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The paper presents a preliminary design activity and virtual prototyping of an innovative boat equipped with hydrofoils and hybrid propulsion, with the aim of extending the foil technology from the field of competition boats to recreational day-cruiser yachts and creating a craft with minimal environmental impact. Hydrofoils allow boats to rise from the water, greatly reducing resistance and increasing performance. The current work dealt with the preliminary design of a daysailer with foil technology and hybrid propulsion that allow to combine green and comfortable navigation both under sail and motor and that, when required, can sail in a more performing way by exploiting the foil technology and the thrust of the wind. After having deepened the theory and physics of sailing on foils, a MATLAB code was created to integrate the stability equations that characterize hydrofoil sailboats: connecting the acting forces and allowing to define the dimensions of the geometries, the code was fundamental in speeding up the iterative preliminary design process. The next step was to model the geometry of the hull and the appendages in the CAD environment and, subsequently, the wing movement mechanism so that it could both manage the incidence of the wings and retract the foils when the boat is moored. The hull, profiles, and wings were subsequently placed in a CFD and VPP virtual environment for testing their resistance. Future developments will include a detailed design and the physical prototyping of a first boat for water testing.

Building on a partner-switching mechanism, we experimentally test two theories that posit different reasons why promises breed trust and cooperation. The expectation-based explanation (EBE) operates via belief-dependent guilt aversion, while the commitment-based explanation (CBE) suggests that promises offer commitment power via a (belief-independent) preference to keep one’s word. Previous research performed a similar test, which we argue should be interpreted as concerning informal agreements rather than (unilateral) promises.

Nowadays, the adoption of In Vitro Fertilization (IVF) techniques is undergoing an impressive increase. In light of this, one of the most promising strategies is the novel use of non-physiological materials and naturally derived compounds for advanced sperm preparation methods. Here, sperm cells were exposed during capacitation to MoS2/Catechin nanoflakes and catechin (CT), a flavonoid with antioxidant properties, at concentrations of 10, 1, 0.1 ppm. The results showed no significant differences in terms of sperm membrane modifications or biochemical pathways among the groups, allowing the hypothesis that MoS2/CT nanoflakes do not induce any negative effect on the parameters evaluated related to sperm capacitation. Moreover, the addition of CT alone at a specific concentration (0.1 ppm) increased the spermatozoa fertilizing ability in an IVF assay by increasing the number of fertilized oocytes with respect to the control group. Our findings open interesting new perspectives regarding the use of catechins and new materials obtained using natural or bio compounds, which could be used to implement the current strategies for sperm capacitation.

Cytolethal distending toxin (CDT) is produced by a range of Gram-negative pathogenic bacteria such as Campylobacter jejuni. CDT represents an important virulence factor that is a heterotrimeric complex composed of CdtA, CdtB, and CdtC. CdtA and CdtC constitute regulatory subunits whilst CdtB acts as the catalytic subunit exhibiting phosphatase and DNase activities, resulting in cell cycle arrest and cell death. Extracellular vesicle (EV) secretion is an evolutionarily conserved process that is present throughout all kingdoms. Mammalian EVs play important roles in regular cell-to-cell communications but can also spread pathogen- and host-derived molecules during infections to alter immune responses. Here, we demonstrate that CDT targets the endo-lysosomal compartment, partially evading lysosomal degradation and exploiting unconventional secretion (EV release), which is largely involved in bacterial infections. CDT-like effects are transferred by Caco-2 cells to uninfected heterologous U937 and homologous Caco-2 cells. The journey of EVs derived from CDT-treated Caco-2 cells is associated with both intestinal and myeloid tumour cells. EV release represents the primary route of CDT dissemination, revealing an active toxin as part of the cargo. We demonstrated that bacterial toxins could represent suitable tools in cancer therapy, highlighting both the benefits and limitations. The global cell response involves a moderate induction of apoptosis and autophagic features may play a protective role against toxin-induced cell death. EVs from CDT-treated Caco-2 cells represent reliable CDT carriers, potentially suitable in colorectal cancer treatments. Our data present a potential bacterial-related biotherapeutic supporting a multidrug anticancer protocol.

Factory acceptance test is the inspection of equipment and components at the supplier’s premises before delivery or final inspection. However, this control can represent a considerable cost for the customer, especially when the manufacturer’s company is geographically far from the customer one and inspections must be frequent. In this paper, the authors present a framework to support the factory acceptance test based on augmented reality (AR) techniques and model-based definition aimed at dimensional checks that does not require the physical presence of the customer at the supplier's premises. The supplier must be previously equipped with an automatic measuring machine. Once the component under inspection is placed inside the machine, this reads the type and the position of the features to be measured along with the related specification limits directly from the annotated 3D model of the component. The results are automatically transmitted to the customer’s site. Through a tablet, the supplier, guided by the customer, reads the results of the measures directly on the measured object through augmented or mixed reality techniques. Any out-of-specification dimension can be remeasured in real time with the customer’s remote assistance using traditional measurement techniques. The proposed architecture, at an advanced stage of experimentation, is discussed with reference to an industrial case study proposed and using an entry level commercial 3D scanner.

Cytolethal distending toxin (CDT) is produced by a range of Gram-negative pathogenic bacteria such as

Federica Sola,1,2 Barbara Canonico,1 Mariele Montanari,1 Angela Volpe,2 Chiara Barattini,1,2 Chiara Pellegrino,2 Erica Cesarini,1 Michele Guescini,1 Michela Battistelli,1 Claudio Ortolani,1 Alfredo Ventola,2 Stefano Papa1 1Department of Biomolecular Sciences, University of Urbino Carlo Bo, Urbino, PU, 61029, Italy; 2AcZon Srl, Monte San Pietro, BO, 40050, ItalyCorrespondence: Barbara CanonicoDepartment of Biomolecular Sciences, University of Urbino Carlo Bo, Via Ca’ Le Suore 2-4, Urbino, PU, 61029, ItalyTel +39 0722 304280Email barbara.canonico@uniurb.itIntroduction: Since most biologically active macromolecules are natural nanostructures, operating in the same scale of biomolecules gives the great advantage to enhance the interaction with cellular components. Noteworthy efforts in nanotechnology, particularly in biomedical and pharmaceutical fields, have propelled a high number of studies on the biological effects of nanomaterials. Moreover, the determination of specific physicochemical properties of nanomaterials is crucial for the evaluation and design of novel safe and efficient therapeutics and diagnostic tools. In this in vitro study, we report a physicochemical characterisation of fluorescent silica nanoparticles (NPs), interacting with biological models (U937 and PBMC cells), describing the specific triggered biologic response.Methods: Flow Cytometric and Confocal analyses are the main method platforms. However TEM, NTA, DLS, and chemical procedures to synthesize NPs were employed.Results: NTB 700 NPs, employed in this study, are fluorescent core-shell silica nanoparticles, synthesized through a micelle-assisted method, where the fluorescence energy transfer process, known as FRET, occurs at a high efficiency rate. Using flow cytometry and confocal microscopy, we observed that NTB 700 NP uptake seemed to be a rapid, concentration-, energy- and cell type-dependent process, which did not induce significant cytotoxic effects. We did not observe a preferred route of internalization, although their size and the possible aggregated state could influence their extrusion. At this level of analysis, our investigation focuses on lysosome and mitochondria pathways, highlighting that both are involved in NP co-localization. Despite the main mitochondria localization, NPs did not induce a significant increase of intracellular ROS, known inductors of apoptosis, during the time course of analyses. Finally, both lymphoid and myeloid cells are able to release NPs, essential to their biosafety.Discussion: These data allow to consider NTB 700 NPs a promising platform for future development of a multifunctional system, by combining imaging and localized therapeutic applications in a unique tool.Keywords: nanoparticles, uptake, intracellular trafficking, exocytosis, multifunctional tool

Copper(II) carbosilane metallodendrimers are promising nanosized anticancer metallodrugs. The precise control on their design enables an accurate structure-to-activity study. We hypothesized that different structural features, such as the dendrimer generation and metal counterion, modulate the interaction with tumor cells, and subsequently, the effectivity and selectivity of the therapy. A computer-aided analysis of the electron paramagnetic resonance (EPR) spectra allowed us to obtain dynamical and structural details on the interactions over time between the dendrimers and the cells, the myeloid U937 tumor cells and peripheral blood mononuclear cells (PBMC). The intracellular fate of the metallodendrimers was studied through a complete in vitro evaluation, including cytotoxicity, cytostaticity, and sublethal effects regarding mitochondria function, lysosomal compartments, and autophagic organelle involvement. EPR results confirmed a higher membrane stabilization for chloride dendrimers and low generation complexes, which ultimately influence the metallodrug uptake and intracellular fate. The in vitro evaluation revealed that Cu(II) metallodendrimers are cytostatic and moderate cytotoxic agents for U937 tumor cells, inducing death processes through the mitochondria-lysosome axis as well as autophagic vacuole formation, while barely affecting healthy monocytes. The study provided valuable insight into the mechanism of action of these nanosized metallodrugs and relevant structural parameters affecting the activity.

Fluorescent silica nanoparticles (SiNPs) appear to be a promising imaging platform, showing a specific subcellular localization. In the present study, we first investigated their preferential mitochondrial targeting in myeloid cells, by flow cytometry, confocal microscopy and TEM on both cells and isolated mitochondria, to acquire knowledge in imaging combined with therapeutic applications. Then, we conjugated SiNPs to one of the most used anticancer drugs, doxorubicin (DOX). As an anticancer agent, DOX has high efficacy but also an elevated systemic toxicity, causing multiple side effects. Nanostructures are usually employed to increase the drug circulation time and accumulation in target tissues, reducing undesired cytotoxicity. We tested these functionalized SiNPs (DOX-NPs) on breast cancer cell line MCF-7. We evaluated DOX-NP cytotoxicity, the effect on the cell cycle and on the expression of CD44 antigen, a molecule involved in adhesion and in tumor invasion, comparing DOX-NP to free DOX and stand-alone SiNPs. We found a specific ability to release a minor amount of CD44+ extracellular vesicles (EVs), from both CD81 negative and CD81 positive pools. Modulating the levels of CD44 at the cell surface in cancer cells is thus of great importance for disrupting the signaling pathways that favor tumor progression.

The main aim of this article is to describe the design of a new sensor to study the electromagnetic field portions of gravitational waves. On August 17, 2017, the observation of the gravitational wave event started the era of multi-messenger astronomy. Therefore, new tools and optimal synchronization of the available telescopes are needed. The sensor that is designed is a cross-cutting technology, it is named Crystal Eye: a wide field of view in the energy field from 10 keV to 10 meV with a structure made of pixels. As the detector will be involved in the mission in 2023, the virtual prototype phase needed for optimization and production of the payload has been completed. Particular attention was paid to the results of the FEM analysis carried out to examine and predict the thermal and vibration behavior of the conceived mock-up during the launch phase and under strong temperature variations in the space environment.

According to Kant’s concept of natural religion, the moral concept of God consists in the coordinated aggregate of the concepts of holiness, goodness and justice. I argue that this concept can be used to define a critical account of religion’s role within the public sphere. In order to do so, I refer to Hermann Cohen’s philosophy of religion. Cohen undertakes to explicate a concept of religion as progress toward the “dominion of the good on earth”, especially in relation to Kant’s ideas of natural religion and ethical community. It is inferred that Cohen’s difference between progress in religion and religious progress opens a path to a definition of religion as pre-institution (religion without religion). The goal is to make the concept of religion distinct in the tradition of critical philosophy and its logic. I argue that the emancipatory project of Kantian public reason presupposes a set of rules defining the translation from postulates (Kant’s rational theism) to problems and assignments. Since natural religion is a pure practical concept of reason, religions are subject to moral evaluation. The latter being guided by the pragmatic maxim of overcoming logical and moral egoism, means that any community, even many communities at once (different cultures) can occasionally represent an ethical community, if not in the sense that an ethical community is constituted.

In a game with pre-play bilateral communication, messages may trigger moral incentives to honor promises or agreements. We hypothesize that individuals' inclination to keep a promise is highest if the counterpart requited the promise. We interpret this as an inclination to honor informal agreements. We report supporting results from an experiment.(c) 2022 Elsevier B.V. All rights reserved.

The activity and interacting ability of a polyamidoamine (PAMAM) dendrimer modified with 4-N-methylpiperazine-1,8-naphthalimide units (termed D) and complexed by Cu(ii) ions, towards healthy and cancer cells were studied. Comparative electron paramagnetic resonance (EPR) studies of the Cu(ii)-D complex are presented: coordination mode, chemical structure, flexibility and stability of these complexes, in the absence and presence of myeloid cancer cells and peripheral blood mononuclear cells (PBMC). The interactions of Cu(ii) ions in the biological media at different equilibrium times were studied, highlighting different stability and interacting conditions with the cells. Furthermore, flow cytometry and confocal analysis, trace the peculiar properties of the dendrimers in PBMC and U937 cells. Indeed, a new probe (Fly) was used as a potential fluorescent tool for biological imaging of Cu(ii). The study highlights that dendrimer and, mainly, the Cu(ii) metallodendrimer are cytotoxic agents for the cells, specifically for U937 tumor cells, inducing mitochondrial dysfunction, ROS increase and lysosome involvement. The metallodendrimer shows antitumor selectivity, fewer affecting healthy PBMC, inducing a massive apoptotic cell death on U937 cells, in line with the high stability of this complex, as verified by EPR studies. The results underline the potentiality of this metallodendrimer to be used as anticancer drug.

This paper presents an innovative safety training method based on digital ergonomics simulations and serious games, which are games that focus on education. Digital ergonomics is intended to disseminate the culture of safety among workers, while serious games are used to train the operators on specific safety procedures and verify their skills. The results of the experimentation in a real industrial environment showed that, compared to the traditional training methodology, multimedia contents and quantitative ergonomic analyses improve the level of attention and the awareness of the workers about their own safety. However, serious games turned out to be promising training tools with regard to standard operating procedures that are usually difficult or dangerous to simulate in a real working scenario without stopping production. Practitioner summary: Digital ergonomics and serious games are used to disseminate the culture of safety among the workers and for safety training. Our results show that the proposed methodology improves the level of attention and provides a better feedback about the actual skills of the workers than the standard educational strategies. Abbreviations.

First aim of this paper is to describe a methodology developed to create virtual fragments of archeological archetypes in CAD (Computer Aided Design) environment. A simple Reverse Engineering (RE) technique was adopted to reconstruct the shape of vases allowing the archeologists, and so the CAD inexpert personnel, to use it. Moreover, another relevant aspect is the definition of a procedure to simulate shape errors on the virtual prototypes to make more realistic the results. The characteristics of the fragments to be reproduced were selected by means of Design of Experiment (DOE) techniques. So, an algorithm was implemented to simulate the shape error, related to the working operations, that represents the typical noise for the feature recognition of archeological findings. Furthermore, this algorithm can make more complex the hypotheses related to the Gaussian model of simulation of the error and can adapt the value of the shape error (i.e. increasing it) according to the data gathered in archaeological excavation. The case study was based on the definition of a catalogue of archetypes of the black Campanian vases studied and classified by the archeologist J.P. Morel. The procedure conceived was applied to five (among one hundred) vases of the virtual catalogue obtaining forty instances of fragments affected by errors and so creating virtual mock-ups of typical pieces which may be found in the archeological site considered for the case study.

The fluorescent probes represent an important tool in the biological study, in fact characterization of cellular structures and organelles are an important tool-target for understanding the mechanisms regulating most biological processes. Recently, a series of polyamino-macrocycles based on 1,4,7,10-tetraazacyclododecane was synthesized, bearing one or two NBD units (AJ2NBD·4HCl) useful as sensors for metal cations and halides able to target and to detect apolar environment, as lipid membranes. In this paper, we firstly illustrate the chemical synthesis of the AJ2NBD probe, its electronic absorption spectra and its behavior regarding pH of the environment. Lack of any cellular toxicity and an efficient labelling on fresh, living cells was demonstrated, allowing the use of AJ2NBD in biological studies. In particular, this green fluorescent probe may represent a potential dye for the compartments involved in the endosomal/autophagic pathway. This research’s field should benefit from the use of AJ2NBD as a vesicular tracer, however, to ensure the precise nature of vesicles/vacuoles traced by this new probe, other more specific tests are needed.

Background We previously demonstrated how mouse spermatozoa can be efficiently stored for two years in a -80°C freezer, maintaining their ability to fertilize mouse eggs. Objectives The main objective here was to evaluate the effects of five years at -80°C compared to liquid nitrogen storage (LN2 , control condition) on mouse sperm viability, physiological parameters, and fertilization capacity. Materials and methods Three different strains were used: C57BL/6N, C57BL/6J and CD1. Flow cytometry experiments were performed to analyze sperm viability (SYBR-14 + Propidium Iodide +Hoechst33342), the intracellular calcium concentration (Fluo 3-AM), the membrane lipid disorder (Merocyanine 540), and the mitochondrial activity (MitoTracker Red) in live spermatozoa. The in vitro fertilization (IVF) was used to evaluate the sperm fertilizing ability. Results Flow cytometry analysis showed that the percentage of live cells are reduced in B6N and B6J, but not in CD1 mice. However, in the live population no differences in terms of intracellular calcium concentration, membrane lipid disorder, and mitochondrial activity were reported when comparing both biobanking methods. Spermatozoa stored at -80°C for 5 years successfully fertilized the eggs and developed mouse embryo normally both in culture and in vivo, generating live pups with no differences compared to control samples stored in LN2 . Discussion Long-term mouse sperm storage at -80°C (five years) could be considered an ideal alternative to the most common LN2 approach, giving economical and logistic advantages. Moreover, the precise information originated from the flow cytometry analysis stands up this technique as an optimal strategy to evaluate the sperm quality and ranking. Conclusion It is demonstrated here the possibility to store mouse spermatozoa for up to five years in a -80°C freezer with no significant differences compared to the storage in LN2 in terms of fertilizing ability, sperm viability, intracellular calcium concentration, membrane lipid disorder, and mitochondrial activity.

Main targets of this activity research are the making and the optimization of new detectors by means of the Systems Engineering methods. With the observation of the gravitational wave event of August 17th, 2017 and then with those of the extragalactic neutrino of September 22nd, the Multimessenger Astrophysics era began. It is a new way of exploring the Universe, powered by globally coordinated observations of several experiments. So, new X and gamma rays’ detectors solutions are needed in order to provide competitive results in the energy range 10 keV–10 meV. Here is briefly described how the Systems Engineering can improve the development of the proposal of a new technique: The Crystal Eye, a wide field of view detector with a good spatial resolution obtained thanks to a high pixelation.

Mitochondrial dysfunction is considered one of the hallmarks of ischemia/reperfusion injury. Mitochondria are plastic organelles that undergo continuous biogenesis, fusion, and fission. They can be transferred between cells through tunneling nanotubes (TNTs), dynamic structures that allow the exchange of proteins, soluble molecules, and organelles. Maintaining mitochondrial dynamics is crucial to cell function and survival. The present study aimed to assess the effects of melatonin on mitochondrial dynamics, TNT formation, and mitochondria transfer in HT22 cells exposed to oxygen/glucose deprivation followed by reoxygenation (OGD/R). The results showed that melatonin treatment during the reoxygenation phase reduced mitochondrial reactive oxygen species (ROS) production, improved cell viability, and increased the expression of PGC1α and SIRT3. Melatonin also preserved the expression of the membrane translocase proteins TOM20 and TIM23, and of the matrix protein HSP60, which are involved in mitochondrial biogenesis. Moreover, it promoted mitochondrial fusion and enhanced the expression of MFN2 and OPA1. Remarkably, melatonin also fostered mitochondrial transfer between injured HT22 cells through TNT connections. These results provide new insights into the effect of melatonin on mitochondrial network reshaping and cell survival. Fostering TNTs formation represents a novel mechanism mediating the protective effect of melatonin in ischemia/reperfusion injury.

Copper(II) carbosilane metallodendrimers are promising nanosized anticancer metallodrugs. The precise control on their design enables an accurate structure-to-activity study. We hypothesized that different structural features, such as the dendrimer generation and metal counterion, modulate the interaction with tumor cells, and subsequently, the effectivity and selectivity of the therapy. A computer-aided analysis of the electron paramagnetic resonance (EPR) spectra allowed us to obtain dynamical and structural details on the interactions over time between the dendrimers and the cells, the myeloid U937 tumor cells and peripheral blood mononuclear cells (PBMC). The intracellular fate of the metallodendrimers was studied through a complete

Heavy metals are one of the most hazardous pollutants in marine environments because of their bioaccumulation and biomagnification capabilities. Among them, cadmium (Cd) has been considered as one of the most dangerous for marine organisms. Here we incubated Ammonia cf. parkinsoniana specimens, a benthic foraminiferal taxon used in previous experiments, for up to 48 h in natural seawater with different concentrations of Cd to unravel the physiological change. We document a reduced pseudopodial activity of the Cd-treated specimens at concentrations &gt, 10&ndash, 100 ppb in comparison with the control specimens. Moreover, confocal images of Cd-treated specimens using Nile Red as a fluorescent probe reveal an enhanced intracellular neutral lipid accumulation in the form of lipid droplets at 6 h and 12 h. This bioassay experiment allows for the direct evaluation of Cd-dose to A. cf. parkinsoniana-response relationships under laboratory controlled conditions and provides complementary information to field observations as well as to water quality guidelines and thresholds.

The Gram-negative Campylobacter jejuni is a major cause of foodborne gastroenteritis in humans worldwide. The cytotoxic effects of Campylobacter have been mainly ascribed to the actions of the cytolethal distending toxin (CDT): it is mandatory to put in evidence risk factors for sequela development, such as reactive arthritis (ReA) and Guillain–Barré syndrome (GBS). Several researches are directed to managing symptom severity and the possible onset of sequelae. We found for the first time that rapamycin (RM) is able to largely inhibit the action of C. jejuni lysate CDT in U937 cells, and to partially avoid the activation of specific sub-lethal effects. In fact, we observed that the ability of this drug to redirect lysosomal compartment, stimulate ER-remodeling (highlighted by ER–lysosome and ER–mitochondria contacts), protect mitochondria network, and downregulate CD317/tetherin, is an important component of membrane microdomains. In particular, lysosomes are involved in the process of the reduction of intoxication, until the final step of lysosome exocytosis. Our results indicate that rapamycin confers protection against C. jejuni bacterial lysate insults to myeloid cells.

The Gram-negative Campylobacter jejuni is a major cause of foodborne gastroenteritis in humans worldwide. The cytotoxic effects of Campylobacter have been mainly ascribed to the actions of the cytolethal distending toxin (CDT): it is mandatory to put in evidence risk factors for sequela development, such as reactive arthritis (ReA) and Guillain&ndash, Barr&eacute, syndrome (GBS). Several researches are directed to managing symptom severity and the possible onset of sequelae. We found for the first time that rapamycin (RM) is able to largely inhibit the action of C. jejuni lysate CDT in U937 cells, and to partially avoid the activation of specific sub-lethal effects. In fact, we observed that the ability of this drug to redirect lysosomal compartment, stimulate ER-remodeling (highlighted by ER&ndash, lysosome and ER&ndash, mitochondria contacts), protect mitochondria network, and downregulate CD317/tetherin, is an important component of membrane microdomains. In particular, lysosomes are involved in the process of the reduction of intoxication, until the final step of lysosome exocytosis. Our results indicate that rapamycin confers protection against C. jejuni bacterial lysate insults to myeloid cells.

Extracellular vesicles (EVs) play a crucial role in the intercellular crosstalk. Mesenchymal stem cell-derived EVs (MSC-EVs), displaying promising therapeutic roles, contribute to the strong rationale for developing EVs as an alternative therapeutic option. EV analysis still represents one of the major issues to be solved in order to translate the use of MSC-EV detection in clinical settings. Even if flow cytometry (FC) has been largely applied for EV studies, the lack of consensus on protocols for FC detection of EVs generated controversy. Standard FC procedures, based on scatter measurements, only allows the detection of the &ldquo, tip of the iceberg&rdquo, of all EVs. We applied an alternative FC approach based on the use of a trigger threshold on a fluorescence channel. The EV numbers obtained by the application of the fluorescence triggering resulted significantly higher in respect to them obtained from the same samples acquired by placing the threshold on the side scatter (SSC) channel. The analysis of EV concentrations carried out by three different standardized flow cytometers allowed us to achieve a high level of reproducibility (CV &lt, 20%). By applying the here-reported method highly reproducible results in terms of EV analysis and concentration measurements were obtained.