A unified high-level Petri net formalism for time-critical systems

The authors introduce a high-level Petri net formalism-environment/relationship (ER) nets-which can be used to specify control, function, and timing issues. In particular, they discuss how time can be modeled via ER nets by providing a suitable axiomatization. They use ER nets to define a time notation that is shown to generalize most time Petri-net-based formalisms which appeared in the literature. They discuss how ER nets can be used in a specification support environment for a time-critical system and, in particular, the kind of analysis supported     

Program load adaptive voltage generator for flash memories

This paper describes a program load voltage generator for flash memories. It is based on an adaptive feedback loop which senses the current delivered to the memory cells during programming and adjusts the output voltage accordingly to compensate for the voltage drop caused by the programming current across the bit-line select transistors. The proposed circuit (silicon area=0.065 mm²) was integrated in a 0.8-μm CMOS 4 Mb flash memory device (0.6 μm in the matrix). Experimental evaluations showed that very effective compensation is achieved, with bit-line voltage kept at the desired value during the whole programming operation. A spread as small as 70 mV was measured between the single-bit and 16-b programming cases     

On requirement verification for evolving Statecharts specifications

Software development processes have been evolving from rigid, pre-specified, and sequential to incremental, and iterative. This evolution has been dictated by the need to accommodate evolving user requirements and reduce the delay between design decision and feedback from users. Formal verification techniques, however, have largely ignored this evolution and even when they made enormous improvements and found significant uses in practice, like in the case of model checking, they remained confined into the niches of safety-critical systems. Model checking verifies if a system’s model \(\mathcal{M}\) satisfies a set of requirements, formalized as a set of logic properties \(\Phi\) . Current model-checking approaches, however, implicitly rely on the assumption that both the complete model \(\mathcal{M}\) and the whole set of properties \(\Phi\) are fully specified when verification takes place. Very often, however, \(\mathcal{M}\) is subject to change because its development is iterative and its definition evolves through stages of incompleteness, where alternative design decisions are explored, typically to evaluate some quality trade-offs. Evolving systems specifications of this kind ask for novel verification approaches that tolerate incompleteness and support incremental analysis of alternative designs for certain functionalities. This is exactly the focus of this paper, which develops an incremental model-checking approach for evolving Statecharts. Statecharts have been chosen both because they are increasingly used in practice natively support model refinements.     

SEON: a pyramid of ontologies for software evolution and its applications

The Semantic Web provides a standardized, well-established framework to define and work with ontologies. It is especially apt for machine processing. However, researchers in the field of software evolution have not really taken advantage of that so far. In this paper, we address the potential of representing software evolution knowledge with ontologies and Semantic Web technology, such as Linked Data and automated reasoning. We present Seon, a pyramid of ontologies for software evolution, which describes stakeholders, their activities, artifacts they create, and the relations among all of them. We show the use of evolution-specific ontologies for establishing a shared taxonomy of software analysis services, for defining extensible meta-models, for explicitly describing relationships among artifacts, and for linking data such as code structures, issues (change requests), bugs, and basically any changes made to a system over time. For validation, we discuss three different approaches, which are backed by Seon and enable semantically enriched software evolution analysis. These techniques have been fully implemented as tools and cover software analysis with web services, a natural language query interface for developers, and large-scale software visualization.     

Host Restriction Factors Modulating HIV Latency and Replication in Macrophages

In addition to CD4⁺ T lymphocytes, myeloid cells and, particularly, differentiated macrophages are targets of human immunodeficiency virus type-1 (HIV-1) infection via the interaction of gp120Env with CD4 and CCR5 or CXCR4. Both T cells and macrophages support virus replication, although with substantial differences. In contrast to activated CD4⁺ T lymphocytes, HIV-1 replication in macrophages occurs in nondividing cells and it is characterized by the virtual absence of cytopathicity both in vitro and in vivo. These general features should be considered in evaluating the role of cell-associated restriction factors aiming at preventing or curtailing virus replication in macrophages and T cells, particularly in the context of designing strategies to tackle the viral reservoir in infected individuals receiving combination antiretroviral therapy. In this regard, we will here also discuss a model of reversible HIV-1 latency in primary human macrophages and the role of host factors determining the restriction or reactivation of virus replication in these cells.     

X-ray study of heterogeneous nucleation of dislocations in P-diffused silicon

X-ray topography was employed in order to study the nucleation of dislocation lines at surface heterogeneities in (111) Si wafers during phosphorus diffusion. Star-like patterns of 60° dislocations nucleated at phosphorus decorated surface defects were observed and were proved to be localized within the diffused layer. The analysis of the X-ray contrast and the results of some heating experiments suggested a mechanism of growth of the dislocation lines which was based on climb processes.     

Pharmacological modulation of fatty acid desaturation and of cholesterol biosynthesis in THP-1 cells

In THP-1 cells, simvastatin decreases, in a concentration-dependent manner, cholesterol synthesis and increases linoleic acid (LA) conversion to its long-chain derivatives, in particular to arachidonic acid, activating Δ6 and Δ5 fatty acid (FA) desaturases. The intermediates in cholesterol synthesis, mevalonate and geranylgeraniol, partially reverse the effects of simvastatin on the LA conversion. The aims of this work were to evaluate: (i) the correlation between cholesterol synthesis and desaturase activity and (ii) the possible involvement of protein isoprenylation in desaturase activity, assessed through pharmacological treatments. THP-1 cells were incubated with [1-¹⁴C]LA or with [1-¹⁴C]di-homo-γ-linolenic acid (DHGLA) and treated with simvastatin or with curcumin and nicardipine, inhibitors of desaturases. Curcumin was more active than nicardipine in inhibiting LA and DHGLA conversion: 20 μM curcumin, alone or with simvastatin, totally inhibited Δ6 and Δ5 desaturation steps; 10 μM nicardipine only partially inhibited the enzymes, being more active on Δ5 desaturase. Simvastatin treatment decreased the incorporation of acetate in cholesterol (−93.8%) and cholesterol esters (−70.2%), as expected. Curcumin and nicardipine also decreased cholesterol synthesis and potentiated simvastatin. Finally, the isoprenylation inhibitors (perillic acid and GGTI-286) neither affected the conversion of LA nor inhibited the Δ5 desaturase activity. In conclusion, our results indicate that there is no direct relationship between cholesterol synthesis and desaturase activity. In fact, simvastatin decreased cholesterol synthesis and enhanced LA conversion (mainly Δ5 desaturation), whereas curcumin and nicardipin decreased Δ5 desaturation, with a limited effect on cholesterol synthesis.     

Validation of web service compositions

Web services support software architectures that can evolve dynamically. In particular, in this paper the focus is on architectures where services are composed (orchestrated) through a workflow described in the business process execution language (BPEL). It is assumed that the resulting composite service refers to external services through assertions that specify their expected functional and non-functional properties. On the basis of these assertions, the composite service may be verified at design time by checking that it ensures certain relevant properties. Because of the dynamic nature of Web services and the multiple stakeholders involved in their provision, however, the external services may evolve dynamically, and even unexpectedly. They may become inconsistent with respect to the assertions against which the workflow was verified during development. As a consequence, validation of the composition must extend to run time. In this work, an assertion language, called assertion language for BPEL process interactions (ALBERT), is introduced; it can be used to specify both functional and non-functional properties. An environment which supports design-time verification of ALBERT assertions for BPEL workflows via model checking is also described. At run time, the assertions can be turned into checks that a software monitor performs on the composite system to verify that it continues to guarantee its required properties. A TeleAssistance application is provided as a running example to illustrate our validation framework.     

Biological evaluation of two anomeric glucose analogues iodinated in position 6

Two anomeric analogues of glucose labelled with 123 iodine in position 6, proposed as tracers of glucose transport in vivo, have been synthesized: alpha- and beta-methyl-6-deoxy-6-iodo-D-glucopyranoside (alpha MDIG and beta MDIG). The aim of this study was to determine whether these molecules interact with the glucose transporter and whether they could be used as tracers of glucose transport in vivo. The biodistribution of alpha MDIG and beta MDIG was studied in the mouse in vivo. To determine if these two anomers enter the cell via the glucose transporter, their uptake was measured in isolated perfused rat hearts, in human erythrocytes in suspension, and in cardiomyocytes of neonatal rat in culture. Both alpha MDIG and beta MDIG had similar repartitions in the mouse: myocardial uptake averaged 7% of the injected dose/g of organ at 2 min postinjection and alpha MDIG competed with D-glucose to enter the cells. Insulin produced a 123% increase of its uptake in isolated perfused rat hearts and a 100% increase in cardiomyocytes of neonatal rat in culture. alpha MDIG uptake was lowered in the presence of glucose transport inhibitors in each experimental model. An interaction between beta MDIG and glucose transporters was observed only in human erythrocytes in suspension. Only alpha MDIG interacts with the glucose transporter, and thus could be used to estimate glucose transport in vivo.