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At least 649 records · Page 36

Apc bridges Wnt/{beta}-catenin and BMP signaling during osteoblast differentiation of KS483 cells

The canonical Wnt signaling pathway influences the differentiation of mesenchymal cell lineages in a quantitative and qualitative fashion depending on the dose of {beta}-catenin signaling. Adenomatous polyposis coli (Apc) is the critical intracellular regulator of {beta}-catenin turnover. To better understand the molecular mechanisms underlying the role of Apc in regulating the differentiation capacity of skeletal progenitor cells, we have knocked down Apc in the murine mesenchymal stem cell-like KS483 cells by stable expression of Apc-specific small interfering RNA. In routine culture, KSFrt-Apc{sub si} cells displayed a mesenchymal-like spindle shape morphology, exhibited markedly decreased proliferation and increased apoptosis. Apc knockdown resulted in upregulation of the Wnt/{beta}-catenin and the BMP/Smad signaling pathways, but osteogenic differentiation was completely inhibited. This effect could be rescued by adding high concentrations of BMP-7 to the differentiation medium. Furthermore, KSFrt-Apc{sub si} cells showed no potential to differentiate into chondrocytes or adipocytes. These results demonstrate that Apc is essential for the proliferation, survival and differentiation of KS483 cells. Apc knockdown blocks the osteogenic differentiation of skeletal progenitor cells, a process that can be overruled by high BMP signaling.

60 APPLIED LIFE SCIENCES↗

Distinct hydrophobic “patches” in the N- and C-tails of beta-catenin contribute to nuclear transport

β-catenin is a key mediator of Wnt signaling and its deregulated nuclear accumulation can drive cancer progression. While the central armadillo (Arm) repeats of β-catenin stimulate nuclear entry, the N- and C-terminal “tail” sequences are thought to regulate turnover and transactivation. We show here that the N- and C-tails are also potent transport sequences. The unstructured tails of β-catenin, when individually fused to a GFP-reporter, could enter and exit the nucleus rapidly in live cells. Proximity ligation assays and pull-down assays identified a weak interaction between the tail sequences and the FG-repeats of nucleoporins, consistent with a possible direct translocation of β-catenin through the nuclear pore complex. Extensive alanine mutagenesis of the tail sequences revealed that nuclear translocation of β-catenin was dependent on specific uniformly distributed patches of hydrophobic residues, whereas the mutagenesis of acidic amino acids had no effect. Moreover, the mutation of hydrophobic patches within the N-tail and C-tail of full length β-catenin reduced nuclear transport rate and diminished its ability to activate transcription. We propose that the tail sequences can contribute to β-catenin transport and suggest a possible similar role for hydrophobic unstructured regions in other proteins. - Highlights: • We show that the N- and C-tails of beta-catenin possess nuclear transport activity. • Nuclear transport of the N- or C-tails requires specific hydrophobic amino acids. • Mutagenesis of the N-terminus diminished nuclear entry of full-length beta-catenin. • We propose the N-tail contributes to beta-catenin nuclear entry and transactivation.

60 APPLIED LIFE SCIENCES↗

Mechanism of mismatch recognition revealed by human MutS[beta] bound to unpaired DNA loops

DNA mismatch repair corrects replication errors, thus reducing mutation rates and microsatellite instability. Genetic defects in this pathway cause Lynch syndrome and various cancers in humans. Binding of a mispaired or unpaired base by bacterial MutS and eukaryotic MutS{alpha} is well characterized. We report here crystal structures of human MutS{beta} in complex with DNA containing insertion-deletion loops (IDL) of two, three, four or six unpaired nucleotides. In contrast to eukaryotic MutS{alpha} and bacterial MutS, which bind the base of a mismatched nucleotide, MutS{beta} binds three phosphates in an IDL. DNA is severely bent at the IDL; unpaired bases are flipped out into the major groove and partially exposed to solvent. A normal downstream base pair can become unpaired; a single unpaired base can thereby be converted to an IDL of two nucleotides and recognized by MutS{beta}. The C-terminal dimerization domains form an integral part of the MutS structure and coordinate asymmetrical ATP hydrolysis by Msh2 and Msh3 with mismatch binding to signal for repair.

59 BASIC BIOLOGICAL SCIENCES↗

The Nab experiment: A precision measurement of unpolarized neutron beta decay

Neutron beta decay is one of the most fundamental processes in nuclear physics and provides sensitive means to uncover the details of the weak interaction. Neutron beta decay can evaluate the ratio of axial-vector to vector coupling constants in the standard model, λ = gA/gV, through multiple decay correlations. The Nab experiment will carry out measurements of the electron-neutrino correlation parameter a with a precision of δa/a = 10 -3 and the Fierz interference term b to δb = 3 × 10 -3 in unpolarized free neutron beta decay. These results, along with a more precise measurement of the neutron lifetime, aim to deliver an independent determination of the ratio λ with a precision of δλ/λ = 0.03% that will allow an evaluation of Vud and sensitively test CKM unitarity, independent of nuclear models. Nab utilizes a novel, long asymmetric spectrometer that guides the decay electron and proton to two large area silicon detectors in order to precisely determine the electron energy and an estimation of the proton momentum from the proton time of flight. The Nab spectrometer is being commissioned at the Fundamental Neutron Physics Beamline at the Spallation Neutron Source at Oak Ridge National Lab. We present an overview of the Nab experiment and recent updates on the spectrometer, analysis, and systematic effects.

Fry, Jason↗

Transport properties of finite-beta microturbulence

Via nonlinear gyrokinetic simulations, microturbulent transport is investigated for electromagnetic trapped electron mode (TEM) and ion temperature gradient (ITG) tokamak core turbulence with beta up to and beyond the kinetic ballooning mode threshold. Deviations from linear expectations are explained by zonal flow activity in the TEM case. For the ITG scenario, beta-induced changes are observed in the nonlinear critical gradient upshift--from a certain beta, a strong increase is observed in the Dimits shift. Additionally, a Rechester-Rosenbluth-type model for magnetic transport is applied, and the amplitudes of magnetic field fluctuations are quantified for different types of turbulence.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Tridiagonal realization of the antisymmetric Gaussian {beta}-ensemble

The Householder reduction of a member of the antisymmetric Gaussian unitary ensemble gives an antisymmetric tridiagonal matrix with all independent elements. The random variables permit the introduction of a positive parameter {beta}, and the eigenvalue probability density function of the corresponding random matrices can be computed explicitly, as can the distribution of (q{sub i}), the first components of the eigenvectors. Three proofs are given. One involves an inductive construction based on bordering of a family of random matrices which are shown to have the same distributions as the antisymmetric tridiagonal matrices. This proof uses the Dixon-Anderson integral from Selberg integral theory. A second proof involves the explicit computation of the Jacobian for the change of variables between real antisymmetric tridiagonal matrices, its eigenvalues, and (q{sub i}). The third proof maps matrices from the antisymmetric Gaussian {beta}-ensemble to those realizing particular examples of the Laguerre {beta}-ensemble. In addition to these proofs, we note some simple properties of the shooting eigenvector and associated Pruefer phases of the random matrices.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

Seebeck and thermal conductivity analysis in amorphous/crystalline {beta}-K{<_2}Bi{<_8}Se{<_13} nanocomposite materials.

In this work, ball milling is applied on {beta}-K{sub 2}Bi{sub 8}Se{sub 13} compounds in order to explore the potential of the process for the fabrication of nano-based material. Polycrystalline {beta}-K{sub 2}Bi{sub 8}Se{sub 13}, synthesized from melt, was ball milled under inert atmosphere. Powder x-ray diffraction showed a significantly increased disorder with ball milling time. TEM studies confirmed the presence of nanocrystalline material in an amorphous matrix, suggesting the development of crystalline/amorphous {beta}-K{sub 2}Bi{sub 8}Se{sub 13} nanocomposite material via ball milling process. Seebeck coefficient and thermal conductivity were analyzed based on the effective medium theory and show a significant contribution of a nanocrystalline phase.

36 MATERIALS SCIENCE↗

The MAJORANA DEMONSTRATOR: A Search for Neutrinoless Double-beta Decay of Germanium-76

The observation of neutrinoless double-beta decay would determine whether the neutrino is a Majorana particle and provide information on the absolute scale of neutrino mass. The MAJORANA Collaboration is constructing the DEMONSTRATOR, an array of germanium detectors, to search for neutrinoless double-beta decay of 76Ge. The DEMONSTRATOR will contain 40 kg of germanium; up to 30 kg will be enriched to 86% in 76Ge. The DEMONSTRATOR will be deployed deep underground in an ultra-low-background shielded environment. Operation of the DEMONSTRATOR aims to determine whether a future tonne-scale germanium experiment can achieve a background goal of one count per tonne-year in a 4-keV region of interest around the 76Ge neutrinoless double-beta decay Q-value of 2039 keV.

Schubert, Alexis G.↗

Effect of geometrical configuration of radioactive sources on radiation intensity in beta-voltaic nuclear battery system: A preliminary result

It is known that one main problem in the application of beta-voltaic nuclear battery system is its low efficiency. The efficiency of the beta-voltaic nuclear battery system mainly depends on three aspects: source of radioactive radiation, interface between materials in the system and process of converting electron-hole pair to electric current in the semiconductor material. In this work, we show the effect of geometrical configuration of radioactive sources on radiation intensity of beta-voltaic nuclear battery system.

07 ISOTOPE AND RADIATION SOURCES↗

Extending the validation of multi-mode model for anomalous transport to high beta poloidal tokamak scenario in DIII-D

The Multi-Mode Model (MMM7.1) for anomalous transport is tested in predictive modeling of temperature profiles of a high beta poloidal DIII-D discharge. This new H-mode plasma regime, with high beta poloidal and high bootstrap currents, has been studied in DIII-D tokamak discharges. The role of instabilities that can drive the anomalous transport described by MMM7.1 is investigated. The temperature profiles for a high beta poloidal DIII-D discharge are computed using the NCLASS model for the neoclassical transport and the Weiland and Electron Temperature Gradient (ETG) components of the MMM7.1 model for the anomalous transport. Here, the neoclassical transport is found to be the main contributor to the ion thermal transport in the plasma core.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

Close coupling of the peeling ballooning and external kink modes in high poloidal-beta discharges with strong shape and large pedestal width

In plasmas with strong shape and large pedestal width, like DIII-D high poloidal-beta discharges, the eigenvalue spectrum of the peeling ballooning mode (PBM) is shown to shift to the very low-n regime near one, where n is the toroidal mode number. This peeling-type eigenvalue spectrum has a further shift to n = 1, thus being smoothly connected to the n = 1 external kink mode (EKM), as the normalized beta (β N ) increases. Once this connection occurs, the mode takes a mixture form of the PBM and EKM with its mode structure varying from the PBM-like to the EKM-like one as β N increases. The mode stability also becomes sensitive to both the local pedestal gradient and global β N , thus allowing an anti-correlation between the two driving forces. Further, these results appear to provide a qualitative explanation of the two unexpected features observed in the DIII-D high poloidal-beta discharges, that is, the dominance of the n = 1 mode in the edge-localized-modes and the negative correlation between the pedestal height and the internal transport barrier strength.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

THE STRUCTURE OF THE {beta} LEONIS DEBRIS DISK

We combine nulling interferometry at 10 {mu}m using the MMT and Keck Telescopes with spectroscopy, imaging, and photometry from 3 to 100 {mu}m using Spitzer to study the debris disk around {beta} Leo over a broad range of spatial scales, corresponding to radii of 0.1 to {approx}100 AU. We have also measured the close binary star o Leo with both Keck and MMT interferometers to verify our procedures with these instruments. The {beta} Leo debris system has a complex structure: (1) relatively little material within 1 AU; (2) an inner component with a color temperature of {approx}600 K, fitted by a dusty ring from about 2-3 AU; and (3) a second component with a color temperature of {approx}120 K fitted by a broad dusty emission zone extending from about {approx}5 AU to {approx}55 AU. Unlike many other A-type stars with debris disks, {beta} Leo lacks a dominant outer belt near 100 AU.

79 ASTRONOMY AND ASTROPHYSICS↗

H{beta} LINE WIDTHS AS AN ORIENTATION INDICATOR FOR LOW-IONIZATION BROAD ABSORPTION LINE QUASARS

There is evidence from radio-loud quasars to suggest that the distribution of the H{beta} broad emission line (BEL) gas is arranged in a predominantly planar orientation, and this result may well also apply to radio-quiet quasars. This would imply that the observed FWHM of the H{beta} BELs is dependent on the orientation of the line of sight to the gas. If this view is correct then we propose that the FWHM can be used as a surrogate, in large samples, to determine the line of sight to the H{beta} BELs in broad absorption line quasars (BALQSOs). The existence of broad UV absorption lines (BALs) means that the line of sight to BALQSOs must also pass through the BAL out-flowing gas. It is determined that there is a statistically significant excess of narrow-line profiles in the SDSS DR7 archival spectra of low-ionization broad absorption line quasars (LoBALQSOs), indicating that BAL gas flowing close to the equatorial plane does not commonly occur in these sources. We also find that the data is not well represented by random lines of sight to the BAL gas. Our best fit indicates two classes of LoBALQSOs, the majority ({approx}2/3) are polar outflows that are responsible for the enhanced frequency of narrow-line profiles, and the remainder are equatorial outflows. We further motivated the line of sight explanation of the narrow-line excess in LoBALQSOs by considering the notion that the skewed distribution of line profiles is driven by an elevated Eddington ratio in BALQSOs. We constructed a variety of control samples comprised of non-LoBALQSOs matched to a de-reddened LoBALQSO sample in redshift, luminosity, black hole mass, and Eddington ratio. It is demonstrated that the excess of narrow profiles persists within the LoBALQSO sample relative to each of the control samples with no reduction of the statistical significance. Thus, we eliminate the possibility that the excess narrow lines seen in the LoBALQSOs arise from an enhanced Eddington ratio.

79 ASTRONOMY AND ASTROPHYSICS↗

COLDER AND HOTTER: INTERFEROMETRIC IMAGING OF {beta} CASSIOPEIAE AND {alpha} LEONIS

Near-infrared interferometers have recently imaged a number of rapidly rotating A-type stars, finding levels of gravity darkening inconsistent with theoretical expectations. Here, we present new imaging of both a cooler star {beta} Cas (F2IV) and a hotter one {alpha} Leo (B7V) using the CHARA array and the MIRC instrument at the H band. Adopting a solid-body rotation model with a simple gravity darkening prescription, we modeled the stellar geometric properties and surface temperature distributions, confirming that both stars are rapidly rotating and show gravity darkening anomalies. We estimate the masses and ages of these rapid rotators on L-R{sub pol} and H-R diagrams constructed for non-rotating stars by tracking their non-rotating equivalents. The unexpected fast rotation of the evolved sub-giant {beta} Cas offers a unique test of the stellar core-envelope coupling, revealing quite efficient coupling over the past {approx}0.5 Gyr. Lastly, we summarize all our interferometric determinations of the gravity darkening coefficient for rapid rotators, finding that none match the expectations from the widely used von Zeipel gravity darkening laws. Since the conditions of the von Zeipel law are known to be violated for rapidly rotating stars, we recommend using the empirically derived {beta} = 0.19 for such stars with radiation-dominated envelopes. Furthermore, we note that no paradigm exists for self-consistently modeling heavily gravity-darkened stars that show hot radiative poles with cool convective equators.

79 ASTRONOMY AND ASTROPHYSICS↗

A STUDY OF THE ROLE OF Ly{beta} FLUORESCENCE ON O I LINE STRENGTHS IN Be STARS

The possibility of the Ly{beta} fluorescence mechanism being operational in classical Be (CBe) stars and thereby contributing to the strength of the O I {lambda}8446 line has been recognized for long. However, this supposition needs to be quantified by comparing observed and predicted O I line ratios. In the present work, optical and near-infrared spectra of CBe stars are presented. We analyze the observed strengths of the O I {lambda}7774, {lambda}8446, {lambda}11287, and {lambda}13165 lines, which have been theoretically proposed as diagnostics for identifying the excitation mechanism. We have considered and examined the effects of Ly{beta} fluorescence, collisional excitation, recombination, and continuum fluorescence on these O I line strengths. From our analysis it appears that the Ly{beta} fluorescence process is indeed operative in Be stars.

79 ASTRONOMY AND ASTROPHYSICS↗

Variable-spectrum mode control of high poloidal beta discharges

DIII-D experiments demonstrate that high pressure, broad current profile equilibria can be accessed in the high poloidal beta regime by optimizing the MHD mode control poloidal spectrum. A novel, variable spectrum (VS) magnetic feedback scheme implemented using the DIII-D internal non-axisymmetric coils (I-coils) facilitated access to reduced internal inductance $l$ i operation above the no-wall beta limit compared with both no feedback and fixed spectrum feedback. In addition, the VS feedback helped avoid beta collapses caused by marginally unstable resistive wall mode activity. The lower and upper I-coil rows were configured in two independent feedback loops, allowing the feedback field's poloidal spectrum to vary and track changes in the plasma mode structure as the edge safety factor q 95 varied from 11 to 6 during the discharges. The q 95 dependence of the measured phase difference between the lower and upper I-coil rows during VS feedback is qualitatively compatible with ideal MHD simulations of the least-stable plasma kink mode and with plasma response simulations that included kinetic modifications to ideal MHD. The VS feedback approach is a straightforward way to improve resilience to variations in mode structure that occur as plasma parameters change. The demonstrated expansion of the operating space to lower $l$ i is expected to improve the coupling of the plasma kink mode to external fields and beneficial wall eddy currents, and is compatible with high bootstrap fraction operation.

70 PLASMA PHYSICS AND FUSION TECHNOLOGY↗

FIRST MAGNETIC FIELD MODELS FOR RECENTLY DISCOVERED MAGNETIC {beta} CEPHEI AND SLOWLY PULSATING B STARS

In spite of recent detections of magnetic fields in a number of {beta} Cephei and slowly pulsating B (SPB) stars, their impact on stellar rotation, pulsations, and element diffusion has not yet been sufficiently studied. The reason for this is the lack of knowledge of rotation periods, the magnetic field strength distribution and temporal variability, and the field geometry. New longitudinal field measurements of four {beta} Cephei and candidate {beta} Cephei stars, and two SPB stars were acquired with FORS 2 at the Very Large Telescope. These measurements allowed us to carry out a search for rotation periods and to constrain the magnetic field geometry for four stars in our sample.

79 ASTRONOMY AND ASTROPHYSICS↗

Computational design of an endo-1,4-[beta]-xylanase ligand binding site

The field of computational protein design has experienced important recent success. However, the de novo computational design of high-affinity protein-ligand interfaces is still largely an open challenge. Using the Rosetta program, we attempted the in silico design of a high-affinity protein interface to a small peptide ligand. We chose the thermophilic endo-1,4-{beta}-xylanase from Nonomuraea flexuosa as the protein scaffold on which to perform our designs. Over the course of the study, 12 proteins derived from this scaffold were produced and assayed for binding to the target ligand. Unfortunately, none of the designed proteins displayed evidence of high-affinity binding. Structural characterization of four designed proteins revealed that although the predicted structure of the protein model was highly accurate, this structural accuracy did not translate into accurate prediction of binding affinity. Crystallographic analyses indicate that the lack of binding affinity is possibly due to unaccounted for protein dynamics in the 'thumb' region of our design scaffold intrinsic to the family 11 {beta}-xylanase fold. Further computational analysis revealed two specific, single amino acid substitutions responsible for an observed change in backbone conformation, and decreased dynamic stability of the catalytic cleft. These findings offer new insight into the dynamic and structural determinants of the {beta}-xylanase proteins.

59 BASIC BIOLOGICAL SCIENCES↗