Material Characterization for Reliable Resin Transfer Molding Process Simulation

Resin transfer molding (RTM) technologies are widely used in automotive, marine, and aerospace applications. The need to evaluate the impact of design and production critical choices, also in terms of final costs, leads to the wider use of numerical simulation in the preliminary phase of component development. The main issue for accurate RTM analysis is the reliable characterization of the involved materials. The aim of this paper is to present a validated methodology for material characterization to be implemented and introduce data elaboration in the ESI PAM-RTM software. Experimental campaigns for reinforcement permeabilities and resin viscosity measurement are presented and discussed. Finally, the obtained data are implemented in the software and then compared to experimental results in order to validate the described methodology

Multiphoton microscopy and ultrafast spectroscopy: Imaging meets quantum (MUSIQ) roadmap

In April 2019 the EU Marie Skłodowska-Curie Actions (MSCA) Innovative Training Networks (ITN) MUSIQ officially started. The network brought together a unique team of world-leading academics and industrial partners at the forefront of optical micro-spectroscopy and ultrafast laser technology developments merged with fundamental studies of coherent light-matter interaction phenomena, development of quantitative image analysis tools beyond state-of-the-art, and biomedical/pharmaceutical real-world applications. The unique vision of MUSIQ has been to develop and apply the next-generation optical microscopy technologies exploiting quantum coherent nonlinear phenomena. This Roadmap has been written collectively by the MUSIQ early-stage researchers and their supervisors. It provides a summary of the achievements within MUSIQ to date, with an outlook towards future directions

The Knoevenagel condensation catalysed by ionic liquids: a mass spectrometric insight into the reaction mechanism

The creation of carbon-carbon bonds is still a highly required topic in organic chemistry for the capacity to give a wide variety of new products of industrial value. Accordingly, the Knoevenagel condensation between activated methylene compounds and aldehydes is one of the most known carbon coupling reactions. In this work, the catalytic activity of imidazolium-based ionic liquids (1-butyl-3-methylimidazolium acetate, 1-butyl-3-methylimidazolium chloride, 1-methyl-3-carboxymethylimidazolium chloride) was studied under solvent-free conditions and compared with that of sodium salts (sodium chloride, sodium acetate). Mass spectrometric techniques were used to monitor the formation of the reaction products and to detect the key intermediates of the process. Based on the catalyst employed different reaction mechanisms were highlighted, thus laying the foundation for the design of more specific and efficient catalysts

Free N-heterocyclic carbenes from Br{\o}nsted acidic ionic liquids: Direct detection by electrospray ionization mass spectrometry

Rationale The occurrence of N-heterocyclic carbenes in imidazolium-based ionic liquids has long been discussed, but no spectroscopic evidence has been reported yet due to their transient nature. The insertion of an ionizable acid group into the cation scaffold of an ionic liquid which acts as a charge tag allows for the direct detection of free carbenes by mass spectrometry. Methods Three different Bronsted acidic ionic liquids were synthesized: 1-methyl-3-carboxymethylimidazolium chloride (MAICl), 1-methyl-3-carboxymethylimidazolium acetate (MAIAc) and the corresponding 2-(3-methyl-1H-imidazol-3-ium-1-yl)acetate zwitterion (MAI - H). The speciation of these compounds was then analysed by electrospray ionization ion-trap mass spectrometry in the negative ion mode. Results The C2-H deprotonation of the imidazolium cation leading to the formation of the corresponding carbene is highly affected by the basic properties of the counter-anion. In the case of MAICl and MAI - H ionic liquids, no charged species corresponding to the free N-heterocyclic carbene was detected. On the contrary, in the presence of a sufficiently basic anion, such as acetate of MAIAc ionic liquid, an intense signal related to the free carbenic species was observed without the addition of an external base. Conclusions In situ formation of free N-heterocyclic carbenes from Bronsted acidic ionic liquids was demonstrated, highlighting the crucial role of anion basicity in promoting the C2-H proton abstraction from imidazolium cations with a carboxylic side chain

Alternative macrophage polarisation associated with resistance to anti-PD1 blockade is possibly supported by the splkcing of FKBP51 immunophilin in melanoma patients

Background: FKBP51 immunophilin is abundantly expressed by immune cells. Co-inhibitory immune receptor signalling generates the splicing isoform FKBP51s. Tregs stained by FKBP51s are increased in melanoma patients and their counts are associated with anti-CTLA-4 response. An expansion of FKBP51s+PD-L1+ monocytes was measured in a group of non-responding patients to anti-CTLA-4. The aim of this work was to confirm the predictive value of response of FKBP51s+Tregs in a cohort of patients undergoing anti-PD1 treatment and shed light on a monocyte subset co-expressing PD-L1/FKBP51s. Methods: Co-cultures of organoids and autologous lymphocytes were used to confirm that tumour T-cell interaction can induce FKBP51s. PBMC immunophenotype and flow cytometry served to assess and monitor FKBP51s+Treg and FKBP51s+PD-L1+ monocytes in 22 advanced melanoma patients treated with anti-PD1. Silencing and overexpression of FKBP51s in human macrophages served to address the protein role in the tolerant macrophages' behaviour. Results: FKBP51s+Tregs count was increased in responders and had a prognostic value. Non-responders showed an early increase in FKBP51s+ PD-L1+ monocytes during anti-PD1 treatment. Manipulation of FKBP51s modulated the macrophage-phenotype, with forced protein expression promoting aspects associated with tolerance. Conclusions: FKBP51s may guide in the selection and monitoring of melanoma patient candidates to immune-checkpoint-targeted therapy. Manipulation of FKBP51s may overcome resistance

Ancient landscape changes in the North Marche region : an archaeological and geomorphological appraisal in the Cesano valley

il contributo prende in analisi il rapporto tra il popolamento antio della valle del cesano e l'evoluzione della geografia fisica, allo scopo di ricostruire le variazioni del paesaggio legate in particolare alle vicende della citt\ue0 romana di suas

VSSP-activated macrophages mediate senescence and tumor inhibition in a preclinical model of advanced prostate cancer

: Androgen deprivation therapy (ADT) is a standard therapy for prostate cancer (PCa). Though disseminated disease is initially sensitive to ADT, an important fraction of the patients progresses to castration-resistant prostate cancer (CRPC). For this reason, the identification of novel effective therapies for treating CRPC is needed. Immunotherapeutic strategies focused on macrophages as antitumor effectors, directly enhancing their tumoricidal potential at the tumor microenvironment or their adoptive transfer after ex vivo activation, have arisen as promising therapies in several cancer types. Despite several approaches centered on the activation of tumor-associated macrophages (TAMs) in PCa are under investigation, to date there is no evidence of clinical benefit in patients. In addition, the evidence of the effectiveness of macrophage adoptive transfer on PCa is poor. Here we find that VSSP, an immunomodulator of the myeloid system, decreases TAMs and inhibits prostatic tumor growth when administered to castrated Pten-deficient prostate tumor-bearing mice. In mice bearing castration-resistant Ptenpc-/-; Trp53pc-/- tumors, VSSP administration showed no effect. Nevertheless, adoptive transfer of macrophages activated ex vivo with VSSP inhibited Ptenpc-/-; Trp53pc-/- tumor growth through reduction of angiogenesis and tumor cell proliferation and induction of senescence. Taken together, our results highlight the rationale of exploiting macrophage functional programming as a promising strategy for CRPC therapy, with particular emphasis on ex vivo-activated proinflammatory macrophage adoptive transfer. Video abstract