Now showing items 1-20 of 6281

    • Unpeeling a Homoclinic Banana in the FitzHugh--Nagumo System

      Carter, Paul; Sandstede, Björn; Univ Arizona, Dept Math, Tucson, AZ 85721 USA (SIAM PUBLICATIONS, 2018)
      The FitzHugh Nagumo equations are known to admit fast traveling pulse solutions with monotone tails. It is also known that this system admits traveling pulses with exponentially decaying oscillatory tails. Upon numerical continuation in parameter space, it has been observed that the oscillations in the tails of the pulses grow into a secondary excursion resembling a second copy of the primary pulse. In this paper, we outline in detail the geometric mechanism responsible for this single-to-double-pulse transition, and we construct the transition analytically using geometric singular perturbation theory and blow-up techniques.
    • The maximum angular-diameter distance in cosmology

      Melia, Fulvio; Yennapureddy, Manoj K.; Univ Arizona, Dept Phys, Appl Math Program; Univ Arizona, Dept Astron (OXFORD UNIV PRESS, 2018-07-23)
      Unlike other observational signatures in cosmology, the angular-diameter distance dA(z) uniquely reaches a maximum (at zmax) and then shrinks to zero towards the big bang. The location of this turning point depends sensitively on the model, but has been difficult to measure. In this paper, we estimate and use zmax inferred from quasar cores: (1) by employing a sample of 140 objects yielding a much reduced dispersion due to pre-constrained limits on their spectral index and luminosity, (2) by reconstructing dA(z) using Gaussian processes, and (3) comparing the predictions of seven different cosmologies and showing that the measured value of zmax can effectively discriminate between them. We find that zmax = 1.70 ± 0.20 – an important new probe of the Universe’s geometry. The most strongly favoured model is Rh = ct, followed by PlanckΛCDM. Several others, including Milne, Einstein-de Sitter, and Static tired light are strongly rejected. According to these results, the Rh = ct universe, which predicts zmax = 1.718, has a ∼92.8 per cent probability of being the correct cosmology. For consistency, we also carry out model selection based on dA(z) itself. This test confirms that Rh = ct and PlanckΛCDM are among the few models that account for angular-size data better than those that are disfavoured by zmax. The dA(z) comparison, however, is less discerning than that with zmax, due to the additional free parameter, H0. We find that H0 = 63.4 ± 1.2 km s−1 Mpc−1 for Rh = ct, and 69.9 ± 1.5 km s−1 Mpc−1 for ΛCDM. Both are consistent with previously measured values in each model, though they differ from each other by over 4σ. In contrast, model selection based on zmax is independent of H0.
    • Model selection with strong-lensing systems

      Leaf, Kyle; Melia, Fulvio; Univ Arizona, Dept Phys; Univ Arizona, Dept Phys, Appl Math Program; Univ Arizona, Dept Astron (OXFORD UNIV PRESS, 2018-05-24)
      In this paper, we use an unprecedentedly large sample (158) of confirmed strong lens systems for model selection, comparing five well-studied Friedmann–Robertson–Walker cosmologies: ΛCDM, wCDM (the standard model with a variable dark-energy equation of state), the Rh = ct universe, the (empty) Milne cosmology, and the classical Einstein-de Sitter (matter-dominated) universe. We first use these sources to optimize the parameters in the standard model and show that they are consistent with Planck, though the quality of the best fit is not satisfactory. We demonstrate that this is likely due to underreported errors, or to errors yet to be included in this kind of analysis. We suggest that the missing dispersion may be due to scatter about a pure single isothermal sphere (SIS) model that is often assumed for the mass distribution in these lenses. We then use the Bayes information criterion, with the inclusion of a suggested SIS dispersion, to calculate the relative likelihoods and ranking of these models, showing that Milne and Einstein-de Sitter are completely ruled out, while Rh = ct is preferred over ΛCDM/wCDM with a relative probability of ∼73percent versus ∼24percent⁠. The recently reported sample of new strong lens candidates by the Dark Energy Survey, if confirmed, may be able to demonstrate which of these two models is favoured over the other at a level exceeding 3σ.
    • The apparent (gravitational) horizon in cosmology

      Melia, Fulvio; Univ Arizona, Dept Phys, Appl Math Program; Univ Arizona, Dept Astron (AMER ASSOC PHYSICS TEACHERS, 2018-08)
      In general relativity, a gravitational horizon (more commonly known as the "apparent horizon") an imaginary surface beyond which all null geodesics recede from the observer. The Universe has an apparent (gravitational) horizon, but unlike its counterpart in the Schwarzschild and Kerr metrics, it is not static. It may eventually turn into an event horizon-an asymptotically defined membrane that forever separates causally connected events from those that are not-depending on the equation of state of the cosmic fluid. In this paper, we examine how and why an apparent (gravitational) horizon is manifested in the Friedmann-Robertson-Walker metric, and why it is becoming so pivotal to our correct interpretation of the cosmological data. We discuss its observational signature and demonstrate how it alone defines the proper size of our visible Universe. In so doing, we affirm its physical reality and its impact on cosmological models. (C) 2018 American Association of Physics Teachers.
    • Evidence of a truncated spectrum in the angular correlation function of the cosmic microwave background

      Melia, F.; López-Corredoira, M.; Univ Arizona, Dept Phys, Appl Math Program; Univ Arizona, Dept Astron (EDP SCIENCES S A, 2018-03-09)
      Aim. The lack of large-angle correlations in the fluctuations of the cosmic microwave background (CMB) conflicts with predictions of slow-roll inflation. But while probabilities (≲0.24%) for the missing correlations disfavour the conventional picture at ≳3σ, factors not associated with the model itself may be contributing to the tension. Here we aim to show that the absence of large-angle correlations is best explained with the introduction of a non-zero minimum wave number kmin for the fluctuation power spectrum P(k). Methods. We assumed that quantum fluctuations were generated in the early Universe with a well-defined power spectrum P(k), although with a cut-off kmin ≠ 0. We then re-calculated the angular correlation function of the CMB and compared it with Planck observations. Results. The Planck 2013 data rule out a zero kmin at a confidence level exceeding 8σ. Whereas purely slow-roll inflation would have stretched all fluctuations beyond the horizon, producing a P(k) with kmin = 0 – and therefore strong correlations at all angles – a kmin ≠ 0 would signal the presence of a maximum wavelength at the time (tdec) of decoupling. This argues against the basic inflationary paradigm, and perhaps even suggests non-inflationary alternatives, for the origin and growth of perturbations in the early Universe. In at least one competing cosmology, the Rh = ct universe, the inferred kmin corresponds to the gravitational radius at tdec.
    • Model selection based on the angular-diameter distance to the compact structure in radio quasars

      Melia, F.; Univ Arizona, Dept Phys, Appl Math Program; Univ Arizona, Dept Astron (IOP PUBLISHING LTD, 2018-09-03)
      Of all the distance arid temporal measures in cosmology, the angular-diameter distance, d(A)(z), uniquely reaches a maximum value at some finite redshift z(max )and then decreases to zero towards the Big Bang. This effect has been difficult to observe due to a lack of reliable, standard rulers, though refinements to the identification of the compact structure in radio quasars may have overcome this deficiency. In this letter, we assemble a catalog of 140 such sources with 0 less than or similar to z less than or similar to 3 for model selection and the measurement of z(max). In flat Lambda CDM, we find that Omega(m) = 0.24(-0.09)(+0.1) fully consistent with the Planck optimized value, with z(max) = 1.69. Both of these values are associated with a d(A)(z) indistinguishable from that predicted by the zero active mass condition, rho + 3p = 0, in terms of the total pressure rho and total energy density rho of the cosmic fluid. An expansion driven by this constraint, known as the Rh = ct universe, has z(max )= 1.718, which differs from the Lambda CDM optimized value by less than similar to 1.6%. Indeed, the Bayes Information Criterion favours R-h = ct over flat Lambda CDM with a likelihood of similar to 81% vs. 19%, suggesting that the optimized parameters in Planck Lambda CDM mimic the constraint p = -rho/3.
    • A cosmological solution to the Impossibly Early Galaxy Problem

      Yennapureddy, Manoj K.; Melia, Fulvio; Univ Arizona, Dept Phys; Univ Arizona, Dept Phys, Appl Math Program; Univ Arizona, Dept Astron (ELSEVIER SCIENCE BV, 2018-03-26)
      To understand the formation and evolution of galaxies at redshifts 0 less than or similar to z less than or similar to 10, one must invariably introduce specific models (e.g., for the star formation) in order to fully interpret the data. Unfortunately, this tends to render the analysis compliant to the theory and its assumptions, so consensus is still some-what elusive. Nonetheless, the surprisingly early appearance of massive galaxies challenges the standard model, and the halo mass function estimated from galaxy surveys at z greater than or similar to 4 appears to be inconsistent with the predictions of Lambda CDM, giving rise to what has been termed "The Impossibly Early Galaxy Problem" by some workers in the field. A simple resolution to this question may not be forthcoming. The situation with the halos themselves, however, is more straightforward and, in this paper, we use linear perturbation theory to derive the halo mass function over the redshift range 0 less than or similar to z less than or similar to 10 for the R-h = ct universe. We use this predicted halo distribution to demonstrate that both its dependence on mass and its very weak dependence on redshift are compatible with the data. The difficulties with Lambda CDM may eventually be overcome with refinements to the underlying theory of star formation and galaxy evolution within the halos. For now, however, we demonstrate that the unexpected early formation of structure may also simply be due to an incorrect choice of the cosmology, rather than to yet unknown astrophysical issues associated with the condensation of mass fluctuations and subsequent galaxy formation.
    • A comparison of the R_h=ct and LCDM cosmologies using the Cosmic Distance Duality Relation

      Melia, Fulvio; Univ Arizona, Dept Phys, Program Appl Math; Univ Arizona, Dept Astron (OXFORD UNIV PRESS, 2018-09-21)
      The cosmic distance duality (CDD) relation (based on the Etherington reciprocity theorem) plays a crucial role in a wide assortment of cosmological measurements. Attempts at confirming it observationally have met with mixed results, though the general consensus appears to be that the data do support its existence in nature. A common limitation with past approaches has been their reliance on a specific cosmological model, or on measurements of the luminosity distance to Type Ia SNe, which introduces a dependence on the presumed cosmology in spite of beliefs to the contrary. Confirming that the CDD is actually realized in nature is crucial because its violation would require exotic new physics. In this paper, we study the CDD using the observed angular size of compact quasar cores and a Gaussian Process reconstruction of the H II galaxy Hubble diagram – without pre-assuming any particular background cosmology. In so doing, we confirm at a very high level of confidence that the angular-diameter and luminosity distances do indeed satisfy the CDD. We then demonstrate the potential power of this result by utilizing it in a comparative test of two competing cosmological models – the Rh = ct universe and ΛCDM – and show that Rh = ct is favoured by the CDD data with a likelihood ∼82.3 per cent compared with ∼17.7 per cent for the standard model.
    • Dopamine D1 receptor activation contributes to light-adapted changes in retinal inhibition to rod bipolar cells.

      Flood, Michael D.; Moore-Dotson, Johnnie M.; Eggers, Erika D.; Univ Arizona, Dept Physiol; Univ Arizona, Dept Biomed Engn (AMER PHYSIOLOGICAL SOC, 2018-08-01)
      Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels, but the role of dopamine modulation of retinal inhibition is not clear. We previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. In this study, we determined how dopamine D1 receptors in the inner retina contribute to this modulation. We found that D1 receptor activation significantly decreased the magnitude of inhibitory light responses from rod bipolar cells, whereas D1 receptor blockade during light adaptation partially prevented this decline. To determine what mechanisms were involved in the modulation of inhibitory light responses, we measured the effect of D1 receptor activation on spontaneous currents and currents evoked from electrically stimulating amacrine cell inputs to rod bipolar cells. D1 receptor activation decreased the frequency of spontaneous inhibition with no change in event amplitudes, suggesting a presynaptic change in amacrine cell activity in agreement with previous reports that rod bipolar cells lack D1 receptors. Additionally, we found that D1 receptor activation reduced the amplitude of electrically evoked responses, showing that D1 receptors can modulate amacrine cells directly. Our results suggest that D1 receptor activation can replicate a large portion but not all of the effects of light adaptation, likely by modulating release from amacrine cells onto rod bipolar cells. NEW & NOTEWORTHY We demonstrated a new aspect of dopaminergic signaling that is involved in mediating light adaptation of retinal inhibition. This D1 receptor-dependent mechanism likely acts through receptors located directly on amacrine cells, in addition to its potential role in modulating the strength of serial inhibition between amacrine cells. Our results also suggest that another D2/D4 receptor-dependent or dopamine-independent mechanism must also be involved in light adaptation of inhibition to rod bipolar cells.
    • Principal 2-blocks and Sylow 2-subgroups

      Taylor, Jay; Schaeffer Fry, Amanda A.; MSU Denver; Univ Arizona, Dept Math (John Wiley & Sons, 2018-07-16)
      Let G be a finite group with Sylow 2-subgroup P. Navarro–Tiep–Vallejo have conjectured that the principal 2-block of N_G(P) contains exactly one irreducible Brauer character if and only if all odd-degree ordinary irreducible characters in the principal 2-block of G are fixed by a certain Galois automorphism. Recent work of Navarro–Vallejo has reduced this conjecture to a problem about finite simple groups. We show that their conjecture holds for all finite simple groups, thus establishing the conjecture for all finite groups.
    • Target patterns in a 2D array of oscillators with nonlocal coupling

      Jaramillo, Gabriela; Venkataramani, Shankar; Univ Arizona, Dept Math (Institute of Physics, London, 2018-07-26)
      We analyze the effect of adding a weak, localized, inhomogeneity to a two dimensional array of oscillators with nonlocal coupling. We propose and also justify a model for the phase dynamics in this system. Our model is a generalization of a viscous eikonal equation that is known to describe the phase modulation of traveling waves in reaction–diffusion systems. We show the existence of a branch of target pattern solutions that bifurcates from the spatially homogeneous state when , the strength of the inhomogeneity, is nonzero and we also show that these target patterns have an asymptotic wavenumber that is small beyond all orders in . The strategy of our proof is to pose a good ansatz for an approximate form of the solution and use the implicit function theorem to prove the existence of a solution in its vicinity. The analysis presents two challenges. First, the linearization about the homogeneous state is a convolution operator of diffusive type and hence not invertible on the usual Sobolev spaces. Second, a regular perturbation expansion in does not provide a good ansatz for applying the implicit function theorem since the nonlinearities play a major role in determining the relevant approximation, which also needs to be 'correct' to all orders in . We overcome these two points by proving Fredholm properties for the linearization in appropriate Kondratiev spaces and using a refined ansatz for the approximate solution which was obtained using matched asymptotics.
    • Automating Wavefront Parallelization for Sparse Matrix Computations

      Venkat, Anand; Mohammadi, Mahdi Soltan; Park, Jongsoo; Rong, Hongbo; Barik, Rajkishore; Strout, Michelle Mills; Hall, Mary; Univ Arizona, Dept Comp Sci (IEEE, 2016)
      This paper presents a compiler and runtime framework for parallelizing sparse matrix computations that have loop-carried dependences. Our approach automatically generates a runtime inspector to collect data dependence information and achieves wavefront parallelization of the computation, where iterations within a wavefront execute in parallel, and synchronization is required across wavefronts. A key contribution of this paper involves dependence simplification, which reduces the time and space overhead of the inspector. This is implemented within a polyhedral compiler framework, extended for sparse matrix codes. Results demonstrate the feasibility of using automatically-generated inspectors and executors to optimize ILU factorization and symmetric Gauss-Seidel relaxations, which are part of the Preconditioned Conjugate Gradient (PCG) computation. Our implementation achieves a median speedup of 2.97x on 12 cores over the reference sequential PCG implementation, significantly outperforms PCG parallelized using Intel's Math Kernel Library (MKL), and is within 6% of the median performance of manually-parallelized PCG.
    • Galician coda restrictions and plural clusters

      Colina, S.; Simonet, M.; Univ Arizona, Dept Linguist (WALTER DE GRUYTER, 2014-11)
      The present study investigates the phonology and phonetics of Galician post-vocalic velar nasals. Galician has very strict coda restrictions – it does not allow for complex codas. One exception to this restriction is found in the plurals of words ending in a nasal consonant, which add /s/ to the “right” of a noun or adjective: man ‘hand’, mans ‘hands’; pan ‘bread’, pans ‘breads’. The present study puts forward a proposal, initially based on synchronic, formal phonological grounds, according to which post-vocalic, pre-/s/ nasals in plural forms are not nasal stops, but nasal glides. Their nature as nasal glides allows for their syllabification in the nucleus rather than in the coda, thus preserving (i.e., not violating) the restriction on complex codas. This proposal is then tested with a production experiment based on quantitative acoustic data. The acoustic study reveals indeed a difference in the degree of weakening of post-vocalic nasals, with pre-/s/ nasals in the plural forms showing a significantly higher degree of weakening than pre-/s/ nasals in the singular forms. The article concludes with an Optimality-Theoretic analysis of the phonological facts.
    • Epigenetic reactivation of LINE-1 retrotransposon disrupts NuRD corepressor functions and induces oncogenic transformation in human bronchial epithelial cells

      Bojang, Pasano, Jr.; Ramos, Kenneth S.; Univ Arizona, Coll Med, Div Pulm Allergy Crit Care & Sleep Med; Univ Arizona Hlth Sci, Ctr Appl Genet & Genom Med (WILEY, 2018-08)
      Long interspersed nuclear element-1 (LINE-1 or L1) reactivation is linked to poor prognosis in non-small-cell lung carcinoma (NSCLC), but the molecular bases of this response remain largely unknown. In this report, we show that challenge of human bronchial epithelial cells (HBECs) with the lung carcinogen, benzo(a)pyrene (BaP), shifted the L1 promoter from a heterochromatic to euchromatic state through disassembly of the nucleosomal and remodeling deacetylase (NuRD) complex. Carcinogen challenge was also associated with partial displacement of constituent proteins from the nuclear to the cytoplasmic compartment. Disruption of NuRD corepression by genetic ablation or carcinogen treatment correlated with accumulation of L1 mRNA and proteins. Mi2 bound directly to the L1 promoter to effect retroelement silencing, and this response required the DNA- and ATPase-binding domains of Mi2. Sustained expression of L1 in HBECs was tumorigenic in a human-SCID mouse xenograft model, giving rise to tumors that regressed over time. Together, these results show that functional modulation of the NuRD constituent proteins is a critical molecular event in the activation of L1 retrotransposon. L1 expression creates a microenvironment in HBECs that is conducive to neoplasia and malignant transformation.
    • A Multicellular Vascular Model of the Renal Myogenic Response

      Ciocanel, Maria-Veronica; Stepien, Tracy; Sgouralis, Ioannis; Layton, Anita; Univ Arizona, Dept Math (MDPI, 2018-07)
      The myogenic response is a key autoregulatory mechanism in the mammalian kidney. Triggered by blood pressure perturbations, it is well established that the myogenic response is initiated in the renal afferent arteriole and mediated by alterations in muscle tone and vascular diameter that counterbalance hemodynamic perturbations. The entire process involves several subcellular, cellular, and vascular mechanisms whose interactions remain poorly understood. Here, we model and investigate the myogenic response of a multicellular segment of an afferent arteriole. Extending existing work, we focus on providing an accurate-but still computationally tractable-representation of the coupling among the involved levels. For individual muscle cells, we include detailed Ca2+ signaling, transmembrane transport of ions, kinetics of myosin light chain phosphorylation, and contraction mechanics. Intercellular interactions are mediated by gap junctions between muscle or endothelial cells. Additional interactions are mediated by hemodynamics. Simulations of time-independent pressure changes reveal regular vasoresponses throughout the model segment and stabilization of a physiological range of blood pressures (80-180 mmHg) in agreement with other modeling and experimental studies that assess steady autoregulation. Simulations of time-dependent perturbations reveal irregular vasoresponses and complex dynamics that may contribute to the complexity of dynamic autoregulation observed in vivo. The ability of the developed model to represent the myogenic response in a multiscale and realistic fashion, under feasible computational load, suggests that it can be incorporated as a key component into larger models of integrated renal hemodynamic regulation.
    • Consistency of modularity clustering on random geometric graphs

      Davis, Erik; Sethuraman, Sunder; Univ Arizona, Dept Math (INST MATHEMATICAL STATISTICS, 2018-08)
      Given a graph, the popular "modularity" clustering method specifies a partition of the vertex set as the solution of a certain optimization problem. In this paper, we discuss scaling limits of this method with respect to random geometric graphs constructed from i.i.d. points X-n = {X-1, X-2,..., X-n}, distributed according to a probability measure nu supported on a bounded domain D subset of R-d. Among other results, we show, via a Gamma convergence framework, a geometric form of consistency: When the number of clusters, or partitioning sets of X-n is a priori bounded above, the discrete optimal modularity clusterings converge in a specific sense to a continuum partition of the underlying domain D, characterized as the solution to a "soap bubble" or "Kelvin"-type shape optimization problem.
    • Possible Enzymatic Downregulation of the Natriuretic Peptide System in Patients with Reduced Systolic Function and Heart Failure: A Pilot Study

      Zaidi, Syed S.; Ward, Ryan D.; Ramanathan, Kodangudi; Yu, Xinhua; Gladysheva, Inna P.; Reed, Guy L.; Univ Arizona, Dept Med, Coll Med Phoenix (HINDAWI LTD, 2018)
      Background. In patients with reduced systolic function, the natriuretic peptide system affects heart failure (HF) progression, but the expression of key activating (corin) and degrading enzymes (neprilysin) is not well understood. Methods and Results. This pilot study (n=48) compared plasma levels of corin, neprilysin, ANP, BNP, and cGMP in control patients with normal ejection fractions (mean EF 63 +/- 3%) versus patients with systolic dysfunction, with (EF 24 +/- 8%) and without (EF 27 +/- 7%) decompensated HF (dHF), as defined by Framingham and BNP criteria. Mean ages, use of beta blockers, and ACE-inhibitors-angiotensin receptor blockers were similar between the groups. Corin levels were depressed in systolic dysfunction patients (797 +/- 346 pg/ml) versus controls (1188 +/- 549, p<0.02), but levels were not affected by dHF (p=0.77). In contrast, levels of neprilysin (p<0.01), cGMP (p<0.001), and ANP (p<0.001) were higher in systolic dysfunction patients than controls and were the highest in patients with dHF. Conclusions. Levels of neprilysin, ANP, BNP, and cGMP increased in patients with reduced systolic function and were the highest in dHF patients. Conversely, corin levels were low in patients with reduced EF with or without dHF. This pattern suggests possible enzymatic downregulation of natriuretic peptide activity in patients with reduced EF, which may have diagnostic and prognostic implications.
    • Modeling temperature and moisture dependent emissions of carbon dioxide and methane from drying dairy cow manure

      HU, Enzhu; SUTITARNNONTR, Pakorn; TULLER, Markus; JONES, Scott B.; Univ Arizona, Dept Soil Water & Environm Sci (HIGHER EDUCATION PRESS, 2018-05)
      Greenhouse gas emissions due to biological degradation processes of animal wastes are significant sources of air pollution from agricultural areas. The major environmental controls on these microbe-induced gas fluxes are temperature and moisture content. The objective of this study was to model the effects of temperature and moisture content on emissions of CO2 and CH4 during the ambient drying process of dairy manure under controlled conditions. Gas emissions were continuously recorded over 15 d with paired fully automated closed dynamic chambers coupled with a Fourier Transformed Infrared gas analyzer. Water content and temperature were measured and monitored with capacitance sensors. In addition, on days 0, 3, 6, 9, 12 and 15, pH, moisture content, dissolved organic carbon and total carbon (TC) were determined. An empirical model derived from the Arrhenius equation confirmed high dependency of carbon emissions on temperature and moisture content. Results indicate that for the investigated dairy manure, 6.83% of TC was lost in the form of C-O2 and 0.047% of TC was emitted as CH4. Neglecting the effect of temperature, the moisture contents associated with maximum gas emissions were estimated as 0.75 and 0.79 g center dot g(-1) for CO2 and CH4, respectively.
    • Enteropathogenic Escherichia coli EspH-Mediated Rho GTPase Inhibition Results in Desmosomal Perturbations

      Roxas, Jennifer Lising; Monasky, Ross Calvin; Roxas, Bryan Angelo P.; Agellon, Al B.; Mansoor, Asad; Kaper, James B.; Vedantam, Gayatri; Viswanathan, V.K.; Univ Arizona, Sch Anim & Comparat Biomed Sci; Univ Arizona, BIO5 Inst Collaborat Res; Univ Arizona, Dept Immunobiol (ELSEVIER INC, 2018)
      BACKGROUND & AIMS: The diarrheagenic pathogen, enteropathogenic Escherichia coli (EPEC), uses a type III secretion system to deliver effector molecules into intestinal epithelial cells (IECs). While exploring the basis for the lateral membrane separation of EPEC-infected IECs, we observed infection-induced loss of the desmosomal cadherin desmoglein-2 (DSG2). We sought to identify the molecule(s) involved in, and delineate the mechanisms and consequences of, EPEC-induced DSG2 loss. METHODS: DSG2 abundance and localization was monitored via immunoblotting and immunofluorescence, respectively. Junctional perturbations were visualized by electron microscopy, and cell-cell adhesion was assessed using dispase assays. EspH alanine-scan mutants as well as pharmacologic agents were used to evaluate impacts on desmosomal alterations. EPEC-mediated DSG2 loss, and its impact on bacterial colonization in vivo, was assessed using a murine model. RESULTS: The secreted virulence protein EspH mediates EPEC-induced DSG2 degradation, and contributes to desmosomal perturbation, loss of cell junction integrity, and barrier disruption in infected IECs. EspH sequesters Rho guanine nucleotide exchange factors and inhibits Rho guanosine triphosphatase signaling; EspH mutants impaired for Rho guanine nucleotide exchange factor interaction failed to inhibit RhoA or deplete DSG2. Cytotoxic necrotizing factor 1, which locks Rho guanosine triphosphatase in the active state, jasplakinolide, a molecule that promotes actin polymerization, and the lysosomal inhibitor bafilomycin A, respectively, rescued infected cells from EPEC-induced DSG2 loss. Wild-type EPEC, but not an espH-deficient strain, colonizes mouse intestines robustly, widens paracellular junctions, and induces DSG2 re-localization in vivo. CONCLUSIONS: Our studies define the mechanism and consequences of EPEC-induced desmosomal alterations in IECs. These perturbations contribute to the colonization and virulence of EPEC, and likely related pathogens. (Cell Mol Gastroenterol Hepatol 2018;6:163-180; https:/

      Menjívar, Cecilia; Simmons, William Paul; Alvord, Daniel; Salerno Valdez, Elizabeth; Univ Arizona, Gender & Womens Studies; Univ Arizona, Online Grad Programs Human Rights Practice; Univ Arizona, Mel & Enid Zuckerman Coll Publ Hlth (CAMBRIDGE UNIV PRESS, 2018-08-18)
      The immigration enforcement system today affects different subgroups of Latinos; it reaches beyond the undocumented to immigrants who hold legal statuses and even to the U.S.-born. States have enacted their own enforcement collaboration agreements with federal authorities and thus Latinos may have dissimilar experiences based on where they live. This article examines the effects of enforcement schemes on Latinos' likelihood of reporting crimes to police and views of law enforcement. It includes documented and U.S-born Latinos to capture the spillover beyond the undocumented, and it is based on four metropolitan areasLos Angeles, Houston, Phoenix, and Chicagoto comparatively assess the effects of various enforcement contexts. Empirically, it relies on data from a random sample survey of over 2000 Latinos conducted in 2012 in these four cities. Results show that spillover effects vary by context and legal/citizenship status: Latino immigrants with legal status are less inclined to report to the police as compared to U.S.-born Latinos in Houston, Los Angeles, and Phoenix but not in Chicago. At the other end, the spillover effect in Phoenix is so strong that it almost reaches to U.S.-born Latinos. The spillover effect identified is possible due to the close association between being Latino or Mexican and being undocumented, underscoring the racialization of legal status and of immigration enforcement today.