A Faithful Semantics for Generalised Symbolic Trajectory Evaluation

Generalised Symbolic Trajectory Evaluation (GSTE) is a high-capacity formal verification technique for hardware. GSTE uses abstraction, meaning that details of the circuit behaviour are removed from the circuit model. A semantics for GSTE can be used to predict and understand why certain circuit properties can or cannot be proven by GSTE. Several semantics have been described for GSTE. These semantics, however, are not faithful to the proving power of GSTE-algorithms, that is, the GSTE-algorithms are incomplete with respect to the semantics. The abstraction used in GSTE makes it hard to understand why a specific property can, or cannot, be proven by GSTE. The semantics mentioned above cannot help the user in doing so. The contribution of this paper is a faithful semantics for GSTE. That is, we give a simple formal theory that deems a property to be true if-and-only-if the property can be proven by a GSTE-model checker. We prove that the GSTE algorithm is sound and complete with respect to this semantics

Expertise and the interpretation of computerized physiological data: implications for the design of computerized monitoring in neonatal intensive care

This paper presents the outcomes from a cognitive engineering project addressing the design problems of computerized monitoring in neonatal intensive care. Cognitive engineering is viewed, in this project, as a symbiosis between cognitive science and design practice. A range of methodologies has been used: interviews with neonatal staff, ward observations and experimental techniques. The results of these investigations are reported, focusing specifically on the differences between junior and senior physicians in their interpretation of monitored physiological data. It was found that the senior doctors made better use of the different knowledge sources available than the junior doctors. The senior doctors were able to identify more relevant physiological patterns and generated more and better inferences than did their junior colleagues. Expertise differences are discussed in the context of previous psychological research in medical expertise. Finally, the paper discusses the potential utility of these outcomes to inform the design of computerized decision support in neonatal intensive care

Archeologische prospectie met ingreep in de bodem Neerlinter - Droogstraat

Dit rapport werd ingediend bij het agentschap samen met een aantal afzonderlijke digitale bijlagen. Een aantal van deze bijlagen zijn niet inbegrepen in dit pdf document en zijn niet online beschikbaar. Sommige bijlagen (grondplannen, fotos, spoorbeschrijvingen, enz.) kunnen van belang zijn voor een betere lezing en interpretatie van dit rapport. Indien u deze bijlagen wenst te raadplegen kan u daarvoor contact opnemen met: [email protected]

Meizothrombin formation during factor Xa-catalyzed prothrombin activation:Formation in a purified system and in plasma

Meizothrombin and thrombin formation were quantitated during factor Xa-catalyzed activation of human prothrombin in reaction systems containing purified proteins and in plasma. In the purified system considerable amounts of meizothrombin accumulated when prothrombin was activated by factor Xa (with or without accessory components) under initial steady state conditions. The ratio of the rates of meizothrombin and thrombin formation was not influenced by variation of the pH, temperature, or ionic strength of the reaction medium. When 2-mu-M prothrombin was activated by the complete prothrombinase complex (factor Xa, factor Va, Ca2+, and phospholipid) 80-90% of the initially formed reaction product was meizothrombin. Lowering the prothrombin concentration from 2 to 0.03-mu-M caused a gradual decrease in the ratio of meizothrombin/thrombin formation from 5 to 0.6. When the phosphatidylserine content of the phospholipid vesicles was varied between 20 and 1 mol% and prothrombin activation was analyzed at 2-mu-M prothrombin the relative amount of meizothrombin formed decreased from 85 to 55%. With platelets, cephalin, or thromboplastin as procoagulant lipid, thrombin was the major reaction product and only 30-40% of the activation product was meizothrombin. We also analyzed complete time courses of prothrombin activation both with purified proteins and in plasma. In reaction systems with purified proteins substantial amounts of meizothrombin accumulated under a wide variety of experimental conditions. However, little or no meizothrombin was detected in plasma in which coagulation was initiated via the extrinsic pathway with thromboplastin or via the intrinsic pathway with kaolin plus phospholipid (cephalin, platelets, or phosphatidylserine-containing vesicles). Thus, thrombin was the only active prothrombin activation product that accumulated during ex vivo coagulation experiments in plasma

Archeologische prospectie met ingreep in de bodem Betekom - Pastorijstraat/Corneel Vissenaekenplein

Dit rapport werd ingediend bij het agentschap samen met een aantal afzonderlijke digitale bijlagen. Een aantal van deze bijlagen zijn niet inbegrepen in dit pdf document en zijn niet online beschikbaar. Sommige bijlagen (grondplannen, fotos, spoorbeschrijvingen, enz.) kunnen van belang zijn voor een betere lezing en interpretatie van dit rapport. Indien u deze bijlagen wenst te raadplegen kan u daarvoor contact opnemen met: [email protected]

Reducing GBA2 activity ameliorates neuropathology in niemann-pick type C mice

The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2). Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/-) mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs), one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC

A patient-specific echogenic soft robotic left ventricle embedded into a closed-loop cardiovascular simulator for advanced device testing

Cardiovascular medical devices undergo a large number of pre- and post-market tests before their approval for clinical practice use. Sophisticated cardiovascular simulators can significantly expedite the evaluation process by providing a safe and controlled environment and representing clinically relevant case scenarios. The complex nature of the cardiovascular system affected by severe pathologies and the inherently intricate patient-device interaction creates a need for high-fidelity test benches able to reproduce intra- and inter-patient variability of disease states. Therefore, we propose an innovative cardiovascular simulator that combines in silico and in vitro modeling techniques with a soft robotic left ventricle. The simulator leverages patient-specific and echogenic soft robotic phantoms used to recreate the intracardiac pressure and volume waveforms, combined with an in silico lumped parameter model of the remaining cardiovascular system. Three different patient-specific profiles were recreated, to assess the capability of the simulator to represent a variety of working conditions and mechanical properties of the left ventricle. The simulator is shown to provide a realistic physiological and anatomical representation thanks to the use of soft robotics combined with in silico modeling. This tool proves valuable for optimizing and validating medical devices and delineating specific indications and boundary conditions.</p