Luísa Maria Ferreira

A decomposition approach to optimal remote controlled switch allocation in distribution systems

The growing demand for improved quality of service increases the importance of network automation, namely the investment in remote-controlled switch (RCS) devices. These allow improving the fault isolation and reconfiguration time and therefore increasing the system quality of service. The investment in switch devices comes at a cost and thus must be optimized. The problem of determining the optimal number of devices and their optimal location is a difficult problem: the solution space is combinatorial and the objective function is nonanalytical. We propose to address this problem in a two-stage decomposition approach. Results are presented to i) divide the solution space into independent subspaces, and then ii) solve the optimization problems in each subspace. The solution approach is illustrated for a real distribution network problem.

Brown Pigments Produced by Yarrowia lipolytica Result from Extracellular Accumulation of Homogentisic Acid

ABSTRACT Yarrowia lipolytica produces brown extracellular pigments that correlate with tyrosine catabolism. During tyrosine depletion, the yeast accumulated homogentisic acid,p-hydroxyphenylethanol, andp-hydroxyphenylacetic acid in the medium. Homogentisic acid accumulated under all aeration conditions tested, but its concentration decreased as aeration decreased. With moderate aeration, equimolar concentrations of alcohol andp-hydroxyphenylacetic acid (1:1) were detected, but with lower aeration the alcohol concentration was twice that of the acid (2:1). p-Hydroxyphenylethanol andp-hydroxyphenylacetic acid may result from the spontaneous disproportionation of the corresponding aldehyde,p-hydroxyphenylacetaldehyde. The catabolic pathway of tyrosine in Y. lipolytica involves the formation ofp-hydroxyphenylacetaldehyde, which is oxidized top-hydroxyphenylacetic acid and then further oxidized to homogentisic acid. Brown pigments are produced when homogentisic acid accumulates in the medium. This acid can spontaneously oxidize and polymerize, leading to the formation of pyomelanins. Mn2+accelerated and intensified the oxidative polymerization of homogentisic acid, and lactic acid enhanced the stimulating role of Mn2+. Alkaline conditions also accelerated pigment formation. The proposed tyrosine catabolism pathway appears to be unique for yeast, and this is the first report of a yeast producing pigments involving homogentisic acid.

Pro-oxidant effects of Ecstasy and its metabolites in mouse brain synaptosomes.

3,4‐Methylenedioxymethamphetamine (MDMA or ‘Ecstasy’) is a worldwide major drug of abuse known to elicit neurotoxic effects. The mechanisms underlying the neurotoxic effects of MDMA are not clear at present, but the metabolism of dopamine and 5‐HT by monoamine oxidase (MAO), as well as the hepatic biotransformation of MDMA into pro‐oxidant reactive metabolites is thought to contribute to its adverse effects.

Distribution network expansion planning under uncertainty: a hedging algorithm in an evolutionary approach

The paper addresses the problem of distribution network expansion planning under uncertainty. The deterministic problem is itself a large-scale, complex, difficult-to-define one; the combinatorial nature of the decision making can be efficiently handled by a specific evolutionary approach. The authors develop, in the evolutionary optimization context, a hedging algorithm to deal with scenario representation of uncertainty; decision making results in a convergence process for the first-stage naturally conflicting decisions. The process robustness is discussed and illustration is provided for a comprehensive example.

Antioxidant activity of unexplored indole derivatives: synthesis and screening.

The present study envisaged the development of novel antioxidant candidates using the indole scaffold. Several tryptophan and tryptamine derivatives were synthesized, in particular prenylated indole compounds, and their scavenging activity for reactive oxygen species (ROS) and reactive nitrogen species (RNS) was investigated. The library substitution pattern included several alkyl chains at positions N-1, C-2 of the indole nucleus, including prenyl and isopentyl chain, as well as different groups at the side chain (C-3) that allowed the investigation of a possible radical stabilization. The results obtained showed that tryptophan (8), tryptamine (9), N-phthaloyl tryptamine (5) and N-prenyl tryptophan (13) were the most active against peroxyl radical (ROO(•)) with activities higher than Trolox, which was used as control. The scavenging of hypochlorous acid (HOCl) was also evaluated and tryptophan (8) and tryptamine (9) showed IC(50) of 3.50 ± 0.4 and 6.00 ± 0.60 μM, respectively. Significant activity was also found for the N-prenyl tryptophan (13) with an IC(50) of 4.13 ± 0.17 μM and C-2 prenylated derivative (14), with 4.56 ± 0.48 μM. The studies were extended to RNS and best results were obtained against peroxynitrite anion (ONOO(-)) in the presence of NaHCO(3). N-alkylated tryptophan (18) showed a high activity with an IC(50) of 14.0 ± 6.8 μM. The results show that the tested compounds are effective scavengers of ROS and RNS, and suggest that the radical stabilization is strongly dependent on the type of substituents on the indolic moiety and on their relative positions. In addition, the radical dissipation inside the indolic system is mandatory for the observed antioxidant activity.

Production of brown tyrosine pigments by the yeast Yarrowia lipolytica.

Aims: To study the mechanism of production of brown pigments from tyrosine in the yeast Yarrowia lipolytica.

The mixture of "ecstasy" and its metabolites is toxic to human SH-SY5Y differentiated cells at in vivo relevant concentrations.

The neurotoxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA) is thought to involve hepatic metabolism, though its real contribution is not completely understood. Most in vitro neurotoxicity studies concern isolated exposures of MDMA or its metabolites, at high concentrations, not considering their mixture, as expected in vivo. Therefore, our postulate is that combined deleterious effects of MDMA and its metabolites, at low micromolar concentrations that may be attained into the brain, may elicit neurotoxicity. Using human SH-SY5Y differentiated cells as dopaminergic neuronal model, we studied the neurotoxicity of MDMA and its MDMA metabolites α-methyldopamine and N-methyl-α-methyldopamine and their correspondent glutathione and N-acetylcysteine monoconjugates, under isolated exposure and as a mixture, at normothermic or hyperthermic conditions. The results showed that the mixture of MDMA and its metabolites was toxic to SH-SY5Y differentiated cells, an effect potentiated by hyperthermia and prevented by N-acetylcysteine. As a mixture, MDMA and its metabolites presented a different toxicity profile, compared to each compound alone, even at equimolar concentrations. Caspase 3 activation, increased reactive oxygen species production, and intracellular Ca2+ raises were implicated in the toxic effect. The mixture increased intracellular glutathione levels by increasing its de novo synthesis. In conclusion, this study demonstrated, for the first time, that the mixture of MDMA and its metabolites, at low micromolar concentrations, which represents a more realistic approach of the in vivo scenario, elicited toxicity to human SH-SY5Y differentiated cells, thus constituting a new insight into the context of MDMA-related neurotoxicity.

The effect of a remifentanil bolus on the bispectral index of the EEG (BIS) in anaesthetized patients independently from intubation and surgical stimuli.

Background and objective: Remifentanil boluses are used in different clinical situations and the effects on bispectral index monitoring are unclear. We analysed the effect of a remifentanil bolus on the bispectral index of the electroencephalogram (bispectral index) under total intravenous anaesthesia with propofol and remifentanil. Methods: ASA I–III patients were included in this study. All patients received a 2 μg k g−1 remifentanil bolus in a period free from stimuli. Bispectral index and haemodynamic data were collected from an A‐2000XP bispectral index monitor (every second) and an AS/3 Datex monitor (every 5 s). Bispectral index data were analysed using the area under the curve. Mean arterial pressure and heart rate were averaged at each 30‐s period and analysed using analysis of variance. Results: A total of 240 bispectral index values were obtained per patient. The area under the curve between 90 and 120 s after the bolus was significantly lower than the basal area under the curve (average of all areas before the bolus, P < 0.05). Mean arterial pressure and heart rate were significantly reduced from 96.4 ± 19.9 mmHg at the time of the bolus to 74.2 ± 16.6 mmHg 120 s after, and from 70 ± 16.4 bpm at the time of the bolus to 61 ± 13.6 bpm after (P < 0.001), respectively. Conclusions: There was a significant reduction in the areas under the curve between 90–120 s following the bolus. Heart rate and blood pressure also showed significant reductions. Thus, remifentanil bolus given under total intravenous anaesthesia with propofol and remifentanil decreases bispectral index, an effect independent of intubation and surgical stimuli.

Gas chromatography–ion trap mass spectrometry method for the simultaneous measurement of MDMA (ecstasy) and its metabolites, MDA, HMA, and HMMA in plasma and urine

The investigation of 3,4-methylenedioxymethamphetamine (MDMA; ecstasy) abuse requires very robust methods with high sensitivity and wide linearity ranges for the quantification of this drug of abuse and its main metabolites in body fluids. An optimized gas chromatography-ion trap mass spectrometry (GC-IT/MS) methodology with electron impact ionization addressing these issues is presented. The sample preparation involves an enzymatic hydrolysis of urine and plasma for conjugate cleavage, a SPE extraction, and a derivatization process. The method was fully validated in rat plasma and urine. Linearity for a wide concentration range was achieved for MDMA, and the metabolites 3,4-methylenedioxyamphetamine (MDA), 4-hydroxy-3-methoxyamphetamine (HMA) and 4-hydroxy-3-methoxymethamphetamine (HMMA). Limits of quantification were 2 ng/mL in plasma and 3.5 ng/mL in urine using a Selected Ion Monitoring detection mode. Selectivity, accuracy, precision, and recovery met the required criteria for the method validation. This GC-IT/MS method provides high sensitivity and adequate performance characteristics for the simultaneous quantification of MDMA, MDA, HMA and HMMA in the studied matrices.

Indolizidine and quinolizidine alkaloids structure and bioactivity

Abstract A review of the structural identification and bioactivity of simple indolizidine and quinolizidine alkaloids isolated from amphibians, ants,fungi, plants and marine sources, covering the period from 1994 to 1999,is herein presented. Some of the new alkaloids do not have complete structural assignments due to the minute amounts that were isolated and the proposed structures rely on GC-MS and GC-FTIR analyses. Some previously known structures were corrected and others now have complete spectral assignments. The configurational and conformational analysis of new alkaloids is discussed and the alkaloids whose structures were established by X-ray analysis are also presented. Indolizidine and quinolizidine alkaloids from amphibians and ants have been described as noxious compounds and are believed to play an important role in the self defence system of these animals. Their biological activity is likely to arise from interference with ion channels in nerve and muscles cells. Polyhydroxylated indolizidines form an important group of bioactive alkaloids. Different structures are referred as potent inhibitors of glycosidases, as immunosuppressants, as anticancer agents and others are described as anti-HIV agents. Lupine alkaloids (quinolizidine alkaloids from Lupinus species) are associated with plant ecological equilibrium because they are important protectors of plants against herbivores, microorganisms and competing species. They are responsible for the toxic and teratogenic effects observed in livestock and theiraction can be associated with their affinity for nicotinic and muscarinic receptors. Important bioactivity of specific alkaloids is outlined.