Investigation of the mechanisms governing doxorubicin and irinotecan release from drug-eluting beads: mathematical modeling and experimental verification

Drug-eluting beads (DEBs) are embolising devices in clinical use for the treatment of liver cancer by transarterial chemoembolisation. In this study, release kinetics of doxorubicin (DOX) and irinotecan (IRI) were investigated by experimental evaluations and mathematical modeling, based on Langmuir isotherm and two phenomenological models (Boyd/Bhaskar) developed to determine the actual mechanisms controlling drug release rate. The model was validated through release studies, in particular by assessing how drug loading, ionic strength of the release medium and device swelling during release influence drug release kinetics. Results demonstrated that IRI is released much faster than DOX, and that DEB volume strongly depends upon drug loading and fractional release. This effect was properly taken into account in developing the mathematical model. Experimental results were well fit by numerical simulations, and two different rate-controlling mechanisms were found to govern DOX and IRI delivery.     

Ambidextrous strategy and execution in entrepreneurial project-oriented organizations: The case of Pagani supercars

This research explores the dynamics underpinning entrepreneurial project-oriented organizations. Specifically, it focuses on how strategy and execution by projects are managed and how ambidexterity – a firm's ability to exploit old certainties while exploring new possibilities – operates as a logic. The empirical findings from an explorative longitudinal research of supercar maker Pagani Automobili in the period 2007–2019, offer an insight of a complex entrepreneurially led project-oriented organization and suggest three integrative mechanisms that describe the ambidextrous management of the interplay within and between strategy and project levels. Additionally, this research recognizes the critical role of projects also in entrepreneurial environments and suggests that the accomplishment of ambidexterity is unique in nature as it is aimed at reconciling the uniqueness of competitive propositions and that of projects within a unique entrepreneurial environment, opening avenues for more theoretical and empirical studies at the intersection of project management and entrepreneurship.     

Does carbon nanopowder threaten amphibian development?

Lethal and teratogenic potentials of carbon nanoparticles (CNPs) in their amorphous form were investigated by the standardized Frog Embryo Teratogenesis Assay-Xenopus (FETAX), a 96-h in vitro whole-embryo toxicity test based on the amphibian Xenopus laevis. Embryos were acutely exposed to 1, 10, 100 and 500 mg/L CNP suspensions and evaluated for lethality, malformations and growth inhibition. Larvae were processed for histological and ultrastructural analyses to detect the main affected organs, to look for specific lesions at the subcellular level and to image and track CNPs into tissues. Only the highest CNP suspension resulted in being embryolethal for X. laevis larvae, while malformed larva percentages significantly differed from controls starting from 100 mg/L. The stomach and gut were the preferential CNP accumulation sites, on the contrary, the digestive epithelium remained intact. The analyses showed the presence of isolated nanoparticles and/or aggregates in different secondary target organs. CNPs were found in circulating erythrocytes. The research confirms the good tolerance of X. laevis towards pure elemental carbon in its nanoparticulate amorphous form, but highlights the possibility of CNP transfer toward all body areas.     

Optimization by record dynamics

Large dynamical changes in thermalizing glassy systems are triggered by trajectories crossing record sized barriers, a behavior revealing the presence of a hierarchical structure in configuration space. The observation is here turned into a novel local search optimization algorithm dubbed record dynamics optimization, or RDO. RDO uses the Metropolis rule to accept or reject candidate solutions depending on the value of a parameter akin to the temperature and minimizes the cost function of the problem at hand through cycles where its ‘temperature’ is raised and subsequently decreased in order to expediently generate record high (and low) values of the cost function. Below, RDO is introduced and then tested by searching for the ground state of the Edwards–Anderson spin-glass model, in two and three spatial dimensions. A popular and highly efficient optimization algorithm, parallel tempering (PT), is applied to the same problem as a benchmark. RDO and PT turn out to produce solutions of similar quality for similar numerical effort, but RDO is simpler to program and additionally yields geometrical information on the system’s configuration space which is of interest in many applications. In particular, the effectiveness of RDO strongly indicates the presence of the above mentioned hierarchically organized configuration space, with metastable regions indexed by the cost (or energy) of the transition states connecting them.     

Role of Btg2 in the Progression of a PDGF-Induced Oligodendroglioma Model

Tumor progression is a key aspect in oncology. Not even the overexpression of a powerful oncogenic stimulus such as platelet derived growth factor-B (PDGF-B) is sufficient per se to confer full malignancy to cells. In previous studies we showed that neural progenitors overexpressing PDGF-B need to undergo progression to acquire the capability to give rise to secondary tumor following transplant. By comparing the expression profile of PDGF-expressing cells before and after progression, we found that progressed tumors consistently downregulate the expression of the antiproliferative gene Btg2. We therefore tested whether the downregulation of Btg2 is sufficient and necessary for glioma progression with loss and gain of function experiments. Our results show that downregulation of Btg2 is not sufficient but is necessary for tumor progression since the re-introduction of Btg2 in fully progressed tumors dramatically impairs their gliomagenic potential. These results suggest an important role of Btg2 in glioma progression. Accordingly with this view, the analysis of public datasets of human gliomas showed that reduced level of Btg2 expression correlates with a significantly worse prognosis.     

Optimal radio resources and transmission formats assignment in OFDMA systems

The problem of assigning radio resources and transmission formats to users in the downlink of an OFDMA network is addressed. In particular, a single cell environment with a realistic interference model and a margin adaptive approach is considered, i.e., the aim is of minimizing the total transmission power while maintaining a certain given rate for each user. The computational complexity issues of the problem are discussed, and an approximation analysis is presented. Heuristic approaches, based on rounding techniques and graph models, are also proposed. Computational experiences show that, in a comparison with a commercial state-of-the-art optimization solver and with alternatives from the literature, the proposed algorithms are effective in terms of solution quality and CPU times.     

Relationship between Non-Alcoholic Fatty Liver Disease and Psoriasis: A Novel Hepato-Dermal Axis?

Over the past 10 years, it has become increasingly evident that nonalcoholic fatty liver disease (NAFLD) is a multisystem disease that affects multiple extra-hepatic organ systems and interacts with the regulation of several metabolic and immunological pathways. In this review we discuss the rapidly expanding body of clinical and epidemiological evidence supporting a strong association between NAFLD and chronic plaque psoriasis. We also briefly discuss the possible biological mechanisms underlying this association, and discuss treatment options for psoriasis that may influence NAFLD development and progression. Recent observational studies have shown that the prevalence of NAFLD (as diagnosed either by imaging or by histology) is remarkably higher in psoriatic patients (occurring in up to 50% of these patients) than in matched control subjects. Notably, psoriasis is associated with NAFLD even after adjusting for metabolic syndrome traits and other potential confounding factors. Some studies have also suggested that psoriatic patients are more likely to have the more advanced forms of NAFLD than non-psoriatic controls, and that psoriatic patients with NAFLD have more severe psoriasis than those without NAFLD. In conclusion, the published evidence argues for more careful evaluation and surveillance of NAFLD among patients with psoriasis.