Por una filosofía del límite: Servio Cotta, intérprete de Montesquieu

Junto a André Masson y a Robert Shackleton, Sergio Cotta ha sido el mayor estudioso e intérprete deMontesquieu en el siglo XX. Además de haber cuidado la primera edición crítica completa del Esprit des lois (Lo spirito delle leggi, Torino, 1952), tiene elSergio Cotta, along with André Masson and Robert Shackleton, has been the most important interpreter of Montesquieu in the 20th century. Not only because he edited, although in Italian translation, the fi rst complete critical edition of the Esprit des l

Eksperimentalno ponašanje prototipa matričnog pretvarača izvedenog s novim energetskim modulima

This paper describes the design and the solutions adopted for a matrix converter prototype of 10 kW, based on new integrated power modules. The performance of the converter is verified by means of experimental tests.Članak opisuje projekt i rješenja usvojena za prototip 10 kW matričnog pretvarača, izvedenog s novim integriranim energetskim modulima. Svojstva pretvarača provjerena su eksperimentalnim ispitivanjima

Eksperimentalno ponašanje prototipa matričnog pretvarača izvedenog s novim energetskim modulima

This paper describes the design and the solutions adopted for a matrix converter prototype of 10 kW, based on new integrated power modules. The performance of the converter is verified by means of experimental tests.Članak opisuje projekt i rješenja usvojena za prototip 10 kW matričnog pretvarača, izvedenog s novim integriranim energetskim modulima. Svojstva pretvarača provjerena su eksperimentalnim ispitivanjima

ULTRASOUND AS FIRST LINE STEP IN ANAEMIA DIAGNOSTICS

This review covers the role of ultrasonography as an essential non-invasive diagnosti

Rotor magnet demagnetisation diagnosis in asymmetrical six-phase surface-mounted AC PMSM drives

Multiphase permanent-magnet synchronous machines (PMSMs) are receiving more and more interest in safety-critical modern industries owing to their higher reliability when compared with conventional three-phase PMSMs. Rotor magnets are critical components, which, in case of fault, directly affect the performance of the PMSMs. Thus, monitoring the rotor magnets status is essential to ensure both high level of efficiency and service continuity. The present study focuses on the investigation of a new approach for the detection of rotor magnet demagnetisation in a vector-controlled asymmetrical six-phase surface-mounted AC PMSM. The main contribution of the proposed technique is the assessment of a rotor demagnetisation fault index derived from the fifth and seventh harmonics of the stator voltage space vector evaluated in the α 5–β 5-plane, and already available in the control system platform. The performance of the proposed approach is evaluated using finite element analysis and numerical simulations, both validated by experimental tests

Simulated microgravity promotes the formation of tridimensional cultures and stimulates pluripotency and a glycolytic metabolism in human hepatic and biliary tree stem/progenitor cells

Many pivotal biological cell processes are affected by gravity. The aim of our study was to evaluate biological and functional effects, differentiation potential and exo-metabolome profile of simulated microgravity (SMG) on human hepatic cell line (HepG2) and human biliary tree stem/progenitor cells (hBTSCs). Both hBTSCs and HepG2 were cultured in a weightless and protected environment SGM produced by the Rotary Cell Culture System (Synthecon) and control condition in normal gravity (NG). Self-replication and differentiation toward mature cells were determined by culturing hBTSCs in Kubota's Medium (KM) and in hormonally defined medium (HDM) tailored for hepatocyte differentiation. The effects on the expression and cell exo-metabolome profiles of SMG versus NG cultures were analyzed. SMG promotes tridimensional (3D) cultures of hBTSCs and HepG2. Significative increase of stemness gene expression (p < 0.05) has been observed in hBTSCs cultured in SMG when compared to NG condition. At the same time, the expression of hepatocyte lineage markers in hBTSCs differentiated by HDM was significantly lower (p < 0.05) in SMG compared to NG, demonstrating an impaired capability of hBTSCs to differentiate in vitro toward mature hepatocytes when cultured in SMG condition. Furthermore, in HepG2 cells the SMG caused a lower (p < 0.05 vs controls) transcription of CYP3A4, a marker of late-stage (i.e. Zone 3) hepatocytes. Exo-metabolome NMR-analysis showed that both cell cultures consumed a higher amount of glucose and lower glutamate in SMG respect to NG (p < 0.05). Moreover, hBTSCs media cultures resulted richer of released fermentation (lactate, acetate) and ketogenesis products (B-hydroxybutyrate) in SGM (p < 0.05) than NG. While, HepG2 cells showed higher consumption of amino acids and release of ketoacids (3-Methyl-2-oxovalerate, 2-oxo-4-methyl-valerate) and formiate with respect to normogravity condition (p < 0.05). Based on our results, SMG could be helpful for developing hBTSCs-derived liver devices. In conclusion, SMG favored the formation of hBTSCs and HepG2 3D cultures and the maintenance of stemness contrasting cell differentiation; these effects being associated with stimulation of glycolytic metabolism. Interestingly, the impact of SMG on stem cell biology should be taken into consideration for workers involved in space medicine programs

Aberrant Metabolism in Hepatocellular Carcinoma Provides Diagnostic and Therapeutic Opportunities

Hepatocellular carcinoma (HCC) accounts for over 80% of liver cancer cases and is highly malignant, recurrent, drug-resistant, and often diagnosed in the advanced stage. It is clear that early diagnosis and a better understanding of molecular mechanisms contributing to HCC progression is clinically urgent. Metabolic alterations clearly characterize HCC tumors. Numerous clinical parameters currently used to assess liver functions reflect changes in both enzyme activity and metabolites. Indeed, differences in glucose and acetate utilization are used as a valid clinical tool for stratifying patients with HCC. Moreover, increased serum lactate can distinguish HCC from normal subjects, and serum lactate dehydrogenase is used as a prognostic indicator for HCC patients under therapy. Currently, the emerging field of metabolomics that allows metabolite analysis in biological fluids is a powerful method for discovering new biomarkers. Several metabolic targets have been identified by metabolomics approaches, and these could be used as biomarkers in HCC. Moreover, the integration of different omics approaches could provide useful information on the metabolic pathways at the systems level. In this review, we provided an overview of the metabolic characteristics of HCC considering also the reciprocal influences between the metabolism of cancer cells and their microenvironment. Moreover, we also highlighted the interaction between hepatic metabolite production and their serum revelations through metabolomics researches

Sequence, "subtle" alternative splicing and expression of the CYYR1 (cysteine/tyrosine-rich 1) mRNA in human neuroendocrine tumors

BACKGROUND: CYYR1 is a recently identified gene located on human chromosome 21 whose product has no similarity to any known protein and is of unknown function. Analysis of expressed sequence tags (ESTs) have revealed high human CYYR1 expression in cells belonging to the diffuse neuroendocrine system (DNES). These cells may be the origin of neuroendocrine (NE) tumors. The aim of this study was to conduct an initial analysis of sequence, splicing and expression of the CYYR1 mRNA in human NE tumors. METHODS: The CYYR1 mRNA coding sequence (CDS) was studied in 32 NE tumors by RT-PCR and sequence analysis. A subtle alternative splicing was identified generating two isoforms of CYYR1 mRNA differing in terms of the absence (CAG(- )isoform, the first described mRNA for CYYR1 locus) or the presence (CAG(+ )isoform) of a CAG codon. When present, this specific codon determines the presence of an alanine residue, at the exon 3/exon 4 junction of the CYYR1 mRNA. The two mRNA isoform amounts were determined by quantitative relative RT-PCR in 29 NE tumors, 2 non-neuroendocrine tumors and 10 normal tissues. A bioinformatic analysis was performed to search for the existence of the two CYYR1 isoforms in other species. RESULTS: The CYYR1 CDS did not show differences compared to the reference sequence in any of the samples, with the exception of an NE tumor arising in the neck region. Sequence analysis of this tumor identified a change in the CDS 333 position (T instead of C), leading to the amino acid mutation P111S. NE tumor samples showed no significant difference in either CYYR1 CAG(- )or CAG(+ )isoform expression compared to control tissues. CYYR1 CAG(- )isoform was significantly more expressed than CAG(+ )isoform in NE tumors as well as in control samples investigated. Bioinformatic analysis revealed that only the genomic sequence of Pan troglodytes CYYR1 is consistent with the possible existence of the two described mRNA isoforms. CONCLUSION: A new "subtle" splicing isoform (CAG(+)) of CYYR1 mRNA, the sequence and the expression of this gene were defined in a large series of NE tumors

Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer

Objectives: To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B). Methods: Thirty-seven patients randomized to either chemotherapy (C) plus B or C alone were considered for this study. D-CEUS was performed at baseline and after the first treatment cycle (day 15). Four D-CEUS perfusion parameters were considered: derived peak intensity (DPI), area under the curve (AUC), slope of wash-in (A) and time to peak intensity (TPI). Results: In patients treated with C plus B, a ≥22.5 % reduction in DPI, ≥20 % increase in TPI and ≥10 % reduction in AUC were correlated with higher progression-free survival in the C+B arm (p = 0.048, 0.024 and 0.010, respectively) but not in the C arm. None of the evaluated parameter modifications had a correlation with tumour response or overall survival. Conclusions: D-CEUS could be useful for detecting and quantifying dynamic changes in tumour vascularity as early as 15 days after the start of B-based therapy. Although these changes may be predictive of progression-free survival, no correlation with response or overall survival was found. Key Points: • D-CEUS showed early changes in liver metastasis perfusion in colorectal cancer. • A decrease in tumour perfusion was associated with longer progression-free survival. • The decrease in perfusion was not correlated with higher overall survival