Quality of Service Networking for High Performance Grid Applications

This paper reports on different efforts to provide quality of service (QoS) Networking to Grid applications done in the context of the MB-NG, GRS and DataTAG EU projects. These are leading edge network research projects involving more that 50 researchers in the UK, Europe and North America, concerned with the development and testing of protocols and standards for the next generation of high speed networks. We have implemented and tested the Differentiated Services Architecture (DiffServ) in a multi-domain, 2.5 Gbits/s network (the first such deployment) defining appropriate Service Level Agreements (SLAs) to be used between administrative domains to guarantee end-to-end Quality of Service. We characterised several hardware implementations of DiffServ and concluded on their appropriateness for several network scenarios. Since current and future Grid applications will have to use modified mechanisms of congestion control we have evaluated old and new TCP implementations over a Differentiated Services Networks. These quality of service tests have also included innovative MPLS (Multi-Protocol Label Switching) experiments to establish guaranteed bandwidth connections to Grid applications in a fast and efficient way. We have also developed a software based bandwidth broker architecture for Grids based on IETF standards which allows applications to transparently request dynamic and advanced reservations and implemented it in a real experimental network. We finally report on experiences delivering Quality of Service networking to high performance applications like Particle Physics data transfer and High Performance Computation. This includes quantitative results on the performance improvements that QoS brought to real data transfers in the context of High Performance Computing.     

Formal methods integration for the specification of dependable distributed systems

This paper describes a real-world case study in the specification and analysis of dependable distributed systems. The case study is an automated transport system with safety requirements. In order to manage the complexity of the problem of specifying the dynamic behavior of the whole system, a compositional approach is used, based on the integration of the trace logic of the Communicating Sequential Processes (CSP) theory, and stochastic Petri nets (SPNs). It is argued that the integration of different formal methods is a useful approach in the definition of practical engineering methodologies for the specification, design and analysis of complex dependable distributed systems.     

An Autonomous Spacecraft Agent Prototype

This paper describes the New Millennium Remote Agent (NMRA) architecture for autonomous spacecraft control systems. The architecture supports challenging requirements of the autonomous spacecraft domain not usually addressed in mobile robot architectures, including highly reliable autonomous operations over extended time periods in the presence of tight resource constraints, hard deadlines, limited observability, and concurrent activity. A hybrid architecture, NMRA integrates traditional real-time monitoring and control with heterogeneous components for constraint-based planning and scheduling, robust multi-threaded execution, and model-based diagnosis and reconfiguration. Novel features of this integrated architecture include support for robust closed-loop generation and execution of concurrent temporal plans and a hybrid procedural/deductive executive.We implemented a prototype autonomous spacecraft agent within the architecture and successfully demonstrated the prototype in the context of a challenging autonomous mission scenario on a simulated spacecraft. As a result of this success, the integrated architecture has been selected to fly as an autonomy experiment on Deep Space One (DS-1), the first flight of NASA';s New Millennium Program (NMP), which will launch in 1998. It will be the first AI system to autonomously control an actual spacecraft.     

Scale-effects on mean and standard deviation of the mechanical properties of condensed matter: an energy-based unified approach

The size effects on the mean values of the mechanical properties of condensed matter and on the related variances are analysed by means of a unified approach based on the multiscale character of energy dissipation. In particular, the scaling law for fragmentation energy density is obtained taking into account the self-similarity of fragments. It is based on a generalization of the three classical comminution laws that has been performed to evaluate the energy dissipation, computing volume and surface area of the particles for one- two- and three-dimensional fragmented objects. The result is general and can be applied to different fractal energy dissipation mechanisms, e.g., plasticity. Based on this approach, the scaling laws for mean and standard deviation values of the main mechanical properties of materials can be derived, like Young's and shear elastic moduli, ultimate normal and shear stresses and strains, fracture energy and toughness.     

Scaling of energy dissipation in crushing and fragmentation: a fractal and statistical analysis based on particle size distribution

An extensive experimental investigation on concrete specimens under crushing and fragmentation over a large scale range (1:10) – exploring even very small specimen dimensions (1 cm) – was carried out to evaluate the influence of fragment size distribution on energy density dissipation and related size effect. To obtain a statistically significant fragment production as well as the total energy dissipated in a given specimen, the experimental procedure was unusually carried out up to a strain of approximately –95%, practically corresponding to the initial fragment compaction between the loading platens. The experimental fragment analysis suggests a fractal law for the distribution in particle size; this simply means that fragments derived from a given specimen appear geometrically self-similar at each observation scale. In addition, clear size effects on dissipated energy density are experimentally observed. Fractal concepts permit to quantify the correlation between fragment size distribution and size effect on dissipated energy density, the latter being governed by the total surface area of produced fragments. The experimental results agree with the proposed multi-scale interpretation satisfactorily.     

Reliable regulation in centralized control systems

This paper addresses the design of a reliable control system for a linear, asymptotically stable plant. Specifically, the considered problem consists in finding a regulator which guarantees asymptotic stability, signal tracking and disturbance rejection when all the instrumentation is operational, and ensures that these properties are preserved, to the maximum possible extent, when an arbitrary number of sensors and/or actuators faults occur, that is, some of the feedback loops open. With reference to a centralized control structure and exogenous signals with multiple poles on the imaginary axis, the paper supplies a necessary and sufficient condition for the problem to admit a solution, and a possible least order regulator.     

PCSK9 Affects Astrocyte Cholesterol Metabolism and Reduces Neuron Cholesterol Supplying In Vitro: Potential Implications in Alzheimer’s Disease

The Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) involvement in Alzheimer’s disease (AD) is poorly investigated. We evaluated the in vitro PCSK9 modulation of astrocyte cholesterol metabolism and neuronal cholesterol supplying, which is fundamental for neuronal functions. Moreover, we investigated PCSK9 neurotoxic effects. In human astrocytoma cells, PCSK9 reduced cholesterol content (−20%; p < 0.05), with a greater effect in presence of beta amyloid peptide (Aβ) (−37%; p < 0.01). PCSK9 increased cholesterol synthesis and reduced the uptake of apoE-HDL-derived cholesterol (−36%; p < 0.0001), as well as the LDL receptor (LDLR) and the apoE receptor 2 (ApoER2) expression (−66% and −31%, respectively; p < 0.01). PCSK9 did not modulate ABCA1- and ABCG1-cholesterol efflux, ABCA1 levels, or membrane cholesterol. Conversely, ABCA1 expression and activity, as well as membrane cholesterol, were reduced by Aβ (p < 0.05). In human neuronal cells, PCSK9 reduced apoE-HDL-derived cholesterol uptake (−41%; p < 0.001) and LDLR/apoER2 expression (p < 0.05). Reduced cholesterol internalization occurred also in PCSK9-overexpressing neurons exposed to an astrocyte-conditioned medium (−39%; p < 0.001). PCSK9 reduced neuronal cholesterol content overall (−29%; p < 0.05) and increased the Aβ-induced neurotoxicity (p < 0.0001). Our data revealed an interfering effect of PCSK9, in cooperation with Aβ, on brain cholesterol metabolism leading to neuronal cholesterol reduction, a potentially deleterious effect. PCSK9 also exerted a neurotoxic effect, and thus represents a potential pharmacological target in AD.     

Bi-Allelic Mutations in Zebrafish pank2 Gene Lead to Testicular Atrophy and Perturbed Behavior without Signs of Neurodegeneration

Coenzyme A (CoA) is an essential cofactor in all living organisms, being involved in a large number of chemical reactions. Sequence variations in pantothenate kinase 2 (PANK2), the first enzyme of CoA biosynthesis, are found in patients affected by Pantothenate Kinase Associated Neurodegeneration (PKAN), one of the most common forms of neurodegeneration, with brain iron accumulation. Knowledge about the biochemical and molecular features of this disorder has increased a lot in recent years. Nonetheless, the main culprit of the pathology is not well defined, and no treatment option is available yet. In order to contribute to the understanding of this disease and facilitate the search for therapies, we explored the potential of the zebrafish animal model and generated lines carrying biallelic mutations in the pank2 gene. The phenotypic characterization of pank2-mutant embryos revealed anomalies in the development of venous vascular structures and germ cells. Adult fish showed testicular atrophy and altered behavioral response in an anxiety test but no evident signs of neurodegeneration. The study suggests that selected cell and tissue types show a higher vulnerability to pank2 deficiency in zebrafish. Deciphering the biological basis of this phenomenon could provide relevant clues for better understanding and treating PKAN.