Complexity in cancer stem cells and tumor evolution: towards precision medicine

In this review, we discuss recent advances on the plasticity of cancer stem cells and highlight their relevance to understand the metastatic process and to guide therapeutic interventions. Recent results suggest that the strict hierarchical structure of cancer cell populations advocated by the cancer stem cell model must be reconsidered since the depletion of cancer stem cells leads the other tumor cells to switch back into the cancer stem cell phenotype. This plasticity has important implications for metastasis since migrating cells do not need to be cancer stem cells in order to seed a metastasis. We also discuss the important role of the immune system and the microenvironment in modulating phenotypic switching and suggest possible avenues to exploit our understanding of this process to develop an effective strategy for precision medicine.Comment: 2 Figures, to appear in Seminars in Cancer Biology, Available online 23 February 201

Generation Engineering of Heralded Narrowband Colour Entangled States

Efficient heralded generation of entanglement together with its manipulation is of great importance for quantum communications. In addition, states generated with bandwidths naturally compatible with atomic transitions allow a more efficient mapping of light into matter which is an essential requirement for long distance quantum communications. Here we propose a scheme where the indistinguishability between two spontaneous four-wave mixing processes is engineered to herald generation of single-photon frequency-bin entangled states, i.e., single-photons shared by two distinct frequency modes. We show that entanglement can be optimised together with the generation probability, while maintaining absorption negligible. Besides, the scheme illustrated for cold rubidium atoms is versatile and can be implemented in several other physical systems

Turbulent heat transfer in spacer-filled channels: Experimental and computational study and selection of turbulence models

Heat transfer in spacer-filled channels of the kind used in Membrane Distillation was studied in the Reynolds number range 100–2000, encompassing both steady laminar and early-turbulent flow conditions. Experimental data, including distributions of the local heat transfer coefficient h, were obtained by Liquid Crystal Thermography and Digital Image Processing. Alternative turbulence models, both of first order (k-ε, RNG k-ε, k-ω, BSL k-ω, SST k-ω) and of second order (LRR RS, SSG RS, ω RS, BSL RS), were tested for their ability to predict measured distributions and mean values of h. The best agreement with the experimental results was provided by first-order ω-based models able to resolve the viscous/conductive sublayer, while all other models, and particularly ε-based models using wall functions, yielded disappointing predictions

Developmental Regulation of Small-Conductance Ca²⁺-Activated K⁺ Channel Expression and Function in Rat Purkinje Neurons

Calcium transients play an important role in the early and later phases of differentiation and maturation of single neurons and neuronal networks. Small-conductance calcium-activated potassium channels of the SK type modulate membrane excitability and are important determinants of the firing properties of central neurons. Increases in the intracellular calcium concentration activate SK channels, leading to a hyperpolarization of the membrane potential, which in turn reduces the calcium inflow into the cell. This feedback mechanism is ideally suited to regulate the spatiotemporal occurrence of calcium transients. However, the role of SK channels in neuronal development has not been addressed so far. We have concentrated on the ontogenesis and function of SK channels in the developing rat cerebellum, focusing particularly on Purkinje neurons. Electrophysiological recordings combined with specific pharmacological tools have revealed for the first time the presence of an afterhyperpolarizing current (I_{AHP}) in immature Purkinje cells in rat cerebellar slices. The channel subunits underlying this current were identified as SK2 and localized by in situ hybridization and subunit-specific antibodies. Their expression level was shown to be high at birth and subsequently to decline during the first 3 weeks of postnatal life, both at the mRNA and protein levels. This developmental regulation was tightly correlated with the expression of I_{AHP} and the prominent role of SK2 channels in shaping the spontaneous firing pattern in young, but not in adult, Purkinje neurons. These results provide the first evidence of the developmental regulation and function of SK channels in central neurons