On the ontological expressiveness of information systems analysis and design grammars

Abstract. Information systems analysis and design (ISAD) methodologies provide facilities for describing existing or conceived real-world systems. These facilities are ontologically expressive if they are capable of describing all real-world phenomena completely and clearly. In this paper we formally examine the notion of the ontological expressiveness of a grammar and discuss some of its implications for the design and use of ISAD methodologies. We identify some generic ways in which ontological expressiveness may be undermined in a grammar and some potential consequences of these violations. We also examine ontological expressiveness within the context of some other desirable features that might be considered in the design of ISAD methodologies.     

Dynamic effects in hot-carrier degradation relevant for CMOS operation

We describe different dynamic degradation effects in n- and p-MOSFETs as they are clearly proven and generally accepted to date. It turns out that they are connected with time constants in the oxide and at the interface and that time constants related to the device operation are too short to be relevant in this context. The effects are detrapping of fixed charges, the slow movement of holes in the oxide, an enhanced-degradation effect caused by alternating voltage conditions, during dynamic stress, and a post-stress interface state formation effect in nitride passivated n-MOSFETs. Furthermore, we discuss the relevance of those effects, under different operation conditions, finding that the fast non-stationary effects are of little significance. Only the “slow” effects, with time constants of seconds and above, play a role in reliability issues of MOSFETs.     

Meningitis after acute Borrelia burgdorferi infection in HIV infection

HISTORY AND CLINICAL FINDINGS: A 39-year-old HIV positive patient developed myalgia, headache and cough 4 weeks after a tick bite. His temperature was 37.4 degrees C and a circular pale erythema was noted over the left lower leg. INVESTIGATIONS: C-reactive protein was raised to 120 mg/l, white blood cell count was 5860/microliter, CD4-lymphocyte count 250/microliter. The chest radiogram showed pneumonitic infiltration in the left lower lobe. There were IgM antibodies against Borrelia burgdorferi. TREATMENT AND COURSE: Left lower lobe pneumonia and chronic erythema migrans were diagnosed and he was given oral azithromycin (500 mg on the first day and 250 mg for 4 days). The pneumonia cleared up, but 2 weeks later he developed symptoms of meningitis (496 cells per microliter, 87% lymphocytes, positive Borrelia burgdorferi antibody titer), which quickly and lastingly responded to ceftriaxon (2 g daily by brief infusion for 14 days). CONCLUSION: This immune-compromised HIV-infected patient developed disseminated borreliosis with CNS involvement 2 weeks after the occurrence of chronic erythema migrans. The initial treatment of the latter with azithromycin was unable to prevent the meningitis. It is unlikely that there was a causal connection between the borreliosis and the pneumonia.     

Activation of the anti-cancer drug ifosphamide by rat liver microsomal P450 enzymes

The NADPH-dependent metabolism of ifosphamide catalyzed by rat liver microsomes was investigated in order to identify individual P450 enzymes that activate this anti-cancer drug and to ascertain their relationship to the P450 enzymes that activate the isomeric drug cyclophosphamide. Pretreatment of rats with phenobarbital or clofibrate increased by up to 8-fold the activation of both ifosphamide and cyclophosphamide catalyzed by isolated liver microsomes. Studies using P450 form-selective inhibitory antibodies demonstrated that constitutively expressed P450s belonging to subfamily 2C (forms 2C11/2C6) make significant contributions to the activation of both oxazaphosphorines in uninduced male rat liver microsomes, while the phenobarbital-inducible P450 2B1 was shown to be a major catalyst of these activations in phenobarbital-induced microsomes. Pretreatment of rats with dexamethasone increased liver microsomal activation of ifosphamide approximately 6-fold without a corresponding effect on cyclophosphamide activation rates. Ifosphamide activation catalyzed by dexamethasone-induced liver microsomes was minimally inhibited by anti-P450 2B or anti-P450 2C antibodies, but was selectively inhibited by anti-P450 3A antibodies. Selective inhibition of liver microsomal ifosphamide activation was also effected by the macrolide antibiotic triacetyloleandomycin, an inhibitor of several dexamethasone-inducible 3A P450s. These studies establish that a dexamethasone-inducible family 3A P450 can make an important contribution to rat liver microsomal ifosphamide activation, and suggest that dexamethasone pretreatment might provide a useful approach for modulation of ifosphamide metabolism in order to improve its therapeutic efficacy in cancer patients.