TGF-beta-induced apoptosis of cerebellar granule neurons is prevented by depolarization

The regulation of programmed cell death in the developing nervous system involves target-derived survival factors, afferent synaptic activity, and hormone- and cytokine-dependent signaling. Cultured immature cerebellar granule neurons die by apoptosis within several days in vitro unless maintained in depolarizing (high) concentrations of potassium (25 mM K+). Here we report that transforming growth factors (TGF)-beta1, -beta2, and -beta3 accelerate apoptosis of these neurons when maintained in physiological (low) K+ medium (5mM K+) as assessed by measures of viability, quantitative DNA fragmentation, and nuclear morphology. TGF-beta-induced apoptosis of these neurons is not blocked by CNTF and LIF, cytokines that enhance neuronal survival when applied alone, or by IGF-I, which prevents apoptosis upon potassium withdrawal. In contrast, neurons that differentiate in high K+ medium for several days in vitro acquire resistance to TGF-beta-mediated cell death. Granule neurons maintained in either low or high K+ medium produce latent, but not bioactive, TGF-beta1 and -beta2. Because neutralizing TGF-beta antibodies fail to augment survival of low K+ neurons, the cerebellar neurons are apparently unable to activate latent TGF-beta. Thus, apoptosis of low K+ neurons is not attributable to endogenous production of TGF-beta. Taken together, our data suggest that TGF-beta may limit the expansion of postmitotic neuronal precursor populations by promoting their apoptosis but may support survival of those neurons that have maturated, differentiated, and established supportive synaptic connectivity.     

Symmetry properties and bifurcation analysis of a class of periodically forced chemical reactors

In this work, we discuss how periodic forcing may induce symmetry properties into mathematical models of chemical reactors. We define a class of reactors subjected to discontinuous periodic forcing, and show that all the reactors belonging to this class have spatio-temporal symmetry. This symmetry and its influence on the possible bifurcation scenarios are discussed. The bifurcation analysis is carried out with suitable discrete systems that exploit a property of the Poincaré map. In fact, it is shown that the spatio-temporal symmetry induced by the forcing makes the Poincaré map of the continuous system an iterate of another map. On this basis, a technique to implement parameter continuation methods is proposed. With such a technique, it is also possible to characterize symmetric and nonsymmetric regimes and unstable limit sets otherwise undetected with “bruteforce” approaches. Examples for reverseflow reactors and networks of n-reactors with periodically switched feed and discharge positions are presented.     

Active state estimation for nonlinear systems: a neural approximation approach.

In this paper, we consider the problem of actively providing an estimate of the state of a stochastic dynamic system over a (possibly long) finite time horizon. The active estimation problem (AEP) is formulated as a stochastic optimal control one, in which the minimization of a suitable uncertainty measure is carried out. Toward this end, the use of the Renyi entropy as an information measure is proposed and motivated. A neural control scheme, based on the application of the extended Ritz method (ERIM) and on the use of a Gaussian sum filter (GSF), is then presented. Simulation results show the effectiveness of the proposed approach.     

Large band simulation of the wind speed for real time wind turbine simulators

In this paper, the authors propose two modeling procedures for wind speed simulation. These procedures could be implemented on the structure of a wind turbine simulator during studies concerning stand-alone or hybrid wind systems. The evolution of a horizontal wind speed has been synthesized taking into account two components. The medium- and long-term component is described by a power spectrum associated to a specific site. The turbulence component is assumed to be dependent on the medium- and long-term wind speed evolution. It is considered as a nonstationary process. Two simulation methods for this component, using rational and nonrational filters are proposed. In both procedures, the turbulence model is defined by two parameters, which are either obtained experimentally, or adopted a priori, according to information from the considered site. Numerical results and implementation aspects are also discussed.     

Timing and causality in process algebra

 There has been considerable controversy in concurrency theory between the ‘interleaving’ and ‘true concurrency’ schools. The former school advocates associating a transition system with a process which captures concurrent execution via the interleaving of occurrences; the latter adopts more complex semantic structures to avoid reducing concurrency to interleaving. In this paper we show that the two approaches are not irreconcilable. We define a timed process algebra where occurrences are associated with intervals of time, and give it a transition system semantics. This semantics has many of the advantages of the interleaving approach; the algebra admits an expansion theorem, and bisimulation semantics can be used as usual. Our transition systems, however, incorporate timing information, and this enables us to express concurrency: merely adding timing appropriately generalises transition systems to asynchronous transition systems, showing that time gives a link between true concurrency and interleaving. Moreover, we can provide a complete axiomatisation of bisimulation for our algebra; a result that is often problematic in a timed setting. Another advantage of incorporating timing information into the calculus is that it allows a particularly simple definition of action refinement; this we present. The paper concludes with a comparison of the equivalence we present with those in the literature, and an example system specification in our formalism. Received December 20, 1993/February 23, 1995     

DYRE: a DYnamic REconfigurable solution to increase GPGPU’s reliability

The Journal of Supercomputing - General-purpose graphics processing units (GPGPUs) are extensively used in high-performance computing. However, it is well known that these devices’...     

Structural Investigation and Molecular Modeling Studies of Strobilurin-Based Fungicides Active against the Rice Blast Pathogen Pyricularia oryzae

The increasing emergence of fungicide-resistant pathogens requires urgent solutions for crop disease management. Here, we describe a structural investigation of new fungicides obtained by combining strobilurin and succinate dehydrogenase inhibitor pharmacophores. We identified compounds endowed with very good activity against wild-type Pyricularia oryzae, combined in some cases with promising activity against strobilurin-resistant strains. The first three-dimensional model of P. oryzae cytochrome bc1 complex containing azoxystrobin as a ligand was developed. The model was validated with a set of commercially available strobilurins, and it well explains both the resistance mechanism to strobilurins mediated by the mutation G143A and the activity of metyltetraprole against strobilurin-resistant strains. The obtained results shed light on the key recognition determinants of strobilurin-like derivatives in the cytochrome bc1 active site and will guide the further rational design of new fungicides able to overcome resistance caused by G143A mutation in the rice blast pathogen.     

Proinflammatory Interleukin-33 Induces Dichotomic Effects on Cell Proliferation in Normal Gastric Epithelium and Gastric Cancer

Interleukin (IL)-33 is a member of the interleukin (IL)-1 family of cytokines linked to the development of inflammatory conditions and cancer in the gastrointestinal tract. This study is designed to investigate whether IL-33 has a direct effect on human gastric epithelial cells (GES-1), the human gastric adenocarcinoma cell line (AGS), and the gastric carcinoma cell line (NCI-N87) by assessing its role in the regulation of cell proliferation, migration, cell cycle, and apoptosis. Cell cycle regulation was also determined in ex vivo gastric cancer samples obtained during endoscopy and surgical procedures. Cell lines and tissue samples underwent stimulation with rhIL-33. Proliferation was assessed by XTT and CFSE assays, migration by wound healing assay, and apoptosis by caspase 3/7 activity assay and annexin V assay. Cell cycle was analyzed by means of propidium iodine assay, and gene expression regulation was assessed by RT-PCR profiling. We found that IL-33 has an antiproliferative and proapoptotic effect on cancer cell lines, and it can stimulate proliferation and reduce apoptosis in normal epithelial cell lines. These effects were also confirmed by the analysis of cell cycle gene expression, which showed a reduced expression of pro-proliferative genes in cancer cells, particularly in genes involved in G0/G1 and G2/M checkpoints. These results were confirmed by gene expression analysis on bioptic and surgical specimens. The aforementioned results indicate that IL-33 may be involved in cell proliferation in an environment- and cell-type-dependent manner.