84 research outputs found

    ARID1A loss is associated with increased NRF2 signaling in human head and neck squamous cell carcinomas

    Get PDF
    Prior to the next generation sequencing and characterization of the tumor genome landscape, mutations in the SWI/SNF chromatin remodeling complex and the KEAP1-NRF2 signaling pathway were underappreciated. While these two classes of mutations appeared to independently contribute to tumor development, recent reports have demonstrated a mechanistic link between these two regulatory mechanisms in specific cancer types and cell models. In this work, we expand upon these data by exploring the relationship between mutations in BAF and PBAF subunits of the SWI/SNF complex and activation of NRF2 signal transduction across many cancer types. ARID1A/B mutations were strongly associated with NRF2 transcriptional activity in head and neck squamous carcinomas (HNSC). Many additional tumor types showed significant association between NRF2 signaling and mutation of specific components of the SWI/SNF complex. Different effects of BAF and PBAF mutations on the polarity of NRF2 signaling were observed. Overall, our results support a context-dependent functional link between SWI/SNF and NRF2 mutations across human cancers and implicate ARID1A inactivation in HPV-negative HNSC in promoting tumor progression and survival through activation of the KEAP1-NRF2 signaling pathway. The tumorspecific effects of these mutations open a new area of study for how mutations in the KEAP1-NRF2 pathway and the SWI/SNF complex contribute to cancer

    Interacting Random Walkers and Non-Equilibrium Fluctuations

    Full text link
    We introduce a model of interacting Random Walk, whose hopping amplitude depends on the number of walkers/particles on the link. The mesoscopic counterpart of such a microscopic dynamics is a diffusing system whose diffusivity depends on the particle density. A non-equilibrium stationary flux can be induced by suitable boundary conditions, and we show indeed that it is mesoscopically described by a Fourier equation with a density dependent diffusivity. A simple mean-field description predicts a critical diffusivity if the hopping amplitude vanishes for a certain walker density. Actually, we evidence that, even if the density equals this pseudo-critical value, the system does not present any criticality but only a dynamical slowing down. This property is confirmed by the fact that, in spite of interaction, the particle distribution at equilibrium is simply described in terms of a product of Poissonians. For mesoscopic systems with a stationary flux, a very effect of interaction among particles consists in the amplification of fluctuations, which is especially relevant close to the pseudo-critical density. This agrees with analogous results obtained for Ising models, clarifying that larger fluctuations are induced by the dynamical slowing down and not by a genuine criticality. The consistency of this amplification effect with altered coloured noise in time series is also proved.Comment: 8 pages, 7 figure

    Crackling Noise, Power Spectra and Disorder Induced Critical Scaling

    Full text link
    Crackling noise is observed in many disordered non-equilibrium systems in response to slowly changing external conditions. Examples range from Barkhausen noise in magnets to acoustic emission in martensites to earthquakes. Using the non-equilibrium random field Ising model, we derive universal scaling predictions for the dependence of the associated power spectra on the disorder and field sweep rate, near an underlying disorder-induced non-equilibrium critical point. Our theory applies to certain systems in which the crackling noise results from avalanche-like response to a (slowly) increasing external driving force, and is characterized by a broad power law scaling regime of the power spectra. We compute the critical exponents and discuss the relevance of the results to experiments.Comment: 27 Latex Pages, 14 eps figure

    Demagnetization via Nucleation of the Nonequilibrium Metastable Phase in a Model of Disorder

    Full text link
    We study both analytically and numerically metastability and nucleation in a two-dimensional nonequilibrium Ising ferromagnet. Canonical equilibrium is dynamically impeded by a weak random perturbation which models homogeneous disorder of undetermined source. We present a simple theoretical description, in perfect agreement with Monte Carlo simulations, assuming that the decay of the nonequilibrium metastable state is due, as in equilibrium, to the competition between the surface and the bulk. This suggests one to accept a nonequilibrium "free-energy" at a mesoscopic/cluster level, and it ensues a nonequilibrium "surface tension" with some peculiar low-T behavior. We illustrate the occurrence of intriguing nonequilibrium phenomena, including: (i) Noise-enhanced stabilization of nonequilibrium metastable states; (ii) reentrance of the limit of metastability under strong nonequilibrium conditions; and (iii) resonant propagation of domain walls. The cooperative behavior of our system may also be understood in terms of a Langevin equation with additive and multiplicative noises. We also studied metastability in the case of open boundaries as it may correspond to a magnetic nanoparticle. We then observe burst-like relaxation at low T, triggered by the additional surface randomness, with scale-free avalanches which closely resemble the type of relaxation reported for many complex systems. We show that this results from the superposition of many demagnetization events, each with a well- defined scale which is determined by the curvature of the domain wall at which it originates. This is an example of (apparent) scale invariance in a nonequilibrium setting which is not to be associated with any familiar kind of criticality.Comment: 26 pages, 22 figure

    1/f Noise in Electron Glasses

    Full text link
    We show that 1/f noise is produced in a 3D electron glass by charge fluctuations due to electrons hopping between isolated sites and a percolating network at low temperatures. The low frequency noise spectrum goes as \omega^{-\alpha} with \alpha slightly larger than 1. This result together with the temperature dependence of \alpha and the noise amplitude are in good agreement with the recent experiments. These results hold true both with a flat, noninteracting density of states and with a density of states that includes Coulomb interactions. In the latter case, the density of states has a Coulomb gap that fills in with increasing temperature. For a large Coulomb gap width, this density of states gives a dc conductivity with a hopping exponent of approximately 0.75 which has been observed in recent experiments. For a small Coulomb gap width, the hopping exponent approximately 0.5.Comment: 8 pages, Latex, 6 encapsulated postscript figures, to be published in Phys. Rev.

    The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

    Get PDF
    This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

    Metastable States in Spin Glasses and Disordered Ferromagnets

    Full text link
    We study analytically M-spin-flip stable states in disordered short-ranged Ising models (spin glasses and ferromagnets) in all dimensions and for all M. Our approach is primarily dynamical and is based on the convergence of a zero-temperature dynamical process with flips of lattice animals up to size M and starting from a deep quench, to a metastable limit. The results (rigorous and nonrigorous, in infinite and finite volumes) concern many aspects of metastable states: their numbers, basins of attraction, energy densities, overlaps, remanent magnetizations and relations to thermodynamic states. For example, we show that their overlap distribution is a delta-function at zero. We also define a dynamics for M=infinity, which provides a potential tool for investigating ground state structure.Comment: 34 pages (LaTeX); to appear in Physical Review

    Roughness distributions for 1/f^alpha signals

    Full text link
    The probability density function (PDF) of the roughness, i.e., of the temporal variance, of 1/f^alpha noise signals is studied. Our starting point is the generalization of the model of Gaussian, time-periodic, 1/f noise, discussed in our recent Letter [T. Antal et al., PRL, vol. 87, 240601 (2001)], to arbitrary power law. We investigate three main scaling regions, distinguished by the scaling of the cumulants in terms of the microscopic scale and the total length of the period. Various analytical representations of the PDF allow for a precise numerical evaluation of the scaling function of the PDF for any alpha. A simulation of the periodic process makes it possible to study also non-periodic signals on short intervals embedded in the full period. We find that for alpha=<1/2 the scaled PDF-s in both the periodic and the non-periodic cases are Gaussian, but for alpha>1/2 they differ from the Gaussian and from each other. Both deviations increase with growing alpha. That conclusion, based on numerics, is reinforced by analytic results for alpha=2 and alpha->infinity. We suggest that our theoretical and numerical results open a new perspective on the data analysis of 1/f^alpha processes.Comment: 12 pages incl. 6 figures, with RevTex4, for A4 paper, in v2 some references were correcte

    Nitric oxide and cyclic nucleotides: Their roles in junction dynamics and spermatogenesis

    Get PDF
    Spermatogenesis is a highly complicated process in which functional spermatozoa (haploid, 1n) are generated from primitive mitotic spermatogonia (diploid, 2n). This process involves the differentiation and transformation of several types of germ cells as spermatocytes and spermatids undergo meiosis and differentiation. Due to its sophistication and complexity, testis possesses intrinsic mechanisms to modulate and regulate different stages of germ cell development under the intimate and indirect cooperation with Sertoli and Leydig cells, respectively. Furthermore, developing germ cells must translocate from the basal to the apical (adluminal) compartment of the seminiferous epithelium. Thus, extensive junction restructuring must occur to assist germ cell movement. Within the seminiferous tubules, three principal types of junctions are found namely anchoring junctions, tight junctions, and gap junctions. Other less studied junctions are desmosome-like junctions and hemidesmosome junctions. With these varieties of junction types, testes are using different regulators to monitor junction turnover. Among the uncountable junction modulators, nitric oxide (NO) is a prominent candidate due to its versatility and extensive downstream network. NO is synthesized by nitric oxide synthase (NOS). Three traditional NOS, specified as endothelial NOS (eNOS), inducible NOS (iNOS), and neuronal NOS (nNOS), and one testis-specific nNOS (TnNOS) are found in the testis. For these, eNOS and iNOS were recently shown to have putative junction regulation properties. More important, these two NOSs likely rely on the downstream soluble guanylyl cyclase/cGMP/protein kinase G signaling pathway to regulate the structural components at the tight junctions and adherens junctions in the testes. Apart from the involvement in junction regulation, NOS/NO also participates in controlling the levels of cytokines and hormones in the testes. On the other hand, NO is playing a unique role in modulating germ cell viability and development, and indirectly acting on some aspects of male infertility and testicular pathological conditions. Thus, NOS/NO bears an irreplaceable role in maintaining the homeostasis of the microenvironment in the seminiferous epithelium via its different downstream signaling pathways
    • …
    corecore