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Modifications of the cationic head and the ethylene linker of 2(triethylammonium)ethyl ether of 4-stilbenol (MG624) have been proved to produce selective alpha 9*-nAChR antagonism devoid of any effect on the alpha 7-subtype. Here, single structural changes at the styryl portion of MG624 lead to prevailing alpha 7-nAChR antagonism without abolishing alpha 9*-nAChR antagonism. Nevertheless, rigidification of the styryl into an aromatic bicycle, better if including a H-bond donor NH, such as 5-indolyl (31), resulted in higher and more selective alpha 7-nAChR affinity. Hybridization of this modification with the constraint of the 2-triethylammoniumethyloxy portion into (R)-N,N-dimethyl-3-pyrrolidiniumoxy substructure, previously reported as the best modification for the alpha 7-nAChR affinity of MG624 (2), was a winning strategy. The resulting hybrid 33 had a subnanomolar alpha 7-nAChR affinity and was a potent and selective alpha 7-nAChR antagonist, producing at the alpha 7-, but not at the alpha 9*-nAChR, a profound loss of subsequent ACh function.

Modifications of the cationic head and the ethylene linker of 2(triethylammonium)ethyl ether of 4-stilbenol (MG624) have been proved to produce selective alpha 9*-nAChR antagonism devoid of any effect on the alpha 7-subtype. Here, single structural changes at the styryl portion of MG624 lead to prevailing alpha 7-nAChR antagonism without abolishing alpha 9*-nAChR antagonism. Nevertheless, rigidification of the styryl into an aromatic bicycle, better if including a H-bond donor NH, such as 5-indolyl (31), resulted in higher and more selective alpha 7-nAChR affinity. Hybridization of this modification with the constraint of the 2-triethylammoniumethyloxy portion into (R)-N,N-dimethyl-3-pyrrolidiniumoxy substructure, previously reported as the best modification for the alpha 7-nAChR affinity of MG624 (2), was a winning strategy. The resulting hybrid 33 had a subnanomolar alpha 7-nAChR affinity and was a potent and selective alpha 7-nAChR antagonist, producing at the alpha 7-, but not at the alpha 9*-nAChR, a profound loss of subsequent ACh function.

[EN] This paper contains a numerical study based on tests carried out at the Universitat Politècnica de València (Spain) on a U-shaped unreinforced and TRM-reinforced masonry building structure subjected to horizontal loads. The masonry was composed of clay bricks with 10 mm thick mortar joints arranged in an English bond manner. The prototype was tested by applying pseudo-dynamic displacement-driven cycles and varying cyclic amplitudes and frequencies in two different stages: (i) on the as-built structure and (ii) after the repair and the application of Textile Reinforced Mortar (TRM) material. A series of non-linear numerical simulations were performed adopting the ABAQUS/Explicit FE software. The FE calibration was carried out using the results obtained during ambient vibration tests. Simulations were then used to evaluate the effectiveness of the proposed TRM technique to increasing the strength of low-rise old masonry building structures.

[EN] This paper contains a numerical study based on tests carried out at the Universitat Politècnica de València (Spain) on a U-shaped unreinforced and TRM-reinforced masonry building structure subjected to horizontal loads. The masonry was composed of clay bricks with 10 mm thick mortar joints arranged in an English bond manner. The prototype was tested by applying pseudo-dynamic displacement-driven cycles and varying cyclic amplitudes and frequencies in two different stages: (i) on the as-built structure and (ii) after the repair and the application of Textile Reinforced Mortar (TRM) material. A series of non-linear numerical simulations were performed adopting the ABAQUS/Explicit FE software. The FE calibration was carried out using the results obtained during ambient vibration tests. Simulations were then used to evaluate the effectiveness of the proposed TRM technique to increasing the strength of low-rise old masonry building structures.

[EN] This paper contains a numerical study based on tests carried out at the Universitat Politècnica de València (Spain) on a U-shaped unreinforced and TRM-reinforced masonry building structure subjected to horizontal loads. The masonry was composed of clay bricks with 10 mm thick mortar joints arranged in an English bond manner. The prototype was tested by applying pseudo-dynamic displacement-driven cycles and varying cyclic amplitudes and frequencies in two different stages: (i) on the as-built structure and (ii) after the repair and the application of Textile Reinforced Mortar (TRM) material. A series of non-linear numerical simulations were performed adopting the ABAQUS/Explicit FE software. The FE calibration was carried out using the results obtained during ambient vibration tests. Simulations were then used to evaluate the effectiveness of the proposed TRM technique to increasing the strength of low-rise old masonry building structures.

This paper contains a numerical study based on tests carried out at the Universitat Politècnica de València (Spain) on a U-shaped unreinforced and Textile Reinforced Mortar (TRM)-reinforced masonry structure subjected to horizontal loads. The masonry was composed of clay bricks with 10 mm thick mortar joints arranged in an English bond pattern. The prototype was tested by applying pseudodynamic displacement-driven cycles and varying cyclic amplitudes and frequencies in two different stages: (1) on the as-built structure and (2) after the application of the TRM material. A series of nonlinear numerical simulations were performed adopting the ABAQUS/Explicit version 6.14 finite-element (FE) software. The FE calibration was carried out using the results obtained during ambient vibration tests. Simulations were then used to evaluate the effectiveness of the proposed TRM strengthening technique in improving the behaviour of low-rise old masonry building subjected to horizontal loads.

This paper contains a numerical study based on tests carried out at the Universitat Politècnica de València (Spain) on a U-shaped unreinforced and Textile Reinforced Mortar (TRM)-reinforced masonry structure subjected to horizontal loads. The masonry was composed of clay bricks with 10 mm thick mortar joints arranged in an English bond pattern. The prototype was tested by applying pseudodynamic displacement-driven cycles and varying cyclic amplitudes and frequencies in two different stages: (1) on the as-built structure and (2) after the application of the TRM material. A series of nonlinear numerical simulations were performed adopting the ABAQUS/Explicit version 6.14 finite-element (FE) software. The FE calibration was carried out using the results obtained during ambient vibration tests. Simulations were then used to evaluate the effectiveness of the proposed TRM strengthening technique in improving the behaviour of low-rise old masonry building subjected to horizontal loads.

[EN] This paper presents the experimental results obtained from tests on a 2/3 scale U-shaped masonry building constructed in one of the ICITECH laboratories at the Universitat Politecnica de Valencia (Spain). The prototype measured 3.31 x 4.19 m(2) by 2.15 m high and had a wall thickness of 230 mm. The masonry was composed of 230 x 110 x 50 mm(3) solid clay bricks with approximately 10 mm-thick mortar joints arranged in English bond. The tests were aimed at evaluating the effectiveness of cement-based reinforcing materials (Textile Reinforced Mortar) applied to weak masonry substrates severely damaged by horizontal loads such as those induced by a seismic event. The tests were carried out in three phases: (i) testing of the as-built structure, (ii) application of one external layer of TRM to restore the masonry's original load-bearing capacity and then (iii) testing the TRM-strengthened structure. Dynamic behaviour was monitored by both traditional and fibre optic sensors (FO), including 28 Linear Variable Displacement Transducers (LVDTs) and 3 long-gauge optical sensors. Strengthening effectiveness was evaluated by several parameters: hysteretic curves, strength degradation, computed cumulative energy dissipation and cracking mechanisms. TRM reinforcement was shown to significantly extend the load-bearing and displacement capacity of the masonry prototype, reducing seismic-induced damage applied by pseudodynamic excitation, although it had a limited effect on cumulative energy dissipation.

[EN] This paper presents the experimental results obtained from tests on a 2/3 scale U-shaped masonry building constructed in one of the ICITECH laboratories at the Universitat Politecnica de Valencia (Spain). The prototype measured 3.31 x 4.19 m(2) by 2.15 m high and had a wall thickness of 230 mm. The masonry was composed of 230 x 110 x 50 mm(3) solid clay bricks with approximately 10 mm-thick mortar joints arranged in English bond. The tests were aimed at evaluating the effectiveness of cement-based reinforcing materials (Textile Reinforced Mortar) applied to weak masonry substrates severely damaged by horizontal loads such as those induced by a seismic event. The tests were carried out in three phases: (i) testing of the as-built structure, (ii) application of one external layer of TRM to restore the masonry's original load-bearing capacity and then (iii) testing the TRM-strengthened structure. Dynamic behaviour was monitored by both traditional and fibre optic sensors (FO), including 28 Linear Variable Displacement Transducers (LVDTs) and 3 long-gauge optical sensors. Strengthening effectiveness was evaluated by several parameters: hysteretic curves, strength degradation, computed cumulative energy dissipation and cracking mechanisms. TRM reinforcement was shown to significantly extend the load-bearing and displacement capacity of the masonry prototype, reducing seismic-induced damage applied by pseudodynamic excitation, although it had a limited effect on cumulative energy dissipation.

In the twenty-six years that characterize the last six Italian legislatures (1994-2020) Italy has seen, from the political-institutional point of view, an intense activity that was accompanied by a very similar vitality of the political party system. In this context, the electoral system and its continuous modifications with new electoral laws has strongly influenced the form of government, marking, by the decisive conditioning factor that represents the party system, its dynamics, both directly and indirectly. However, the rapid change of the different electoral systems in recent years has not been accompanied by an equal change in the constitutional text, so there has been an asymmetry in the functioning of the new electoral systems that were being adopted gradually, making them substantially incomplete, inconsistent and ultimately fragile. Faced with an immutability of the constitutional system, this continuous mutability in the electoral system has not only made the whole political-institutional system very weak, but also degraded it in its function in the eyes of the voters, as it seemed a clearly inefficient tool with respect to the needs of the constitutional system. Therefore, the present contribution aims to highlight the transformations that have taken place on the electoral system, trying to underline the difficulties of its consolidation, within the framework of the so-called Second Republic (1994-2020) and its new system of political parties., En los veintiséis años que caracterizan a las seis últimas legislaturas italianas (1994-2020) ha habido una intensa actividad político-institucional, acompañada de una fuerte modificación del sistema de los partidos políticos. En este contexto, el sistema electoral y sus continuas modificaciones con nuevas leyes electorales ha influido fuertemente en la forma de gobierno, marcando su dinámica, tanto directa como indirectamente. Sin embargo, el rápido cambio de los diferentes sistemas electorales en los últimos años no ha estado acompañado de reformas parejas en el texto constitucional, produciéndose una asimetría en el funcionamiento de los nuevos sistemas electorales que se iban adoptando gradualmente, que los hacía sustancialmente incompletos, incoherentes y, en definitiva, frágiles. Todo ello ha terminado degradando el sistema a ojos de la ciudadanía. Las presentes notas tienen por objeto poner de relieve las transformaciones que se han producido sobre el sistema electoral, tratando de subrayar las dificultades de su consolidación, en el marco de la llamada Segunda República (1994-2020) y de su nuevo sistema de partidos políticos.

A set of racemic spirocyclic quinuclidinyl-¿(2) -isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (a7) and heteromeric (a4ß2) nicotinic acetylcholine receptors. ¿(2) -Isoxazolines 3¿a (3-Br), 6¿a (3-OMe), 5¿a (3-Ph), 8¿a (3-OnPr), and 4¿a (3-Me) were the ligands with the highest affinity for the a7 subtype (K(i) values equal to 13.5, 14.2, 25.0, 71.6, and 96.2 nM, respectively), and showed excellent a7 versus a4ß2 subtype selectivity. These compounds, tested in electrophysiological experiments against human a7 and a4ß2 receptors stably expressed in cell lines, behaved as partial a7 agonists with varying levels of potency. The two enantiomers of (±)-3-methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene sesquifumarate 6¿a were prepared using (+)-dibenzoyl-L- or (-)-dibenzoyl-D-tartaric acid as resolving agents. Enantiomer (R)-(-)-6¿a was found to be the eutomer, with K(i) values of 4.6 and 48.7 nM against rat and human a7 receptors, respectively.

A set of racemic spirocyclic quinuclidinyl-¿(2) -isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (a7) and heteromeric (a4ß2) nicotinic acetylcholine receptors. ¿(2) -Isoxazolines 3¿a (3-Br), 6¿a (3-OMe), 5¿a (3-Ph), 8¿a (3-OnPr), and 4¿a (3-Me) were the ligands with the highest affinity for the a7 subtype (K(i) values equal to 13.5, 14.2, 25.0, 71.6, and 96.2 nM, respectively), and showed excellent a7 versus a4ß2 subtype selectivity. These compounds, tested in electrophysiological experiments against human a7 and a4ß2 receptors stably expressed in cell lines, behaved as partial a7 agonists with varying levels of potency. The two enantiomers of (±)-3-methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene sesquifumarate 6¿a were prepared using (+)-dibenzoyl-L- or (-)-dibenzoyl-D-tartaric acid as resolving agents. Enantiomer (R)-(-)-6¿a was found to be the eutomer, with K(i) values of 4.6 and 48.7 nM against rat and human a7 receptors, respectively.

A set of racemic spirocyclic quinuclidinyl-¿(2) -isoxazoline derivatives was synthesized using a 1,3-dipolar cycloaddition-based approach. Target compounds were assayed for binding affinity toward rat neuronal homomeric (a7) and heteromeric (a4ß2) nicotinic acetylcholine receptors. ¿(2) -Isoxazolines 3¿a (3-Br), 6¿a (3-OMe), 5¿a (3-Ph), 8¿a (3-OnPr), and 4¿a (3-Me) were the ligands with the highest affinity for the a7 subtype (K(i) values equal to 13.5, 14.2, 25.0, 71.6, and 96.2 nM, respectively), and showed excellent a7 versus a4ß2 subtype selectivity. These compounds, tested in electrophysiological experiments against human a7 and a4ß2 receptors stably expressed in cell lines, behaved as partial a7 agonists with varying levels of potency. The two enantiomers of (±)-3-methoxy-1-oxa-2,7-diaza-7,10-ethanospiro[4.5]dec-2-ene sesquifumarate 6¿a were prepared using (+)-dibenzoyl-L- or (-)-dibenzoyl-D-tartaric acid as resolving agents. Enantiomer (R)-(-)-6¿a was found to be the eutomer, with K(i) values of 4.6 and 48.7 nM against rat and human a7 receptors, respectively.

A group of novel 4,5-dihydro-3-methylisoxazolyl derivatives, structurally related to epiboxidine (=(1R,4S,6S)-6-(3-methylisoxazol-5-yl)-7-azabicyclo[2.2.1]heptane), was prepared via 1,3-dipolar cycloaddition of acetonitrile oxide to different olefins. Target compounds 1a and 1b, 2a and 2b, 3, 4, and 5 were tested for affinity at neuronal nicotinic heteromeric (alpha4beta2) and homomeric (alpha7) acetylcholine receptors. Notably, diastereoisomers 1a and 1b were characterized by a massive drop of the affinity at the alpha4beta2 subtypes (K(i) values spanning the range 4.3-126 microM), when compared with that of epiboxidine (K(i)=0.6 nM). Therefore, the replacement of the 3-methylisoxazole ring of epiboxidine with the 4,5-dihydro-3-methylisoxazole nucleus is detrimental for the affinity at alpha4beta2 receptors. A comparable lack of affinity/selectivity for the two nAChR subtypes under study was evidenced for the remaining epiboxidine-related dihydroisoxazole derivatives 2a and 2b, and 3-5. Diastereoisomers 1a and 1b, and spirocyclic derivative 3 were docked into molecular models of the receptor subtypes under study, and their binding mode was compared with that of reference ligands endowed with high binding affinity.

A group of novel 4,5-dihydro-3-methylisoxazolyl derivatives, structurally related to epiboxidine (=(1R,4S,6S)-6-(3-methylisoxazol-5-yl)-7-azabicyclo[2.2.1]heptane), was prepared via 1,3-dipolar cycloaddition of acetonitrile oxide to different olefins. Target compounds 1a and 1b, 2a and 2b, 3, 4, and 5 were tested for affinity at neuronal nicotinic heteromeric (alpha4beta2) and homomeric (alpha7) acetylcholine receptors. Notably, diastereoisomers 1a and 1b were characterized by a massive drop of the affinity at the alpha4beta2 subtypes (K(i) values spanning the range 4.3-126 microM), when compared with that of epiboxidine (K(i)=0.6 nM). Therefore, the replacement of the 3-methylisoxazole ring of epiboxidine with the 4,5-dihydro-3-methylisoxazole nucleus is detrimental for the affinity at alpha4beta2 receptors. A comparable lack of affinity/selectivity for the two nAChR subtypes under study was evidenced for the remaining epiboxidine-related dihydroisoxazole derivatives 2a and 2b, and 3-5. Diastereoisomers 1a and 1b, and spirocyclic derivative 3 were docked into molecular models of the receptor subtypes under study, and their binding mode was compared with that of reference ligands endowed with high binding affinity.