Coupling Interrupted Fischer and Multicomponent Joullié-Ugi to Chase Chemical Diversity: from Batch to Sustainable Flow Synthesis of Peptidomimetics

The generation of peptidomimetic substructures for medicinal chemistry purposes requires effective and divergent synthetic methods. We present in this work an efficient flow process that allows quick modulation of reagents for Joullié-Ugi multicomponent reaction, using spiroindolenines as core motifs. This sterically hindered imine equivalent could successfully be diversified using various isocyanides and amino acids in generally good space-time yields. A telescoped flow process combining interrupted Fischer reaction for spiroindolenine synthesis and subsequent Joullié-Ugi-type modification resulted in product formation in very good overall yield in less than 2 hours compared to 48 hours required in batch mode. The developed protocol can be seen as a general tool for rapid and facile generation of peptidomimetic compounds. We also showcase preliminary biological assessments for the prepared compounds.     

Application of a multicriteria methodology for evaluation of energy alternatives for hydrogen production for the automotive sector – Case study

This paper presents a case study focusing on fourteen most used energy alternatives in Brazil, possible to feed large scale hydrogen production plants for the automotive sector. The evaluations are made using a Decision Making Support Method, MACBETH - Measuring Attractiveness by a Categorical Based Evaluation Technique, with the computational code M-MACBETH 3.2.0, using criteria that include economic and financial, technological, environmental and social aspects. The selected criteria that were used in the assessment, for each of the energy alternatives are capital to be invested in a plant, leveled cost of electric energy produced, CO₂ emissions, mortality rate due to the technology use and energy efficiency of technology. The main results obtained showed that photovoltaics off grid electric energy is the most attractive alternative, followed by the photovoltaic on grid alternative, for an eventual automotive hydrogen program in Brazil.     

<i>Trypanosoma rangeli:</i> growth in mammalian cells <i>in vitro</i> and action of a repositioned drug (17-AAG) and a natural extract (<i>Artemisia sp</i>. essential oil)

Trypanosoma rangeli and T. cruzi are both parasitic unicellular species that infect humans. Unlike T. cruzi, the causative agent of Chagas disease, T. rangeli is an infective and non-pathogenic parasite for humans, but pathogenic for vectors from the Rhodnius genus. Because both species can coexist in different hosts and overlap their infective cycles but very little is known about the infection of T. rangeli in mammalian cells, we decided to characterize both the development of this parasite in cell culture and the effect of therapeutic agents with potential trypanocidal action on it. We found that T. rangeli exhibits a cycle of infection in Vero cells similar to that for T. cruzi and that the repurposed drug, 17-AAG, and the natural extract Artemisia sp. essential oil produce a toxic effect on epimastigotes showing a trypanocidal action from the fifth day of culture. Both treatments also affected the infection of trypomastigotes and reduced the capacity of replication of amastigotes of T. rangeli. Since T. cruzi / T. rangeli coinfection cases have been reported, the finding of drugs with potential activity against both species could be significant in the future. Furthermore, studies of susceptibility of both species to drugs could also help to know the different mechanisms of pathogenicity in humans displayed by T. cruzi that are absent in T. rangeli     

Spermatozoa Transcriptional Response and Alterations in PL Proteins Properties after Exposure of Mytilus galloprovincialis to Mercury

Mercury (Hg) is an environmental pollutant that impacts human and ecosystem health. In our previous works, we reported alterations in the properties of Mytilus galloprovincialis protamine-like (PL) proteins after 24 h of exposure to subtoxic doses of toxic metals such as copper and cadmium. The present work aims to assess the effects of 24 h of exposure to 1, 10, and 100 pM HgCl₂ on spermatozoa and PL proteins of Mytilus galloprovincialis. Inductively coupled plasma–mass spectrometry indicated accumulation of this metal in the gonads of exposed mussels. Further, RT-qPCR analyses showed altered expression levels of spermatozoa mt10 and hsp70 genes. In Mytilus galloprovincialis, PL proteins represent the major basic component of sperm chromatin. These proteins, following exposure of mussels to HgCl₂, appeared, by SDS-PAGE, partly as aggregates and showed a decreased DNA-binding capacity that rendered them unable to prevent DNA damage, in the presence of CuCl₂ and H₂O₂. These results demonstrate that even these doses of HgCl₂ exposure could affect the properties of PL proteins and result in adverse effects on the reproductive system of this organism. These analyses could be useful in developing rapid and efficient chromatin-based genotoxicity assays for pollution biomonitoring programs.     

In Situ Attenuated Total Reflection (ATR/FT-IR) Tribometry: A Powerful Tool for Investigating Tribochemistry at the Lubricant–Substrate Interface

To investigate the chemical changes occurring at metal/lubricant interfaces under tribological conditions in the boundary-lubrication regime, an in situ system for conducting quantitative tribological measurements has been constructed by combining an attenuated total reflection Fourier-transform infrared (ATR/FT-IR) spectrometer with a reciprocating tribometer. By periodically acquiring ATR/FT-IR spectra during sliding, spectroscopic changes due to thermal and/or tribochemical reactions occurring at the metal/oil interface can be monitored and correlated with friction measurements. The usefulness of this tribological test system has been demonstrated by performing ATR tribological experiments in the presence of a poly-α-olefin base oil at high temperature (423 K) on iron-coated germanium ATR crystals.     

Implementation and evaluation of an Asbru-based decision support system for adjuvant treatment in breast cancer

The domain of cancer treatment is a promising field for the implementation and evaluation of a protocol-based clinical decision support system, because of the algorithmic nature of treatment recommendations. However, many factors can limit such systems’ potential to support the decision of clinicians: technical challenges related to the interoperability with existing electronic patient records and clinical challenges related to the inherent complexity of the decisions, often collectively taken by panels of different specialists. In this paper, we evaluate the performances of an Asbru-based decision support system implementing treatment protocols for breast cancer, which accesses data from an oncological electronic patient record. Focusing on the decision on the adjuvant pharmaceutical treatment for patients affected by early invasive breast cancer, we evaluate the matching of the system's recommendations with those issued by the multidisciplinary panel held weekly in a hospital.     

Modeling and control of an airbrake electro‐hydraulic smart actuator

In this paper, an accurate model of an airbrake electro‐hydraulic smart actuator is obtained by physical considerations, and then different control strategies (variable‐gain proportional control, PT₁ control with switching integrator, and second order sub‐optimal sliding mode control) are proposed and analyzed. This application is innovative in the avionic field, and is one of the first attempts to realize a fly‐by‐wire system for airbrakes, oriented to its immediate employment and installation on current aircraft. The project was carried on with the participation of the Italian Ministry of Defense, and was commissioned to MAG, a leading provider of integrated systems and aviation services for aerospace. Copyright © 2011 John Wiley and Sons Asia Pte Ltd and Chinese Automatic Control Society     

Effect of stocking density and group size on growth performance,carcass traits and meat quality of outdoor-reared rabbits

The effect of stocking density (16 rabbits/m², 5 rabbits/m², 2.5 rabbits/m², n = 60, Experiment 1) and group size (4 rabbits/cage, 8 rabbits/cage, 16 rabbits/cage, n = 88, Experiment 2) on productive performance, carcass and meat quality of a slow-growing rabbit population reared outdoors was investigated in two experiments. The highest stocking density induced the highest skin percentage. Lower stocking densities showed lower lightness of Biceps femoris and higher redness of Longissimus lumborum muscles. Four rabbits/cage group (Experiment 2) showed the highest daily weight gain and slaughter weight and the lowest skin percentage. The muscles of 16 rabbits/cage showed significantly higher pHu than 8 and 4 rabbits/cage. BF of 16 and 4 rabbits/cage showed higher L* value. Productive performance and meat quality of rabbits reared outdoors improved in low group size while stocking density needs more experiments. The best combination of density, group size and total available surface that showed the best production and carcass traits was of 5 rabbits/m², 4 rabbits/cage, and 0.8 m².