Plasmonic modes of extreme subwavelength nanocavities

We study the physics of a new type of subwavelength nanocavities. They are based on U-shaped metal-insulator-metal waveguides supporting the excitation of surface plasmon polaritons. The waveguides are simultaneously excited from both sides of the U by incident plane waves. Due to their finite length discrete modes emerge within the nanocavity. We show that the excitation symmetry with respect to the cavity ends permits the observation of even and odd modes. Our investigations include near and far field simulations and predict a strong spectral far field response of the comparable small nanoresonators. The strong near field enhancement observed in the cavity at resonance might be suitable to increase the efficiency of nonlinear optical effects, quantum analogies and might facilitate the development of active optical elements, such as active plasmonic elements

The macroscopic effects of microscopic heterogeneity

Over the past decade, advances in super-resolution microscopy and particle-based modeling have driven an intense interest in investigating spatial heterogeneity at the level of single molecules in cells. Remarkably, it is becoming clear that spatiotemporal correlations between just a few molecules can have profound effects on the signaling behavior of the entire cell. While such correlations are often explicitly imposed by molecular structures such as rafts, clusters, or scaffolds, they also arise intrinsically, due strictly to the small numbers of molecules involved, the finite speed of diffusion, and the effects of macromolecular crowding. In this chapter we review examples of both explicitly imposed and intrinsic correlations, focusing on the mechanisms by which microscopic heterogeneity is amplified to macroscopic effect.Comment: 20 pages, 5 figures. To appear in Advances in Chemical Physic

Anomalous fluctuation relations

We study Fluctuation Relations (FRs) for dynamics that are anomalous, in the sense that the diffusive properties strongly deviate from the ones of standard Brownian motion. We first briefly review the concept of transient work FRs for stochastic dynamics modeled by the ordinary Langevin equation. We then introduce three generic types of dynamics generating anomalous diffusion: L\'evy flights, long-time correlated Gaussian stochastic processes and time-fractional kinetics. By combining Langevin and kinetic approaches we calculate the work probability distributions in the simple nonequilibrium situation of a particle subject to a constant force. This allows us to check the transient FR for anomalous dynamics. We find a new form of FRs, which is intimately related to the validity of fluctuation-dissipation relations. Analogous results are obtained for a particle in a harmonic potential dragged by a constant force. We argue that these findings are important for understanding fluctuations in experimentally accessible systems. As an example, we discuss the anomalous dynamics of biological cell migration both in equilibrium and in nonequilibrium under chemical gradients.Comment: book chapter; 25 pages, 10 figures. see http://www.maths.qmul.ac.uk/~klages/smallsys/smallsys_rk.htm

Zebrafish models of the immune response: taking it on the ChIn

The zebrafish is proving to be an extremely versatile new experimental model for unraveling the mysteries of innate immunity and has considerable promise as a system for the identification of novel modulators of this crucial biological process. A rate-limiting factor, however, is the mechanical stimulus required to induce the inflammatory response. A new chemically induced inflammation assay ('ChIn' assay) published in BMC Biology obviates this requirement and seems set to accelerate progress in the field

Synergistic melanoma cell death mediated by inhibition of both MCL1 and BCL2 in high-risk tumors driven by NF1/PTEN loss

Melanomas driven by loss of the NF1 tumor suppressor have a high risk of treatment failure and effective therapies have not been developed. Here we show that loss-of-function mutations of nf1 and pten result in aggressive melanomas in zebrafish, representing the first animal model of NF1-mutant melanomas harboring PTEN loss. MEK or PI3K inhibitors show little activity when given alone due to cross-talk between the pathways, and high toxicity when given together. The mTOR inhibitors, sirolimus, everolimus, and temsirolimus, were the most active single agents tested, potently induced tumor-suppressive autophagy, but not apoptosis. Because addition of the BCL2 inhibitor venetoclax resulted in compensatory upregulation of MCL1, we established a three-drug combination composed of sirolimus, venetoclax, and the MCL1 inhibitor S63845. This well-tolerated drug combination potently and synergistically induces apoptosis in both zebrafish and human NF1/PTEN-deficient melanoma cells, providing preclinical evidence justifying an early-stage clinical trial in patients with NF1/PTEN-deficient melanoma

A comprehensive computational model of facilitated diffusion in prokaryotes

Motivation: Gene activity is mediated by site-specific transcription factors (TFs). Their binding to defined regions in the genome determines the rate at which their target genes are transcribed

Evolution of the hypoxia-sensitive cells involved in amniote respiratory reflexes

The evolutionary origins of the hypoxia-sensitive cells that trigger amniote respiratory reflexes – carotid body glomus cells, and ‘pulmonary neuroendocrine cells’ (PNECs) - are obscure. Homology has been proposed between glomus cells, which are neural crest-derived, and the hypoxia-sensitive ‘neuroepithelial cells’ (NECs) of fish gills, whose embryonic origin is unknown. NECs have also been likened to PNECs, which differentiate in situ within lung airway epithelia. Using genetic lineage-tracing and neural crest-deficient mutants in zebrafish, and physical fate-mapping in frog and lamprey, we find that NECs are not neural crest-derived, but endoderm-derived, like PNECs, whose endodermal origin we confirm. We discover neural crest-derived catecholaminergic cells associated with zebrafish pharyngeal arch blood vessels, and propose a new model for amniote hypoxia-sensitive cell evolution: endoderm-derived NECs were retained as PNECs, while the carotid body evolved via the aggregation of neural crest-derived catecholaminergic (chromaffin) cells already associated with blood vessels in anamniote pharyngeal arches

Localized behavior in the Lyapunov vectors for quasi-one-dimensional many-hard-disk systems

We introduce a definition of a "localization width" whose logarithm is given by the entropy of the distribution of particle component amplitudes in the Lyapunov vector. Different types of localization widths are observed, for example, a minimum localization width where the components of only two particles are dominant. We can distinguish a delocalization associated with a random distribution of particle contributions, a delocalization associated with a uniform distribution and a delocalization associated with a wave-like structure in the Lyapunov vector. Using the localization width we show that in quasi-one-dimensional systems of many hard disks there are two kinds of dependence of the localization width on the Lyapunov exponent index for the larger exponents: one is exponential, and the other is linear. Differences, due to these kinds of localizations also appear in the shapes of the localized peaks of the Lyapunov vectors, the Lyapunov spectra and the angle between the spatial and momentum parts of the Lyapunov vectors. We show that the Krylov relation for the largest Lyapunov exponent $\lambda\sim-\rho\ln\rho$ as a function of the density $\rho$ is satisfied (apart from a factor) in the same density region as the linear dependence of the localization widths is observed. It is also shown that there are asymmetries in the spatial and momentum parts of the Lyapunov vectors, as well as in their $x$ and $y$-components.Comment: 41 pages, 21 figures, Manuscript including the figures of better quality is available from http://www.phys.unsw.edu.au/~gary/Research.htm