4,814 research outputs found

    Modulation of CXCR4, CXCL12, and Tumor Cell Invasion Potential In Vitro by Phytochemicals.

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    CXCR4 is a chemokine receptor frequently overexpressed on primary tumor cells. Organs to which these cancers metastasize secrete CXCL12, the unique ligand for CXCR4, which stimulates invasion and metastasis to these sites. Similar to our previous work with the chemoprotective phytochemical, 3,3'-diindolylmethane (DIM), we show here that genistein also downregulates CXCR4 and CXCL12 and subsequently lowers the migratory and invasive potentials of breast and ovarian cancer cells. Moreover, genistein and DIM elicit a significantly greater cumulative effect in lowering CXCR4 and CXCL12 levels than either compound alone. Our data suggest a novel mechanism for the protective effects of phytochemicals against cancer progression and indicate that in combination, these compounds may prove even more efficacious

    Motion of Contact Line of a Crystal Over the Edge of Solid Mask in Epitaxial Lateral Overgrowth

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    Mathematical model that allows for direct tracking of the homoepitaxial crystal growth out of the window etched in the solid, pre-deposited layer on the substrate is described. The growth is governed by the normal (to the crystal-vapor interface) flux from the vapor phase and by the interface diffusion. The model accounts for possibly inhomogeneous energy of the mask surface and for strong anisotropies of crystal-vapor interfacial energy and kinetic mobility. Results demonstrate that the motion of the crystal-mask contact line slows down abruptly as radius of curvature of the mask edge approaches zero. Numerical procedure is suggested to overcome difficulties associated with ill-posedness of the evolution problem for the interface with strong energy anisotropy. Keywords: Thin films, epitaxy, MOCVD, surface diffusion, interface dynamics, contact lines, rough surfaces, wetting, regularization of ill-posed evolution problems.Comment: 21 pages, 11 figures; to appear in Computational Materials Scienc

    Total IgE Variability Is Associated with Future Asthma Exacerbations: A 1-Year Prospective Cohort Study.

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    BACKGROUND: Few prospective studies have investigated the relationship between IgE variability and risk for asthma exacerbations (AEs). OBJECTIVE: To explore the relationship between IgE variability and AEs. METHODS: Recruited patients with stable asthma underwent two serum total IgE tests within a month (at screening [baseline IgE] and at 1 month) to obtain the coefficient of variation (CV) of base 10 log-transformed IgE. Patients with IgE CV were divided into IgE CV-high and IgE CV-low cohorts based on the CV median and were observed within 12 months, during which the association between IgE variability and AEs was explored using a negative binomial regression model. RESULTS: The IgE CV levels obtained from 340 patients classified patients into two groups (n = 170 for the IgE CV-high and IgE CV-low groups, respectively) based on the serum total IgE CV median of 2.12% (quartiles 1 and 3: 0.98% and 3.91%, respectively). The IgE CV-high patients exhibited worse asthma control and lung function and more marked airway inflammation, and received more intensive medication use compared with IgE CV-low patients. The IgE CV-high patients exhibited increased rates of moderate-to-severe (adjusted rate ratio = 2.88; 95% confidence interval, 1.65-5.03; P < .001) and severe (adjusted rate ratio = 2.16; 95% confidence interval, 1.08-4.32; P = .029) AEs during the follow-up year compared with IgE CV-low patients. Furthermore, sputum IL-6 partially mediated the associations between IgE CV with moderate-to-severe and severe AEs. CONCLUSIONS: Variability in total serum IgE levels is an easily obtained and practical measure for predicting AEs. Future studies are needed to investigate whether IgE variability can be used to guide precision medicine in asthma

    Magnetotransport properties of a polarization-doped three-dimensional electron slab

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    We present evidence of strong Shubnikov-de-Haas magnetoresistance oscillations in a polarization-doped degenerate three-dimensional electron slab in an Alx_{x}Ga1x_{1-x}N semiconductor system. The degenerate free carriers are generated by a novel technique by grading a polar alloy semiconductor with spatially changing polarization. Analysis of the magnetotransport data enables us to extract an effective mass of m=0.19m0m^{\star}=0.19 m_{0} and a quantum scattering time of τq=0.3ps\tau_{q}= 0.3 ps. Analysis of scattering processes helps us extract an alloy scattering parameter for the Alx_{x}Ga1x_{1-x}N material system to be V0=1.8eVV_{0}=1.8eV

    Self-similar Bianchi type VIII and IX models

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    It is shown that in transitively self-similar spatially homogeneous tilted perfect fluid models the symmetry vector is not normal to the surfaces of spatial homogeneity. A direct consequence of this result is that there are no self-similar Bianchi VIII and IX tilted perfect fluid models. Furthermore the most general Bianchi VIII and IX spacetime which admit a four dimensional group of homotheties is given.Comment: 5 pages, Latex; One reference and minor clarifications added. To appear in General Relativity and Gravitatio

    The BAH domain of Rsc2 is a histone H3 binding domain

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    Bromo-adjacent homology (BAH) domains are commonly found in chromatin-associated proteins and fall into two classes; Remodels the Structure of Chromatin (RSC)-like or Sir3-like. Although Sir3-like BAH domains bind nucleosomes, the binding partners of RSC-like BAH domains are currently unknown. The Rsc2 subunit of the RSC chromatin remodeling complex contains an RSC-like BAH domain and, like the Sir3-like BAH domains, we find Rsc2 BAH also interacts with nucleosomes. However, unlike Sir3-like BAH domains, we find that Rsc2 BAH can bind to recombinant purified H3 in vitro, suggesting that the mechanism of nucleosome binding is not conserved. To gain insight into the Rsc2 BAH domain, we determined its crystal structure at 2.4 Å resolution. We find that it differs substantially from Sir3-like BAH domains and lacks the motifs in these domains known to be critical for making contacts with histones. We then go on to identify a novel motif in Rsc2 BAH that is critical for efficient H3 binding in vitro and show that mutation of this motif results in defective Rsc2 function in vivo. Moreover, we find this interaction is conserved across Rsc2-related proteins. These data uncover a binding target of the Rsc2 family of BAH domains and identify a novel motif that mediates this interaction

    Chemical transport model ozone simulations for spring 2001 over the western Pacific: Regional ozone production and its global impacts

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    The spatial and temporal variation in ozone production over major source regions in East Asia during the NASA Transport and Chemical Evolution over the Pacific (TRACE-P) measurement campaign in spring 2001 is assessed using a global chemical transport model. There is a strong latitudinal gradient in ozone production in springtime, driven by regional photochemistry, which rapidly diminishes as the season progresses. The great variability in meteorological conditions characteristic of East Asia in springtime leads to large daily variability in regional ozone formation, but we find that it has relatively little impact on the total global production. We note that transport processes effectively modulate and thus stabilize total ozone production through their influence over its location. However, the impact on the global ozone burden, important for assessing the effects of precursor emissions on tropospheric oxidizing capacity and climate, is sensitive to local meteorology through the effects of location on chemical lifetime. Stagnant, anticyclonic conditions conducive to substantial boundary layer ozone production typically allow little lifting of precursors into the free troposphere where greater ozone production could occur, and the consequent shorter chemical lifetime for ozone leads to relatively small impacts on global ozone. Conversely, cyclonic conditions with heavy cloud cover suppressing regional ozone production are often associated with substantial cloud convection, enhancing subsequent production in the free troposphere where chemical lifetimes are longer, and the impacts on global ozone are correspondingly greater. We find that ozone formation in the boundary layer and free troposphere outside the region of precursor emissions dominates total gross production from these sources in springtime, and that it makes a big contribution to the long range transport of ozone, which is greatest in this season

    Rat strain differences in brain structure and neurochemistry in response to binge alcohol

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    RATIONALE: Ventricular enlargement is a robust phenotype of the chronically dependent alcoholic human brain, yet the mechanism of ventriculomegaly is unestablished. Heterogeneous stock Wistar rats administered binge EtOH (3 g/kg intragastrically every 8 h for 4 days to average blood alcohol levels (BALs) of 250 mg/dL) demonstrate profound but reversible ventricular enlargement and changes in brain metabolites (e.g., N-acetylaspartate (NAA) and choline-containing compounds (Cho)). OBJECTIVES: Here, alcohol-preferring (P) and alcohol-nonpreferring (NP) rats systematically bred from heterogeneous stock Wistar rats for differential alcohol drinking behavior were compared with Wistar rats to determine whether genetic divergence and consequent morphological and neurochemical variation affect the brain's response to binge EtOH treatment. METHODS: The three rat lines were dosed equivalently and approached similar BALs. Magnetic resonance imaging and spectroscopy evaluated the effects of binge EtOH on brain. RESULTS: As observed in Wistar rats, P and NP rats showed decreases in NAA. Neither P nor NP rats, however, responded to EtOH intoxication with ventricular expansion or increases in Cho levels as previously noted in Wistar rats. Increases in ventricular volume correlated with increases in Cho in Wistar rats. CONCLUSIONS: The latter finding suggests that ventricular volume expansion is related to adaptive changes in brain cell membranes in response to binge EtOH. That P and NP rats responded differently to EtOH argues for intrinsic differences in their brain cell membrane composition. Further, differential metabolite responses to EtOH administration by rat strain implicate selective genetic variation as underlying heterogeneous effects of chronic alcoholism in the human condition

    Diffraction studies for stoichiometry effects in BaTiO3 grown by molecular beam epitaxy on Ge(001)

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    In this work, we present a systematic study of the effect of the stoichiometry of BaTiO3 (BTO) films grown on the Ge(001) substrate by molecular-beam-epitaxy using different characterization methods relying on beam diffraction, including reflection high-energy electron diffraction (RHEED), X-ray diffraction (XRD), and selected-area electron diffraction in transmission electron microscopy. Surprisingly, over a wide range of [Ba]/[Ti] ratios, as measured by the Rutherford backscattering spectrometry, all the BTO layers exhibit the same epitaxial relationship BTO(001)// Ge(001) with the substrate, describing a 45 degrees lattice rotation of the BTO lattice with respect to the Ge lattice. However, varying the [Ba]/[Ti] ratio does change the diffraction behavior. From RHEED patterns, we can derive that excessive [Ba] and [Ti] generate twinning planes and a rougher surface in the non-stoichiometric BTO layers. XRD allows us to follow the evolution of the lattice constants as a function of the [Ba]/[Ti] ratio, providing an option for tuning the tetragonality of the BTO layer. In addition, we found that the intensity ratio of the 3 lowest-order Bragg peaks I-(001)/I-(002), I-(101)/I-(002), and I-(111)/I-(002) derived from omega - 2 theta scans characteristically depend on the BTO stoichiometry. To explain the relation between observed diffraction patterns and the stoichiometry of the BTO films, we propose a model based on diffraction theory explaining how excess [Ba] or [Ti] in the layer influences the diffraction response. Published by AIP Publishing

    Global tropospheric ozone modelling:quantifying errors due to grid resolution.

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    Ozone production in global chemical models is dependent on model resolution because ozone chemistry is inherently nonlinear, the timescales for chemical production are short, and precursors are artificially distributed over the spatial scale of the model grid. In this study we examine the sensitivity of ozone, its precursors, and its production to resolution by running a global chemical transport model at four different resolutions between T21 (5.6° × 5.6°) and T106 (1.1° × 1.1°) and by quantifying the errors in regional and global budgets. The sensitivity to vertical mixing through the parameterization of boundary layer turbulence is also examined. We find less ozone production in the boundary layer at higher resolution, consistent with slower chemical production in polluted emission regions and greater export of precursors. Agreement with ozonesonde and aircraft measurements made during the NASA TRACE-P campaign over the western Pacific in spring 2001 is consistently better at higher resolution. We demonstrate that the numerical errors in transport processes on a given resolution converge geometrically for a tracer at successively higher resolutions. The convergence in ozone production on progressing from T21 to T42, T63, and T106 resolution is likewise monotonic but indicates that there are still large errors at 120 km scales, suggesting that T106 resolution is too coarse to resolve regional ozone production. Diagnosing the ozone production and precursor transport that follow a short pulse of emissions over east Asia in springtime allows us to quantify the impacts of resolution on both regional and global ozone. Production close to continental emission regions is overestimated by 27% at T21 resolution, by 13% at T42 resolution, and by 5% at T106 resolution. However, subsequent ozone production in the free troposphere is not greatly affected. We find that the export of short-lived precursors such as NO x by convection is overestimated at coarse resolution
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