לוח שנה משולב

Tumor-specific combinations of oncogenic mutations often free cancer cells from their reliance on growth factors. One important example comprises the epidermal growth factor receptor (EGFR) and its kin, HER2. In tumors, both EGFR and HER2 frequently display overexpression, internal deletions and point mutations. Accordingly, monoclonal antibodies (mAbs) and tyrosine kinase inhibitors (TKIs) specific to these receptors have been approved for clinical applications. My lecture will introduce EGFR and HER2 in the context of a signaling network comprising two additional receptors, HER3 and HER4, and 11 growth factors, all sharing an EGF-like structure and binding to HER family members.
The principles of network biology, such as rewiring, robustness and pathway redundancy, translate to short–term responses to oncology drugs. In other words, patients treated with drugs intercepting EGFR or HER2 often develop resistance due to emergence of compensatory mechanisms. My lecture will exemplify these principles in context of several relatively hard to treat tumors. The tumors I will discuss include breast cancers, both HER2-enriched and triple-negative, ovarian cancer and advanced non-small cell lung tumors that acquired resistance to EGFR’s TKIs.

TBA

The complex pattern of river networks has inspired decades of studies. However, the evolution and the dynamics of a growing channel remain elusive. Here we show that the principle of local symmetry, a concept originating in fracture mechanics, explains the path followed by growing streams fed by groundwater. Although path selection does not by itself imply a rate of growth, we additionally show how local symmetry may be used to infer how rates of growth scale with water flux. Our methods are applicable to other problems of unstable pattern formation, such as the growth of hierarchical crack patterns and geologic fault networks, where dynamics is not well understood.

Turbulent flows are ubiquitous in nature, present in the atmosphere, the oceans, in industrial flows and also in one's own bathtub. From an abstract point of view, turbulence is an elemental problem in out-of-equilibrium statistical mechanics. The flow is driven out of equilibrium by forcing and dissipation acting on disparate scales, forming a chaotic motion that spans many interacting scales. Particles placed in a turbulent flow are therefore driven by an out-of-equilibrium fluctuating medium. I will discuss how the breaking of time reversibility of the flow manifests itself in the dynamics of such particles, focusing on tracers following the turbulent velocity field. I will present exact results for time irreversibility of pair dynamics in incompressible as well as compressible flows. For the latter there is an unexpected jump in the dynamics when time is reversed. For the former, I will describe the existence of an all time statistical conservation law for pair dispersion at small scales. In two dimensional or Hamiltonian flows, this conservation law is extended to an exact relation for the probability distribution function of the finite-time Lyapunov exponent. I will show that it can be interpreted as a fluctuation relation in phase space. Lastly, I will review how time irreversibility can be measured for a single particle and will discuss the application of this idea to a simple model of turbulence flow