Role of Epithelial–Mesenchymal Plasticity in Pseudomyxoma Peritonei: Implications for Locoregional Treatments

The mechanisms by which neoplastic cells disseminate from the primary tumor to metastatic sites, so-called metastatic organotropism, remain poorly understood. Epithelial–mesenchymal transition (EMT) plays a role in cancer development and progression by converting static epithelial cells into the migratory and microenvironment-interacting mesenchymal cells, and by the modulation of chemoresistance and stemness of tumor cells. Several findings highlight that pathways involved in EMT and its reverse process (mesenchymal–epithelial transition, MET), now collectively called epithelial–mesenchymal plasticity (EMP), play a role in peritoneal metastases. So far, the relevance of factors linked to EMP in a unique peritoneal malignancy such as pseudomyxoma peritonei (PMP) has not been fully elucidated. In this review, we focus on the role of epithelial–mesenchymal dynamics in the metastatic process involving mucinous neoplastic dissemination in the peritoneum. In particular, we discuss the role of expression profiles and phenotypic transitions found in PMP in light of the recent concept of EMP. A better understanding of EMP-associated mechanisms driving peritoneal metastasis will help to provide a more targeted approach for PMP patients selected for locoregional interventions involving cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.     

A comparison between the axial flux and the radial flux structures for PM synchronous motors

The aim of this paper is the comparison of the axial flux (AF) structures versus the conventional radial flux (RF) structures for permanent-magnet synchronous motors. The comparison procedure is based on simple thermal considerations. Two motor typologies are chosen and compared in terms of delivered electromagnetic torque. The comparison is developed for different motor dimensions and the pole number influence is put into evidence. The paper reports the complete comparison procedure and the related results analysis. The obtained results show that, when the axial length is very short and the pole number is high, the AF motors can be an attractive alternative to the conventional RF solutions.     

No tooling cost process for induction motors energy efficiency improvements

In this paper, the analysis of some possibilities for increasing the induction motor efficiency using production technological process modifications is reported. This approach is known as the "no tooling cost" (NTC) strategy because it does not require a complete redesign of new laminations with a consistent cost in terms of investments. The paper shows the results obtained by a full experimental approach, using "ad hoc" prototypes. The NTC design modification and the technological processes analyzed in this paper have been done on totally enclosed fan-cooled standard induction motors. Obviously, the original motors have been compared from the energetic point of view with these prototypes. The energetic performance has been measured in accordance with the IEEE Std. 112-96 Method B. In particular, the following modifications, for obtaining an increase in efficiency, have been taken into consideration: rotor with copper bar included in the slot before the aluminum die cast, increase of the core axial length, and annealing of the stator core.     

Rationally designed inhibitors as tools for comparing the mechanism of squalene-hopene cyclase with oxidosqualene cyclase

The inhibition of squalene-hopene cyclase (SHC) (E.C. 5.4.99.-), an enzyme of bacterial membranes catalyzing the formation of pentacyclic sterol-like triterpenes, was studied by using different classes of compounds originally developed as inhibitors of oxidosqualene cyclase (OCS) (E.C. 5.4.99.7), the enzyme of eukaryotes responsible for the formation of tetracyclic precursors of sterols. The mechanism of cyclization of squalene by SHC, beginning with a protonation of the 2,3 double bond by an acidic residue of the enzyme, followed by a series of electrophilic additions of the carbocationic intermediates to the double bonds, is similar to the mechanism of cyclization of 2,3-oxidosqualene by OSC. The inhibitors studied included: (i) analogs of the carbocationic intermediates formed during cyclization, such as aza-analogs of squalene and 2,3-oxidosqualene; (ii) affinity-labeling inhibitors bearing a methylidene reactive group; and (iii) vinyldioxidosqualenes and vinylsulfide derivatives of the substrates. Comparison of the results obtained with the two enzymes, SHC and OSC, showed that many of the most effective inhibitors of OSC were also able to inhibit SHC, while some derivatives acted as specific inhibitors. Differences could be easily explained on the basis of the different substrate specificity of the two enzymes.     

THROO: a Tracked Hybrid Rover to Overpass Obstacles

In this paper, the design, simulation and experimental tests are presented for THROO: a Tracked Hybrid Rover, which has been developed to Overpass Obstacles. The proposed mobile robot has 3-DOFs and it is capable of straight motion, turning ability and two operations, namely rover-like motion with tracks on flat terrain and walking-like motion with track and legs to overpass obstacles to move on uneven terrain. The leg mechanism is composed of a four-bar linkage, which has been synthesized according to the desired features. In particular, the Burmester problem, which aims at finding the geometric parameters of a four-bar linkage required for a prescribed set of finitely separated poses are solved for the case understudy. Dynamic simulations have been carried out and a prototype has been built. The proposed results show the hybrid rover ability to overpass obstacles, for which size is comparable or greater than the track high.     

Synthesis and catalytic activity of optically active polymers containing oxime groups

Optically active polymers containing oxime groups have been prepared: (i) by partial quaternization of poly(4-vinyl pyridine) (P4VP) with phenacyloxime bromide and with (+)-(S)-1-bromo-2-methylbutane; and (ii) by reaction of the copolymer from 4VP and (+)-(S)-5-methyl-1-hepten-3-one with hydroxylamine. These polymers have been used as catalysts for the esterolysis of esters of p-nitrophenol with non-chiral and with chiral acids. The kinetic parameters of the catalytic process are markedly dependent on the structure of polymer and substrate. A moderate chiral discrimination of the antipodes of p-nitrophenyl 2-methylbutanoate is observed with the catalyst obtained from the copolymer of 4VP with (+)-(S)-5-methyl-1-hepten-3-one.     

Access of the substrate to the active site of yeast oxidosqualene cyclase: an inhibition and site-directed mutagenesis approach

A structural model of Saccharomyces cerevisiae oxidosqualene cyclase (SceOSC) suggests that some residues of the conserved sequence Pro-Ala-Glu-Val-Phe-Gly (residues 524-529) belong to a channel constriction that gives access to the active-site cavity. Starting from the SceOSC C457D mutant, which lacks the cysteine residue next to the catalytic Asp456 residue Cys457 has been replaced but Asp456 is still there, we prepared two further mutants where the wild-type residues Ala525 and Glu526 were individually replaced by cysteine. These mutants, especially E526C, were very sensitive to the thiol-reacting agent dodecyl-maleimide. Moreover, both the specific activity and the thermal stability of E526C were severely reduced. A similar decrease of the enzyme functionality was obtained by replacing Glu526 with alanine, while substitution with the conservative residues aspartate or glutamine did not alter catalytic activity. Molecular modeling of the yeast wild-type OSC and mutants on the template structure of human OSC confirms that the channel constriction is an important aspect of the protein structure and suggests a critical structural role for Glu526.