Regular Methods for Operator Precedence Languages

The operator precedence languages (OPLs) represent the largest known subclass of the context-free languages which enjoys all desirable closure and decidability properties. This includes the decidability of language inclusion, which is the ultimate verification problem. Operator precedence grammars, automata, and logics have been investigated and used, for example, to verify programs with arithmetic expressions and exceptions (both of which are deterministic pushdown but lie outside the scope of the visibly pushdown languages). In this paper, we complete the picture and give, for the first time, an algebraic characterization of the class of OPLs in the form of a syntactic congruence that has finitely many equivalence classes exactly for the operator precedence languages. This is a generalization of the celebrated Myhill-Nerode theorem for the regular languages to OPLs. As one of the consequences, we show that universality and language inclusion for nondeterministic operator precedence automata can be solved by an antichain algorithm. Antichain algorithms avoid determinization and complementation through an explicit subset construction, by leveraging a quasi-order on words, which allows the pruning of the search space for counterexample words without sacrificing completeness. Antichain algorithms can be implemented symbolically, and these implementations are today the best-performing algorithms in practice for the inclusion of finite automata. We give a generic construction of the quasi-order needed for antichain algorithms from a finite syntactic congruence. This yields the first antichain algorithm for OPLs, an algorithm that solves the ExpTime-hard language inclusion problem for OPLs in exponential time

Neuronal Activation in the Central Nervous System of Rats in the Initial Stage of Chronic Kidney Disease-Modulatory Effects of Losartan and Moxonidine.

The effect of mild chronic renal failure (CRF) induced by 4/6-nephrectomy (4/6NX) on central neuronal activations was investigated by c-Fos immunohistochemistry staining and compared to sham-operated rats. In the 4/6 NX rats also the effect of the angiotensin receptor blocker, losartan, and the central sympatholyticum moxonidine was studied for two months. In serial brain sections Fos-immunoreactive neurons were localized and classified semiquantitatively. In 37 brain areas/nuclei several neurons with different functional properties were strongly affected in 4/6NX. It elicited a moderate to high Fos-activity in areas responsible for the monoaminergic innervation of the cerebral cortex, the limbic system, the thalamus and hypothalamus (e.g. noradrenergic neurons of the locus coeruleus, serotonergic neurons in dorsal raphe, histaminergic neurons in the tuberomamillary nucleus). Other monoaminergic cell groups (A5 noradrenaline, C1 adrenaline, medullary raphe serotonin neurons) and neurons in the hypothalamic paraventricular nucleus (innervating the sympathetic preganglionic neurons and affecting the peripheral sympathetic outflow) did not show Fos-activity. Stress- and pain-sensitive cortical/subcortical areas, neurons in the limbic system, the hypothalamus and the circumventricular organs were also affected by 4/6NX. Administration of losartan and more strongly moxonidine modulated most effects and particularly inhibited Fos-activity in locus coeruleus neurons. In conclusion, 4/6NX elicits high activity in central sympathetic, stress- and pain-related brain areas as well as in the limbic system, which can be ameliorated by losartan and particularly by moxonidine. These changes indicate a high sensitivity of CNS in initial stages of CKD which could be causative in clinical disturbances

Health effects of selected nanoparticles in vivo: liver function and hepatotoxicity following intravenous injection of titanium dioxide and Na-oleate-coated iron oxide nanoparticles in rodents.

The study determined the effect of intravenous administration of acutely toxic or sub-lethal doses of Na-oleate-coated Fe3O4 (OC-Fe3O4) nanoparticles (NPs) on liver structure and function in Wistar rats, compared to titanium dioxide (TiO2) NPs and saline-injected controls. The acute study, using a modified OECD 425 progressive dosing procedure, found LD50 values of 59.22 and 36.42 mg/kg for TiO2 and OC-Fe3O4 NPs, respectively. In the sub-lethal study, rats were either injected with saline (negative controls), a sub-lethal reference (0.592 mg/kgTiO2 NPs, equal to 1% of LD50 on a body weight basis) or OC-Fe3O4 NPs in doses equivalent to 0.1, 1 or 10% of the LD50, respectively (corresponding to 0.0364, 0.364 and 3.64 mg Fe3O4/kg body weight). Animals were sampled 24 h, 1, 2 and 4 weeks post-injection for adverse effects. Mitochondrial respiration was significantly increased 2 weeks after injection of 10% OC-Fe3O4 NPs compared to controls, but the effect was transient. Cholesterol and triacylglycerol concentrations in the liver tissue did not increase in any treatment. There were some disturbances to antioxidant enzymes after OC-Fe3O4 NPs treatment in the livers of animals 1 week post-exposure; with the most sensitive changes occurring in glutathione peroxidase (GPx) and glutathione S-transferase (GST) activities. Lipidosis and mild necrosis with changes in sinusoid space were also observed in histological sections of the liver. Overall, these data suggest that the liver likely retains functional integrity with acute and sub-lethal doses of OC-Fe3O4 NPs, albeit with some stimulation of redox defences and evidence of some tissue injury

LIPIcs

The operator precedence languages (OPLs) represent the largest known subclass of the context-free languages which enjoys all desirable closure and decidability properties. This includes the decidability of language inclusion, which is the ultimate verification problem. Operator precedence grammars, automata, and logics have been investigated and used, for example, to verify programs with arithmetic expressions and exceptions (both of which are deterministic pushdown but lie outside the scope of the visibly pushdown languages). In this paper, we complete the picture and give, for the first time, an algebraic characterization of the class of OPLs in the form of a syntactic congruence that has finitely many equivalence classes exactly for the operator precedence languages. This is a generalization of the celebrated Myhill-Nerode theorem for the regular languages to OPLs. As one of the consequences, we show that universality and language inclusion for nondeterministic operator precedence automata can be solved by an antichain algorithm. Antichain algorithms avoid determinization and complementation through an explicit subset construction, by leveraging a quasi-order on words, which allows the pruning of the search space for counterexample words without sacrificing completeness. Antichain algorithms can be implemented symbolically, and these implementations are today the best-performing algorithms in practice for the inclusion of finite automata. We give a generic construction of the quasi-order needed for antichain algorithms from a finite syntactic congruence. This yields the first antichain algorithm for OPLs, an algorithm that solves the ExpTime-hard language inclusion problem for OPLs in exponential time

A novel way of liver preservation improves rat liver viability upon reperfusion

Background/aim: Currently, the liver is cold-preserved at 0~4 °C for experimental and clinical purposes. Here, we investigated whether milder hypothermia during the initial phase of the preservation period was beneficial for liver viability upon reperfusion. Methods: In the first set of experiments, rat livers were preserved either conventionally in clinically used histidine-trypthopan-ketoglutarate (HTK) solution (Group A: 45 min and Group B: 24 h) or by slow cooling HTK solution (from 13 °C to 3 °C) during the initial 45 min of preservation (Group C: 24 h). In the second set of experiments, additional groups of livers were evaluated: Group BB—preservation according to Group B and Group CC—preservation according to Group C. Further, some livers were preserved at 13 °C for 24 h. Livers were then reperfused using a blood-free perfusion model. Results: Bile production was approximately 2-fold greater in Group C compared to Group B. Alanine transaminase (ALT) and aspartate transaminase (AST) release into perfusate were 2~3-fold higher in Group B compared to Group C. No significant differences were found in ALT and AST release between Group C and Group A. Livers in Group CC compared to Group BB exhibited significantly lower portal resistance, greater oxygen consumption and bromosulfophthalein excretion into bile and lower lactate dehydrogenase (LDH) release into perfusate. Histological evaluation of tissue sections in Group BB showed parenchymal dystrophy of hepatocytes, while dystrophy of hepatocytes was absent in Group CC. Livers preserved at 13 °C for 24 h exhibited severe ischemic injury. Conclusion: These results suggest that the conventional way of liver preservation is not suitable at least for rat livers and that slow cooling of HTK solution during the initial phase of cold storage can improve liver viability during reperfusion

Ninety-day oral toxicity studies on two genetically modified maize MON810 varieties in Wistar Han RCC rats (EU 7th Framework Programme project GRACE)

The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event

Ninety-day oral toxicity studies on two genetically modified maize MON810 varieties in Wistar Han RCC rats (EU 7th Framework Programme project GRACE)

The GMO Risk Assessment and Communication of Evidence (GRACE; www.grace-fp7.eu) project is funded by the European Commission within the 7th Framework Programme. A key objective of GRACE is to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of two 90-day feeding trials with two different GM maize MON810 varieties, their near-isogenic non-GM varieties and four additional conventional maize varieties are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 408. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after subchronic exposure, independently of the two different genetic backgrounds of the event

One-year oral toxicity study on a genetically modified maize MON810 variety in Wistar Han RCC rats (EU 7th Framework Programme project GRACE)

The GRACE (GMO Risk Assessment and Communication of Evidence; www.grace-fp7.eu) project was funded by the European Commission within the 7th Framework Programme. A key objective of GRACE was to conduct 90-day animal feeding trials, animal studies with an extended time frame as well as analytical, in vitro and in silico studies on genetically modified (GM) maize in order to comparatively evaluate their use in GM plant risk assessment. In the present study, the results of a 1-year feeding trial with a GM maize MON810 variety, its near-isogenic non-GM comparator and an additional conventional maize variety are presented. The feeding trials were performed by taking into account the guidance for such studies published by the EFSA Scientific Committee in 2011 and the OECD Test Guideline 452. The results obtained show that the MON810 maize at a level of up to 33 % in the diet did not induce adverse effects in male and female Wistar Han RCC rats after a chronic exposure