Qualitative analysis of kinetic-based models for tumor-immune system interaction

A mathematical model, based on a mesoscopic approach, describing the competition between tumor cells and immune system in terms of kinetic integro-differential equations is presented. Four interacting populations are considered, representing, respectively, tumors cells, cells of the host environment, cells of the immune system, and interleukins, which are capable to modify the tumor-immune system interaction and to contribute to destroy tumor cells. The internal state variable (activity) measures the capability of a cell of prevailing in a binary interaction. Under suitable assumptions, a closed set of autonomous ordinary differential equations is then derived by a moment procedure and two three-dimensional reduced systems are obtained in some partial quasi-steady state approximations. Their qualitative analysis is finally performed, with particular attention to equilibria and their stability, bifurcations, and their meaning. Results are obtained on asymptotically autonomous dynamical systems, and also on the occurrence of a particular backward bifurcation

Sensitivity of semiclassical vibrational spectroscopy to potential energy surface accuracy: A test on formaldehyde.

A set of permutationally invariant potential energy surfaces for the electronic ground state of formaldehyde is built at several levels of electronic theory and atomic orbital basis sets starting from a database of more than 34000 ab initio energies. The reliability of the fitted surfaces is determined by comparing the calculated harmonic frequencies with the corresponding ab initio values. Semiclassical estimates of the quantum frequencies of vibration are presented, and their dependence on the employed level of theory, type of atomic orbital basis set, and complexity of the fit is investigated. Comparisons to experimental data show that anharmonic frequencies are influenced by the precision of the fit, while accurate frequency values are obtained also with density functional theory. Results and conclusions support the use of ab initio \u201con-the-fly\u201d semiclassical dynamics as a means of spectroscopic investigation when high level analytical potential energy surfaces are not available

Proposal for a Data Visualization and Assessment System to Rebalance Landscape Quality

The landscape can be considered a complex system described as a non-linear entity, organized accord- ing to the connections between the different elements that characterize its state. The latter cannot be determined a priori but emerges from the multiple interactions between assets and relationships that are no longer found when the phenomenon is traced back to the individual components. Territorial development is closely connected to social, economic, cultural and symbolic issues that determine the transformative practices of space and the territorial palimpsest. If not carefully managed, these forces can lead to the dissolution of the landscape and environmental values that have been stratified in a specific land. This paper proposes the construction of a numerical spatial model that describes the territorial settlement patterns, based on methodologies and techniques typical of AI, to develop tools for re-balancing the man-landscape relationship

Muscle-specific Perilipin2 down-regulation affects lipid metabolism and induces myofiber hypertrophy.

BACKGROUND: Perilipin2 (Plin2) belongs to a family of five highly conserved proteins, known for their role in lipid storage. Recent data indicate that Plin2 has an important function in cell metabolism and is involved in several human pathologies, including liver steatosis and Type II diabetes. An association between Plin2 and lower muscle mass and strength has been found in elderly and inactive people, but its function in skeletal muscle is still unclear. Here, we addressed the role of Plin2 in adult muscle by gain and loss of function experiments. METHODS: By mean of in vivo Plin2 down-regulation (shPlin2) and overexpression (overPlin2) in murine tibialis anterior muscle, we analysed the effects of Plin2 genetic manipulations on myofiber size and lipid composition. An analysis of skeletal muscle lipid composition was also performed in vastus lateralis samples from young and old patients undergoing hip surgery. RESULTS: We found that Plin2 down-regulation was sufficient to induce a 30% increase of myofiber cross-sectional area, independently of mTOR pathway. Alterations of lipid content and modulation of genes involved in lipid synthesis occurred in hypertrophic muscles. In particular, we showed a decrease of triglycerides, ceramides, and phosphatidylcoline:phosphatidylethanolamine ratio, a condition known to impact negatively on muscle function. Plin2 overexpression did not change fibre size; however, lipid composition was strongly affected in a way that is similar to that observed in human samples from old patients. CONCLUSIONS: Altogether these data indicate that Plin2 is a critical mediator for the control of muscle mass, likely, but maybe not exclusively, through its critical role in the regulation of intracellular lipid content and composition

Lipidic Formulations Inspired by COVID Vaccines as Smart Coatings to Enhance Nanoparticle-Based Cancer Therapy

Recent advances in nanomedicine have led to the introduction and subsequent establishment of nanoparticles in cancer treatment and diagnosis. Nonetheless, their application is still hindered by a series of challenges related to their biocompatibility and biodistribution. In this paper, we take inspiration from the recently produced and widely spread COVID vaccines, based on the combinational use of ionizable solid lipid nanoparticles, cholesterol, PEGylated lipids, and neutral lipids able to incorporate mRNA fragments. Here, we focus on the implementation of a lipidic formulation meant to be used as a smart coating of solid-state nanoparticles. The composition of this formulation is finely tuned to ensure efficient and stable shielding of the cargo. The resulting shell is a highly customized tool that enables the possibility of further functionalizations with targeting agents, peptides, antibodies, and fluorescent moieties for future in vitro and in vivo tests and validations. Finally, as a proof of concept, zinc oxide nanoparticles doped with iron and successively coated with this lipidic formulation are tested in a pancreatic cancer cell line, BxPC-3. The results show an astonishing increase in cell viability with respect to the same uncoated nanoparticles. The preliminary results presented here pave the way towards many different therapeutic approaches based on the massive presence of highly biostable and well-tolerated nanoparticles in tumor tissues, such as sonodynamic therapy, photodynamic therapy, hyperthermia, and diagnosis by means of magnetic resonance imaging

Modification by an R determinant for streptomycin of his-sd phenotype in mutant strain of Escherichia coli B.

When an R determinant for streptomycin is transferred into a conditionally streptomycin-dependent E. coli B mutant—which requires in minimal medium either histidine or streptomycin—the latter behaves like a histidineless strain. This phenotype modification shows that the repairing action of streptomycin is prevented. The specific requirement of the strain is not now replaced even by streptomycin concentrations up to 10000 µg/ml at which the conditionally streptomycin-dependent mutant could originally grow, and which are well beyond the resistance level characteristic of the R determinant itself. These data seem to suggest that a reduction in permeability of the cell membrane cannot be held responsible for the phenomenon observed