DesyreML: a SysML profile for heterogeneous embedded systems

International audienceWe propose a novel language for the formal description of heterogeneous embedded systems (DesyreML). As the main contribution, the language is formally described in terms of semantics and concrete syntax based on the SysML language. We define the concept of thick connector to allow for heterogeneous components communication and computation for multiple semantic domains (synchronous reactive, continuous time, discrete time, discrete-event). As technological application, a verification flow based on model-transformation techniques is described showing the use of an enriched version of the SystemC-AMS simulation kernel that is capable of simulating heterogeneous systems containing combinatorial loops. Finally, the language and the analysis flow are applied to a cruise control case study

Heritability and Demographic Analyses in the Large Isolated Population of Val Borbera Suggest Advantages in Mapping Complex Traits Genes

Isolated populations are a useful resource for mapping complex traits due to shared stable environment, reduced genetic complexity and extended Linkage Disequilibrium (LD) compared to the general population. Here we describe a large genetic isolate from the North West Apennines, the mountain range that runs through Italy from the North West Alps to the South.The study involved 1,803 people living in 7 villages of the upper Borbera Valley. For this large population cohort, data from genealogy reconstruction, medical questionnaires, blood, anthropometric and bone status QUS parameters were evaluated. Demographic and epidemiological analyses indicated a substantial genetic component contributing to each trait variation as well as overlapping genetic determinants and family clustering for some traits.The data provide evidence for significant heritability of medical relevant traits that will be important in mapping quantitative traits. We suggest that this population isolate is suitable to identify rare variants associated with complex phenotypes that may be difficult to study in larger but more heterogeneous populations

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO

Objectives: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. Methods: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. Results: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). Conclusions: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. Clinical relevance: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients

Anti-proliferative effect of Rosmarinus officinalis L. extract on human melanoma A375 cells

Rosemary (Rosmarinus officinalis L.) has been used since ancient times in traditional medicine, while nowadays various rosemary formulations are increasingly exploited by alternative medicine to cure or prevent a wide range of health disorders. Rosemary's bioproperties have prompted scientific investigation, which allowed us to ascertain antioxidant, anti-inflammatory, cytostatic, and cytotoxic activities of crude extracts or of pure components. Although there is a growing body of experimental work, information about rosemary's anticancer properties, such as chemoprotective or anti-proliferative effects on cancer cells, is very poor, especially concerning the mechanism of action. Melanoma is a skin tumor whose diffusion is rapidly increasing in the world and whose malignancy is reinforced by its high resistance to cytotoxic agents; hence the availability of new cytotoxic drugs would be very helpful to improve melanoma prognosis. Here we report on the effect of a rosemary hydroalcoholic extract on the viability of the human melanoma A375 cell line. Main components of rosemary extract were identified by liquid chromatography coupled to tandem mass spectrometry (LC/ESI-MS/MS) and the effect of the crude extract or of pure components on the proliferation of cancer cells was tested by MTT and Trypan blue assays. The effect on cell cycle was investigated by using flow cytometry, and the alteration of the cellular redox state was evaluated by intracellular ROS levels and protein carbonylation analysis. Furthermore, in order to get information about the molecular mechanisms of cytotoxicity, a comparative proteomic investigation was performed

AIRO Breast Cancer Group Best Clinical Practice 2022 Update

Introduction: Breast cancer is the most common tumor in women and represents the leading cause of cancer death. Radiation therapy plays a key-role in the treatment of all breast cancer stages. Therefore, the adoption of evidence-based treatments is warranted, to ensure equity of access and standardization of care in clinical practice.Method: This national document on the highest evidence-based available data was developed and endorsed by the Italian Association of Radiation and Clinical Oncology (AIRO) Breast Cancer Group.We analyzed literature data regarding breast radiation therapy, using the SIGN (Scottish Intercollegiate Guidelines Network) methodology (www.sign.ac.uk). Updated findings from the literature were examined, including the highest levels of evidence (meta-analyses, randomized trials, and international guidelines) with a significant impact on clinical practice. The document deals with the role of radiation therapy in the treatment of primary breast cancer, local relapse, and metastatic disease, with focus on diagnosis, staging, local and systemic therapies, and follow up. Information is given on indications, techniques, total doses, and fractionations.Results: An extensive literature review from 2013 to 2021 was performed. The work was organized according to a general index of different topics and most chapters included individual questions and, when possible, synoptic and summary tables. Indications for radiation therapy in breast cancer were examined and integrated with other oncological treatments. A total of 50 questions were analyzed and answered.Four large areas of interest were investigated: (1) general strategy (multidisciplinary approach, contraindications, preliminary assessments, staging and management of patients with electronic devices); (2) systemic therapy (primary, adjuvant, in metastatic setting); (3) clinical aspects (invasive, non-invasive and micro-invasive carcinoma; particular situations such as young and elderly patients, breast cancer in males and cancer during pregnancy; follow up with possible acute and late toxicities; loco-regional relapse and metastatic disease); (4) technical aspects (radiation after conservative surgery or mastectomy, indications for boost, lymph node radiotherapy and partial breast irradiation).Appendixes about tumor bed boost and breast and lymph nodes contouring were implemented, including a dedicated web application. The scientific work was reviewed and validated by an expert group of breast cancer key-opinion leaders.Conclusions: Optimal breast cancer management requires a multidisciplinary approach sharing therapeutic strategies with the other involved specialists and the patient, within a coordinated and dedicated clinical path. In recent years, the high-level quality radiation therapy has shown a significant impact on local control and survival of breast cancer patients. Therefore, it is necessary to offer and guarantee accurate treatments according to the best standards of evidence-based medicine

SINTESI E CARATTERIZZAZIONE DI BASI DI LEWIS E IL LORO UTILIZZO COME COMPONENTE DEI CATALIZZATORI DI ZIEGLER-NATTA PER LA POLIMERIZZAZIONE DEL PROPILENE

Grazie alle sue eccellenti proprietà di polimero termoplastico, il polipropilene e i copolimeri a base di propilene la sua produzione e utilizzo hanno avuto una rapida crescita dalla prima commercializzazione nel 1957. La catalisi di Ziegler-Natta è il più importante processo per la produzione industriale di polipropilene con un elevato grado di cristallinità (espressa come isotatticità). La maggior parte dei catalizzatori di Ziegler-Natta per la polimerizzazione stereospecifica delle olefine sono a base di MgCl2 (che funge da supporto), TiCl4 che è la reale specie catalitica, un co-catalizzatore, che di solito è un trialchilalluminio derivato, e una coppia di base di Lewis denominate donor interno ed esterno. In particolare, il donor interno, che è aggiunta in fase di preparazione del catalizzatore, gioca un ruolo fondamentale nell’impartire al catalizzatore l’attività e la stereospecificità durante la polimerizzazione. Quindi, lo scouting di nuovi donor interni è una parte importante nella ricerca e sviluppo a livello industriale, in quanto assicura un continuo avanzamento tecnologico e una vantaggio competitivo sugli altri players industriali. In questa tesi, una nuova classe di molecole da utilizzare come donor interni è stata valutata. Questa classe di donor non era mai stata descritta prima d’ora della letteratura brevettuale. La prima parte del lavoro di sintesi è stata focalizzata sulla preparazione di una libreria di molecole con diversi tipi di sostituenti, in modo da identificare quali frammenti fossero in grado di impartire al catalizzatore le migliori prestazioni in polimerizzazione. Successivamente, una seconda fase di sintesi di nuove strutture ha permesso l’identificazione della migliore combinazione di sostituenti sulla scheletro strutturale del donor. Allo stesso tempo, un lavoro teorico computazione è stato effettuato al fine di razionalizzare l’effetto dei sostituenti (dal punto di vista sterico ed elettronico) di una classe di donor interni sulle performance in polimerizzazione. Diversi modelli di fitting sono stati costruiti e quelli con la migliore correlazione (R2) tra dati calcolati e sperimentali sono stati utilizzati per predire la struttura di nuovi donor con elevate prestazioni in polimerizzazione.Due to the excellent properties as thermoplastic polymers, polypropylene and polypropylene-based copolymers, have become the fastest growing general resins since their commercialization in 1957. Ziegler-Natta catalysis is one of the most important industrial process in the mass production of polypropylene with a high degree of isotacticity. Most of the Ziegler- Natta catalysts for stereospecific olefin polymerization contain MgCl2 as support, TiCl4 as the actual catalytic center, a trialkyl aluminum as cocatalyst, and two Lewis bases acting as internal and external donors. In particular, the internal donor, which is added during catalyst synthesis, plays a fundamental role in defining the activity and stereospecificity of the catalyst during polymerization. So, scouting of new internal donors is a crucial task for R&D in industry, which ensure continuous technology advancement and competitive advantage over the principal industrial players. In this thesis, a new class of molecules to be used as internal donors, never described before in patent literature, has been scouted. The first part of the synthetic work has been focused on preparation of a library of compounds with different kind of substituents on their structures. This allowed us to identify which moieties were able to impart the best performance to the catalysts. Then, a second round of donors synthesis has been done in order to fine-tune the structure/performance relationship and thus to find the best combination of substituents on the donor. At the same time, a computational work has been done to rationalize the effect of substituents on the internal donors (from a steric and electronic point of view) on polymerization catalyst performance and different fitting training models (calculated molecular descriptors vs experimental catalysts property) have been built. Using the models which gave the best correlation (R2) between calculated and experimental data, an in silico prediction of structures of new performing internal donors has been attempted

Progettazione di un gruppo test di integrità per sacche farmaceutiche

Nel quarto capitolo introduco il problema e spiego il funzionamento generale della macchina senza essere troppo dettagliato per mantenere i segreti industriali che siamo tenuti a rispettare. Le proposte di soluzioni sono state sviluppate sia da me, ragionando sul gruppo singolo ma anche sul gruppo complessivo in generale, altre invece sono state proposte dal mio correlatore, l’ingegner Fabrizio Rimondi, e anche il confronto con altri colleghi dell’ufficio tecnico è stato fondamentale per la realizzazione e il funzionamento del gruppo. Nel capitolo successivo ho spiegato in dettaglio le mie idee di soluzioni mettendo i relativi disegni di ogni componente di volta in volta dopo ogni modifica significativa. Ad ogni proposta ho cercato sempre di mettere le mie opinioni in merito cercando di valutare al meglio ogni tipo di approccio. Durante lo studio dei vari casi mi sono interfacciato continuamente con i fornitori per sapere se alcune delle nostre idee fossero realizzabili e quindi capire se continuare con una certa decisione o cambiare metodo di risoluzione. Dopo aver ideato 4 tipi di soluzioni abbiamo avuto un confronto con l’azienda cliente sentendo anche la loro opinione e arrivando alla decisione finale, portando delle modifiche a una delle soluzioni che ci è sembrata la più adatta al caso. Successivamente per capire se quel tipo di soluzione fosse possibile da implementare ho cercato vari fornitori per sentire la loro opinione e sapere se alcuni componenti fossero realizzabili portando le ultime modifiche alle singole parti. Successivamente nel settimo capitolo ho iniziato uno studio sul gruppo pompa da scegliere per collegarlo al gruppo oggetto di studio. Inizialmente ho fatto un’introduzione generale sulle pompe a vuoto e compressori volumetrici, dopodiché ho cercato, tra i vari cataloghi disponibili su internet, una pompa a vuoto idonea per i parametri richiesti dall’azienda cliente