OATP1B2 deficiency protects against paclitaxel-induced neurotoxicity

Paclitaxel is among the most widely used anticancer drugs and is known to cause a dose-limiting peripheral neurotoxicity, the initiating mechanisms of which remain unknown. Here, we identified the murine solute carrier organic anion–transporting polypeptide B2 (OATP1B2) as a mediator of paclitaxel-induced neurotoxicity. Additionally, using established tests to assess acute and chronic paclitaxel-induced neurotoxicity, we found that genetic or pharmacologic knockout of OATP1B2 protected mice from mechanically induced allodynia, thermal hyperalgesia, and changes in digital maximal action potential amplitudes. The function of this transport system was inhibited by the tyrosine kinase inhibitor nilotinib through a noncompetitive mechanism, without compromising the anticancer properties of paclitaxel. Collectively, our findings reveal a pathway that explains the fundamental basis of paclitaxel-induced neurotoxicity, with potential implications for its therapeutic management

The Backward in Time Problem of Double Porosity Material with Microtemperature

In the present study, the theory of thermoelastodynamics is considered in the case of materials with double porosity structure and microtemperature. The novelty of this study consists in the investigation of a backward in time problem associated with double porous thermoelastic materials with microtemperature. In the first part of the paper, in case of the bounded domains the impossibility of time localization of solutions is obtained. This study is equivalent to the uniqueness of solutions for the backward in time problem. In the second part of the paper, a Phragmen-Lindelof alternative in the case of semi-infinite cylinders is obtained

The Backward in Time Problem of Double Porosity Material with Microtemperature

In the present study, the theory of thermoelastodynamics is considered in the case of materials with double porosity structure and microtemperature. The novelty of this study consists in the investigation of a backward in time problem associated with double porous thermoelastic materials with microtemperature. In the first part of the paper, in case of the bounded domains the impossibility of time localization of solutions is obtained. This study is equivalent to the uniqueness of solutions for the backward in time problem. In the second part of the paper, a Phragmen-Lindelof alternative in the case of semi-infinite cylinders is obtained

Analytic study of a rolling sphere on a rough surface

In this paper it is realized an analytic study of the rolling’s sphere on a rough horizontal plane under the action of its own gravity. The necessities of integration of the system of dynamical equations of motion lead us to find a reference system where the motion equations should be transformed into simpler expressions and which, in the presence of some significant hypothesis to permit the application of some original methods of analytical integration. In technical applications, the bodies may have a free rolling motion or a motion constrained by geometrical relations in assemblies of parts and machine parts. This study involves a lot of investigations in the field of tribology and of applied dynamics accompanied by experiments. Multiple recordings of several trajectories of the sphere, as well as their treatment of images, also followed by statistical processing experimental data allowed highlighting a very good agreement between the theoretical findings and experimental results