Shock waves in disordered media

We experimentally investigate the interplay between spatial shock waves and the degree of disorder during nonlinear optical propagation in a thermal defocusing medium. We characterize the way the shock point is affected by the amount of disorder and scales with wave amplitude. Evidence for the existence of a phase diagram in terms of nonlinearity and amount of randomness is reported. The results are in quantitative agreement with a theoretical approach based on the hydrodynamic approximation.Comment: 4 pages, 5 figure

Phase diagram and complexity of mode-locked lasers: from order to disorder

We investigate mode-locking processes in lasers displaying a variable degree of structural randomness, from standard optical cavities to multiple-scattering media. By employing methods mutuated from spin-glass theory, we analyze the mean-field Hamiltonian and derive a phase-diagram in terms of the pumping rate and the degree of disorder. Three phases are found: i) paramagnetic, corresponding to a noisy continuous wave emission, ii) ferromagnetic, that describes the standard passive mode-locking, and iii) the spin-glass in which the phases of the electromagnetic field are frozen in a exponentially large number of configurations. The way the mode-locking threshold is affected by the amount of disorder is quantified. The results are also relevant for other physical systems displaying a random Hamiltonian, like Bose-Einstein condensates and nonlinear optical beams.Comment: 4 pages, 2 figure

Beam Instabilities in the Scale Free Regime

The instabilities arising in a one-dimensional beam sustained by the diffusive photorefractive nonlinearity in out-of-equilibrium ferroelectrics are theoretically and numerically investigated. In the "scale-free model", in striking contrast with the well-known spatial modulational instability, two different beam instabilities dominate: a defocusing and a fragmenting process. Both are independent of the beam power and are not associated to any specific periodic pattern.Comment: 4 pages, 3 figure

The frustrated Brownian motion of nonlocal solitary waves

We investigate the evolution of solitary waves in a nonlocal medium in the presence of disorder. By using a perturbational approach, we show that an increasing degree of nonlocality may largely hamper the Brownian motion of self-trapped wave-packets. The result is valid for any kind of nonlocality and in the presence of non-paraxial effects. Analytical predictions are compared with numerical simulations based on stochastic partial differential equationComment: 4 pages, 3 figures

Disorder-induced soliton transmission in nonlinear photonic lattices

We address soliton transmission and reflection in nonlinear photonic lattices embedded into uniform Kerr nonlinear media. We show that by introducing disorder into the guiding lattice channels, one may achieve soliton transmission even under conditions where regular lattices reflect the input beam completely. In contrast, in the parameter range where the lattice is almost transparent for incoming solitons, disorder may induce a significant reflection.Comment: 5 pages, 4 figures, to appear in Optics Letter

Measurement of scaling laws for shock waves in thermal nonlocal media

We are able to detect the details of spatial optical collisionless wave-breaking through the high aperture imaging of a beam suffering shock in a fluorescent nonlinear nonlocal thermal medium. This allows us to directly measure how nonlocality and nonlinearity affect the point of shock formation and compare results with numerical simulations.Comment: 4 pages, 4 figure

Collective behavior and self-organization in neural rosette morphogenesis

Neural rosettes develop from the self-organization of differentiating human pluripotent stem cells. This process mimics the emergence of the embryonic central nervous system primordium, i.e., the neural tube, whose formation is under close investigation as errors during such process result in severe diseases like spina bifida and anencephaly. While neural tube formation is recognized as an example of self-organization, we still do not understand the fundamental mechanisms guiding the process. Here, we discuss the different theoretical frameworks that have been proposed to explain self-organization in morphogenesis. We show that an explanation based exclusively on stem cell differentiation cannot describe the emergence of spatial organization, and an explanation based on patterning models cannot explain how different groups of cells can collectively migrate and produce the mechanical transformations required to generate the neural tube. We conclude that neural rosette development is a relevant experimental 2D in-vitro model of morphogenesis because it is a multi-scale self-organization process that involves both cell differentiation and tissue development. Ultimately, to understand rosette formation, we first need to fully understand the complex interplay between growth, migration, cytoarchitecture organization, and cell type evolution

Neoadjuvant eribulin mesylate following anthracycline and taxane in triple negative breast cancer: Results from the HOPE study

Background Eribulin mesylate (E) is indicated for metastatic breast cancer patients previously treated with anthracycline and taxane. We argued that E could also benefit patients eligible for neoadjuvant chemotherapy. Methods Patients with primary triple negative breast cancer 2 cm received doxorubicin 60 mg/m2 and paclitaxel 200 mg/m2 x 4 cycles (AT) followed by E 1.4 mg/m2 x 4 cycles. Primary endpoint was pathological complete response (pCR) rate; secondary and explorative endpoints included clinical/metabolic response rates and safety, and biomarker analysis, respectively. Using a two-stage Simon design, 43 patients were to be included provided that 4 of 13 patients had achieved pCR in the first stage of the study. Results In stage I of the study 13 women were enrolled, median age 43 years, tumor size 2–5 cm in 9/13 (69%), positive nodal status in 8/13 (61%). Main grade 3 adverse event was neutropenia (related to AT and E in 4 and 2 cases, respectively). AT followed by E induced clinical complete + partial responses in 11/13 patients (85%), pCR in 3/13 (23%). Median measurements of maximum standardized uptake value (SUVmax) resulted 13, 3, and 1.9 at baseline, after AT and E, respectively. Complete metabolic response (CMR) occurred after AT and after E in 2 and 3 cases, respectively. Notably, 2 of the 5 (40%) patients with CMR achieved pCR at surgery. Immunostaining of paired pre-/post-treatment tumor specimens showed a reduction of β-catenin, CyclinD1, Zeb-1, and c-myc expression, in the absence of N-cadherin modulation. The study was interrupted at stage I due to the lack of the required patients with pCR. Conclusions Despite the early study closure, preoperative E following AT showed clinical and biological activity in triple negative breast cancer patients. Furthermore, the modulation of β-catenin pathway core proteins, supposedly outside the domain of epithelial–mesenchymal transition, claims for further investigation. Trial registration EU Clinical Trial Register, EudraCT number 2012-004956-12

Caenorhabditis elegans provides an efficient drug screening platform for GNAO1-related disorders and highlights the potential role of caffeine in controlling dyskinesia

Dominant GNAO1 mutations cause an emerging group of childhood-onset neurological disorders characterized by developmental delay, intellectual disability, movement disorders, drug-resistant seizures and neurological deterioration. GNAO1 encodes the α-subunit of an inhibitory GTP/GDP-binding protein regulating ion channel activity and neurotransmitter release. The pathogenic mechanisms underlying GNAO1-related disorders remain largely elusive and there are no effective therapies. Here, we assessed the functional impact of two disease-causing variants associated with distinct clinical features, c.139A > G (p.S47G) and c.662C > A (p.A221D), using Caenorhabditis elegans as a model organism. The c.139A > G change was introduced into the orthologous position of the C. elegans gene via CRISPR/Cas9, whereas a knock-in strain carrying the p.A221D variant was already available. Like null mutants, homozygous knock-in animals showed increased egg laying and were hypersensitive to aldicarb, an inhibitor of acetylcholinesterase, suggesting excessive neurotransmitter release by different classes of motor neurons. Automated analysis of C. elegans locomotion indicated that goa-1 mutants move faster than control animals, with more frequent body bends and a higher reversal rate and display uncoordinated locomotion. Phenotypic profiling of heterozygous animals revealed a strong hypomorphic effect of both variants, with a partial dominant-negative activity for the p.A221D allele. Finally, caffeine was shown to rescue aberrant motor function in C. elegans harboring the goa-1 variants; this effect is mainly exerted through adenosine receptor antagonism. Overall, our findings establish a suitable platform for drug discovery, which may assist in accelerating the development of new therapies for this devastating condition, and highlight the potential role of caffeine in controlling GNAO1-related dyskinesia

Light localization in nonuniformly randomized lattices

We address Anderson localization of light in disordered optical lattices where the disorder strength varies across the transverse direction. Such variation changes the preferred domains where formation of localized eigenmodes is most probable, hence drastically impacting light localization properties. Thus, step-like disorder results in formation of modes with different decay rates at both sides of the interface, while a smoothly varying disorder yields appearance of modes that are extended within weakly disordered domains and rapidly fade away in strongly disordered domains.Comment: 3 pages, 5 figures, to appear in Optics Letter