Synthesis and Biological Evaluation of Papain‐Family Cathepsin L‐Like Cysteine Protease Inhibitors Containing a 1,4‐Benzodiazepine Scaffold as Antiprotozoal Agents

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.     

Development of an Expert Model to Assess Falls from Height Hazards in Construction Sites

This paper reports on the current state of an ongoing research project which is aimed at implementing intelligent models for hardly predictable hazard scenarios identification in construction sites. As any programmatic actions cannot deal with the unpredictable nature of many risk dynamics, an attempt to improve the current approach for safety management in the construction industry will be presented in this paper. To this aim, the features offered by Bayesian networks have been exploited. The present research has led to the definition of a probabilistic model using elicitation techniques from subjective knowledge. This model, which might be meant as a reliable knowledge map about accident dynamics, showed that a relevant part of occurrences fall in the ＂hardly predictable hazards＂ category, which cannot be warded off by programmatic safety measures. Hence, more effort turned out to be needed in order to manage those hardly predictable hazardous scenarios. Consequently, further developments of this research project will focus on a real time monitoring system for the identification of unpredictable hazardous events in construction.     

Influence of Boundaries on Shear-driven Flow of Liquids in Open Cavities

In recent years, the development of two-phase flow cooling systems in micro-electronic as well as surface coating/patterning technologies, often based on thin films and liquid filled micro-enclosures, has renewed the interest in the classical problem of the cavity flow driven by a shear stress imposed at the gas-liquid boundary. In this paper, we study, numerically, the influence of the cavity geometry and boundaries on the three dimensional velocity field driven by a shear flow of inert gas. This study has been performed in the frame of the ESA sponsored Space Program on heat and mass transfer CIMEX-1 and it has to be considered as a contribution in the preparation of the Space experiment. The reference values for the flow parameters as well as the geometrical features encountered in the present paper target the main features of the CIMEX-1 experiment, although the main conclusions can be considered of general validity.     

Microwave-assisted photochemical reactor for the online oxidative decomposition and determination of p-hydroxymercurybenzoate and its thiolic complexes by cold vapor generation atomic fluorescence detection

We developed a photochemical method for the online oxidation of p-hydroxymercurybenzoate (PHMB), an organic mercury species widely used for mercaptan and thiolic compound labeling. The method is based on a fully integrated online UV/microwave (MW) photochemical reactor for the digestion of PHMB, followed by cold vapor generation atomic fluorescence spectrometry (CVG-AFS) detection. The MW/UV process led to the quantitative conversion of PHMB and thiol-PHMB complexes to Hg(II), with a yield between 91% and 98%, without using chemical oxidizing reagents and avoiding the use of toxic carcinogenic compounds. This reaction was followed by the reduction of Hg(II) to Hg(0), performed in a knitted reaction coil with NaBH(4) solution, and AFS detection in an Ar/H(2) miniaturized flame. The low MW power applied (18 W) allowed us to keep constant the temperature of the photochemical reactor (21 ± 1 °C), using a flowing water bath. This avoided peak widening due to diffusion processes generally occurring at high temperatures and in the additional cooling coil. This method has been applied to the determination of thiols in human plasma, blood, and wine.     

Enantiodifferentiation of solerol isomers in dried figs and dates

Concentrates of dried fig (Ficus carica L.) and dried date (Phoenix dactylifera L.) fruits were obtained by solvent extraction (pentane: dichloromethane, 2∶1 by vol) and subsequently analysed by HRGC-MS. Using multidimensional gas chromatography (DB-Wax/oktakis2, 6-di-O-methyl-3-O-pentyl-γ-cyclodextrin) simultaneous enantiodifferentiation of 4,5-dihydroxyhexanoic acid-γ-lactone isomers (solerol) was carried out. The presence of this constituent is reported for the first time in figs and dates. Enantiomeric excesses of 80% and 90% were determined for the (4R,5R)-isomer in figs and dates, respectively.     

Gender and smoking cessation: A factor structure comparison of processes of change.

This study examined gender differences in the pattern of process use for smoking cessation using the Processes of Change Questionnaire (J. O. Prochaska et al; see record 1989-03620-001). The goals were (a) to determine the degree to which the covariance structure of the Processes of Change Questionnaire is invariant across gender, (b) to test the existence of the theoretical 2-factor process model using confirmatory factor analysis, and (c) to explore mean differences, if found, in the use of the 10 processes of change across 4 stages of change (precontemplation, contemplation, preparation, and action). The sample (N?=?516) had an equal distribution of men and women across the stages of change. Results demonstrated that the structure of the measure for men and women was invariant at the level of the variance–covariance matrices and that the hypothesized 2-factor model fit the data. Only stage of change predicted the experiential and behavioral process factors. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

A note on optimal metering schemes

A metering scheme is a method by which an audit agency is able to measure the interaction between servers (e.g., web servers) and clients (e.g., browsers) during a certain number of time frames. Metering schemes involve distributing information to clients and servers. Obviously, such information distribution affects the overall communication complexity. A metering scheme is said to be optimal if the information distributed to clients and servers is the minimum possible.Optimal metering schemes have been proposed by Naor and Pinkas [Lecture Notes in Comput. Sci., Vol. 1403, pp. 576-590] and Masucci and Stinson [Lecture Notes in Comput. Sci., Vol. 1895, pp. 72-87). In this paper we show a construction for optimal metering schemes, called the vector space construction, that generalizes previous constructions for optimal metering schemes.