). Located in the base, FR1 contains two internal fusion loops (FLs) and is the site of gB-lipid interaction (the fusion domain). Many of the MAbs to FR1 are neutralizing, block cell-cell fusion, and prevent the association of gB with lipid, suggesting that these MAbs affect FL function. Here we characterize FR1 epitopes by using electron microscopy to visualize purified Fab-gB ectodomain complexes, thus confirming the locations of several epitopes and localizing those of MAbs DL16 and SS63. We also generated MAb-resistant viruses in order to localize the SS55 epitope precisely. Because none of the epitopes of our anti-FR1 MAbs mapped to the FLs, we hyperimmunized rabbits with FL1 or FL2 peptides to generate polyclonal antibodies (PAbs). While the anti-FL1 PAb failed to bind gB, the anti-FL2 PAb had neutralizing activity, implying that the FLs become exposed during virus entry. Unexpectedly, the anti-FL2 PAb (and the anti-FR1 MAbs) bound to liposome-associated gB, suggesting that their epitopes are accessible even when the FLs engage lipid. These studies provide possible mechanisms of action for HSV neutralization and insight into how gB FR1 contributes to viral fusion. IMPORTANCE: For herpesviruses, such as HSV, entry into a target cell involves transfer of the capsid-encased genome of the virus to the target cell after fusion of the lipid envelope of the virus with a lipid membrane of the host. Virus-encoded glycoproteins in the envelope are responsible for fusion. Antibodies to these glycoproteins are important biological tools, providing a way of examining how fusion works. Here we used electron microscopy and other techniques to study a panel of anti-gB antibodies. Some, with virus-neutralizing activity, impair gB-lipid association. We also generated a peptide antibody against one of the gB fusion loops; its properties provide insight into the way the fusion loops function as gB transits from its prefusion form to an active fusogen

The mucous cyst, a rare and delayed complication after rhinoplasty

Rhinoplasty is frequently performed worldwide, and patients and surgeons both expect good cosmetic results without any deformity recurrence. We report a rare case of mucous cyst occurred after post-traumatic rhinoseptoplasty. Observation A 27-year old woman presented a median mass of the nose root 7 years after prior rhinoseptoplasty. Investigations showed a subcutaneous lesion of 10.5 × 24.5 mm. The surgery consisted on an external rhinoplasty allowing cyst removal, bilateral osteotomies and reconstruction of the nasal dorsum by deep temporal fascia graft. Histological examination confirmed the diagnosis of begnin mucous cyst. No recurrence was observed at 1-year follow-up. Discussion Mucous cyst post rhinoplasty is rare and is probably due to accidental mucosal material implantation into the subcutaneous plane during rhinoplasty. This complication can be avoided by adequate infiltration and hydrodissection, careful dissection, and avoidance of unnecessary trauma during osteotomies

Teleparallel Lagrange Geometry and a Unified Field Theory

In this paper, we construct a field theory unifying gravity and electromagnetism in the context of Extended Absolute Parallelism (EAP-) geometry. This geometry combines, within its structure, the geometric richness of the tangent bundle and the mathematical simplicity of Absolute Parallelism (AP-) geometry. The constructed field theory is a generalization of the Generalized Field Theory (GFT) formulated by Mikhail and Wanas. The theory obtained is purely geometric. The horizontal (resp. vertical) field equations are derived by applying the Euler-Lagrange equations to an appropriate horizontal (resp. vertical) scalar Lagrangian. The symmetric part of the resulting horizontal (resp. vertical) field equations gives rise to a generalized form of Einstein's field equations in which the horizontal (resp. vertical) energy-momentum tensor is purely geometric. The skew-symmetric part of the resulting horizontal (resp. vertical) field equations gives rise to a generalized form of Maxwell equations in which the electromagnetic field is purely geometric. Some interesting special cases, which reveal the role of the nonlinear connection in the obtained field equations, are examined. Finally, the condition under which our constructed field equations reduce to the GFT is explicitly established.Comment: Latex file, 33 page

Nonholonomic Ricci Flows, Exact Solutions in Gravity, and Symmetric and Nonsymmetric Metrics

We provide a proof that nonholonomically constrained Ricci flows of (pseudo) Riemannian metrics positively result into nonsymmetric metrics (as explicit examples, we consider flows of some physically valuable exact solutions in general relativity). There are constructed and analyzed three classes of solutions of Ricci flow evolution equations defining nonholonomic deformations of Taub NUT, Schwarzschild, solitonic and pp--wave symmetric metrics into nonsymmetric ones.Comment: latex2e, 12pt, 40 pages, version 2 with minor modifications, to be published in Int. J. Theor. Phy

Structural characteristics and antiviral activity of multiple peptides derived from MDV glycoproteins B and H

<p>Abstract</p> <p>Background</p> <p>Marek's disease virus (MDV), which is widely considered to be a natural model of virus-induced lymphoma, has the potential to cause tremendous losses in the poultry industry. To investigate the structural basis of MDV membrane fusion and to identify new viral targets for inhibition, we examined the domains of the MDV glycoproteins gH and gB.</p> <p>Results</p> <p>Four peptides derived from the MDV glycoprotein gH (gHH1, gHH2, gHH3, and gHH5) and one peptide derived from gB (gBH1) could efficiently inhibit plaque formation in primary chicken embryo fibroblast cells (CEFs) with 50% inhibitory concentrations (IC₅₀) of below 12 μM. These peptides were also significantly able to reduce lesion formation on chorioallantoic membranes (CAMs) of infected chicken embryos at a concentration of 0.5 mM in 60 μl of solution. The HR2 peptide from Newcastle disease virus (NDVHR2) exerted effects on MDV specifically at the stage of virus entry (i.e., in a cell pre-treatment assay and an embryo co-treatment assay), suggesting cross-inhibitory effects of NDV HR2 on MDV infection. None of the peptides exhibited cytotoxic effects at the concentrations tested. Structural characteristics of the five peptides were examined further.</p> <p>Conclusions</p> <p>The five MDV-derived peptides demonstrated potent antiviral activity, not only in plaque formation assays in vitro, but also in lesion formation assays in vivo. The present study examining the antiviral activity of these MDV peptides, which are useful as small-molecule antiviral inhibitors, provides information about the MDV entry mechanism.</p

Herpesvirus Glycoproteins Undergo Multiple Antigenic Changes before Membrane Fusion

Herpesvirus entry is a complicated process involving multiple virion glycoproteins and culminating in membrane fusion. Glycoprotein conformation changes are likely to play key roles. Studies of recombinant glycoproteins have revealed some structural features of the virion fusion machinery. However, how the virion glycoproteins change during infection remains unclear. Here using conformation-specific monoclonal antibodies we show in situ that each component of the Murid Herpesvirus-4 (MuHV-4) entry machinery—gB, gH/gL and gp150—changes in antigenicity before tegument protein release begins. Further changes then occurred upon actual membrane fusion. Thus virions revealed their final fusogenic form only in late endosomes. The substantial antigenic differences between this form and that of extracellular virions suggested that antibodies have only a limited opportunity to block virion membrane fusion

Biophysical Characterization and Membrane Interaction of the Two Fusion Loops of Glycoprotein B from Herpes Simplex Type I Virus

The molecular mechanism of entry of herpesviruses requires a multicomponent fusion system. Cell invasion by Herpes simplex virus (HSV) requires four virally encoded glycoproteins: namely gD, gB and gH/gL. The role of gB has remained elusive until recently when the crystal structure of HSV-1 gB became available and the fusion potential of gB was clearly demonstrated. Although much information on gB structure/function relationship has been gathered in recent years, the elucidation of the nature of the fine interactions between gB fusion loops and the membrane bilayer may help to understand the precise molecular mechanism behind herpesvirus-host cell membrane fusion. Here, we report the first biophysical study on the two fusion peptides of gB, with a particular focus on the effects determined by both peptides on lipid bilayers of various compositions. The two fusion loops constitute a structural subdomain wherein key hydrophobic amino acids form a ridge that is supported on both sides by charged residues. When used together the two fusion loops have the ability to significantly destabilize the target membrane bilayer, notwithstanding their low bilayer penetration when used separately. These data support the model of gB fusion loops insertion into cholesterol enriched membranes