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101.
Synthesis and Biological Evaluation of Papain‐Family Cathepsin L‐Like Cysteine Protease Inhibitors Containing a 1,4‐Benzodiazepine Scaffold as Antiprotozoal Agents
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Dr. Roberta Ettari Dr. Andrea Pinto Dr. Lucia Tamborini Dr. Ilenia C. Angelo Prof. Silvana Grasso Prof. Maria Zappalà Dr. Natale Capodicasa Dr. Laura Yzeiraj Dr. Esther Gruber Dr. Makoah N. Aminake Dr. Gabriele Pradel Prof. Tanja Schirmeister Prof. Carlo De Micheli Prof. Paola Conti 《ChemMedChem》2014,9(8):1817-1825
Novel papain‐family cathepsin L‐like cysteine protease inhibitors endowed with antitrypanosomal and antimalarial activity were developed, through an optimization study of previously developed inhibitors. In the present work, we studied the structure–activity relationships of these derivatives, with the aim to develop new analogues with a simplified and more synthetically accessible structure and with improved antiparasitic activity. The structure of the model compounds was significantly simplified by modifying or even eliminating the side chain appended at the C3 atom of the benzodiazepine scaffold. In addition, a simple methylene spacer of appropriate length was inserted between the benzodiazepine ring and the 3‐bromoisoxazoline moiety. Several rhodesain and falcipain‐2 inhibitors displaying single‐digit micromolar or sub‐micromolar antiparasitic activity against one or both parasites were identified, with activities that were one order of magnitude more potent than the model compounds. 相似文献
102.
Emmanuelle Dupont Jacques J.F. Commandeur Sylvain Lassarre Frits Bijleveld Heike Martensen Constantinos Antoniou Eleonora Papadimitriou George Yannis Elke Hermans Katherine Pérez Elena Santamariña-Rubio Davide Shingo Usami Gabriele Giustiniani 《Accident; analysis and prevention》2014
In this paper a unified methodology is presented for the modelling of the evolution of road safety in 30 European countries. For each country, annual data of the best available exposure indicator and of the number of fatalities were simultaneously analysed with the bivariate latent risk time series model. This model is based on the assumption that the amount of exposure and the number of fatalities are intrinsically related. It captures the dynamic evolution in the fatalities as the product of the dynamic evolution in two latent trends: the trend in the fatality risk and the trend in the exposure to that risk. Before applying the latent risk model to the different countries it was first investigated and tested whether the exposure indicator at hand and the fatalities in each country were in fact related at all. If they were, the latent risk model was applied to that country; if not, a univariate local linear trend model was applied to the fatalities series only, unless the latent risk time series model was found to yield better forecasts than the univariate local linear trend model. In either case, the temporal structure of the unobserved components of the optimal model was established, and structural breaks in the trends related to external events were identified and captured by adding intervention variables to the appropriate components of the model. As a final step, for each country the optimally modelled developments were projected into the future, thus yielding forecasts for the number of fatalities up to and including 2020. 相似文献
103.
William G. Buttlar Brian C. Hill Y. Richard Kim M. Emin Kutay Anne Millien Antonio Montepara Glaucio H. Paulino Christophe Petit Ion Octavian Pop Elena Romeo Riccardo Roncella Seyed Amirshayan Safavizadeh Gabriele Tebaldi Andrew Wargo 《Materials and Structures》2014,47(8):1373-1390
This paper is the outcome of a specific task group of the RILEM Technical Committee 241-MCD “Mechanisms of Cracking and Debonding in Asphalt and Composite Pavements”. The group on “Advanced Measurement Techniques” was established in 2011 to investigate DIC applications for non-destructive and non-contact measurements of strain fields during laboratory testing. The paper illustrates different DIC/optical flow applications in measuring strain distribution during laboratory testing. Specific applications of DIC for evaluating crack initiation and crack propagation in asphalt materials are presented. 相似文献
104.
Bucci S Pratesi G Viti ML Pantani M Bochicchio F Venoso G 《Radiation protection dosimetry》2011,145(2-3):202-205
Extensive radon surveys have been carried out in many countries only in dwellings, whereas surveys in workplaces are rather sparse and generally restricted to specific workplaces/activities, e.g. schools, spas and caves. Moreover, radon-prone areas are generally defined on the basis of radon surveys in dwellings, while radon regulations use this concept to introduce specific requirements in workplaces in such areas. This approach does not take into account that work activities and workplace characteristics can significantly affect radon concentration. Therefore, an extensive survey on radon in different workplaces have been carried out in a large region of Italy (Tuscany), in order to evaluate radon distribution in workplaces over the whole territory and to identify activities and workplace characteristics affecting radon concentration. The results of this extensive survey are compared with the results of the survey carried out in dwellings in the same period. The workplaces monitored were randomly selected among the main work activities in the region, including both public and industrial buildings. The survey monitored over 3500 rooms in more than 1200 buildings for two consecutive periods of ~6 months. Radon concentration was measured by means of passive nuclear track detectors. 相似文献
105.
106.
The use of wavelet transforms in thermally excited dynamic force spectroscopy allows us to gain insight into the fundamental thermodynamical properties of a cantilever's Brownian motion as well as giving a meaningful and intuitive representation of the cantilever dynamics in time and frequency caused by the interaction with long- and short-range forces. The possibility of carrying out measurements across the jump-to-contact transition without interruption, providing information on both van der Waals forces and short-range adhesion surface forces, is remarkable. 相似文献
107.
Emphasis in this article is on the design of a co‐ordinated voltage control strategy for doubly fed induction generator (DFIG) wind turbines that enhances their capability to provide grid support during grid faults. In contrast to its very good performance in normal operation, the DFIG wind turbine concept is quite sensitive to grid faults and requires special power converter protection. The fault ride‐through and grid support capabilities of the DFIG address therefore primarily the design of DFIG wind turbine control with special focus on power converter protection and voltage control issues. A voltage control strategy is designed and implemented in this article, based on the idea that both converters of the DFIG (i.e. rotor‐side converter and grid‐side converter) participate in the grid voltage control in a co‐ordinated manner. By default the grid voltage is controlled by the rotor‐side converter as long as it is not blocked by the protection system, otherwise the grid‐side converter takes over the voltage control. Moreover, the article presents a DFIG wind farm model equipped with a grid fault protection system and the described co‐ordinated voltage control. The whole DFIG wind farm model is implemented in the power system simulation toolbox PowerFactory DIgSILENT. The DFIG wind farm ride‐through capability and contribution to voltage control in the power system are assessed and discussed by means of simulations with the use of a transmission power system generic model developed and delivered by the Danish Transmission System Operator Energinet.dk. The simulation results show how a DFIG wind farm equipped with voltage control can help a nearby active stall wind farm to ride through a grid fault, without implementation of any additional ride‐through control strategy in the active stall wind farm. Copyright © 2006 John Wiley &Sons, Ltd. 相似文献
108.
Gloria Lazzeri Carla L. Busceti Francesca Biagioni Cinzia Fabrizi Gabriele Morucci Filippo S. Giorgi Michela Ferrucci Paola Lenzi Stefano Puglisi-Allegra Francesco Fornai 《International journal of molecular sciences》2021,22(13)
Norepinephrine (NE) neurons and extracellular NE exert some protective effects against a variety of insults, including methamphetamine (Meth)-induced cell damage. The intimate mechanism of protection remains difficult to be analyzed in vivo. In fact, this may occur directly on target neurons or as the indirect consequence of NE-induced alterations in the activity of trans-synaptic loops. Therefore, to elude neuronal networks, which may contribute to these effects in vivo, the present study investigates whether NE still protects when directly applied to Meth-treated PC12 cells. Meth was selected based on its detrimental effects along various specific brain areas. The study shows that NE directly protects in vitro against Meth-induced cell damage. The present study indicates that such an effect fully depends on the activation of plasma membrane β2-adrenergic receptors (ARs). Evidence indicates that β2-ARs activation restores autophagy, which is impaired by Meth administration. This occurs via restoration of the autophagy flux and, as assessed by ultrastructural morphometry, by preventing the dissipation of microtubule-associated protein 1 light chain 3 (LC3) from autophagy vacuoles to the cytosol, which is produced instead during Meth toxicity. These findings may have an impact in a variety of degenerative conditions characterized by NE deficiency along with autophagy impairment. 相似文献
109.
Gabriele Rocchini 《Corrosion Science》1993,34(12)
The characteristics of the electrochemical system and the criteria for a correct application of the method of polarization resistance aimed at the evaluation of the corrosion current density are carefully discussed. The mathematical theory of the validity of the linear approximation of the kinetic law, over a suitable interval round the mixed potential, is based on the integral representation of the remainder of the series expansion of i(ΔE). This scheme makes it possible to compare the contribution of the linear term with that due to the non-linear remainder by introducing a criterion which permits the goodness of the approximation to be verified. Numerical examples have shown that the interval width, where the system could exhibit an approximate linear behaviour, depends on the three parameters α, β and and is independent of the bending radius of the curve i = i(ΔE) at ΔE = 0. Furthermore, the absolute values of the left and right bounds ΔE1 and ΔET are usually different. They are equal only when α = β. Examination of some experimental data concerning the behaviour of Armco iron in H2SO4 I N solutions inhibited with n-decylamine has demonstrated that the choice of the proportionality factor (α + β)−1 plays an important role when measurements are aimed at a quantitative evaluation of the corrosion rate. 相似文献
110.