Synthesis,Molecular Docking and Antiplasmodial Activities of New Tetrahydro-β-Carbolines

Malaria is still one of the most dangerous infectious diseases and the emergence of drug resistant parasites only worsens the situation. A series of new tetrahydro-β-carbolines were designed, synthesized by the Pictet–Spengler reaction, and characterized. Further, the compounds were screened for their in vitro antiplasmodial activity against chloroquine-sensitive (D10) and chloroquine-resistant (W2) strains of Plasmodium falciparum. Moreover, molecular modeling studies were performed to assess the potential action of the designed molecules and toxicity assays were conducted on the human microvascular endothelial (HMEC-1) cell line and human red blood cells. Our studies identified N-(3,3-dimethylbutyl)-1-octyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b] indole-3-carboxamide (7) (a mixture of diastereomers) as the most promising compound endowed with the highest antiplasmodial activity, highest selectivity, and lack of cytotoxicity. In silico simulations carried out for (1S,3R)-7 provided useful insights into its possible interactions with enzymes essential for parasite metabolism. Further studies are underway to develop the optimal nanosized lipid-based delivery system for this compound and to determine its precise mechanism of action.     

Molecular Dynamics Simulations of Amorphous Si–C–N Ceramics: Composition Dependence of the Atomic Structure

We have performed classical molecular dynamics simulations of amorphous Si–C–N materials. The dependence of the local order and of the microstructure on the chemical composition was investigated. Our simulations show that for a stoichiometric nitrogen/silicon ratio equal to or higher than 4/3, the amorphous ceramic separates into different amorphous domains, namely C-rich, SiN-rich, and SiC-rich phases. Below this ratio, the material is composed of mixed structures, homogeneously spread within the material. For a very particular composition range, we found that carbon atoms crystallize into monoatomic graphitic layers surrounding the SiN-rich domains.     

Glass-ceramic proppants from sinter-crystallisation of waste-derived glasses

ABSTRACT

The present investigation aims at evidencing the feasibility of glass-ceramic spheres by sinter-crystallisation of fine glass powders (<100?μm), in turn obtained by the melting of inorganic waste, such as red mud from Bayer process or municipal solid waste incinerator fly ash, or low-cost minerals. While dense and highly crystallised monoliths may be achieved by sintering pressed glass powders just at the glass crystallisation temperature (T_C), applying fast heating and short holding times, dense glass-ceramic beads could be obtained only by firing well above T_c (T_c?+?100°C). An increased sintering temperature was applied in order to enhance the viscous flow and promote the spheroidisation of powder clusters, previously formed by casting fine powders on a rotating drum. The high degree of crystallinity and the uniform microstructure were found to contribute positively to the mechanical properties (compressive strength exceeding 120?MPa, for beads with a diameter of 1?mm, approximately).     

Nitrous oxide mitigation potential of reduced tillage and N input in durum wheat in the Mediterranean

In Italy, managed soils account for about 50% of annual national emissions of nitrous oxide (N₂O), thus the effect of agricultural practices on N₂O emissions must be studied in order to develop mitigation strategies. Soil N₂O emissions were measured in two field campaigns (2013–2014 and 2014–2015) on durum wheat in a Mediterranean environment to test the mitigation potential of reduced tillage and nitrogen (N) fertilization rate. N₂O emissions were measured with a fully-transportable instrument developed during the project LIFE?+?IPNOA “Improved flux Prototypes for N₂O emission reduction from Agriculture” and equipped with an infrared laser detector. Reducing tillage from ploughing to minimum tillage had no effect on average daily N₂O flux, while decreasing the N rate from 170 to 110 kg N ha^?1 reduced the average daily N₂O flux, without negatively affecting the grain yield. Furthermore, N₂O daily flux were positively correlated with soil water filled pore space, NO₃-N, and NH₄-N concentrations, and they were largely variable between the two field campaigns as a result of different environmental and management conditions (i.e.: rainfall, different amount of crop residues incorporated in soil). Overall, the innovative fully-transportable instrument performed well in the field and allowed us to conclude that decreasing the N fertilizer rate was a valuable option to mitigate N₂O emissions without negative effects on wheat productivity.     

Photometric assay for polyphenol oxidase activity in olives, olive pastes, and virgin olive oils

A photometric method is proposed that allows the determination of phenolase activity in olive fruits, olive pastes, and virgin olive oil. The method can also be used to quantify partially purified phenolase from olives, and is based on the coupling between 4-methyl-o-benzoquinone, the reaction product of phenolase toward its substrate 4-methylcatechol, and the aromatic amine 4-amino-N,N-diethylaniline. The deep-blue adduct arising from this reaction has been characterized by means of nuclear magnetic resonance and mass spectrometric techniques and identified as 4-(4′-diethylaminophenylimino)-2-hydroxy-5-methyl-cyclohexa-2,5-dienone. This compound shows an absorption band, centered (in dichloromethane) at 617 nm, with an ε of 11,080 M⁻¹cm⁻¹. The main advantage of the proposed method resides in the high absorption coefficient of the adduct and its ultraviolet/visible absorption pattern, with a λ_max in a spectral region void of significant interferences by the pigments that ultimately will probably be present in the extracts to be tested by this proposed method. The method has proven to be sensitive, specific, and reliable. This paper is dedicated to the memory of Professor Francesco Corongiu, Dean of the Faculty of Sciences, University of Cagliari, prematurely deceased one year ago.     

Petri nets for modelling metabolic pathways: a survey

In the last 15 years, several research efforts have been directed towards the representation and the analysis of metabolic pathways by using Petri nets. The goal of this paper is twofold. First, we discuss how the knowledge about metabolic pathways can be represented with Petri nets. We point out the main problems that arise in the construction of a Petri net model of a metabolic pathway and we outline some solutions proposed in the literature. Second, we present a comprehensive review of recent research on this topic, in order to assess the maturity of the field and the availability of a methodology for modelling a metabolic pathway by a corresponding Petri net.     

The Linguistic Design of the EuroWordNet Database

In this paper the linguistic design of the database under construction within the EuroWordNet project is described. This is mainly structured along the same lines as the Princeton WordNet, although some changes have been made to the WordNet overall design due to both theoretical and practical reasons. The most important reasons for such changes are the multilinguality of the EuroWordNet database and the fact that it is intended to be used in Language Engineering applications. Thus, i) some relations have been added to those identified in WordNet; ii) some labels have been identified which can be added to the relations in order to make their implications more explicit and precise; iii) some relations, already present in the WordNet design, have been modified in order to specify their role more clearly.     

LORETO: a tool for reducing state explosion in verification of LOTOS programs

LOTOS is a formal specification language for concurrent and distributed systems. Basic LOTOS is the version of LOTOS without value‐passing. A widely used approach to the verification of temporal properties is model checking. Often, in this approach the formal specification is translated into a labeled transition system on which formulae expressing properties are checked. A problem with this verification technique is state explosion: concurrent systems are often represented by automata with a prohibitive number of states. In this paper we show how, given a set ρ of actions, it is possible to automatically obtain for a Basic LOTOS program a reduced transition system to which only the arcs labeled by actions in ρ belong. The set ρ of actions plays a fundamental role in conjunction with a temporal logic defined by the authors in a previous paper: selective mu‐calculus. The reduced system with respect to ρ preserves the truth value of all selective mu‐calculus formulae with actions from the set ρ. We act at both syntactic and semantic levels. From a syntactic point of view, we define a set of transformation rules obtaining a smaller program. On the semantic side, we define a non‐standard semantics which dynamically reduces the transition system during generation. We present a tool implementing both the syntactic and the semantic reduction. Copyright © 1999 John Wiley & Sons, Ltd.     

A transformation system for concurrent processes

Program transformation techniques have been extensively studied in the framework of functional and logic languages, where they were applied mainly to obtain more efficient and readable programs. All these works are based on the Unfold/Fold program transformation method developed by Burstall and Darlington in the context of their recursive equational language. The use of Unfold/Fold based transformations for concurrent languages is a relevant issue that has not yet received an adequate attention. In this paper we define a transformation methodology for CCS. We give a set of general rules which are a specialization of classical program transformation rules, such as Fold and Unfold. Moreover, we define the general form of other rules, “oriented” to the goal of a transformation strategy, and we give conditions for the correctness of these rules. We prove that a strategy using the general rules and a set of goal oriented rules is sound, i.e. it transforms CCS programs into equivalent ones. We show an example of application of our method. We define a strategy to transform, if possible, a full CCS program into an equivalent program whose semantics is a finite transition system. We show that, by means of our methodology, we are able to a find finite representations for a class of CCS programs which is larger than the ones handled by the other existing methods. Our transformational approach can be seen as unifying in a common framework a set of different techniques of program analysis. A further advantage of our approach is that it is based only on syntactic transformations, thus it does not requires any semantic information. Received: 24 April 1997 / 19 November 1997