Cancer stem cell (CSC) has paved the way to many fundamental and translational studies. Recent studies have highlighted differentiated breast cancer cells (non-CSCs) switching phenotype to CSCs in response to various stimuli, depicting the existence of cancer stem cell plasticity. Although strategies to reduce the phenotypic plasticity of non-CSCs into CSCs are likely to prevent treatment-resilient cancer cells driving recurrence, most phenotypic plasticity mechanisms involve Notch, Wnt or MAPK signaling pathways. In this study, breast cancer cells were irradiated to identify soluble reprogramming factors. Using conditioned medias, protein arrays analyses, flow cytometry and in cellulo/in vivo functional assays, we demonstrated, for the first time, that radiation-induced chemokine expression, especially CXCL1 and CCL5 and their receptors CXCR2, CCR1 and CCR5, stimulates reprogramming of breast non-CSCs into CSCs. Treatment of non-CSCs with recombinant CXCL1 and CCL5 is sufficient to induce cell reprogramming, while their inhibition can be used to prevent reprogramming and sensitize tumor to radiation. Moreover, analysis of gene expression profiles from 38 public merged databases demonstrated that combined over-expression of CXCL1/CXCR2, CCL5/CCR1 or CCL5/CCR5 has a poorer prognosis in patients treated with radiotherapy, suggesting a promising way for patient stratification, where individuals with elevated cytokine levels could benefit from radiotherapy in conjunction with cytokine inhibitors. Taken together, our findings provide a rationale to consider these axes as potential targets and predictive biomarkers in breast cancer patients.

A rare but severe complication of curative-intent radiation therapy is the induction of second primary cancers. These cancers preferentially develop not inside the planning target volume (PTV) but around, over several centimeters, after a latency period of 1-40 years. We show here that normal human or mouse dermal fibroblasts submitted to the out-of-field dose scattering at the margin of a PTV receiving a mimicked patient's treatment do not die but enter in a long-lived senescent state resulting from the accumulation of unrepaired DNA single-strand breaks, in the almost absence of double-strand breaks. Importantly, a few of these senescent cells systematically and spontaneously escape from the cell cycle arrest after a while to generate daughter cells harboring mutations and invasive capacities. These findings highlight single-strand break-induced senescence as the mechanism of second primary cancer initiation, with clinically relevant spatiotemporal specificities. Senescence being pharmacologically targetable, they open the avenue for second primary cancer prevention.

The complexity of urban street networks is well accepted to reside in the information space where roads map to nodes and junctions to links between nodes. Assuming that information networks preserve their amount of surprisal in average leads us to adapt the single-flip Metropolis algorithm to compute information networks with minimal amounts of surprisal.

We investigate urban street networks as a whole within the frameworks of information physics and statistical physics. Urban street networks are envisaged as evolving social systems subject to a Boltzmann-mesoscopic entropy conservation. For self-organized urban street networks, our paradigm has already allowed us to recover the effectively observed scale-free distribution of roads and to foresee the distribution of junctions. The entropy conservation is interpreted as the conservation of the surprisal of the city-dwellers for their urban street network. In view to extend our investigations to other urban street networks, we consider to perturb our model for self-organized urban street networks by adding an external surprisal drift. We obtain the statistics for slightly drifted self-organized urban street networks. Besides being practical and manageable, this statistics separates the macroscopic evolution scale parameter from the mesoscopic social parameters. This opens the door to observational investigations on the universality of the evolution scale parameter. Ultimately, we argue that the strength of the external surprisal drift might be an indicator for the disengagement of the city-dwellers for their city.

Easy and intuitive navigability is of central importance in cities. The actual scale-free networking of urban street networks in their topological space, where navigation information is encoded by mapping roads to nodes and junctions to links between nodes, has still no simple explanation. Emphasizing the road-junction hierarchy in a holistic and systematic way leads us to envisage urban street networks as evolving social systems subject to a Boltzmann-mesoscopic entropy conservation. This conservation, which we may interpret in terms of surprisal, ensures the passage from the road-junction hierarchy to a scale-free coherence. To wit, we recover the actual scale-free probability distribution for natural roads in self-organized cities. We obtain this passage by invoking Jaynes's Maximum Entropy principle (statistical physics), while we capitalize on modern ideas of quantification (information physics) and well known results on structuration (lattice theory) to measure the information network entropy. The emerging paradigm, which applies to systems with more intricate hierarchies as actual cities, appears to reflect well the influential ideas on cities of the urbanist Christopher Alexander.

We investigate urban street networks as a whole within the frameworks of information physics and statistical physics. Urban street networks are envisaged as evolving social systems subject to a logarithmical entropic equilibrium.

Aβ oligomers are potential targets for the diagnosis and therapy of Alzheimer's disease (AD). On the other hand, the molecule curcumin has been shown to possess significant therapeutic potential in many areas. In this paper, we use all-atom explicit solvent molecular dynamics simulations to study the effect of curcumin on the stability of Aβ amyloid protein oligomers. We observed that curcumin decreases the β-sheet secondary structural content within the Aβ oligomers without reducing the contacts between the monomers. The breaking of the β-sheet is found to be preceded by a deformation of the β-sheet structure due to hydrophobic interaction from the nearby curcumin. Furthermore, the π-stacking interaction between curcumin (keto ring and enol ring) and the aromatic residues of Aβ, which exists throughout the simulations, has also contributed to the diminishing of the β-sheet structure. Our analysis of the underwrapped amide-carbonyl hydrogen bonds reveals several stable dehydrons of the oligomer, especially the dehydron pair 34L and 41I, which curcumin tends to hover over. We have examined the paths of curcumin on the Aβ proteins and determined the common routes where curcumin lingers as it traverses around the Aβ. In consequence, our study has provided a detailed interaction picture between curcumin and the Aβ oligomers.

The aggregation of amyloid β peptides resulting in neurotoxic oligomers is an important but yet mysterious process in Alzheimer's disease development. Molecular dynamics simulations were performed to investigate the self-assembly of three full-length amyloid peptides in the zwitterionic dipalmitoylphosphatidylcholine and cholesterol mixed lipid bilayer. During the 1000 ns simulation, the residues 1-27 were found to interact preferentially with the lipid-aqueous interface region, while residues 28-42 show an inclination to remain inside the bilayer hydrophobic tail region. The interaction between peptides and lipids has facilitated the association of Aβ peptides. However, the interaction between cholesterol and peptides is inversely correlated with the extent of the peptide-peptide interactions. Our simulation has uncovered the formation of a short segment of parallel β-sheet between two peptide chains. In another chain, the N- and C-termini came close to each other. All the structural transitions indicate that our simulation has caught a glimpse of the complicated peptide oligomerization process. The full understanding of the underlying mechanism still requires further experimental and theoretical studies.

We present an exact solution to the problem of the global shape description of a spherical vesicle distorted by a grafted latex bead. This solution is derived by treating the nonlinearity in bending elasticity through the (topological) Bogomol'nyi decomposition technique and elastic compatibility. We recover the ``hat-model'' approximation in the limit of a small latex bead and find that the region antipodal to the grafted latex bead flattens. We also derive the appropriate shape equation using the variational principle and relevant constraints.

We consider a Susceptible-Infective-Recovered (SIR) model,where the mechanism for the renewal of susceptibles is demographic,on a ring with next nearest neighbour interactions,and a family of correlated pair approximations (CPA),parametrized by a measure of the relative contributions of loops and open triplets of the sites involved in the infection process. We have found that the phase diagram of the CPA,at fixed coordination number,changes qualitatively as the relative weight of the loops increases,from the phase diagram of the uncorrelated pair approximationto phase diagrams typical of one-dimensional systems.In addition,we have performed computer simulations of the same model and shown thatwhile the CPA with a constant correlation parametercannot describe the global behaviour of the model,a reasonable description of the endemic equilibriaas well as of the phase diagram may be obtainedby allowing the parameter to depend on the demographic rate.

We present a self-dual bending theory that may enable a better understanding of highly nonlinear global behaviour observed in biological vesicles. Adopting this topological approach for spherical vesicles of revolution allows us to describe them as frustrated sine-Gordon kinks. Finally, to illustrate an application of our results, we consider a spherical vesicle globally distorted by two polar latex beads.

We apply the Bogomol'nyi technique, which is usually invoked in the study of solitons or models with topological invariants, to the case of elastic energy of vesicles. We show that spontaneous bending contribution caused by any deformation from metastable bending shapes falls in two distinct topological sets: shapes of spherical topology and shapes of non-spherical topology experience respectively a deviatoric bending contribution a la Fischer and a mean curvature bending contribution a la Helfrich. In other words, topology may be considered to describe bending phenomena. Besides, we calculate the bending energy per genus and the bending closure energy regardless of the shape of the vesicle. As an illustration we briefly consider geometrical frustration phenomena experienced by magnetically coated vesicles.

Classical Heisenberg spins in the continuum limit (i.e. the nonlinear sigma-model) are studied on an elastic cylinder section with homogeneous boundary conditions. The latter may serve as a physical realization of magnetically coated microtubules and cylindrical membranes. The corresponding rigid cylinder model exhibits topological soliton configurations with geometrical frustration due to the finite length of the cylinder section. Assuming small and smooth deformations allows to find shapes of the elastic support by relaxing the rigidity constraint: an inhomogeneous Lam\'e equation arises. Finally, this leads to a novel geometric effect: a global shrinking of the cylinder section with swellings.

Using group theoretical methods we show for both the triangular and square lattices that in the continuum limit the antiferromagnetic order parameter lives on SO3 without respect of the initial lattice. For the antiferromagnetic chain we recover the Haldane decomposition. This order parameter interacts with a local gauge field rather than with a global one as implicitly suggested in the literature which in our approach appears in a rather natural manner. In fact this merely corresponds to a novel extension of the spin group by a local gauge field. This analysis based on the real division algebras applies to low dimensional lattices.

In this thesis I present my research on the exotic configurations of antiferromagnetic systems characterised by a topological invariant. The research presented outlines the construction of novel local antiferromagnetic degrees of freedom for low dimensional antiferromagnetic lattices. This new construction reproduces the real division algebra hierarchy satisfied by the nonlinear sigma-model and reveals the presence of a novel local gauge field. I have also studied elastic magnetic vesicles of spherical and toric genus in the presence of a magnetic soliton. My studies reveal a global shrinking, with local swellings in the regions where the soliton presents a spin-flip. The geometrical origin of this novel phenomena led me to interpret the geometric frustration of magnetic vesicles as the competition between the two topological orders present. The microscopic mechanism and topological competition suggested above go beyond the scope of this thesis, providing a microscopic explanation for the Fermi-Bose transmutation and a way to deal with this type of exotic physics.

Classical Heisenberg spins in the continuum limit (i.e., the nonlinear σ-model) are studied on an elastic torus section with homogeneous boundary conditions. The corresponding rigid model exhibits topological soliton configurations with geometrical frustration due to the torus eccentricity. Assuming small and smooth deformations allows us to find shapes of the elastic support by relaxing the rigidity constraint: an inhomogeneous Lamé equation arises. Finally, this leads to a novel geometric effect: a global shrinking with swellings.