Resistance is futile: overcoming resistance to targeted therapies in lung adenocarcinoma.

The advent of genomics has led to the identification of specific "driver" mutations in oncogenic kinases, and the development of targeted small molecule inhibitors to block their tumor-driving functions. These specific inhibitors have been a clinical success, and often significantly prolong the lives of individuals with cancer. Inevitably, however, the treated tumors recur as resistance to these targeted therapies develops. Here, we review the major mechanisms by which a cancer cell can evade targeted therapy, focusing on mechanisms of resistance to kinase inhibitors in lung cancer. We discuss the promising concept of rational upfront polytherapy in lung cancer, which involves concurrently targeting multiple proteins in critical signaling pathways in a cancer cell to prevent or delay resistance

Modeling of elastically mounted vertical rotor

The evaluation of the dynamic behavior of a rotating system is possible by means of modal parameters (Eigenvalues and Eigenvectors). A mixed analytical and experimetal approach is used to identify the modal parameters of a specially designed test rig. The modal identification is done both for nonrotating as well as rotating systems. These modal parameters are used to validate a developed Finite Element Model

Interior design of a two-dimensional semiclassical black hole: Quantum transition across the singularity

We study the internal structure of a two-dimensional dilatonic evaporating black hole, based on the CGHS model. At the semiclassical level, a (weak) spacelike singularity was previously found to develop inside the black hole. We employ here a simplified quantum formulation of spacetime dynamics in the neighborhood of this singularity, using a minisuperspace-like approach. Quantum evolution is found to be regular and well-defined at the semiclassical singularity. A well-localized initial wave-packet propagating towards the singularity bounces off the latter and retains its well-localized form. Our simplified quantum treatment thus suggests that spacetime may extend semiclassically beyond the singularity, and also signifies the specific extension.Comment: Accepted to Phys. Rev.