Studio 13-C NMR di oli essenziali di <i>Helicrysum Italicum</i> sub. <i>Microphyllum</i>

In questo lavoro mostriamo l'assegnazione dei componenti maggiori dell'olio essenziale di Elicriso provenienti da varie zone della Sardegna. Per l'esatta determinazione di alcuni componenti si è resa necessaria una separazione cromatografica

A multiple role for the coenzyme in the mechanism of action of 6-phosphogluconate dehydrogenase. The oxidative decarbosylation of 2-deoxy-6-phosphogluconate.

Abstract 6-Phosphogluconate dehydrogenase from Candida utilis catalyzes the oxidative decarboxylation of 2-deoxy-6-phosphogluconate. The 3-keto-2-deoxy-6-phosphogluconate, an intermediate of the reaction, is reduced to 2-deoxy-6-phosphogluconate and decarboxylated to 1-deoxyribulose 5-phosphate when incubated with the enzyme and TPNH. The decarboxylation process does not occur in the absence of the reduced coenzyme, which does not have, in this step, an oxidation-reduction role. Since TPNH also has a non-redox role in a tritium exchange reaction catalyzed by the enzyme, it appears that the coenzyme has a multiple role in the mechanism of action of 6-phosphogluconate dehydrogenase: a redox role in the dehydrogenation and another (or others) role(s) in the decarboxylation and tritium exchange reactions. The hydroxyl group present at carbon 2 of 6-phosphogluconate seems to have a dual role in the mechanism of action of the enzyme: one in the binding of the substrate to the enzyme, another in enhancing the decarboxylation of the dehydrogenation product. These findings are discussed with relations to the mechanism of action of isocitrate dehydrogenase and of the malic enzyme. The enzymatic oxidative decarboxylation of 2-deoxy-6-phosphogluconate is a new step for the metabolism of the metabolic inhibitor 2-deoxyglucose

Structure-based drug design e sintesi di nuovi bioisosteri eterociclici della funzione beta-diketoacida come inibitori dell'enzima HIV-1 integrasi

In questo lavoro, seguendo l’approccio della bioisosteria non classica, la porzione β-diketonica I è stata incorporata nei nuclei ossazolico III e pirazolico IV e sono stati disegnati gli acidi indolil-3-ossazolici 4ac e indolil-3-pirazolici 5a-c. Inoltre la funzione β-diketoacida II, sostituita con un nucleo 3-idrossi-pirrolo-2,5-dionico V, contemplato in letteratura come bioisostero di tale struttura, ha portato ai derivati 6a-c. Le molecole progettate sono state sottoposte ad uno studio di docking al fine di di valutare preliminarmente l’attività inibitoria tramite la costante di inibizione Ki in accordo con il razionale Structure-based drug design

ANALYSIS AND DESIGN OF THE ACTUATION SYSTEM FOR THE LHC COLLIMATORS (PHASE I)

In order to cope with the highly destructive particle beam of the LHC, the cleaning and collimation system must fulfill very severe requirements. The actuation system of the LHC Collimators is a key element to meet the specifications, particularly in terms of precision and reliability. Each collimator jaw has to be moved with a very high accuracy to place the active surface at the required position with respect to the proton beam; at the same time the system must be adjustable and flexible to adapt to the uncertainties and variations in the beam tuning. In this note the general design of the actuation system for the various collimator designs is presented and particular emphasis is given to the analysis of the torque which the stepper motors must provide to move the jaws in and back and to the dynamical behaviour of the system in the event of malfunctioning when auto-retraction of the jaws is required. In the appendix, details are given on the estimated performances of the actuation system for different collimator types and orientations

Numerical simulations of tungsten targets hit by LHC proton beam

The unprecedented energy intensities of modern hadron accelerators yield special problems with the materials that are placed close to or into the high intensity beams. The energy stored in a single beam of LHC particle accelerator is equivalent to about 80 kg of TNT explosive, stored in a transverse beam area with a typical value of 0.2 mm×0.2 mm. The materials placed close to the beam are used at, or even beyond, their damage limits. However, it is very difficult to predict structural efficiency and robustness accurately: beam-induced damage for high energy and high intensity occurs in a regime where practical experience does not exist. The interaction between high energy particle beams and metals induces a sudden non uniform temperature increase. This provokes a dynamic response of the structure entailing thermal stress waves and thermally induced vibrations or even the failure of the component. This study is performed in order to estimate the damage on a tungsten component due to the impact with a proton beam generated by LHC. The solved problems represent some accidental cases consequent to an abnormal release of the beam: the energy delivered on the components is calculated using the FLUKA code and then used as input in the numerical simulations, that are carried out via the FEM code LS-DYNA

Searching for novel carbonic anhydrase inhibitors: from virtual screening to the lab bench

Carbonic Anhydrases (CAs) are zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide to bicarbonate both in prokaryotes and eukaryotes. In this context, Computer Aided Drug Design strategies have emerged as powerful tools in the modern drug discovery paradigm. In particular, using ligand- and pharmacophore-based virtual screening approaches, we identified novel chemical entities with original chemotypes, that showed an interesting and selective inhibitory activity in nanomolar/low micromolar range toward CA I and CAII, isoforms. Herein, we present the hit-to-lead optimization process for these prototypes

Modelagem orientada a objetos de estimadores de estados aplicados à supervisão da segurança operativa de redes elétricas

The use of advanced hardware and digital computers in electrical management systems potentially enhance the supervision and control tasks in real time operation mode. These functions allow the safe operation of electrical networks, which effectively improve the operator decision. Specifically, the state estimators applied to power systems have an important role along with the SCADA systems, in order to evaluate the network states as close as possible to the actual states of the monitored system. This work evaluates a robust state estimator algorithm performance when it is written in object-oriented programming language. The program makes use of the Iterative Weighted Least-squares method (IWLS) with equality constraints (EC). The employed methodology has the feature of processing bad data during the iterative search for the problem solution, even when it is extended to the state estimation problem with equality constraints. In this work, the equality constraints can be modeled through two approaches: a) Classical Weighting Method (WM); b) Weighting Method with Iterative Refinement (WMIR). Independently from the fact that regular and/or pseudo measurements have been classified as leverage points, the employed methodology, named IWLS-EC, allows the satisfactory processing of bad data and/or topology errors. The algorithm performances are explicitly tracked throughout the iterations carried out on a small example system of 5 buses. Moreover, the proposed methodology is also evaluated in an actual system in the south of Brazil with 126 buses, and also in other realistic systems with 340, 730 and 1916 buses. The obtained results are compared, analyzed and commented on in the chapter that describes the set of simulations carried out on test systems.A utilização de hardware avançado e computadores digitais em centros de operação de sistemas elétricos potencializam as funções de supervisão da segurança e controle operativo em tempo real. Estas funções permitem operar os sistemas elétricos de forma segura, o que possibilita ao operador tomar decisões mais efetivas. Especificamente, os Estimadores de Estados em Sistemas de Potência têm um importante papel somado aos sistemas de aquisição de dados no sentido de avaliar os estados da rede o mais próximo possível dos estados verdadeiros do sistema supervisionado. Este trabalho verifica experimentalmente o desempenho de um estimador de estados robusto escrito em linguagem de programação orientada a objetos. O programa faz uso do Método de Mínimos Quadrados com Ponderação Variável (MQPV) e Restrições de Igualdade (RI). A metodologia empregada tem a característica de executar o processamento de erros grosseiros durante o processo iterativo de busca de solução do problema, mesmo quando é estendida ao problema de estimação de estados com restrições de igualdade. Neste trabalho, as restrições de Igualdade podem ser processadas através de duas abordagens: a) Método Clássico dos Pesos (MP); b) Método dos Pesos com Refinamento Iterativo (MPRI). Independentemente das medidas e/ou pseudo-medidas terem sido classificadas como pontos de alavancamento, a metodologia proposta, aqui denominada MQPV/RI, permite processar erros grosseiros e/ou topológicos satisfatoriamente. A operacionalização dos algoritmos utilizados é explicitamente demonstrada ao longo do processo iterativo de solução de um sistema exemplo de 5 barras. Além disso, a metodologia também é testada no sistema de uma Companhia de Energia Elétrica do Sul do Brasil contendo 126 barras, além de sistemas realísticos de 340, 730 e 1916 barras. Os resultados produzidos são comparados, analisados e comentados detalhadamente no capítulo que descreve o conjunto de simulações realizadas nos sistemas testes

Strategie di sintesi per la preparazione di bifenili ossidrilati chirali non racemi di interesse agrobiologico

L’attività di ricerca del gruppo è rivolta alla sintesi di bifenili con interessanti caratteristiche stereochimiche, ottenibili mediante metodi semplici e diretti al fine di un loro utilizzo nei sistemi biologici ed in agricoltura

Thermodynamic characterization of substrate and inhibitor binding to Trypanosoma brucei 6-phosphogluconate dehydrogenase

6-Phosphogluconate dehydrogenase is a potential target for new drugs against African trypanosomiasis. Phosphorylated aldonic acids are strong inhibitors of 6-phosphogluconate dehydrogenase, and 4-phospho-d-erythronate (4PE) and 4-phospho-d-erythronohydroxamate are two of the strongest inhibitors of the Trypanosoma brucei enzyme. Binding of the substrate 6-phospho-d-gluconate (6PG), the inhibitors 5-phospho-d-ribonate (5PR) and 4PE, and the coenzymes NADP, NADPH and NADP analogue 3-amino-pyridine adenine dinucleotide phosphate to 6-phospho-d-gluconate dehydrogenase from T. brucei was studied using isothermal titration calorimetry. Binding of the substrate (K(d) = 5 microm) and its analogues (K(d) =1.3 microm and K(d) = 2.8 microm for 5PR and 4PE, respectively) is entropy driven, whereas binding of the coenzymes is enthalpy driven. Oxidized coenzyme and its analogue, but not reduced coenzyme, display a half-site reactivity in the ternary complex with the substrate or inhibitors. Binding of 6PG and 5PR poorly affects the dissociation constant of the coenzymes, whereas binding of 4PE decreases the dissociation constant of the coenzymes by two orders of magnitude. In a similar manner, the K(d) value of 4PE decreases by two orders of magnitude in the presence of the coenzymes. The results suggest that 5PR acts as a substrate analogue, whereas 4PE mimics the transition state of dehydrogenation. The stronger affinity of 4PE is interpreted on the basis of the mechanism of the enzyme, suggesting that the inhibitor forces the catalytic lysine 185 into the protonated state